PDF(Pubmed)
Abstract：
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
Adolescence marks a period of substantial changes in both the mind and body, where alterations in the brain’s structure can influence behavior. One change in behavior exhibited by many adolescents is an increased tendency to take risks, particularly in males. While taking risks can result in positive outcomes, like learning new skills, it can also lead to reckless behaviors that may result in negative outcomes. The nucleus accumbens, a brain region tied to risk-taking and reward perception, is not well-studied during the transition from childhood to adulthood, particularly in terms of sex differences. To fill this gap in understanding, this study examined a specific type of brain cell in the nucleus accumbens of pre- and mid-adolescent male and female mice. We measured the electrical properties of these cells and assessed how they responded to manipulation of their electrical state. We also measured how much and how often excitatory electrical information is sent to these cells from other brain regions. Our results suggest that in pre-adolescent females, these brain cells are more excited by manipulations of their electrical state and that these brain cells in mid-adolescent males may take longer to communicate information to other brain regions than in similarly aged females. Understanding these intricacies of brain cell communication sheds light on potential sex-specific vulnerabilities during the transition from childhood to adulthood.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
Adolescence marks a period of substantial changes in both the mind and body, where alterations in the brain’s structure can influence behavior. One change in behavior exhibited by many adolescents is an increased tendency to take risks, particularly in males. While taking risks can result in positive outcomes, like learning new skills, it can also lead to reckless behaviors that may result in negative outcomes. The nucleus accumbens, a brain region tied to risk-taking and reward perception, is not well-studied during the transition from childhood to adulthood, particularly in terms of sex differences. To fill this gap in understanding, this study examined a specific type of brain cell in the nucleus accumbens of pre- and mid-adolescent male and female mice. We measured the electrical properties of these cells and assessed how they responded to manipulation of their electrical state. We also measured how much and how often excitatory electrical information is sent to these cells from other brain regions. Our results suggest that in pre-adolescent females, these brain cells are more excited by manipulations of their electrical state and that these brain cells in mid-adolescent males may take longer to communicate information to other brain regions than in similarly aged females. Understanding these intricacies of brain cell communication sheds light on potential sex-specific vulnerabilities during the transition from childhood to adulthood.
摘要：
背景：从童年到成年的过渡，或者青春期,一个发展阶段，以心理社会和生物学变化为特征。伏隔核（NAc），由核心（NAcC）和外壳（NAcSh）组成的纹状体大脑区域，与冒险行为有关，并牵涉到寻求奖励和评估。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+)的中刺神经元(MSN)。多巴胺能和谷氨酸能系统的变化发生在青春期，并在NAc中收敛。虽然先前有关于NAc两个分支中膜兴奋性和突触谷氨酸传递的性别差异的研究，根据我们的知识，没有人指定青春期前和青春期中期小鼠的NAcShD1R+MSN。
方法:从B6制备含有NAc的矢状脑切片。Cg-Tg（Drd1a-tdTomato）6Calak/J小鼠，来自出生后第21-25天和35-47天，代表青春期前和青春期中期，分别。从NAcShD1R+MSN收集全细胞电生理记录，以膜电压对电流注入的反应形式，评估膜特性和动作电位波形特征，和自发兴奋性突触后电流（sEPSCs）以评估谷氨酸能突触活动。
结果：相对于青春期前男性，青春期前女性NAcShD1R+MSNs表现出较少的超极化静息膜电位，增加输入电阻，和较小的动作电位后超极化振幅。在青春期中期,女性的输入阻力降低和动作电位持续时间缩短是唯一观察到的性别差异。
结论：综合来看，我们的结果表明，NAcShD1R+MSN小鼠在青春期前表现出膜特性和AP波形的性别差异，这总体上表明女性细胞兴奋性增加，并提示甘氨酸受体可能存在性别差异，向内整流钾通道，和大电导电压门控钾通道。这些差异似乎不会持续到青春期中期，当观察到性别与青春期前相反地影响输入阻力和AP波形时，提示电压门控钾通道存在差异。
青春期标志着身心发生实质性变化的时期，大脑结构的改变会影响行为。许多青少年表现出的一种行为变化是冒险的趋势增加，尤其是男性。虽然承担风险可以带来积极的结果，比如学习新技能，它也可能导致鲁莽的行为，可能导致负面结果。伏隔核,与冒险和奖励感知相关的大脑区域，在从童年到成年的过渡过程中没有得到很好的研究，特别是在性别差异方面。为了填补这个理解上的空白，这项研究检查了青春期前和青春期中期雄性和雌性小鼠伏隔核中一种特定类型的脑细胞。我们测量了这些细胞的电特性，并评估了它们如何对其电状态的操纵做出反应。我们还测量了兴奋性电信息从其他大脑区域发送到这些细胞的数量和频率。我们的结果表明，在青春期前的女性中，这些脑细胞对它们的电状态的操纵更加兴奋，并且与年龄相同的女性相比，青春期中期男性的这些脑细胞可能需要更长的时间来将信息传达给其他大脑区域。了解脑细胞交流的这些复杂性，可以揭示从童年到成年过渡期间潜在的性别特异性漏洞。
方法:从B6制备含有NAc的矢状脑切片。Cg-Tg（Drd1a-tdTomato）6Calak/J小鼠，来自出生后第21-25天和35-47天，代表青春期前和青春期中期，分别。从NAcShD1R+MSN收集全细胞电生理记录，以膜电压对电流注入的反应形式，评估膜特性和动作电位波形特征，和自发兴奋性突触后电流（sEPSCs）以评估谷氨酸能突触活动。
结果：相对于青春期前男性，青春期前女性NAcShD1R+MSNs表现出较少的超极化静息膜电位，增加输入电阻，和较小的动作电位后超极化振幅。在青春期中期,女性的输入阻力降低和动作电位持续时间缩短是唯一观察到的性别差异。
结论：综合来看，我们的结果表明，NAcShD1R+MSN小鼠在青春期前表现出膜特性和AP波形的性别差异，这总体上表明女性细胞兴奋性增加，并提示甘氨酸受体可能存在性别差异，向内整流钾通道，和大电导电压门控钾通道。这些差异似乎不会持续到青春期中期，当观察到性别与青春期前相反地影响输入阻力和AP波形时，提示电压门控钾通道存在差异。
青春期标志着身心发生实质性变化的时期，大脑结构的改变会影响行为。许多青少年表现出的一种行为变化是冒险的趋势增加，尤其是男性。虽然承担风险可以带来积极的结果，比如学习新技能，它也可能导致鲁莽的行为，可能导致负面结果。伏隔核,与冒险和奖励感知相关的大脑区域，在从童年到成年的过渡过程中没有得到很好的研究，特别是在性别差异方面。为了填补这个理解上的空白，这项研究检查了青春期前和青春期中期雄性和雌性小鼠伏隔核中一种特定类型的脑细胞。我们测量了这些细胞的电特性，并评估了它们如何对其电状态的操纵做出反应。我们还测量了兴奋性电信息从其他大脑区域发送到这些细胞的数量和频率。我们的结果表明，在青春期前的女性中，这些脑细胞对它们的电状态的操纵更加兴奋，并且与年龄相同的女性相比，青春期中期男性的这些脑细胞可能需要更长的时间来将信息传达给其他大脑区域。了解脑细胞交流的这些复杂性，可以揭示从童年到成年过渡期间潜在的性别特异性漏洞。
