Department of Biological Sciences, North Carolina State University, Raleigh, NC, USA.
W.M. Keck Center for Behavioral Biology, North Carolina State University, Raleigh, NC, USA.
Eur J Neurosci. 2020 Jul;52(1):2737-2755. doi: 10.1111/ejn.14506. Epub 2019 Jul 29.
The neuroendocrine environment in which the brain operates is both dynamic and differs by sex. How differences in neuroendocrine state affect neuron properties has been significantly neglected in neuroscience research. Behavioral data across humans and rodents indicate that natural cyclical changes in steroid sex hormone production affect sensorimotor and cognitive behaviors in both normal and pathological contexts. These behaviors are critically mediated by the caudate-putamen. In the caudate-putamen, medium spiny neurons (MSNs) are the predominant and primary output neurons. MSNs express membrane-associated estrogen receptors and demonstrate estrogen sensitivity. However, how the cyclical hormone changes across the estrous cycle may modulate caudate-putamen MSN electrophysiological properties remains unknown. Here, we performed whole-cell patch-clamp recordings on male, diestrus female, proestrus female, and estrus female caudate-putamen MSNs. Action potential, passive membrane, and miniature excitatory post-synaptic current properties were assessed. Numerous MSN electrical properties robustly differed by cycle state, including resting membrane potential, rheobase, action potential threshold, maximum evoked action potential firing rate, and inward rectification. Strikingly, when considered independent of estrous cycle phase, all but one of these properties do not significantly differ from male MSNs. These data indicate that female caudate-putamen MSNs are sensitive to the estrous cycle, and more broadly, the importance of considering neuroendocrine state in studies of neuron physiology.
大脑运作的神经内分泌环境既具有动态性，又因性别而异。神经内分泌状态的差异如何影响神经元特性，这在神经科学研究中被严重忽视。人类和啮齿动物的行为数据表明，类固醇性激素产生的自然周期性变化会影响正常和病理情况下的感觉运动和认知行为。这些行为由尾状核-壳核（caudate-putamen）关键介导。在尾状核-壳核中，中型多棘神经元（medium spiny neurons，MSNs）是主要的输出神经元。MSNs 表达膜相关的雌激素受体，并表现出雌激素敏感性。然而，发情周期中周期性激素变化如何调节尾状核-壳核 MSN 的电生理特性尚不清楚。在这里，我们对雄性、发情间期雌性、发情前期雌性和发情期雌性尾状核-壳核 MSNs 进行了全细胞膜片钳记录。评估了动作电位、被动膜和微小兴奋性突触后电流特性。许多 MSN 的电生理特性强烈地随周期状态而变化，包括静息膜电位、电流阈值、动作电位阈值、最大诱发动作电位放电率和内向整流。引人注目的是，当独立于发情周期阶段考虑时，除了一个之外，所有这些特性都与雄性 MSNs 没有显著差异。这些数据表明，雌性尾状核-壳核 MSNs 对发情周期敏感，更广泛地说，在研究神经元生理学时，考虑神经内分泌状态非常重要。
