@misc{godley iii_meitzen_nahman-averbuch_o'neal_yeomans_santoro_riggins_edvinsson_2024, title={How Sex Hormones Affect Migraine: An Interdisciplinary Preclinical Research Panel Review}, volume={14}, ISSN={["2075-4426"]}, DOI={10.3390/jpm14020184}, abstractNote={Sex hormones and migraine are closely interlinked. Women report higher levels of migraine symptoms during periods of sex hormone fluctuation, particularly during puberty, pregnancy, and perimenopause. Ovarian steroids, such as estrogen and progesterone, exert complex effects on the peripheral and central nervous systems, including pain, a variety of special sensory and autonomic functions, and affective processing. A panel of basic scientists, when challenged to explain what was known about how sex hormones affect the nervous system, focused on two hormones: estrogen and oxytocin. Notably, other hormones, such as progesterone, testosterone, and vasopressin, are less well studied but are also highlighted in this review. When discussing what new therapeutic agent might be an alternative to hormone therapy and menopause replacement therapy for migraine treatment, the panel pointed to oxytocin delivered as a nasal spray. Overall, the conclusion was that progress in the preclinical study of hormones on the nervous system has been challenging and slow, that there remain substantial gaps in our understanding of the complex roles sex hormones play in migraine, and that opportunities remain for improved or novel therapeutic agents. Manipulation of sex hormones, perhaps through biochemical modifications where its positive effects are selected for and side effects are minimized, remains a theoretical goal, one that might have an impact on migraine disease and other symptoms of menopause. This review is a call to action for increased interest and funding for preclinical research on sex hormones, their metabolites, and their receptors. Interdisciplinary research, perhaps facilitated by a collaborative communication network or panel, is a possible strategy to achieve this goal.}, number={2}, journal={JOURNAL OF PERSONALIZED MEDICINE}, author={Godley III, Frederick and Meitzen, John and Nahman-Averbuch, Hadas and O'Neal, Mary Angela and Yeomans, David and Santoro, Nanette and Riggins, Nina and Edvinsson, Lars}, year={2024}, month={Feb} }
 @article{proano_miller_krentzel_dorris_meitzen_2024, title={Sex steroid hormones, the estrous cycle, and rapid modulation of glutamatergic synapse properties in the striatal brain regions with a focus on 17β -estradiol and the nucleus accumbens}, volume={201}, ISSN={["1878-5867"]}, DOI={10.1016/j.steroids.2023.109344}, abstractNote={The striatal brain regions encompassing the nucleus accumbens core (NAcc), shell (NAcs) and caudate-putamen (CPu) regulate cognitive functions including motivated behaviors, habit, learning, and sensorimotor action, among others. Sex steroid hormone sensitivity and sex differences have been documented in all of these functions in both normative and pathological contexts, including anxiety, depression and addiction. The neurotransmitter glutamate has been implicated in regulating these behaviors as well as striatal physiology, and there are likewise documented sex differences in glutamate action upon the striatal output neurons, the medium spiny neurons (MSNs). Here we review the available data regarding the role of steroid sex hormones such as 17β-estradiol (estradiol), progesterone, and testosterone in rapidly modulating MSN glutamatergic synapse properties, presented in the context of the estrous cycle as appropriate. Estradiol action upon glutamatergic synapse properties in female NAcc MSNs is most comprehensively discussed. In the female NAcc, MSNs exhibit development period-specific sex differences and estrous cycle variations in glutamatergic synapse properties as shown by multiple analyses, including that of miniature excitatory postsynaptic currents (mEPSCs). Estrous cycle-differences in NAcc MSN mEPSCs can be mimicked by acute exposure to estradiol or an ERα agonist. The available evidence, or lack thereof, is also discussed concerning estrogen action upon MSN glutamatergic synapse in the other striatal regions as well as the underexplored roles of progesterone and testosterone. We conclude that there is strong evidence regarding estradiol action upon glutamatergic synapse function in female NAcs MSNs and call for more research regarding other hormones and striatal regions.}, journal={STEROIDS}, author={Proano, Stephanie B. and Miller, Christiana K. and Krentzel, Amanda A. and Dorris, David M. and Meitzen, John}, year={2024}, month={Jan} }
 @article{long_reich_staicu_meitzen_2023, title={A nonparametric test of group distributional differences for hierarchically clustered functional data}, volume={3}, ISSN={["1541-0420"]}, DOI={10.1111/biom.13846}, abstractNote={Abstract}, journal={BIOMETRICS}, author={Long, Alexander S. and Reich, Brian J. and Staicu, Ana-Maria and Meitzen, John}, year={2023}, month={Mar} }
 @article{miller_krentzel_meitzen_2023, title={ER alpha stimulation rapidly modulates excitatory synapse properties in female rat nucleus accumbens core}, volume={2}, ISSN={["1423-0194"]}, DOI={10.1159/000529571}, abstractNote={<b><i>Introduction:</i></b> The nucleus accumbens core (NAcc) is a sexually differentiated brain region that is modulated by steroid hormones such as 17β-estradiol (estradiol), with consequential impacts on relevant motivated behaviors and disorders such as addiction, anxiety, and depression. NAcc estradiol levels naturally fluctuate, including during the estrous cycle in adult female rats, which is analogous to the menstrual cycle in adult humans. Across the estrous cycle, excitatory synapse properties of medium spiny neurons rapidly change, as indicated by analysis of miniature excitatory postsynaptic currents (mEPSCs). mEPSC frequency decreases during estrous cycle phases associated with high estradiol levels. This decrease in mEPSC frequency is mimicked by acute topical exposure to estradiol. The identity of the estrogen receptor (ER) underlying this estradiol action is unknown. Adult rat NAcc expresses three ERs, all extranuclear: membrane ERα, membrane ERβ, and GPER1. <b><i>Methods:</i></b> In this brief report, we take a first step toward addressing this challenge by testing whether activation of ERs via acute topical agonist application is sufficient for inducing changes in mEPSC properties recorded via whole-cell patch clamp. <b><i>Results:</i></b> An agonist of ERα induced large decreases in mEPSC frequency, while agonists of ERβ and GPER1 did not robustly modulate mEPSC properties. <b><i>Conclusions:</i></b> These data provide evidence that activation of ERα is sufficient for inducing changes in mEPSC frequency and is a likely candidate underlying the estradiol-induced changes observed during the estrous cycle. Overall, these findings extend our understanding of the neuroendocrinology of the NAcc and implicate ERα as a primary target for future studies. }, journal={NEUROENDOCRINOLOGY}, author={Miller, Christiana K. and Krentzel, Amanda A. and Meitzen, John}, year={2023}, month={Feb} }
 @article{beeson_meitzen_2023, title={Estrous cycle impacts on dendritic spine plasticity in rat nucleus accumbens core and shell and caudate-putamen}, volume={2}, ISSN={["1096-9861"]}, DOI={10.1002/cne.25460}, abstractNote={Abstract}, journal={JOURNAL OF COMPARATIVE NEUROLOGY}, author={Beeson, Anna L. S. and Meitzen, John}, year={2023}, month={Feb} }
 @article{seib_tobiansky_meitzen_floresco_soma_2023, title={Neurosteroids and the mesocorticolimbic system}, volume={153}, ISSN={["1873-7528"]}, DOI={10.1016/j.neubiorev.2023.105356}, abstractNote={The mesocorticolimbic system coordinates executive functions, such as working memory and behavioral flexibility. This circuit includes dopaminergic projections from the ventral tegmental area to the nucleus accumbens and medial prefrontal cortex. In this review, we summarize evidence that cells in multiple nodes of the mesocorticolimbic system produce neurosteroids (steroids synthesized in the nervous system) and express steroid receptors. Here, we focus on neuroandrogens (androgens synthesized in the nervous system), neuroestrogens (estrogens synthesized in the nervous system), and androgen and estrogen receptors. We also summarize how (neuro)androgens and (neuro)estrogens affect dopamine signaling in the mesocorticolimbic system and regulate executive functions. Taken together, the data suggest that steroids produced in the gonads and locally in the brain modulate higher-order cognition and executive functions.}, journal={NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS}, author={Seib, Desiree R. and Tobiansky, Daniel J. and Meitzen, John and Floresco, Stan B. and Soma, Kiran K.}, year={2023}, month={Oct} }
 @article{miller_meitzen_2023, title={No detectable changes in anxiety-related and locomotor behaviors in adult ovariectomized female rats exposed to estradiol, the ER beta agonist DPN or the ER alpha agonist PPT}, volume={152}, ISSN={["1095-6867"]}, DOI={10.1016/j.yhbeh.2023.105363}, abstractNote={The sex steroid hormone 17β-estradiol (estradiol) and its Estrogen Receptors (ERs) have been linked to modulation of anxiety-related and locomotor behaviors in female rodents. Research suggests that estradiol mitigates anxiety-related behaviors through activating Estrogen Receptor (ER)β and increases locomotor behaviors through ERα. The influence of ERs on these behaviors cannot always be detected. Here we discuss two experiments in which we tested the hypothesis that anxiety-related behaviors would decrease after ERβ activation and locomotor behaviors would increase after ERα activation, and also assessed the persistence of these behavioral effects by varying the timing of behavioral testing. Two cohorts of adult female ovariectomized rats were exposed to estradiol, the ERβ agonist DPN, the ERα agonist PPT, or oil for four consecutive days. Body mass was assessed throughout as a positive control. In both cohorts, open field behaviors were assessed on the first day of exposure. In one cohort (Experiment 1), open field, light/dark box, and elevated plus maze behaviors were assessed on the final day of injections. In the second cohort (Experiment 2), these behaviors were assessed 24 h after the final exposure. As expected, significant differences in body mass were detected in response to estradiol and PPT exposure, validating the estradiol and ER manipulation. No significant differences were observed in anxiety-related or locomotor behaviors across treatment groups, indicating that the efficacy of these agonists as therapeutic agents may be limited. We review these results in the context of previous literature, emphasizing relevant variables that may obscure ER-related actions on behavior.}, journal={HORMONES AND BEHAVIOR}, author={Miller, Christiana K. and Meitzen, John}, year={2023}, month={Jun} }
 @article{kimble_twiddy_berger_forderhase_mccarty_meitzen_sombers_2023, title={Simultaneous, Real-Time Detection of Glutamate and Dopamine in Rat Striatum Using Fast-Scan Cyclic Voltammetry}, volume={8}, ISSN={["2379-3694"]}, DOI={10.1021/acssensors.3c01267}, abstractNote={Glutamate and dopamine (DA) represent two key contributors to striatal functioning, a region of the brain that is essential to motor coordination and motivated behavior. While electroanalytical techniques can be utilized for rapid, spatially resolved detection of DA in the interferent-rich brain environment, glutamate, a nonelectroactive analyte, cannot be directly detected using electroanalytical techniques. However, it can be probed using enzyme-based sensors, which generate an electroactive reporter in the presence of glutamate. The vast majority of glutamate biosensors have relied on amperometric sensing, which is an inherently nonselective detection technique. This approach necessitates the use of complex and performance-limiting modifications to ensure the desired single-analyte specificity. Here, we present a novel glutamate microbiosensor fabricated on a carbon-fiber microelectrode substrate and coupled with fast-scan cyclic voltammetry (FSCV) to enable the simultaneous quantification of glutamate and DA at single recording sites in the brain, which is impossible when using typical amperometric approaches. The glutamate microbiosensors were characterized for sensitivity, stability, and selectivity by using a voltammetric waveform optimized for the simultaneous detection of both species. The applicability of these sensors for the investigation of neural circuits was validated in the rat ventral striatum. Electrically evoked glutamate and DA release were recorded at single-micrometer-scale locations before and after pharmacological manipulation of glutamatergic signaling. Our novel glutamate microbiosensor advances the state of the art by providing a powerful tool for probing coordination between these two species in a way that has previously not been possible.}, number={11}, journal={ACS SENSORS}, author={Kimble, Laney C. and Twiddy, Jack S. and Berger, Jenna M. and Forderhase, Alexandra G. and Mccarty, Gregory S. and Meitzen, John and Sombers, Leslie A.}, year={2023}, month={Nov}, pages={4091–4100} }
 @article{krentzel_proano_dorris_setzer_meitzen_2022, title={The estrous cycle and 17 beta-estradiol modulate the electrophysiological properties of rat nucleus accumbens core medium spiny neurons}, volume={4}, ISSN={["1365-2826"]}, DOI={10.1111/jne.13122}, abstractNote={Abstract}, journal={JOURNAL OF NEUROENDOCRINOLOGY}, author={Krentzel, Amanda A. and Proano, Stephanie B. and Dorris, David M. and Setzer, Beverly and Meitzen, John}, year={2022}, month={Apr} }
 @article{krentzel_willett_johnson_meitzen_2021, title={Estrogen receptor alpha, G-protein coupled estrogen receptor 1, and aromatase: Developmental, sex, and region-specific differences across the rat caudate-putamen, nucleus accumbens core and shell}, volume={529}, ISSN={["1096-9861"]}, DOI={10.1002/cne.24978}, abstractNote={Abstract}, number={4}, journal={JOURNAL OF COMPARATIVE NEUROLOGY}, author={Krentzel, Amanda A. and Willett, Jaime A. and Johnson, Ashlyn G. and Meitzen, John}, year={2021}, month={Mar}, pages={786–801} }
 @article{krentzel_kimble_dorris_horman_meitzen_patisaul_2021, title={FireMaster (R) 550 (FM 550) exposure during the perinatal period impacts partner preference behavior and nucleus accumbens core medium spiny neuron electrophysiology in adult male and female prairie voles, Microtus ochrogaster}, volume={134}, ISSN={["1095-6867"]}, DOI={10.1016/j.yhbeh.2021.105019}, abstractNote={One of the most widely used flame retardant (FR) mixtures in household products is Firemaster 550 (FM 550). FM 550 leaches from items such as foam-based furniture and infant products, resulting in contamination of the household environment and biota. Previous studies indicate sex-specific behavioral deficits in rodents and zebrafish in response to developmental FM 550 exposure. These deficits include impacts on social and attachment behaviors in a prosocial rodent: the prairie vole (Microtus ochrogaster). The prairie vole is a laboratory-acclimated rodent that exhibits spontaneous attachment behaviors including pair bonding. Here we extend previous work by addressing how developmental exposure to FM 550 impacts pair bonding strength via an extended-time partner preference test, as well as neuron electrophysiological properties in a region implicated in pair bond behavior, the nucleus accumbens (NAcc) core. Dams were exposed to vehicle or 1000 μg of FM 550 via subcutaneous injections throughout gestation, and female and male pups were directly exposed beginning the day after birth until weaning. Pair bond behavior of adult female and male offspring was assessed using a three hour-long partner preference test. Afterwards, acute brain slices of the NAcc core were produced and medium spiny neuron electrophysiological attributes recorded via whole cell patch-clamp. Behavioral impacts were sex-specific. Partner preference behavior was increased in exposed females but decreased in exposed males. Electrophysiological impacts were similar between sexes and specific to attributes related to input resistance. Input resistance was decreased in neurons recorded from both sexes exposed to FM 550 compared to vehicle. This study supports the hypothesis that developmental exposure to FM 550 impacts attachment behaviors and demonstrates a novel FM 550 effect on neural electrophysiology.}, journal={HORMONES AND BEHAVIOR}, author={Krentzel, Amanda A. and Kimble, Laney C. and Dorris, David M. and Horman, Brian M. and Meitzen, John and Patisaul, Heather B.}, year={2021}, month={Aug} }
 @article{miller_halbing_patisaul_meitzen_2021, title={Interactions of the estrous cycle, novelty, and light on female and male rat open field locomotor and anxiety-related behaviors}, volume={228}, ISSN={["1873-507X"]}, DOI={10.1016/j.physbeh.2020.113203}, abstractNote={Animal behavior can be modulated by multiple interacting factors. In rodents such as rats, these factors include, among others, the female estrous cycle, exposure to a novel environment, and light. Here, we used the open field test to disassociate differences in behavior resulting from each of these factors by testing the hypothesis that locomotor and anxiety-related behaviors differ between estrous cycle phases in female rats and that novelty and light exposure concurrently influence these behaviors in both female and male rats. Adult female rats were tested twice under red or white light in estrus and diestrus estrous cycle phases. Adult male rats were also tested twice under either red or white light. In females, an interaction between novelty and estrous cycle phase influenced locomotor and anxiety-related behaviors. In males, novelty influenced locomotor and anxiety-related behaviors differentially under red and white light. Light exposure increased anxiety-related behaviors in both males and females, but reduced locomotor behavior only in females. These findings reveal the complexities of behavioral testing and highlight the importance of factors such as the estrous cycle, novelty, and light exposure.}, journal={PHYSIOLOGY & BEHAVIOR}, author={Miller, Christiana K. and Halbing, Amy A. and Patisaul, Heather B. and Meitzen, John}, year={2021}, month={Jan} }
 @article{cao_meitzen_2021, title={Perinatal activation of ER alpha and ER beta but not GPER-1 masculinizes female rat caudate-putamen medium spiny neuron electrophysiological properties}, volume={125}, ISSN={["1522-1598"]}, DOI={10.1152/jn.00063.2021}, abstractNote={ This study is the first to demonstrate that estradiol and estrogen receptor α and β stimulation during early development sexually differentiates the electrophysiological properties of caudate-putamen medium spiny neurons, the primary output neuron of the striatal regions. Overall, this evidence provides new insight into the neuroendocrine mechanism by which caudate-putamen neuron electrophysiology is sexually differentiated and demonstrates the powerful action of early hormone exposure upon individual neuron electrophysiology. }, number={6}, journal={JOURNAL OF NEUROPHYSIOLOGY}, author={Cao, Jinyan and Meitzen, John}, year={2021}, month={Jun}, pages={2322–2338} }
 @article{proano_krentzel_meitzen_2020, title={Differential and synergistic roles of 17 beta-estradiol and progesterone in modulating adult female rat nucleus accumbens core medium spiny neuron electrophysiology}, volume={123}, ISSN={["1522-1598"]}, DOI={10.1152/jn.00157.2020}, abstractNote={ This research indicates that estradiol and progesterone act both differentially and synergistically to modulate neuron physiology in the nucleus accumbens core. These actions by specific hormones provide key data indicating the endocrine mechanisms underlying how the estrous cycle modulates neuron physiology in this region. Overall, these data reinforce that hormones are an important influence on neural physiology. }, number={6}, journal={JOURNAL OF NEUROPHYSIOLOGY}, author={Proano, Stephanie B. and Krentzel, Amanda A. and Meitzen, John}, year={2020}, month={Jun}, pages={2390–2405} }
 @article{proano_meitzen_2020, title={Estradiol decreases medium spiny neuron excitability in female rat nucleus accumbens core}, volume={123}, ISSN={["1522-1598"]}, DOI={10.1152/jn.00210.2020}, abstractNote={ The present study shows, for the first time, that an estrous cycle-relevant estradiol exposure modulates nucleus accumbens neuron excitability. This evidence provides insight into the neuroendocrine mechanisms by which estradiol cyclically alters neuron properties during the estrous cycle. Overall, these data emphasize the significant influence of hormone action in the brain and especially individual neuron physiology. }, number={6}, journal={JOURNAL OF NEUROPHYSIOLOGY}, author={Proano, Stephanie B. and Meitzen, John}, year={2020}, month={Jun}, pages={2465–2475} }
 @article{miller_krentzel_patisaul_meitzen_2020, title={Metabotropic glutamate receptor subtype 5 (mGlu(5)) is necessary for estradiol mitigation of light-induced anxiety behavior in female rats}, volume={214}, ISSN={["0031-9384"]}, DOI={10.1016/j.physbeh.2019.112770}, abstractNote={Anxiety-related behaviors are influenced by steroid hormones such as 17β-estradiol and environmental stimuli such as acute stressors. For example, rats exhibit increased anxiety-related behaviors in the presence, but not the absence, of light. In females, estradiol potentially mitigates these effects. Experiments across behavioral paradigms and brain regions indicate that estradiol action can be mediated via activation of metabotropic glutamate receptors, including Group I subtype five (mGlu5). mGlu5 has been implicated in mediating estradiol's effects upon psychostimulant-induced behaviors, dopamine release and neuron phenotype in striatal regions. Whether estradiol activation of mGlu5 modulates anxiety or locomotor behavior in the absence of psychostimulants is unknown. Here we test if mGlu5 is necessary for estradiol mitigation of light-induced acute anxiety and locomotor behaviors. Ovariectomized adult female rats were pre-treated with either the mGlu5 antagonist MPEP or saline before estradiol or oil treatment. Anxiety and locomotor behaviors were assessed in the presence or absence of white light to induce high and low acute anxiety behavior phenotypes, respectively. In the presence of white light, estradiol treatment mitigated light-induced anxiety-related behaviors but not overall locomotor activity. MPEP treatment blocked estradiol effects upon light-induced anxiety-related behaviors but did not affect overall locomotor activity. In the absence of white light, estradiol or MPEP treatment did not influence anxiety-related behaviors or locomotor activity, consistent with a low anxiety phenotype. These novel findings indicate that mGlu5 activation is necessary for estradiol mitigation of anxiety-related behaviors induced by an acute stressor.}, journal={PHYSIOLOGY & BEHAVIOR}, author={Miller, Christiana K. and Krentzel, Amanda A. and Patisaul, Heather B. and Meitzen, John}, year={2020}, month={Feb} }
 @misc{mamlouk_dorris_barrett_meitzen_2020, title={Sex bias and omission in neuroscience research is influenced by research model and journal, but not reported NIH funding}, volume={57}, ISSN={["1095-6808"]}, DOI={10.1016/j.yfrne.2020.100835}, abstractNote={Neuroscience research has historically demonstrated sex bias that favors male over female research subjects, as well as sex omission, which is the lack of reporting sex. Here we analyzed the status of sex bias and omission in neuroscience research published across six different journals in 2017. Regarding sex omission, 16% of articles did not report sex. Regarding sex bias, 52% of neuroscience articles reported using both males and females, albeit only 15% of articles using both males and females reported assessing sex as an experimental variable. Overrepresentation of the sole use of males compared to females persisted (26% versus 5%, respectively). Sex bias and omission differed across research models, but not by reported NIH funding status. Sex omission differed across journals. These findings represent the latest information regarding the complex status of sex in neuroscience research and illustrate the continued need for thoughtful and informed action to enhance scientific discovery.}, journal={FRONTIERS IN NEUROENDOCRINOLOGY}, author={Mamlouk, Gabriella M. and Dorris, David M. and Barrett, Lily R. and Meitzen, John}, year={2020}, month={Apr} }
 @article{krentzel_proano_patisaul_meitzen_2020, title={Temporal and bidirectional influences of estradiol on voluntary wheel running in adult female and male rats}, volume={120}, ISSN={["1095-6867"]}, DOI={10.1016/j.yhbeh.2020.104694}, abstractNote={The sex steroid hormone 17β-estradiol (estradiol) regulates animal behavior as both a non-rapid hormone signal and as a rapid-acting neuromodulator. By practical necessity, estradiol's divergent temporal actions on rodent behavior are typically studied singularly and in one sex. We hypothesized that estradiol simultaneously acts through both temporal mechanisms to sex-specifically modulate a single behavior; and furthermore, that estradiol action in one temporal domain may regulate action in another. To test this hypothesis, we utilized one of the most robust rat behaviors exhibiting sex differences and estradiol-responsiveness, voluntary wheel running. Adult female and male rats were gonadectomized and exposed to daily repeated estradiol benzoate (EB) injections. Estradiol-sensitive running behavior was continually assessed in both the rapid and non-rapid temporal domains. We found that in female rats, estradiol rapidly decreased voluntary wheel running, but only after prior daily EB injections, supporting the hypothesis that non-rapid estradiol action influences rapid estradiol actions. Males exhibited a similar but less robust response, demonstrating sex-responsiveness. This rapid estradiol-induced decrease in running contrasted to non-rapid estradiol action which overall increased running in both sexes, revealing a bidirectional nature of estradiol's temporal influence. Non-rapid estradiol action also demonstrated sex-responsiveness, as a higher dose of EB was required to induce increased running in males compared to females. These findings indicate that estradiol rapidly, non-rapidly, and bidirectionally modulates wheel running in a sex-responsive manner, and that rapid estradiol action is modulated by non-rapid estradiol action. Overall, these data illustrate estradiol as a pleiotropic sex-responsive neuromodulator of a single behavior across temporal domains.}, journal={HORMONES AND BEHAVIOR}, author={Krentzel, Amanda A. and Proano, Stephanie and Patisaul, Heather B. and Meitzen, John}, year={2020}, month={Apr} }
 @article{willett_cao_johnson_patel_dorris_meitzen_2020, title={The estrous cycle modulates rat caudate-putamen medium spiny neuron physiology}, volume={52}, ISSN={["1460-9568"]}, DOI={10.1111/ejn.14506}, abstractNote={Abstract}, number={1}, journal={EUROPEAN JOURNAL OF NEUROSCIENCE}, author={Willett, Jaime A. and Cao, Jinyan and Johnson, Ashlyn and Patel, Opal H. and Dorris, David M. and Meitzen, John}, year={2020}, month={Jul}, pages={2737–2755} }
 @article{willett_cao_dorris_johnson_ginnari_meitzen_2019, title={Electrophysiological Properties of Medium Spiny Neuron Subtypes in the Caudate-Putamen of Prepubertal Male and Female Drd1a-tdTomato Line 6 BAC Transgenic Mice}, volume={6}, ISSN={["2373-2822"]}, DOI={10.1523/ENEURO.0016-19.2019}, abstractNote={Abstract}, number={2}, journal={ENEURO}, author={Willett, Jaime A. and Cao, Jinyan and Dorris, David M. and Johnson, Ashlyn G. and Ginnari, Laura A. and Meitzen, John}, year={2019} }
 @article{krentzel_barrett_meitzen_2019, title={Estradiol rapidly modulates excitatory synapse properties in a sex- and region-specific manner in rat nucleus accumbens core and caudate-putamen}, volume={122}, ISSN={["1522-1598"]}, DOI={10.1152/jn.00264.2019}, abstractNote={ Estradiol acutely facilitates sex differences in striatum-dependent behaviors. However, little is understood regarding the underlying mechanism. In striatal regions in adult rodents, estrogen receptors feature exclusively extranuclear expression, suggesting that estradiol rapidly modulates striatal neurons. We tested the hypothesis that estradiol rapidly modulates excitatory synapse properties onto medium spiny neurons (MSNs) of two striatal regions, the nucleus accumbens core and caudate-putamen in adult female and male rats. We predicted there would be sex-specific differences in pre- and postsynaptic locus and sensitivity. We further analyzed whether MSN intrinsic properties are predictive of estrogen sensitivity. Estradiol exhibited sex-specific acute effects in the nucleus accumbens core: miniature excitatory postsynaptic current (mEPSC) frequency robustly decreased in response to estradiol in female MSNs, and mEPSC amplitude moderately increased in response to estradiol in both male and female MSNs. This increase in mEPSC amplitude is associated with MSNs featuring increased intrinsic excitability. No MSN intrinsic electrical property associated with changes in mEPSC frequency. Estradiol did not acutely modulate mEPSC properties in the caudate-putamen of either sex. This is the first demonstration of acute estradiol action on MSN excitatory synapse function. This demonstration of sex and striatal region-specific acute estradiol neuromodulation revises our understanding of sex hormone action on striatal physiology and resulting behaviors. }, number={3}, journal={JOURNAL OF NEUROPHYSIOLOGY}, author={Krentzel, Amanda A. and Barrett, Lily R. and Meitzen, John}, year={2019}, month={Sep}, pages={1213–1225} }
 @article{meitzen_britson_tuomela_mermelstein_2019, title={The expression of select genes necessary for membrane-associated estrogen receptor signaling differ by sex in adult rat hippocampus}, volume={142}, ISSN={["1878-5867"]}, DOI={10.1016/j.steroids.2017.09.012}, abstractNote={17β-estradiol can rapidly modulate neuron function via membrane estrogen receptors (ERs) in a sex-specific manner. For example, female rat hippocampal neurons express palmitoylated versions of ERα and ERβ that associate with the plasma membrane. These membrane-associated ERs are organized by caveolin proteins into functional signaling microdomains with metabotropic glutamate receptors (mGluRs). ER/mGluR signaling mediates several sex-specific estradiol actions on hippocampal neuron function. An important unanswered question regards the mechanism by which sex-specific membrane-associated ER signaling is generated, especially since it has been previously demonstrated that mGluR action is not sex-specific. One possibility is that the genes necessary for the ER membrane complex are differentially expressed between males and females, including genes that encode ERα and β, caveolin 1 and 3, and/or the palmitoylacyltransferases DHHC-7 and -21. Thus we used qPCR to test the hypothesis that these genes show sex differences in expression in neonatal and adult rat hippocampus. As an additional control we tested the expression of the 20 other DHHC palmitoylacyltransferases with no known connections to ER. In neonatal hippocampus, no sex differences were detected in gene expression. In adult hippocampus, the genes that encode caveolin 1 and DHHC-7 showed decreased expression in females compared to males. Thus, select genes differ by sex at specific developmental stages, arguing for a more nuanced model than simple widespread perinatal emergence of sex differences in all genes enabling sex-specific estradiol action. These findings enable the generation of new hypotheses regarding the mechanisms by which sex differences in membrane-associated ER signaling are programmed.}, journal={STEROIDS}, author={Meitzen, John and Britson, Kyla A. and Tuomela, Krista and Mermelstein, Paul G.}, year={2019}, month={Feb}, pages={21–27} }
 @article{krentzel_meitzen_2018, title={Biological Sex, Estradiol and Striatal Medium Spiny Neuron Physiology: A Mini-Review}, volume={12}, ISSN={["1662-5102"]}, DOI={10.3389/fncel.2018.00492}, abstractNote={The caudate-putamen, nucleus accumbens core and shell are important striatal brain regions for premotor, limbic, habit formation, reward, and other critical cognitive functions. Striatal-relevant behaviors such as anxiety, motor coordination, locomotion, and sensitivity to reward, all change with fluctuations of the menstrual cycle in humans and the estrous cycle in rodents. These fluctuations implicate sex steroid hormones, such as 17β-estradiol, as potent neuromodulatory signals for striatal neuron activity. The medium spiny neuron (MSN), the primary neuron subtype of the striatal regions, expresses membrane estrogen receptors and exhibits sex differences both in intrinsic and synaptic electrophysiological properties. In this mini-review, we first describe sex differences in the electrophysiological properties of the MSNs in prepubertal rats. We then discuss specific examples of how the human menstrual and rat estrous cycles induce differences in striatal-relevant behaviors and neural substrate, including how female rat MSN electrophysiology is influenced by the estrous cycle. We then conclude the mini-review by discussing avenues for future investigation, including possible roles of striatal-localized membrane estrogen receptors and estradiol.}, journal={Frontiers in Cellular Neuroscience}, author={Krentzel, A.A. and Meitzen, J.}, year={2018}, pages={492} }
 @article{cao_dorris_meitzen_2018, title={Electrophysiological properties of medium spiny neurons in the nucleus accumbens core of prepubertal male and female Drd1a-tdTomato line 6 BAC transgenic mice}, volume={120}, ISSN={["1522-1598"]}, DOI={10.1152/jn.00257.2018}, abstractNote={ The nucleus accumbens core (AcbC) is a striatal brain region essential for integrating motivated behavior and reward processing with premotor function. In humans and rodents, research has identified sex differences and sex steroid hormone sensitivity in AcbC-mediated behaviors, in disorders, and in rats in the electrophysiological properties of the AcbC output neuron type, the medium spiny neuron (MSN). It is unknown whether the sex differences detected in MSN electrophysiological properties extend to mice. Furthermore, MSNs come in distinct subtypes with subtle differences in electrophysiological properties, and it is unknown whether MSN subtype-specific electrophysiology varies by sex. To address these questions, we used male and female Drd1a-tdTomato line 6 bacterial artificial chromosome transgenic mice. We made acute brain slices of the AcbC, and performed whole cell patch-clamp recordings across MSN subtypes to comprehensively assess AcbC MSN subtype electrophysiological properties. We found that ( 1 mice MSNs did not exhibit the sex differences detected in rat MSNs, and 2) electrophysiological properties differed between MSN subtypes in both sexes, including rheobase, resting membrane potential, action potential properties, intrinsic excitability, input resistance in both the linear and rectified ranges, and miniature excitatory postsynaptic current properties. These findings significantly extend previous studies of MSN subtypes performed in males or animals of undetermined sex and indicate that the influence of sex upon AcbC MSN properties varies between rodent species. }, number={4}, journal={JOURNAL OF NEUROPHYSIOLOGY}, author={Cao, Jinyan and Dorris, David M. and Meitzen, John}, year={2018}, month={Oct}, pages={1712–1727} }
 @article{proano_morris_kunz_dorris_meitzen_2018, title={Estrous cycle-induced sex differences in medium spiny neuron excitatory synaptic transmission and intrinsic excitability in adult rat nucleus accumbens core}, volume={120}, ISSN={["1522-1598"]}, DOI={10.1152/jn.00263.2018}, abstractNote={ Naturally occurring hormone cycles in adult female humans and rodents create a dynamic neuroendocrine environment. These cycles include the menstrual cycle in humans and its counterpart in rodents, the estrous cycle. These hormone fluctuations induce sex differences in the phenotypes of many behaviors, including those related to motivation, and associated disorders such as depression and addiction. This suggests that the neural substrate instrumental for these behaviors, including the nucleus accumbens core (AcbC), likewise differs between estrous cycle phases. It is unknown whether the electrophysiological properties of AcbC output neurons, medium spiny neurons (MSNs), change between estrous cycle phases. This is a critical knowledge gap given that MSN electrophysiological properties are instrumental for determining AcbC output to efferent targets. Here we test whether the intrinsic electrophysiological properties of adult rat AcbC MSNs differ across female estrous cycle phases and from males. We recorded MSNs with whole cell patch-clamp technique in two experiments, the first using gonad-intact adult males and females in differing phases of the estrous cycle and the second using gonadectomized males and females in which the estrous cycle was eliminated. MSN intrinsic electrophysiological and excitatory synaptic input properties robustly changed between female estrous cycle phases and males. Sex differences in MSN electrophysiology disappeared when the estrous cycle was eliminated. These novel findings indicate that AcbC MSN electrophysiological properties change across the estrous cycle, providing a new framework for understanding how biological sex and hormone cyclicity regulate motivated behaviors and other AcbC functions and disorders. }, number={3}, journal={JOURNAL OF NEUROPHYSIOLOGY}, author={Proano, Stephanie B. and Morris, Hannah J. and Kunz, Lindsey M. and Dorris, David M. and Meitzen, John}, year={2018}, month={Sep}, pages={1356–1373} }
 @article{willett_johnson_vogel_patisaul_mcgraw_meitzen_2018, title={Nucleus accumbens core medium spiny neuron electrophysiological properties and partner preference behavior in the adult male prairie vole, Microtus ochrogaster}, volume={119}, ISSN={0022-3077 1522-1598}, url={http://dx.doi.org/10.1152/jn.00737.2017}, DOI={10.1152/jn.00737.2017}, abstractNote={ Medium spiny neurons (MSNs) in the nucleus accumbens have long been implicated in the neurobiological mechanisms that underlie numerous social and motivated behaviors as studied in rodents such as rats. Recently, the prairie vole has emerged as an important model animal for studying social behaviors, particularly regarding monogamy because of its ability to form pair bonds. However, to our knowledge, no study has assessed intrinsic vole MSN electrophysiological properties or tested how these properties vary with the strength of the pair bond between partnered voles. Here we performed whole cell patch-clamp recordings of MSNs in acute brain slices of the nucleus accumbens core (NAc) of adult male voles exhibiting strong and weak preferences for their respective partnered females. We first document vole MSN electrophysiological properties and provide comparison to rat MSNs. Vole MSNs demonstrated many canonical electrophysiological attributes shared across species but exhibited notable differences in excitability compared with rat MSNs. Second, we assessed male vole partner preference behavior and tested whether MSN electrophysiological properties varied with partner preference strength. Male vole partner preference showed extensive variability. We found that decreases in miniature excitatory postsynaptic current amplitude and the slope of the evoked action potential firing rate to depolarizing current injection weakly associated with increased preference for the partnered female. This suggests that excitatory synaptic strength and neuronal excitability may be decreased in MSNs in males exhibiting stronger preference for a partnered female. Overall, these data provide extensive documentation of MSN electrophysiological characteristics and their relationship to social behavior in the prairie vole. }, number={4}, journal={Journal of Neurophysiology}, publisher={American Physiological Society}, author={Willett, Jaime A. and Johnson, Ashlyn G. and Vogel, Andrea R. and Patisaul, Heather B. and McGraw, Lisa A. and Meitzen, John}, year={2018}, month={Apr}, pages={1576–1588} }
 @article{eisinger_woolfrey_swanson_schnell_meitzen_dell'acqua_mermelstein_2018, title={Palmitoylation of caveolin-1 is regulated by the same DHHC acyltransferases that modify steroid hormone receptors}, volume={293}, ISSN={["1083-351X"]}, DOI={10.1074/jbc.RA118.004167}, abstractNote={Palmitoylation is a reversible post-translational addition of a 16-carbon lipid chain involved in trafficking and compartmentalizing target proteins. It is important for many cellular functions, including signaling via membrane-localized estrogen receptors (ERs). Within the nervous system, palmitoylation of ERα is necessary for membrane surface localization and mediation of downstream signaling through the activation of metabotropic glutamate receptors (mGluRs). Substitution of the single palmitoylation site on ERα prevents its physical association with the integral membrane protein caveolin-1 (CAV1), required for the formation of the ER/mGluR signaling complex. Interestingly, siRNA knockdown of either of two palmitoyl acyltransferases, zinc finger DHHC type–containing 7 (DHHC7) or DHHC21, also eliminates this signaling mechanism. Because ERα has only one palmitoylation site, we hypothesized that one of these DHHCs palmitoylates CAV1. We investigated this possibility by using an acyl–biotin exchange assay in HEK293 cells in conjunction with DHHC overexpression and found that DHHC7 increases CAV1 palmitoylation. Substitution of the palmitoylation sites on CAV1 eliminated this effect but did not disrupt the ability of the DHHC enzyme to associate with CAV1. In contrast, siRNA-mediated knockdown of DHHC7 alone was not sufficient to decrease CAV1 palmitoylation but rather required simultaneous knockdown of DHHC21. These findings provide additional information about the overall influence of palmitoylation on the membrane-initiated estrogen signaling pathway and highlight the importance of considering the influence of palmitoylation on other CAV1-dependent processes.}, number={41}, journal={JOURNAL OF BIOLOGICAL CHEMISTRY}, author={Eisinger, Katherine R. Tonn and Woolfrey, Kevin M. and Swanson, Samuel P. and Schnell, Stephen A. and Meitzen, John and Dell'Acqua, Mark and Mermelstein, Paul G.}, year={2018}, month={Oct}, pages={15901–15911} }
 @misc{cao_willett_dorris_meitzen_2018, title={Sex Differences in Medium Spiny neuron excitability and Glutamatergic Synaptic input: Heterogeneity Across Striatal Regions and evidence for Estradiol-Dependent Sexual Differentiation}, volume={9}, ISSN={["1664-2392"]}, DOI={10.3389/fendo.2018.00173}, abstractNote={Steroid sex hormones and biological sex influence how the brain regulates motivated behavior, reward, and sensorimotor function in both normal and pathological contexts. Investigations into the underlying neural mechanisms have targeted the striatal brain regions, including the caudate–putamen, nucleus accumbens core (AcbC), and shell. These brain regions are of particular interest to neuroendocrinologists given that they express membrane-associated but not nuclear estrogen receptors, and also the well-established role of the sex steroid hormone 17β-estradiol (estradiol) in modulating striatal dopamine systems. Indeed, output neurons of the striatum, the medium spiny neurons (MSNs), exhibit estradiol sensitivity and sex differences in electrophysiological properties. Here, we review sex differences in rat MSN glutamatergic synaptic input and intrinsic excitability across striatal regions, including evidence for estradiol-mediated sexual differentiation in the nucleus AcbC. In prepubertal animals, female MSNs in the caudate–putamen exhibit a greater intrinsic excitability relative to male MSNs, but no sex differences are detected in excitatory synaptic input. Alternatively, female MSNs in the nucleus AcbC exhibit increased excitatory synaptic input relative to male MSNs, but no sex differences in intrinsic excitability were detected. Increased excitatory synaptic input onto female MSNs in the nucleus AcbC is abolished after masculinizing estradiol or testosterone exposure during the neonatal critical period. No sex differences are detected in MSNs in prepubertal nucleus accumbens shell. Thus, despite possessing the same neuron type, striatal regions exhibit heterogeneity in sex differences in MSN electrophysiological properties, which likely contribute to the sex differences observed in striatal function.}, journal={FRONTIERS IN ENDOCRINOLOGY}, author={Cao, Jinyan and Willett, Jaime A. and Dorris, David M. and Meitzen, John}, year={2018}, month={Apr} }
 @misc{meitzen_meisel_mermelstein_2018, title={Sex differences and the effects of estradiol on striatal function}, volume={23}, ISSN={["2352-1554"]}, DOI={10.1016/j.cobeha.2018.03.007}, abstractNote={The striatal brain regions, including the caudate-putamen, nucleus accumbens core, and nucleus accumbens shell, mediate critical behavioral functions. These functions include but are not limited to motivated behavior, reward, learning, and sensorimotor function in both pathological and normal contexts. The phenotype and/or incidence of all of these behaviors either differ by sex or are sensitive to the presence of gonadal hormones such as 17β-estradiol and testosterone. All three striatal brain regions express membrane-associated estrogen receptors. Here we present a brief review of the recent literature reporting on sex differences and effects of the estrogenic hormone 17β-estradiol on behavioral and neural function across all three striatal regions, focusing upon the most prominent striatal neuron type, the medium spiny neuron. We emphasize recent findings in three broad domains: (1) select striatal-relevant behaviors and disorders, (2) striatal medium spiny neuron dendritic spine density, and (3), striatal medium spiny neuron electrophysiological properties including excitatory synaptic input and intrinsic cellular excitability. These recent advances in behavior, neuroanatomy, and electrophysiology collectively offer insight into the effects of sex and estrogen on striatal function, especially at the level of individual neurons.}, journal={CURRENT OPINION IN BEHAVIORAL SCIENCES}, author={Meitzen, John and Meisel, Robert L. and Mermelstein, Paul G.}, year={2018}, month={Oct}, pages={42–48} }
 @article{montiel_meitzen_2017, title={Interviewing neuroscientists for an undergraduate honors project}, volume={16}, number={1}, journal={Journal of Undergraduate Neuroscience Education}, author={Montiel, C. and Meitzen, J.}, year={2017}, pages={A89–A94} }
 @article{will_proano_thomas_kunz_thompson_ginnari_jones_lucas_reavis_dorris_et al._2017, title={Problems and Progress regarding Sex Bias and Omission in Neuroscience Research}, volume={4}, ISSN={["2373-2822"]}, DOI={10.1523/eneuro.0278-17.2017}, abstractNote={Neuroscience research has historically ignored female animals. This neglect comes in two general forms. The first is sex bias, defined as favoring one sex over another; in this case, male over female. The second is sex omission, which is the lack of reporting sex. The recognition of this phenomenon has generated fierce debate across the sciences. Here we test whether sex bias and omission are still present in the neuroscience literature, whether studies employing both males and females neglect sex as an experimental variable, and whether sex bias and omission differs between animal models and journals. To accomplish this, we analyzed the largest-ever number of neuroscience articles for sex bias and omission: 6636 articles using mice or rats in 6 journals published from 2010 to 2014. Sex omission is declining, as increasing numbers of articles report sex. Sex bias remains present, as increasing numbers of articles report the sole use of males. Articles using both males and females are also increasing, but few report assessing sex as an experimental variable. Sex bias and omission varies substantially by animal model and journal. These findings are essential for understanding the complex status of sex bias and omission in neuroscience research and may inform effective decisions regarding policy action.}, number={6}, journal={ENEURO}, author={Will, Tyler R. and Proano, Stephanie B. and Thomas, Anly M. and Kunz, Lindsey M. and Thompson, Kelly C. and Ginnari, Laura A. and Jones, Clay H. and Lucas, Sarah-Catherine and Reavis, Elizabeth M. and Dorris, David M. and et al.}, year={2017} }
 @article{wong_cao_dorris_meitzen_2016, title={Genetic sex and the volumes of the caudate-putamen, nucleus accumbens core and shell: original data and a review}, volume={221}, ISSN={["1863-2661"]}, DOI={10.1007/s00429-015-1158-9}, abstractNote={Sex differences are widespread across vertebrate nervous systems. Such differences are sometimes reflected in the neural substrate via neuroanatomical differences in brain region volume. One brain region that displays sex differences in its associated functions and pathologies is the striatum, including the caudate-putamen (dorsal striatum), nucleus accumbens core and shell (ventral striatum). The extent to which these differences can be attributed to alterations in volume is unclear. We thus tested whether the volumes of the caudate-putamen, nucleus accumbens core, and nucleus accumbens shell differed by region, sex, and hemisphere in adult Sprague-Dawley rats. As a positive control for detecting sex differences in brain region volume, we measured the sexually dimorphic nucleus of the medial preoptic area (SDN-POA). As expected, SDN-POA volume was larger in males than in females. No sex differences were detected in the volumes of the caudate-putamen, nucleus accumbens core or shell. Nucleus accumbens core volume was larger in the right than left hemisphere across males and females. These findings complement previous reports of lateralized nucleus accumbens volume in humans, and suggest that this may possibly be driven via hemispheric differences in nucleus accumbens core volume. In contrast, striatal sex differences seem to be mediated by factors other than striatal region volume. This conclusion is presented within the context of a detailed review of studies addressing sex differences and similarities in striatal neuroanatomy.}, number={8}, journal={BRAIN STRUCTURE & FUNCTION}, author={Wong, Jordan E. and Cao, Jinyan and Dorris, David M. and Meitzen, John}, year={2016}, month={Nov}, pages={4257–4267} }
 @article{cao_dorris_meitzen_2016, title={Neonatal Masculinization Blocks Increased Excitatory Synaptic Input in Female Rat Nucleus Accumbens Core}, volume={157}, ISSN={["1945-7170"]}, DOI={10.1210/en.2016-1160}, abstractNote={Steroid sex hormones and genetic sex regulate the phenotypes of motivated behaviors and relevant disorders. Most studies seeking to elucidate the underlying neuroendocrine mechanisms have focused on how 17β-estradiol modulates the role of dopamine in striatal brain regions, which express membrane-associated estrogen receptors. Dopamine action is an important component of striatal function, but excitatory synaptic neurotransmission has also emerged as a key striatal substrate and target of estradiol action. Here, we focus on excitatory synaptic input onto medium spiny neurons (MSNs) in the striatal region nucleus accumbens core (AcbC). In adult AcbC, miniature excitatory postsynaptic current (mEPSC) frequency is increased in female compared with male MSNs. We tested whether increased mEPSC frequency in female MSNs exists before puberty, whether this increased excitability is due to the absence of estradiol or testosterone during the early developmental critical period, and whether it is accompanied by stable neuron intrinsic membrane properties. We found that mEPSC frequency is increased in female compared with male MSNs before puberty. Increased mEPSC frequency in female MSNs is abolished after neonatal estradiol or testosterone exposure. MSN intrinsic membrane properties did not differ by sex. These data indicate that neonatal masculinization via estradiol and/or testosterone action is sufficient for down-regulating excitatory synaptic input onto MSNs. We conclude that excitatory synaptic input onto AcbC MSNs is organized long before adulthood via steroid sex hormone action, providing new insight into a mechanism by which sex differences in motivated behavior and other AbcC functions may be generated or compromised.}, number={8}, journal={ENDOCRINOLOGY}, author={Cao, Jinyan and Dorris, David M. and Meitzen, John}, year={2016}, month={Aug}, pages={3181–3196} }
 @article{willett_will_hauser_dorris_cao_meitzen_2016, title={No Evidence for Sex Differences in the Electrophysiological Properties and Excitatory Synaptic Input onto Nucleus Accumbens Shell Medium Spiny Neurons}, volume={3}, ISSN={["2373-2822"]}, DOI={10.1523/eneuro.0147-15.2016}, abstractNote={Visual Overview Sex differences exist in how the brain regulates motivated behavior and reward, both in normal and pathological contexts. Investigations into the underlying neural mechanisms have targeted the striatal brain regions, including the dorsal striatum and nucleus accumbens core and shell. Sex differences exist in how the brain regulates motivated behavior and reward, both in normal and pathological contexts. Investigations into the underlying neural mechanisms have targeted the striatal brain regions, including the dorsal striatum and nucleus accumbens core and shell. These investigations yield accumulating evidence of sexually different electrophysiological properties, excitatory synaptic input, and sensitivity to neuromodulator/hormone action in select striatal regions both before and after puberty. It is unknown whether the electrical properties of neurons in the nucleus accumbens shell differ by sex, and whether sex differences in excitatory synaptic input are present before puberty. To test the hypothesis that these properties differ by sex, we performed whole-cell patch-clamp recordings on male and female medium spiny neurons (MSNs) in acute brain slices obtained from prepubertal rat nucleus accumbens shell. We analyzed passive and active electrophysiological properties, and miniature EPSCs (mEPSCs). No sex differences were detected; this includes those properties, such as intrinsic excitability, action potential afterhyperpolarization, threshold, and mEPSC frequency, that have been found to differ by sex in other striatal regions and/or developmental periods. These findings indicate that, unlike other striatal brain regions, the electrophysiological properties of nucleus accumbens shell MSNs do not differ by sex. Overall, it appears that sex differences in striatal function, including motivated behavior and reward, are likely mediated by other factors and striatal regions.}, number={1}, journal={ENEURO}, author={Willett, Jaime A. and Will, Tyler and Hauser, Caitlin A. and Dorris, David M. and Cao, Jinyan and Meitzen, John}, year={2016} }
 @article{dorris_cao_willett_hauser_meitzen_2015, title={Intrinsic excitability varies by sex in prepubertal striatal medium spiny neurons}, volume={113}, ISSN={["1522-1598"]}, DOI={10.1152/jn.00687.2014}, abstractNote={ Sex differences in neuron electrophysiological properties were traditionally associated with brain regions directly involved in reproduction in adult, postpubertal animals. There is growing acknowledgement that sex differences can exist in other developmental periods and brain regions as well. This includes the dorsal striatum (caudate/putamen), which shows robust sex differences in gene expression, neuromodulator action (including dopamine and 17β-estradiol), and relevant sensorimotor behaviors and pathologies such as the responsiveness to drugs of abuse. Here we examine whether these sex differences extend to striatal neuron electrophysiology. We test the hypothesis that passive and active medium spiny neuron (MSN) electrophysiological properties in prepubertal rat dorsal striatum differ by sex. We made whole cell recordings from male and females MSNs from acute brain slices. The slope of the evoked firing rate to current injection curve was increased in MSNs recorded from females compared with males. The initial action potential firing rate was increased in MSNs recorded from females compared with males. Action potential after-hyperpolarization peak was decreased, and threshold was hyperpolarized in MSNs recorded from females compared with males. No sex differences in passive electrophysiological properties or miniature excitatory synaptic currents were detected. These findings indicate that MSN excitability is increased in prepubertal females compared with males, providing a new mechanism that potentially contributes to generating sex differences in striatal-mediated processes. Broadly, these findings demonstrate that sex differences in neuron electrophysiological properties can exist prepuberty in brain regions not directly related to reproduction. }, number={3}, journal={JOURNAL OF NEUROPHYSIOLOGY}, author={Dorris, David M. and Cao, Jinyan and Willett, Jaime A. and Hauser, Caitlin A. and Meitzen, John}, year={2015}, month={Feb}, pages={720–729} }
 @article{meitzen_2015, title={Using Tinbergen’s four questions as the framework for a neuroscience capstone course}, volume={14}, number={1}, journal={Journal of Undergraduate Neuroscience Education}, author={Meitzen, J.}, year={2015}, pages={A46–A55} }
 @article{dorris_hauser_minnehan_meitzen_2014, title={An aerator for brain slice experiments in individual cell culture plate wells}, volume={238}, ISSN={["1872-678X"]}, DOI={10.1016/j.jneumeth.2014.09.017}, abstractNote={Ex vivo acute living brain slices are a broadly employed and powerful experimental preparation. Most new technology regarding this tissue has involved the chamber used when performing electrophysiological experiments. Alternatively we instead focus on the creation of a simple, versatile aerator designed to allow maintenance and manipulation of acute brain slices and potentially other tissue in a multi-well cell culture plate. Here we present an easily manufactured aerator designed to fit into a 24-well cell culture plate. It features a nylon mesh and a single microhole to enable gas delivery without compromising tissue stability. The aerator is designed to be individually controlled, allowing both high throughput and single well experiments. The aerator was validated by testing material leach, dissolved oxygen delivery, brain slice viability and neuronal electrophysiology. Example experiments are also presented, including a test of whether β1-adrenergic receptor activation regulates gene expression in ex vivo dorsal striatum using qPCR. Key differences include enhanced control over gas delivery to individual wells containing brain slices, decreased necessary volume, a sample restraint to reduce movement artifacts, the potential to be sterilized, the avoidance of materials that absorb water and small biological molecules, minimal production costs, and increased experimental throughput. This new aerator is of high utility and will be useful for experiments involving brain slices and other potentially tissue samples in 24-well cell culture plates.}, journal={JOURNAL OF NEUROSCIENCE METHODS}, author={Dorris, David M. and Hauser, Caitlin A. and Minnehan, Caitlin E. and Meitzen, John}, year={2014}, month={Dec}, pages={1–10} }
 @article{meitzen_perry_westenbroek_hedges_becker_mermelstein_2013, title={Enhanced Striatal beta 1-Adrenergic Receptor Expression Following Hormone Loss in Adulthood Is Programmed by Both Early Sexual Differentiation and Puberty: A Study of Humans and Rats}, volume={154}, ISSN={["0013-7227"]}, DOI={10.1210/en.2012-2131}, abstractNote={After reproductive senescence or gonadectomy, changes occur in neural gene expression, ultimately altering brain function. The endocrine mechanisms underlying these changes in gene expression beyond immediate hormone loss are poorly understood. To investigate this, we measured changes in gene expression the dorsal striatum, where 17β-estradiol modulates catecholamine signaling. In human caudate, quantitative PCR determined a significant elevation in β1-adrenergic receptor (β1AR) expression in menopausal females when compared with similarly aged males. No differences were detected in β2-adrenergic and D1- and D2-dopamine receptor expression. Consistent with humans, adult ovariectomized female rats exhibited a similar increase in β1AR expression when compared with gonadectomized males. No sex difference in β1AR expression was detected between intact adults, prepubertal juveniles, or adults gonadectomized before puberty, indicating the necessity of pubertal development and adult ovariectomy. Additionally, increased β1AR expression in adult ovariectomized females was not observed if animals were masculinized/defeminized with testosterone injections as neonates. To generate a model system for assessing functional impact, increased β1AR expression was induced in female-derived cultured striatal neurons via exposure to and then removal of hormone-containing serum. Increased β1AR action on cAMP formation, cAMP response element-binding protein phosphorylation and gene expression was observed. This up-regulation of β1AR action was eliminated with 17β-estradiol addition to the media, directly implicating this hormone as a regulator of β1AR expression. Beyond having implications for the known sex differences in striatal function and pathologies, these data collectively demonstrate that critical periods early in life and at puberty program adult gene responsiveness to hormone loss after gonadectomy and potentially reproductive senescence.}, number={5}, journal={ENDOCRINOLOGY}, author={Meitzen, John and Perry, Adam N. and Westenbroek, Christel and Hedges, Valerie L. and Becker, Jill B. and Mermelstein, Paul G.}, year={2013}, month={May}, pages={1820–1831} }
 @article{meitzen_luoma_boulware_hedges_peterson_tuomela_britson_mermelstein_2013, title={Palmitoylation of Estrogen Receptors Is Essential for Neuronal Membrane Signaling}, volume={154}, ISSN={["1945-7170"]}, DOI={10.1210/en.2013-1172}, abstractNote={In addition to activating nuclear estrogen receptor signaling, 17β-estradiol can also regulate neuronal function via surface membrane receptors. In various brain regions, these actions are mediated by the direct association of estrogen receptors (ERs) activating metabotropic glutamate receptors (mGluRs). These ER/mGluR signaling partners are organized into discrete functional microdomains via caveolin proteins. A central question that remains concerns the underlying mechanism by which these subpopulations of ERs are targeted to the surface membrane. One candidate mechanism is S-palmitoylation, a posttranscriptional modification that affects the subcellular distribution and function of the modified protein, including promoting localization to membranes. Here we test for the role of palmitoylation and the necessity of specific palmitoylacyltransferase proteins in neuronal membrane ER action. In hippocampal neurons, pharmacological inhibition of palmitoylation eliminated 17β-estradiol-mediated phosphorylation of cAMP response element-binding protein, a process dependent on surface membrane ERs. In addition, mutation of the palmitoylation site on estrogen receptor (ER) α blocks ERα-mediated cAMP response element-binding protein phosphorylation. Similar results were obtained after mutation of the palmitoylation site on ERβ. Importantly, mutation of either ERα or ERβ did not affect the ability of the reciprocal ER to signal at the membrane. In contrast, membrane ERα and ERβ signaling were both dependent on the expression of the palmitoylacyltransferase proteins DHHC-7 and DHHC-21. Neither mGluR activity nor caveolin or ER expression was affected by knockdown of DHHC-7 and DHHC-21. These data collectively suggest discrete mechanisms that regulate specific isoform or global membrane ER signaling in neurons separate from mGluR activity or nuclear ER function.}, number={11}, journal={ENDOCRINOLOGY}, author={Meitzen, John and Luoma, Jessie I. and Boulware, Marissa I. and Hedges, Valerie L. and Peterson, Brittni M. and Tuomela, Krista and Britson, Kyla A. and Mermelstein, Paul G.}, year={2013}, month={Nov}, pages={4293–4304} }
 @article{thompson_meitzen_replogle_drnevich_lent_wissman_farin_bammler_beyer_clayton_et al._2012, title={Seasonal Changes in Patterns of Gene Expression in Avian Song Control Brain Regions}, volume={7}, ISSN={1932-6203}, url={http://dx.doi.org/10.1371/journal.pone.0035119}, DOI={10.1371/journal.pone.0035119}, abstractNote={Photoperiod and hormonal cues drive dramatic seasonal changes in structure and function of the avian song control system. Little is known, however, about the patterns of gene expression associated with seasonal changes. Here we address this issue by altering the hormonal and photoperiodic conditions in seasonally-breeding Gambel's white-crowned sparrows and extracting RNA from the telencephalic song control nuclei HVC and RA across multiple time points that capture different stages of growth and regression. We chose HVC and RA because while both nuclei change in volume across seasons, the cellular mechanisms underlying these changes differ. We thus hypothesized that different genes would be expressed between HVC and RA. We tested this by using the extracted RNA to perform a cDNA microarray hybridization developed by the SoNG initiative. We then validated these results using qRT-PCR. We found that 363 genes varied by more than 1.5 fold (>log2 0.585) in expression in HVC and/or RA. Supporting our hypothesis, only 59 of these 363 genes were found to vary in both nuclei, while 132 gene expression changes were HVC specific and 172 were RA specific. We then assigned many of these genes to functional categories relevant to the different mechanisms underlying seasonal change in HVC and RA, including neurogenesis, apoptosis, cell growth, dendrite arborization and axonal growth, angiogenesis, endocrinology, growth factors, and electrophysiology. This revealed categorical differences in the kinds of genes regulated in HVC and RA. These results show that different molecular programs underlie seasonal changes in HVC and RA, and that gene expression is time specific across different reproductive conditions. Our results provide insights into the complex molecular pathways that underlie adult neural plasticity.}, number={4}, journal={PLoS ONE}, publisher={Public Library of Science (PLoS)}, author={Thompson, Christopher K. and Meitzen, John and Replogle, Kirstin and Drnevich, Jenny and Lent, Karin L. and Wissman, Anne Marie and Farin, Federico M. and Bammler, Theo K. and Beyer, Richard P. and Clayton, David F. and et al.}, editor={Yamazaki, ShinEditor}, year={2012}, month={Apr}, pages={e35119} }
 @article{meitzen_grove_mermelstein_2012, title={The Organizational and Aromatization Hypotheses Apply to Rapid, Nonclassical Hormone Action: Neonatal Masculinization Eliminates Rapid Estradiol Action in Female Hippocampal Neurons}, volume={153}, ISSN={0013-7227 1945-7170}, url={http://dx.doi.org/10.1210/en.2012-1525}, DOI={10.1210/en.2012-1525}, abstractNote={Abstract}, number={10}, journal={Endocrinology}, publisher={The Endocrine Society}, author={Meitzen, John and Grove, Danielle D. and Mermelstein, Paul G.}, year={2012}, month={Oct}, pages={4616–4621} }
 @article{stern_luoma_meitzen_mermelstein_2011, title={Corticotropin Releasing Factor-Induced CREB Activation in Striatal Neurons Occurs via a Novel Gβγ Signaling Pathway}, volume={6}, ISSN={1932-6203}, url={http://dx.doi.org/10.1371/journal.pone.0018114}, DOI={10.1371/journal.pone.0018114}, abstractNote={The peptide corticotropin-releasing factor (CRF) was initially identified as a critical component of the stress response. CRF exerts its cellular effects by binding to one of two cognate G-protein coupled receptors (GPCRs), CRF receptor 1 (CRFR1) or 2 (CRFR2). While these GPCRs were originally characterized as being coupled to Gαs, leading to downstream activation of adenylyl cyclase (AC) and subsequent increases in cAMP, it has since become clear that CRFRs couple to and activate numerous other downstream signaling cascades. In addition, CRF signaling influences the activity of many diverse brain regions, affecting a variety of behaviors. One of these regions is the striatum, including the nucleus accumbens (NAc). CRF exerts profound effects on striatal-dependent behaviors such as drug addiction, pair-bonding, and natural reward. Recent data indicate that at least some of these behaviors regulated by CRF are mediated through CRF activation of the transcription factor CREB. Thus, we aimed to elucidate the signaling pathway by which CRF activates CREB in striatal neurons. Here we describe a novel neuronal signaling pathway whereby CRF leads to a rapid Gβγ- and MEK-dependent increase in CREB phosphorylation. These data are the first descriptions of CRF leading to activation of a Gβγ-dependent signaling pathway in neurons, as well as the first description of Gβγ activation leading to downstream CREB phosphorylation in any cellular system. Additionally, these data provide additional insight into the mechanisms by which CRF can regulate neuronal function.}, number={3}, journal={PLoS ONE}, publisher={Public Library of Science (PLoS)}, author={Stern, Christopher M. and Luoma, Jessie I. and Meitzen, John and Mermelstein, Paul G.}, editor={Degtyar, VadimEditor}, year={2011}, month={Mar}, pages={e18114} }
 @article{stern_meitzen_mermelstein_2011, title={Corticotropin-releasing factor and urocortin I activate CREB through functionally selective Gβγ signaling in hippocampal pyramidal neurons}, volume={34}, ISSN={0953-816X}, url={http://dx.doi.org/10.1111/j.1460-9568.2011.07812.x}, DOI={10.1111/j.1460-9568.2011.07812.x}, abstractNote={Stress is a perceived perturbation in the environment of the organism that affects numerous extrahypothalamic brain regions including the hippocampus, a limbic structure critical for learning, spatial memory and the regulation of stress hormones. Though many effects of stress on the hippocampus are mediated via local glucocorticoid action, there is now ample evidence for the contributions of the stress peptides corticotropin‐releasing factor (CRF) and urocortin I (UCN). Thus, understanding the intracellular signaling pathways activated by stress peptides is required to fully understand the mechanisms by which stress influences the hippocampus. Here we elucidate molecular mechanisms by which CRF and UCN induce phosphorylation of the activity‐dependent transcription factor CREB, a molecule critical for numerous forms of neuronal plasticity. We report that nanomolar concentrations of both CRF and UCN lead to a rapid, CRF receptor 1 (CRFR1)‐ and Gβγ‐dependent increase in CREB phosphorylation in rat hippocampal pyramidal neurons. Interestingly, CRF‐ and UCN‐induced signaling pathways diverge downstream of Gβγ, with UCN, but not CRF, signaling to CREB via a MEK/MAPK‐dependent pathway. These data suggest novel molecular mechanisms by which stress can directly impact hippocampal neurons, as well as highlight an emerging role for Gβγ signaling in mediating the effects of stress peptides in extrahypothalamic stress‐responsive brain regions.}, number={5}, journal={European Journal of Neuroscience}, publisher={Wiley}, author={Stern, Christopher M. and Meitzen, John and Mermelstein, Paul G.}, year={2011}, month={Aug}, pages={671–681} }
 @article{meitzen_mermelstein_2011, title={Estrogen receptors stimulate brain region specific metabotropic glutamate receptors to rapidly initiate signal transduction pathways}, volume={42}, ISSN={0891-0618}, url={http://dx.doi.org/10.1016/j.jchemneu.2011.02.002}, DOI={10.1016/j.jchemneu.2011.02.002}, abstractNote={Estradiol and other steroid hormones modulate the nervous system and behavior on both acute and long-term time scales. Though estradiol was originally characterized as a regulator of gene expression through the action of nuclear estrogen receptors (ERs) that directly bind DNA, research over the past thirty years has firmly established that estradiol can bind to extra-nuclear ERs associated with the cellular membrane, producing changes in neurons through stimulation of various intracellular signaling pathways. Several studies have determined that the classical ERs, ERα and ERβ, mediate some of these fast-acting signaling pathways through activation of G proteins. Since ERα and ERβ are not G protein-coupled receptors, the mechanisms by which ERs can stimulate signal transduction pathways are a focus of recent research. Here we discuss recent studies illustrating one mechanism by which ERα and ERβ initiate these pathways: through direct association with metabotropic glutamate receptors (mGluRs). Estradiol binding to these membrane-localized estrogen receptors results in mGluR signaling independent of glutamate. ERs are organized with mGluRs into functional signaling microdomains via caveolin proteins. The pairing of ERs to specific mGluRs via caveolins is region specific, with ERs being linked to different mGluRs in hippocampal, striatal, and other neurons. It is becoming clear that ER signaling through mGluRs is one important mechanism by which estrogens can modulate neuron and glial physiology, ultimately impacting various aspects of nervous system function.}, number={4}, journal={Journal of Chemical Neuroanatomy}, publisher={Elsevier BV}, author={Meitzen, John and Mermelstein, Paul G.}, year={2011}, month={Dec}, pages={236–241} }
 @article{meitzen_pflepsen_stern_meisel_mermelstein_2011, title={Measurements of neuron soma size and density in rat dorsal striatum, nucleus accumbens core and nucleus accumbens shell: Differences between striatal region and brain hemisphere, but not sex}, volume={487}, ISSN={0304-3940}, url={http://dx.doi.org/10.1016/j.neulet.2010.10.017}, DOI={10.1016/j.neulet.2010.10.017}, abstractNote={Both hemispheric bias and sex differences exist in striatal-mediated behaviors and pathologies. The extent to which these dimorphisms can be attributed to an underlying neuroanatomical difference is unclear. We therefore quantified neuron soma size and density in the dorsal striatum (CPu) as well as the core (AcbC) and shell (AcbS) subregions of the nucleus accumbens to determine whether these anatomical measurements differ by region, hemisphere, or sex in adult Sprague-Dawley rats. Neuron soma size was larger in the CPu than the AcbC or AcbS. Neuron density was greatest in the AcbS, intermediate in the AcbC, and least dense in the CPu. CPu neuron density was greater in the left in comparison to the right hemisphere. No attribute was sexually dimorphic. These results provide the first evidence that hemispheric bias in the striatum and striatal-mediated behaviors can be attributed to a lateralization in neuronal density within the CPu. In contrast, sexual dimorphisms appear mediated by factors other than gross anatomical differences.}, number={2}, journal={Neuroscience Letters}, publisher={Elsevier BV}, author={Meitzen, John and Pflepsen, Kelsey R. and Stern, Christopher M. and Meisel, Robert L. and Mermelstein, Paul G.}, year={2011}, month={Jan}, pages={177–181} }
 @article{meitzen_luoma_stern_mermelstein_2011, title={β1-Adrenergic receptors activate two distinct signaling pathways in striatal neurons}, volume={116}, ISSN={0022-3042}, url={http://dx.doi.org/10.1111/j.1471-4159.2010.07137.x}, DOI={10.1111/j.1471-4159.2010.07137.x}, abstractNote={ J. Neurochem. (2011) 116, 984–995.}, number={6}, journal={Journal of Neurochemistry}, publisher={Wiley}, author={Meitzen, John and Luoma, Jessie I. and Stern, Christopher M. and Mermelstein, Paul G.}, year={2011}, month={Jan}, pages={984–995} }
 @article{meitzen_weaver_brenowitz_perkel_2009, title={Plastic and Stable Electrophysiological Properties of Adult Avian Forebrain Song-Control Neurons across Changing Breeding Conditions}, volume={29}, ISSN={0270-6474 1529-2401}, url={http://dx.doi.org/10.1523/jneurosci.5571-08.2009}, DOI={10.1523/jneurosci.5571-08.2009}, abstractNote={Steroid sex hormones drive changes in the nervous system and behavior in many animal taxa, but integrating the former with the latter remains challenging. One useful model system for meeting this challenge is seasonally breeding songbirds. In these species, plasma testosterone levels rise and fall across the seasons, altering song behavior and causing dramatic growth and regression of the song-control system, a discrete set of nuclei that control song behavior. Whereas the cellular mechanisms underlying changes in nucleus volume have been studied as a model for neural growth and degeneration, it is unknown whether these changes in neural structure are accompanied by changes in electrophysiological properties other than spontaneous firing rate. Here we test the hypothesis that passive and active neuronal properties in the forebrain song-control nuclei HVC and RA change across breeding conditions. We exposed adult male Gambel's white-crowned sparrows to either short-day photoperiod or long-day photoperiod and systemic testosterone to simulate nonbreeding and breeding conditions, respectively. We made whole-cell recordings from RA and HVC neurons in acute brain slices. We found that RA projection neuron membrane time constant, capacitance, and evoked and spontaneous firing rates were all increased in the breeding condition; the measured electrophysiological properties of HVC interneurons and projection neurons were stable across breeding conditions. This combination of plastic and stable intrinsic properties could directly impact the song-control system's motor control across seasons, underlying changes in song stereotypy. These results provide a valuable framework for integrating how steroid hormones modulate cellular physiology to change behavior.}, number={20}, journal={Journal of Neuroscience}, publisher={Society for Neuroscience}, author={Meitzen, J. and Weaver, A. L. and Brenowitz, E. A. and Perkel, D. J.}, year={2009}, month={May}, pages={6558–6567} }
 @article{meitzen_thompson_choi_perkel_brenowitz_2009, title={Time course of changes in Gambel's white-crowned sparrow song behavior following transitions in breeding condition}, volume={55}, ISSN={0018-506X}, url={http://dx.doi.org/10.1016/j.yhbeh.2008.10.006}, DOI={10.1016/j.yhbeh.2008.10.006}, abstractNote={Seasonal changes in behavior and in its underlying neural substrate are common across animal taxa. These changes are often triggered by steroid sex hormones. Song in seasonally breeding songbirds provides an excellent example of this phenomenon. In these species, dramatic seasonal changes mediated by testosterone and its metabolites occur in adult song behavior and in the neural circuitry controlling song. While song rate can quickly change in response to seasonal breeding cues, it is unknown how quickly other aspects of song change, particularly the stereotypy of song phonology and syntax. In this study we determined whether and how quickly song rate, phonology, and syntax change in response to breeding and non-breeding physiological cues. We asked these questions using Gambel's white-crowned sparrows (Zonotrichia leucophrys gambelii), a closed-ended learner with well-characterized changes in the neural circuitry controlling song behavior. We exposed ten photosensitive sparrows to long-day photoperiod and implanted them with subcutaneous testosterone pellets (day 0) to simulate breeding conditions. We continuously recorded song and found that song rate increased quickly, reaching maximum around day 6. The stereotypy of song phonology changed more slowly, reaching maximum by day 10 or later. Song syntax changed minimally after day 6, the earliest time point examined. After 21 days, we transitioned five birds from breeding to non-breeding condition. Song rate declined precipitously. These results suggest that while song rate changes quickly, song phonology changes more slowly, generally following or in parallel with previously investigated changes in the neural substrate.}, number={1}, journal={Hormones and Behavior}, publisher={Elsevier BV}, author={Meitzen, John and Thompson, Christopher K. and Choi, Heejung and Perkel, David J. and Brenowitz, Eliot A.}, year={2009}, month={Jan}, pages={217–227} }
 @article{meitzen_thompson_2008, title={Seasonal-like growth and regression of the avian song control system: Neural and behavioral plasticity in adult male Gambel’s white-crowned sparrows}, volume={157}, ISSN={0016-6480}, url={http://dx.doi.org/10.1016/j.ygcen.2008.03.014}, DOI={10.1016/j.ygcen.2008.03.014}, abstractNote={Birdsong is regulated by a series of discrete brain nuclei known as the song control system. In seasonally-breeding male songbirds, seasonal changes in steroid sex hormones regulate the structure and electrophysiology of song control system neurons, resulting in dramatic changes in singing behavior. Male songbirds can be brought into the laboratory, where circulating levels of steroid hormone and photoperiod can be abruptly manipulated, providing controlled conditions under which rapid “seasonal-like” changes in behavior and morphology can be carefully studied. In this mini-review, we discuss the steroidal and cellular mechanisms underlying seasonal-like growth and regression of the song control system in adult male Gambel’s white-crowned sparrows (Zonotrichia leucophrys gambelii), and its impact on song behavior. Specifically, we discuss recent advances concerning: (1) the role of androgen and estrogen receptors in inducing seasonal-like growth of the song control system; (2) how photoperiod modulates the time course of testosterone-induced growth of the song control system; (3) how bilateral intracerebral infusion of androgen and estrogen receptor antagonists near the song control nucleus HVC prevents seasonal-like increases in song stereotypy but not song rate; and (4) the steroidal and cellular mechanisms that mediate rapid regression of the song control system. Throughout this mini-review we compare data collected from white-crowned sparrows to that from other songbird species. We conclude by outlining avenues of future research.}, number={3}, journal={General and Comparative Endocrinology}, publisher={Elsevier BV}, author={Meitzen, John and Thompson, Christopher K.}, year={2008}, month={Jul}, pages={259–265} }
 @article{meitzen_perkel_brenowitz_2007, title={Seasonal changes in intrinsic electrophysiological activity of song control neurons in wild song sparrows}, volume={193}, ISSN={0340-7594 1432-1351}, url={http://dx.doi.org/10.1007/s00359-007-0222-1}, DOI={10.1007/s00359-007-0222-1}, abstractNote={Song behavior and its underlying neural substrate can change seasonally in adult songbirds. To test whether environmental cues induce seasonal changes in electrophysiological characteristics of song control neurons, we measured in vitro intrinsic neuronal activity in the song control nucleus RA of adult male song sparrows (Melospiza melodia) in both the fall non-breeding and spring breeding seasons. We found that RA neurons in spring-captured birds show a more than threefold increase in spontaneous firing rate compared to those from fall-captured birds. We conclude that environmental cues are sufficient to induce seasonal changes in electrophysiological properties of song control neurons, and that changes in these properties may underlie seasonal changes in song behavior.}, number={6}, journal={Journal of Comparative Physiology A}, publisher={Springer Science and Business Media LLC}, author={Meitzen, John and Perkel, David J. and Brenowitz, Eliot A.}, year={2007}, month={Apr}, pages={677–683} }
 @article{meitzen_moore_lent_brenowitz_perkel_2007, title={Steroid Hormones Act Transsynaptically within the Forebrain to Regulate Neuronal Phenotype and Song Stereotypy}, volume={27}, ISSN={0270-6474 1529-2401}, url={http://dx.doi.org/10.1523/jneurosci.3289-07.2007}, DOI={10.1523/jneurosci.3289-07.2007}, abstractNote={Steroid sex hormones induce dramatic seasonal changes in reproductive related behaviors and their underlying neural substrates in seasonally breeding vertebrates. For example, in adult white-crowned sparrows, increased Spring photoperiod raises circulating testosterone, causing morphological and electrophysiological changes in song-control nuclei, which modify song behavior for the breeding season. We investigated how photoperiod and steroid hormones induce these changes in morphology, electrophysiology, and behavior. Neurons in a song premotor nucleus, the robust nucleus of the arcopallium (RA), show increased intrinsic spontaneous firing rate and soma size when birds are in breeding condition. Using combinations of systemic and unilateral local intracerebral hormonal manipulations, we show that long-day photoperiod accelerates the effects of systemic testosterone on RA neurons via the estradiol-synthesizing enzyme aromatase (CYP19A1); these changes require inputs from the afferent song control nucleus HVC (used as a proper name) and steroid receptor activation within HVC; local coactivation of androgen and estrogen receptors (ARs and ERs, respectively) within HVC, but not RA, is sufficient to cause neuronal changes in RA; activation of ARs in RA is also permissive. Using bilateral local intracerebral hormone-receptor blockade, we found that ARs and ERs in the song-control nucleus HVC mediate systemic testosterone-induced changes in song stereotypy but not rate. This novel transsynaptic effect of gonadal steroids on activity and morphology of RA neurons is part of a concerted change in key premotor nuclei, enabling stereotyped song.}, number={44}, journal={Journal of Neuroscience}, publisher={Society for Neuroscience}, author={Meitzen, J. and Moore, I. T. and Lent, K. and Brenowitz, E. A. and Perkel, D. J.}, year={2007}, month={Oct}, pages={12045–12057} }
 @article{xie_meitzen_pollak_2005, title={Differing Roles of Inhibition in Hierarchical Processing of Species-Specific Calls in Auditory Brainstem Nuclei}, volume={94}, ISSN={0022-3077 1522-1598}, url={http://dx.doi.org/10.1152/jn.00688.2005}, DOI={10.1152/jn.00688.2005}, abstractNote={ Here we report on response properties and the roles of inhibition in three brain stem nuclei of Mexican-free tailed bats: the inferior colliculus (IC), the dorsal nucleus of the lateral lemniscus (DNLL) and the intermediate nucleus of the lateral lemniscus (INLL). In each nucleus, we documented the response properties evoked by both tonal and species-specific signals and evaluated the same features when inhibition was blocked. There are three main findings. First, DNLL cells have little or no surround inhibition and are unselective for communication calls, in that they responded to ∼97% of the calls that were presented. Second, most INLL neurons are characterized by wide tuning curves and are unselective for species-specific calls. The third finding is that the IC population is strikingly different from the neuronal populations in the INLL and DNLL. Where DNLL and INLL neurons are unselective and respond to most or all of the calls in the suite we presented, most IC cells are selective for calls and, on average, responded to ∼50% of the calls we presented. Additionally, the selectivity for calls in the majority of IC cells, as well as their tuning and other response properties, are strongly shaped by inhibitory innervation. Thus we show that inhibition plays only limited roles in the DNLL and INLL but dominates in the IC, where the various patterns of inhibition sculpt a wide variety of emergent response properties from the backdrop of more expansive and far less specific excitatory innervation. }, number={6}, journal={Journal of Neurophysiology}, publisher={American Physiological Society}, author={Xie, Ruili and Meitzen, John and Pollak, George D.}, year={2005}, month={Dec}, pages={4019–4037} }
 @article{farries_meitzen_perkel_2005, title={Electrophysiological Properties of Neurons in the Basal Ganglia of the Domestic Chick: Conservation and Divergence in the Evolution of the Avian Basal Ganglia}, volume={94}, ISSN={0022-3077 1522-1598}, url={http://dx.doi.org/10.1152/jn.00539.2004}, DOI={10.1152/jn.00539.2004}, abstractNote={ Although the basal ganglia of birds and mammals share an enormous number of anatomical, histochemical, and electrophysiological characteristics, studies in songbirds have revealed some important differences. Specifically, a specialized region of songbird striatum (the input structure of the basal ganglia) has an anatomical projection and a physiologically defined cell type that are characteristic of the globus pallidus. At present, it is not clear if these differences result from adaptations specific to songbirds and perhaps a few other avian taxa or are common to all birds. We shed some light on this issue by characterizing the morphology and electrophysiological properties of basal ganglia neurons in an avian species that is only distantly related to songbirds: the domestic chick. We recorded neurons in chick basal ganglia in a brain slice preparation, using the whole cell technique. We found that chick striatum, like songbird striatum, contains a pallidum-like cell type never reported in mammalian striatum, supporting the hypothesis that this feature is common to all birds. We also discovered that spiny neurons, the most common cell type in the striatum of all amniotes, possess a diverse set of physiological properties in chicks that distinguish them from both mammals and songbirds. This study revealed an unexpectedly complex pattern of conservation and divergence in the properties of neurons recorded in avian striatum. }, number={1}, journal={Journal of Neurophysiology}, publisher={American Physiological Society}, author={Farries, Michael A. and Meitzen, John and Perkel, David J.}, year={2005}, month={Jul}, pages={454–467} }
 @article{park_meitzen_moore_brenowitz_perkel_2005, title={Seasonal-like plasticity of spontaneous firing rate in a songbird pre-motor nucleus}, volume={64}, ISSN={0022-3034 1097-4695}, url={http://dx.doi.org/10.1002/neu.20145}, DOI={10.1002/neu.20145}, abstractNote={Abstract}, number={2}, journal={Journal of Neurobiology}, publisher={Wiley}, author={Park, Kevin H. J. and Meitzen, John and Moore, Ignacio T. and Brenowitz, Eliot A. and Perkel, David J.}, year={2005}, pages={181–191} }
 @article{klug_bauer_hanson_hurley_meitzen_pollak_2002, title={Response Selectivity for Species-Specific Calls in the Inferior Colliculus of Mexican Free-Tailed Bats is Generated by Inhibition}, volume={88}, ISSN={0022-3077 1522-1598}, url={http://dx.doi.org/10.1152/jn.2002.88.4.1941}, DOI={10.1152/jn.2002.88.4.1941}, abstractNote={ Here we show that inhibition shapes diverse responses to species-specific calls in the inferior colliculus (IC) of Mexican free-tailed bats. We presented 10 calls to each neuron of which 8 were social communication and 2 were echolocation calls. We also measured excitatory response regions: the range of tone burst frequencies that evoked discharges at a fixed intensity. The calls evoked highly selective responses in that IC neurons responded to some calls but not others even though those calls swept through their excitatory response regions. By convolving activity in the response regions with the spectrogram of each call, we evaluated whether responses to tone bursts could predict discharge patterns evoked by species-specific calls. The convolutions often predicted responses to calls that evoked no responses and thus were inaccurate. Blocking inhibition at the IC reduced or eliminated selectivity and greatly improved the predictive accuracy of the convolutions. By comparing the responses evoked by two calls with similar spectra, we show that each call evoked a unique spatiotemporal pattern of activity distributed across and within isofrequency contours and that the disparity in the population response was greatly reduced by blocking inhibition. Thus the inhibition evoked by each call can shape a unique pattern of activity in the IC population and that pattern may be important for both the identification of a particular call and for discriminating it from other calls and other signals. }, number={4}, journal={Journal of Neurophysiology}, publisher={American Physiological Society}, author={Klug, Achim and Bauer, Eric E. and Hanson, Joshua T. and Hurley, Laura and Meitzen, John and Pollak, George D.}, year={2002}, month={Oct}, pages={1941–1954} }