Division of Pharmacology and Toxicology, College of Pharmacy, The University of Texas at Austin, 2409 University Avenue, Austin, TX, 78712, USA.
Biol Sex Differ. 2024 Jul 13;15(1):54. doi: 10.1186/s13293-024-00631-1.
The transition from childhood to adulthood, or adolescence, a developmental stage, is characterized by psychosocial and biological changes. The nucleus accumbens (NAc), a striatal brain region composed of the core (NAcC) and shell (NAcSh), has been linked to risk-taking behavior and implicated in reward seeking and evaluation. Most neurons in the NAc are medium spiny neurons (MSNs) that express dopamine D1 receptors (D1R +) and/or dopamine D2 receptors (D2R +). Changes in dopaminergic and glutamatergic systems occur during adolescence and converge in the NAc. While there are previous investigations into sex differences in membrane excitability and synaptic glutamate transmission in both subdivisions of the NAc, to our knowledge, none have specified NAcSh D1R + MSNs from mice during pre- and mid-adolescence.
Sagittal brain slices containing the NAc were prepared from B6.Cg-Tg(Drd1a-tdTomato)6Calak/J mice of both sexes from postnatal days 21-25 and 35-47, representing pre- and mid-adolescence, respectively. Whole-cell electrophysiology recordings were collected from NAcSh D1R + MSNs in the form of membrane-voltage responses to current injections, to assess membrane properties and action potential waveform characteristics, and spontaneous excitatory postsynaptic currents (sEPSCs) to assess glutamatergic synaptic activity.
Relative to pre-adolescent males, pre-adolescent female NAcSh D1R + MSNs exhibited a less hyperpolarized resting membrane potential, increased input resistance, and smaller action potential afterhyperpolarization amplitudes. During mid-adolescence, decreased input resistance and a shorter action potential duration in females were the only sex differences observed.
Taken together, our results indicate that NAcSh D1R + MSNs in mice exhibit sex differences in membrane properties and AP waveform during pre-adolescence that are overall indicative of increased cellular excitability in females and are suggestive of possible sex differences in glycine receptors, inwardly-rectifying potassium channels, and large conductance voltage-gated potassium channels. These differences do not appear to persist into mid-adolescence, when sex was observed to affect input resistance oppositely to that of pre-adolescence and AP waveform in a manner suggestive of differences in voltage-gated potassium channels.
从儿童期到成年期（青春期）的过渡是一个发育阶段，其特征是心理社会和生物变化。伏隔核（NAc）是由核心（NAcC）和壳（NAcSh）组成的纹状体脑区，与冒险行为有关，并涉及到奖励寻求和评估。NAc 中的大多数神经元是表达多巴胺 D1 受体（D1R +）和/或多巴胺 D2 受体（D2R +）的中等棘突神经元（MSNs）。青春期期间多巴胺能和谷氨酸能系统发生变化，并汇聚在 NAc 中。虽然之前有研究调查了 NAc 的两个亚区中性别差异对膜兴奋性和突触谷氨酸传递的影响，但据我们所知，没有一项研究专门针对青春期前和青春期中期的 B6.Cg-Tg（Drd1a-tdTomato）6Calak/J 小鼠的 NAcSh D1R + MSNs 进行研究。
从出生后第 21-25 天和 35-47 天的雄性和雌性 B6.Cg-Tg（Drd1a-tdTomato）6Calak/J 小鼠中制备包含 NAc 的矢状脑切片，分别代表青春期前和青春期中期。通过电流注射记录 NAcSh D1R + MSNs 的膜电压反应，以评估膜特性和动作电位波形特征，以及自发兴奋性突触后电流（sEPSC）以评估谷氨酸能突触活动。
与青春期前的雄性相比，青春期前的雌性 NAcSh D1R + MSNs 的静息膜电位更去极化，输入电阻增加，动作电位后超极化幅度减小。在青春期中期，只有女性的输入电阻降低和动作电位持续时间缩短是观察到的性别差异。
综上所述，我们的结果表明，青春期前的雄性和雌性小鼠的 NAcSh D1R + MSNs 在膜特性和动作电位波形方面存在性别差异，总体上表明雌性细胞兴奋性增加，可能存在甘氨酸受体、内向整流钾通道和大电导电压门控钾通道的性别差异。这些差异似乎不会持续到青春期中期，此时性别似乎以与青春期前相反的方式影响输入电阻，并且动作电位波形的变化提示电压门控钾通道存在差异。
