Selective excitation of subtypes of neocortical interneurons by nicotinic receptors

The cellular mechanisms by which neuronal nicotinic cholinergic receptors i nfluence many aspects of physiology and pathology in the neocortex remain p rimarily unknown. Whole-cell recordings and single-cell reverse transcripti on (RT)-PCR were combined to analyze the effect of nicotinic receptor agoni sts on different types of neurons in acute slices of rat neocortex, Nicotin ic receptor agonists had no effect on pyramidal neurons and on most types o f interneurons, including parvalbumin-expressing fast spiking interneurons and somatostatin-expressing interneurons, but selectively excited a subpopu lation of interneurons coexpressing the neuropeptides vasoactive intestinal peptide (VIP) and cholecystokinin, This excitation persisted in the presen ce of glutamate, GABA, and muscarinic receptor antagonists and in the prese nce of tetrodotoxin and low extracellular calcium, suggesting that the depo larization was mediated through the direct activation of postsynaptic nicot inic receptors. The responses were blocked by the nicotinic receptor antago nists dihydro-beta-erythroidine and mecamylamine and persisted in the prese nce of the alpha 7 selective nicotinic receptor antagonist methyllycaconiti ne, suggesting that the involved nicotinic receptors lacked the alpha 7 sub unit, Single-cell RT-PCR analysis indicated that the majority of the intern eurons that responded to nicotinic stimulation coexpressed the alpha 4, alp ha 5, and beta 2 nicotinic receptor subunits. Therefore, these results prov ide a role for non-alpha 7 nicotinic receptors in the selective excitation of a subpopulation of neocortical interneurons. Because the neocortical int erneurons expressing VIP have been proposed previously to regulate regional cortical blood flow and metabolism these results also provide a cellular b asis for the neuronal regulation of cortical blood flow mediated by acetylc holine.