@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{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_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} }
 @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{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{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} }
 @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} }
 @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{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} }