GABA(B) receptors, monoamine receptors, and postsynaptic inositol trisphosphate-induced Ca2+ release are involved in the induction of long- term potentiation at visual cortical inhibitory synapses

Abstract

γ-Aminobutyric acid (GABA)(A) receptor-mediated inhibitory synaptic transmission in visual codex undergoes long-term potentiation (LTP), which is input-specific and associative. The present study, conducted under a blockade of ionotropic glutamate receptors, demonstrates an induction mechanism of LTP considerably different from those of associative LTP at excitatory synapses. Inhibitory responses of layer V cells evoked by layer IV stimulation were studied in developing rat visual cortex slices by using intracellular and whole-cell recording methods. LTP induction was prevented by the application of an antagonist for GABA(B) receptors but not for GABA(A) or metabotropic glutamate receptors. Inhibition of postsynaptic G-proteins, phospholipase C, inositol trisphosphate (IP3) receptors, or Ca2+ increase prevented the generation of LTP, as did the blockade of GABA(B) receptors. In rat cerebral cortex, GABA(B) receptor activation is not known to affect the IP3 level by itself. However, it facilitates IP3 formation induced by the activation of α1 adrenoceptors, which are believed to be located postsynaptically. Accordingly, I examined the involvement of these and other amine receptors, including histamine H1, muscarinic acetylcholine, and serotonin 5-HT2 receptors, all of which are coupled to IP3 formation. Only the blockade of α1 adrenoceptors or serotonin 5-HT2 receptors prevented LTP induction in most, but not all, of the cells. These results suggest that LTP induction requires the activation of postsynaptic GABA(B) receptors and that its effect is mediated at least partly by facilitation of the monoamine-induced IP3 formation, which then causes Ca2+ release from the internal stores in postsynaptic cells.