Cao Jinyan, Willett Jaime A, Dorris David M, Meitzen John
Department of Biological Sciences, North Carolina State University, Raleigh, NC, United States.
W.M. Keck Center for Behavioral Biology, North Carolina State University, Raleigh, NC, United States.
Front Endocrinol (Lausanne). 2018 Apr 18;9:173. doi: 10.3389/fendo.2018.00173. eCollection 2018.
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.
甾体性激素和生理性别会影响大脑在正常和病理情况下对动机行为、奖赏及感觉运动功能的调节。对潜在神经机制的研究主要针对纹状体脑区，包括尾状核 - 壳核、伏隔核核心（AcbC）和壳部。鉴于这些脑区表达膜相关而非核雌激素受体，以及性甾体激素17β - 雌二醇（雌二醇）在调节纹状体多巴胺系统中已明确的作用，神经内分泌学家对这些脑区尤为关注。事实上，纹状体的输出神经元，即中等棘状神经元（MSNs），表现出对雌二醇的敏感性以及电生理特性上的性别差异。在此，我们综述大鼠MSN谷氨酸能突触输入和跨纹状体区域内在兴奋性的性别差异，包括在伏隔核中雌二醇介导的性分化的证据。在青春期前动物中，尾状核 - 壳核中的雌性MSNs相对于雄性MSNs表现出更高的内在兴奋性，但在兴奋性突触输入方面未检测到性别差异。或者，伏隔核核心中的雌性MSNs相对于雄性MSNs表现出增加的兴奋性突触输入，但在内在兴奋性方面未检测到性别差异。在新生儿关键期接受雄性化雌二醇或睾酮暴露后，伏隔核核心中雌性MSNs上增加的兴奋性突触输入被消除。青春期前伏隔核壳中的MSNs未检测到性别差异。因此，尽管具有相同的神经元类型，但纹状体区域在MSN电生理特性的性别差异方面表现出异质性，这可能导致在纹状体功能中观察到的性别差异。
