Ab. Brussaard et al., Changes in properties and neurosteroid regulation of GABAergic synapses inthe supraoptic nucleus during the mammalian female reproductive cycle, J PHYSL LON, 516(2), 1999, pp. 513-524
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.