Cao Jinyan, Dorris David M, Meitzen John
Department of Biological Sciences, North Carolina State University , Raleigh, North Carolina.
W. M. Keck Center for Behavioral Biology, North Carolina State University , Raleigh, North Carolina.
J Neurophysiol. 2018 Oct 1;120(4):1712-1727. doi: 10.1152/jn.00257.2018. Epub 2018 Jul 5.
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. NEW & NOTEWORTHY This research provides the most comprehensive assessment of medium spiny neuron subtype electrophysiological properties to date in a critical brain region, the nucleus accumbens core. It additionally represents the first evaluation of whether mouse medium spiny neuron subtype electrophysiological properties differ by sex.
伏隔核核心区（AcbC）是一个纹状体脑区，对于将动机行为和奖励处理与运动前功能整合至关重要。在人类和啮齿动物中，研究已经确定了伏隔核核心区介导的行为、疾病以及伏隔核核心区输出神经元类型——中型多棘神经元（MSN）的电生理特性在大鼠中的性别差异和性类固醇激素敏感性。尚不清楚在MSN电生理特性中检测到的性别差异是否也存在于小鼠中。此外，MSN有不同的亚型，其电生理特性存在细微差异，并且尚不清楚MSN亚型特异性电生理是否因性别而异。为了解决这些问题，我们使用了雄性和雌性Drd1a-tdTomato品系6细菌人工染色体转基因小鼠。我们制作了伏隔核核心区的急性脑片，并对MSN亚型进行全细胞膜片钳记录，以全面评估伏隔核核心区MSN亚型的电生理特性。我们发现：（1）小鼠MSN未表现出在大鼠MSN中检测到的性别差异；（2）两性的MSN亚型在电生理特性上存在差异，包括阈强度、静息膜电位、动作电位特性、内在兴奋性、线性和整流范围内的输入电阻以及微小兴奋性突触后电流特性。这些发现显著扩展了之前对雄性或性别未确定动物中MSN亚型的研究，并表明性别对伏隔核核心区MSN特性的影响在啮齿动物物种之间有所不同。新的且值得注意的是，这项研究对关键脑区伏隔核核心区的中型多棘神经元亚型电生理特性进行了迄今为止最全面的评估。此外，它还首次评估了小鼠中型多棘神经元亚型电生理特性是否因性别而异。
