@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_proaño_dorris_setzer_meitzen_2022, title={The estrous cycle and 17β‐estradiol modulate the electrophysiological properties of rat nucleus accumbens core medium spiny neurons}, volume={34}, ISSN={0953-8194 1365-2826}, url={http://dx.doi.org/10.1111/jne.13122}, DOI={10.1111/jne.13122}, abstractNote={AbstractThe nucleus accumbens core is a key nexus within the mammalian brain for integrating the premotor and limbic systems and regulating important cognitive functions such as motivated behaviors. Nucleus accumbens core functions show sex differences and are sensitive to the presence of hormones such as 17β‐estradiol (estradiol) in normal and pathological contexts. The primary neuron type of the nucleus accumbens core, the medium spiny neuron (MSN), exhibits sex differences in both intrinsic excitability and glutamatergic excitatory synapse electrophysiological properties. Here, we provide a review of recent literature showing how estradiol modulates rat nucleus accumbens core MSN electrophysiology within the context of the estrous cycle. We review the changes in MSN electrophysiological properties across the estrous cycle and how these changes can be mimicked in response to exogenous estradiol exposure. We discuss in detail recent findings regarding how acute estradiol exposure rapidly modulates excitatory synapse properties in nucleus accumbens core but not caudate‐putamen MSNs, which mirror the natural changes seen across estrous cycle phases. These recent insights demonstrate the strong impact of sex‐specific estradiol action upon nucleus accumbens core neuron electrophysiology.}, number={6}, journal={Journal of Neuroendocrinology}, publisher={Wiley}, author={Krentzel, Amanda A. and Proaño, Stephanie B. and Dorris, David M. and Setzer, Beverly and Meitzen, John}, year={2022}, month={Apr} }
 @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{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{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.  NEW & NOTEWORTHY This research is the first demonstration that medium spiny neuron electrophysiological properties change across adult female hormone cycle phases in any striatal region. This influence of estrous cycle engenders sex differences in electrophysiological properties that are eliminated by gonadectomy. Broadly, these findings indicate that adult female hormone cycles are an important factor for neurophysiology. }, 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{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} }