Oestradiol rapidly enhances spontaneous glycinergic synaptic inhibition of hypoglossal motoneurones.

Whereas oestradiol is well-known to facilitate excitatory glutamatergic synaptic transmission, its effects on fast inhibitory neurotransmission are not as well established. Possible acute modulation of the spontaneous glycinergic synaptic activity by oestradiol was investigated in voltage-clamped hypoglossal motoneurones by whole-cell patch-clamp recording in rat brainstem slices. The spontaneous glycinergic synaptic activity was continuously recorded in each neurone under control conditions, during 12-20 min of perfusion with 17beta-oestradiol and during washing. When oestradiol was diluted in ethanol, the control solution contained the same amount of ethanol. At 100 nM, oestradiol markedly increased the frequency of the total spontaneous glycinergic activity. Similar experiments were performed after blockade of action potentials by tetrodotoxin, aiming to isolate miniature glycinergic synaptic currents. Oestradiol increased the frequency of glycinergic miniatures in most slices, in some cases within less than 1 min. In some slices, oestradiol also favoured the occurrence of glycinergic miniatures of large amplitude. These effects were slowly reversible during washing. At 1 nm, oestradiol still increased the frequency of glycinergic miniatures. The results were confirmed in the absence of ethanol by using water-soluble cyclodextrin-encapsulated oestradiol. In these experiments, the control solution contained the same amount of (2-hydroxypropyl)-beta-cyclodextrin as the oestradiol-containing solution. In addition, prolonged control recordings were performed without applying oestradiol to check the stability of the glycinergic synaptic activity during prolonged whole-cell recordings. The results show, for the first time, that, within a few minutes, oestradiol can enhance the spontaneous synaptic release of a major inhibitory transmitter, glycine.