Changes in properties and neurosteroid regulation of GABAergic synapses inthe supraoptic nucleus during the mammalian female reproductive cycle

1. GABA(A) receptor-mediated synaptic innervation of oxytocin neurones in t he supraoptic nucleus (SON) was analysed in adult female rats going through their first reproductive cycle by recording the spontaneous inhibitory pos tsynaptic currents (sIPSCs) at six stages of female reproduction. 2. During pregnancy we observed a reduction in the interval between monoqua ntal sIPSCs. The synaptic current amplitude, current decay and neurosteroid sensitivity of postsynaptic GABA(A) receptors observed at this stage were not distinguishable from those measured in virgin stage SON. 3. Upon parturition an increase in monoquantal synaptic current decay occur red, whereas potentiation by the progesterone metabolite allopregnanolone ( 3 alpha-OH-DHP) was suppressed. 4. Throughout a substantial part of the lactation period the decay of synap tic currents remained attenuated, whilst the potentiation by 3 alpha-OH-DHP remained suppressed. 5. Several weeks after the end of lactation sIPBC intervals, their current decay velocity as well as the potentiation by 3 alpha-OH-DHP were restored to pre-pregnancy levels, which is indicative of the cyclical nature of syna ptic plasticity in the adult SON. 6. Competitive polymerase chain reaction (PCR) analysis showed that virgin animals expressed alpha 1 and alpha 2 GABA(A) receptor subunit mRNA at a re lative ratio of 2 : 1. compared with beta-actin. After pregnancy both alpha 1 and alpha 2 subunit mRNA levels were transiently increased, although at a relative ratio of 1.:4, in line with the hypothesis that alpha 2 plays a large role in postsynaptic receptor functioning. During post-lactation both a subunits were downregulated. 7. We propose that synaptic remodelling in the SON during pregnancy include s changes in the putative number of GABA release sites per neurone. At part urition, and during the two consecutive weeks of lactation, a subtype of po stsynaptic GABA(A) receptors was observed, distinct from the one being expr essed before and during pregnancy. Synaptic current densities, calculated i n order to compare the impact of synaptic inhibition, showed that, in parti cular, the differences in 3 alpha-OH-DHP potentiation of these two distinct GABA(A) receptor subtypes produce robust shifts in the impact of synaptic inhibition of oxytocin neurones at the different stages of female reproduct ion.