35
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      Estrous cycle-induced sex differences in medium spiny neuron excitatory synaptic transmission and intrinsic excitability in adult rat nucleus accumbens core

      research-article

      Read this article at

      ScienceOpenPublisherPMC
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          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.

          Related collections

          Most cited references78

          • Record: found
          • Abstract: found
          • Article: not found

          Sex differences in anxiety and depression clinical perspectives.

          Sex differences are prominent in mood and anxiety disorders and may provide a window into mechanisms of onset and maintenance of affective disturbances in both men and women. With the plethora of sex differences in brain structure, function, and stress responsivity, as well as differences in exposure to reproductive hormones, social expectations and experiences, the challenge is to understand which sex differences are relevant to affective illness. This review will focus on clinical aspects of sex differences in affective disorders including the emergence of sex differences across developmental stages and the impact of reproductive events. Biological, cultural, and experiential factors that may underlie sex differences in the phenomenology of mood and anxiety disorders are discussed.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Estradiol and the developing brain.

            Estradiol is the most potent and ubiquitous member of a class of steroid hormones called estrogens. Fetuses and newborns are exposed to estradiol derived from their mother, their own gonads, and synthesized locally in their brains. Receptors for estradiol are nuclear transcription factors that regulate gene expression but also have actions at the membrane, including activation of signal transduction pathways. The developing brain expresses high levels of receptors for estradiol. The actions of estradiol on developing brain are generally permanent and range from establishment of sex differences to pervasive trophic and neuroprotective effects. Cellular end points mediated by estradiol include the following: 1) apoptosis, with estradiol preventing it in some regions but promoting it in others; 2) synaptogenesis, again estradiol promotes in some regions and inhibits in others; and 3) morphometry of neurons and astrocytes. Estradiol also impacts cellular physiology by modulating calcium handling, immediate-early-gene expression, and kinase activity. The specific mechanisms of estradiol action permanently impacting the brain are regionally specific and often involve neuronal/glial cross-talk. The introduction of endocrine disrupting compounds into the environment that mimic or alter the actions of estradiol has generated considerable concern, and the developing brain is a particularly sensitive target. Prostaglandins, glutamate, GABA, granulin, and focal adhesion kinase are among the signaling molecules co-opted by estradiol to differentiate male from female brains, but much remains to be learned. Only by understanding completely the mechanisms and impact of estradiol action on the developing brain can we also understand when these processes go awry.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Sex Differences in Nucleus Accumbens Transcriptome Profiles Associated with Susceptibility versus Resilience to Subchronic Variable Stress.

              Depression and anxiety disorders are more prevalent in females, but the majority of research in animal models, the first step in finding new treatments, has focused predominantly on males. Here we report that exposure to subchronic variable stress (SCVS) induces depression-associated behaviors in female mice, whereas males are resilient as they do not develop these behavioral abnormalities. In concert with these different behavioral responses, transcriptional analysis of nucleus accumbens (NAc), a major brain reward region, by use of RNA sequencing (RNA-seq) revealed markedly different patterns of stress regulation of gene expression between the sexes. Among the genes displaying sex differences was DNA methyltransferase 3a (Dnmt3a), which shows a greater induction in females after SCVS. Interestingly, Dnmt3a expression levels were increased in the NAc of depressed humans, an effect seen in both males and females. Local overexpression of Dnmt3a in NAc rendered male mice more susceptible to SCVS, whereas Dnmt3a knock-out in this region rendered females more resilient, directly implicating this gene in stress responses. Associated with this enhanced resilience of female mice upon NAc knock-out of Dnmt3a was a partial shift of the NAc female transcriptome toward the male pattern after SCVS. These data indicate that males and females undergo different patterns of transcriptional regulation in response to stress and that a DNA methyltransferase in NAc contributes to sex differences in stress vulnerability.
                Bookmark

                Author and article information

                Journal
                J Neurophysiol
                J. Neurophysiol
                jn
                J Neurophysiol
                JN
                Journal of Neurophysiology
                American Physiological Society (Bethesda, MD )
                0022-3077
                1522-1598
                1 September 2018
                27 June 2018
                1 September 2019
                : 120
                : 3
                : 1356-1373
                Affiliations
                [1] 1Graduate Program in Biology, North Carolina State University , Raleigh, North Carolina
                [2] 2W. M. Keck Center for Behavioral Biology, North Carolina State University , Raleigh, North Carolina
                [3] 3Department of Biological Sciences, North Carolina State University , Raleigh, North Carolina
                [4] 4Center for Human Health and the Environment, North Carolina State University , Raleigh, North Carolina
                [5] 5Comparative Medicine Institute, North Carolina State University , Raleigh, North Carolina
                Author notes
                Address for reprint requests and other correspondence: S. B. Proaño, Dept. of Biological Sciences, North Carolina State Univ., Campus Box 7617, Raleigh, NC 27695 (e-mail: sbproano@ 123456ncsu.edu ).
                Article
                PMC6171053 PMC6171053 6171053 JN-00263-2018 JN-00263-2018
                10.1152/jn.00263.2018
                6171053
                29947588
                6c87a3a7-2d64-4f12-a5fa-b5f18a22720e
                Copyright © 2018 the American Physiological Society
                History
                : 23 April 2018
                : 19 June 2018
                : 21 June 2018
                Funding
                Funded by: HHS | NIH | National Institute of Mental Health (NIMH) 10.13039/100000025
                Award ID: R01MH109471
                Funded by: HHS | NIH | National Institute of Environmental Health Sciences (NIEHS) 10.13039/100000066
                Award ID: P30ES025128
                Funded by: HHS | NIH | National Institute of Child Health and Human Development (NICHD) 10.13039/100000071
                Award ID: P50HD28934
                Categories
                Research Article
                Cellular and Molecular Properties of Neurons

                sex steroid hormones,nucleus accumbens,medium spiny neurons,excitability,estrous cycle

                Comments

                Comment on this article