Nicotinic activity depresses synaptic potentiation in layer V pyramidal neurons of mouse insular cortex.

The insular cortex is a critical brain region involved in nicotine addiction. However, its specific cellular and synaptic mechanisms underlying nicotine addiction remains largely unknown. In the present study, we examined how nicotine modulates synaptic transmission and plasticity in layer V pyramidal neurons of the mouse insular cortex. We also examined which type of neurons express functional nicotinic acetylcholine receptors (nAChRs) in layer V of the insular cortex. We found that nicotine suppresses synaptic potentiation induced by combination of presynaptic stimulation with postsynaptic depolarization (paired training). An application of nicotine significantly enhanced both spontaneous excitatory postsynaptic currents (EPSCs) and inhibitory postsynaptic currents (IPSCs): the former effect was mediated by activation of β2-containing nAChRs while the latter one was mediated largely by activation of β2-containing nAChRs and to a minor extent by activation of α7-containing nAChRs. The application of nicotine significantly enhanced evoked IPSCs but had no effect on evoked EPSCs. We also found that in layer V of the mouse insular cortex, majority of non-fast-spiking (non-FS) interneurons have β2-containing nAChRs while about half of pyramidal neurons and FS interneurons have functional nAChRs. Blockade of GABAA receptors or β2-containing nAChRs prevented the effects of nicotine on synaptic potentiation. Taken together, these results suggest that in layer V pyramidal neurons of the insular cortex, activation of β2-containing nAChRs expressed in non-FS interneurons suppresses synaptic potentiation through enhancing GABAergic synaptic transmission. These findings provide important insights into the cellular and synaptic mechanisms of insular cortical changes in nicotine addiction.