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The Journal of Neuroscience, July 1, 1999, 19(13):5228-5235

Selective Excitation of Subtypes of Neocortical Interneurons by Nicotinic Receptors

James T. Porter, Bruno Cauli, Keisuke Tsuzuki, Bertrand Lambolez, Jean Rossier, and Etienne Audinat

Neurobiologie et Diversité Cellulaire, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7637, Ecole Supérieure de Physique et de Chimie Industrielles, 75231 Paris Cedex 05, France

The cellular mechanisms by which neuronal nicotinic cholinergic receptors influence many aspects of physiology and pathology in the neocortex remain primarily unknown. Whole-cell recordings and single-cell reverse transcription (RT)-PCR were combined to analyze the effect of nicotinic receptor agonists on different types of neurons in acute slices of rat neocortex. Nicotinic receptor agonists had no effect on pyramidal neurons and on most types of interneurons, including parvalbumin-expressing fast spiking interneurons and somatostatin-expressing interneurons, but selectively excited a subpopulation of interneurons coexpressing the neuropeptides vasoactive intestinal peptide (VIP) and cholecystokinin. This excitation persisted in the presence of glutamate, GABA, and muscarinic receptor antagonists and in the presence of tetrodotoxin and low extracellular calcium, suggesting that the depolarization was mediated through the direct activation of postsynaptic nicotinic receptors. The responses were blocked by the nicotinic receptor antagonists dihydro-beta -erythroidine and mecamylamine and persisted in the presence of the alpha 7 selective nicotinic receptor antagonist methyllycaconitine, suggesting that the involved nicotinic receptors lacked the alpha 7 subunit. Single-cell RT-PCR analysis indicated that the majority of the interneurons that responded to nicotinic stimulation coexpressed the alpha 4, alpha 5, and beta 2 nicotinic receptor subunits. Therefore, these results provide a role for non-alpha 7 nicotinic receptors in the selective excitation of a subpopulation of neocortical interneurons. Because the neocortical interneurons expressing VIP have been proposed previously to regulate regional cortical blood flow and metabolism, these results also provide a cellular basis for the neuronal regulation of cortical blood flow mediated by acetylcholine.

Key words: single-cell PCR; neuropeptides; calcium-binding proteins; methyllycaconitine; dihydro-beta -erythroidine; acetylcholine; mecamylamine


Copyright © 1999 Society for Neuroscience  0270-6474/99/19135228-08$05.00/0


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