Smith S T, Brennan C, Clark A S, Henderson L P
Department of Physiology, Dartmouth Medical School, Hanover, NH 03755 USA.
Neuroendocrinology. 1996 Aug;64(2):103-13. doi: 10.1159/000127105.
Perinatal exposure of the developing brain to gonadal steroids during a limited critical period induces permanent, organizational differences in neural structures between male and female animals. These differences are believed to underlie the manifestation of sexually dimorphic behaviors. Gamma-aminobutyric acid type A (GABAA) receptors expressed in the ventromedial nucleus (VMN) of the hypothalamus appear to be a key component underlying the expression of sexually dimorphic, and GABAA-mediated transmission within the VMN is critical for the expression of sexual behavior in female, but not male, rats. Here we report that analysis of VMN neurons from neonatal rats revealed significant sex-specific differences in GABAA receptor channel properties. Specifically, GABAA-mediated currents elicited by direct agonist application decayed more rapidly in VMN neurons from females than from males. Kinetic differences became more pronounced during the first 2 weeks of postnatal development. Analysis of small, spontaneous inhibitory postsynaptic currents recorded in intact slices indicated a trend towards slower responses in neurons from males than females, but the differences in decay kinetics were not significant. Sex-specific differences in GABAA receptor kinetics may arise from activation of receptors not receiving synaptic contacts in the slice preparation or may become apparent at intact synapses under conditions of increased activity and evoked release.
在有限的关键时期,发育中的大脑在围产期暴露于性腺类固醇会导致雄性和雌性动物的神经结构产生永久性的组织学差异。这些差异被认为是两性异形行为表现的基础。在下丘脑腹内侧核(VMN)中表达的γ-氨基丁酸A型(GABAA)受体似乎是两性异形表达的关键组成部分,并且VMN内GABAA介导的传递对于雌性而非雄性大鼠性行为的表达至关重要。在此我们报告,对新生大鼠VMN神经元的分析揭示了GABAA受体通道特性存在显著的性别特异性差异。具体而言,直接应用激动剂引发的GABAA介导电流在雌性VMN神经元中比在雄性VMN神经元中衰减得更快。在出生后发育的前两周,动力学差异变得更加明显。对完整切片中记录的微小、自发性抑制性突触后电流的分析表明,雄性神经元的反应有比雌性神经元反应更慢的趋势,但衰减动力学的差异并不显著。GABAA受体动力学的性别特异性差异可能源于切片制备中未接受突触接触的受体的激活,或者在活动增加和诱发释放的条件下,在完整突触处可能会变得明显。