GABAA Receptor-Mediated Responses in the Ventromedial Nucleus of the Hypothalamus of Female and Male Neonatal Rats

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Abstract
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-amino-butyric 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 behaviors in rats. Specifically, GABAA receptor levels are known to be steroid regulated and 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.

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