The insular cortex is known to play a pivotal role in addiction to nicotine. Long-term depression (LTD) in the central nervous system is a major form of synaptic plasticity which is involved in learning and memory and in various pathological conditions such as nicotine addiction. Until now, effects of nicotine on LTD were mainly examined in the hippocampus and striatum, and there is no report showing the effects of nicotine on LTD in the insular cortex. In the present study, I show for the first time that nicotine facilitates LTD which is induced by combination of presynaptic stimulation with postsynaptic depolarization (paired training) in layer 5 pyramidal neurons of the mouse insular cortex using whole-cell patch-clamp recordings. The facilitatory effect of nicotine on LTD was blocked by GABAA receptor antagonists, bicuculline and picrotoxin. Furthermore, blockade of β2-containing nicotinic acetylcholine receptors (nAChRs) prevented the effects of nicotine on LTD. Taken together, these results suggest that in layer 5 pyramidal neurons of the insular cortex, nicotine facilitates LTD through enhancement of GABAergic synaptic transmission, presumably mediated by activation of β2-containing nAChRs. These findings may provide the crucial synaptic basis for the insular cortical changes in nicotine addiction.
Keywords: GABA(A) receptor; Long-term depression; Nicotinic acetylcholine receptor.
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