Layer-specific serotonergic facilitation of IPSC in layer 2/3 pyramidal neurons of the visual cortex.

Serotonin (5-hydroxytryptamine, 5-HT) inhibits the induction of long-term synaptic plasticity in layer 2/3 of the visual cortex at the end of its critical period in rats. However, the cellular and molecular mechanisms remain unclear. Since inhibitory influence is crucial in the induction of synaptic plasticity, the effect of 5-HT on inhibitory transmission was investigated in layer 2/3 pyramidal neurons of the primary visual cortex. The amplitude of inhibitory postsynaptic current (IPSC), but not excitatory postsynaptic current, evoked by stimulation of the underlying layer 4, was increased by ∼20% with a bath application of 5-HT. The amplitude of miniature IPSC was also increased by the application of 5-HT, while the paired-pulse ratio was not changed. The facilitating effect of 5-HT on IPSC was mediated by the activation of 5-HT(2) receptors. An increase in intracellular Ca(2+) via release from inositol 1,4,5-trisphosphate (IP(3))-sensitive stores, which was confirmed by confocal Ca(2+) imaging, and activation of Ca(2+)/calmodulin-dependent kinase II (CaMKII) were involved in the facilitation of IPSC by 5-HT. However, 5-HT failed to facilitate IPSC evoked by the stimulation of layer 1. These results suggest that activation of 5-HT(2) receptors releases intracellular Ca(2+) via IP(3)-sensitive stores, which facilitates GABA(A)ergic transmission via the activation of CaMKII in layer 2/3 pyramidal neurons of the visual cortex in a layer-specific manner. Thus facilitation of inhibitory transmission by 5-HT might be involved in regulating the information flow and the induction of long-term synaptic plasticity, in a pathway-specific manner.