Nicotine Modulates Gabaergic Transmission To Dopaminergic Neurons In Substantia Nigra Pars Compacta

Department

neurobiology

Document Type

Article

Abstract

Aim: Dopaminergic neurons in the substantia nigra pars compacta (SNc) play important roles in motor control and drug addiction. As the major afferent, GABAergic innervation controls the activity of SNc dopaminergic neurons. Although it is clear that nicotine modulates SNc dopaminergic neurons by activating subtypes of somatodendritic nicotinic acetylcholine receptors (nAChRs), the detailed mechanisms of this activation remain to be addressed. Methods: In the current study, we recorded GABA A receptor-mediated spontaneous inhibitory postsynaptic currents (sIPSCs) from dissociated SNc dopaminergic neurons that were obtained using an enzyme-free procedure. These neurons preserved some functional terminals after isolation, including those that release GABA. Results: We found that both extra- and intra-cellular calcium modulates sIPSCs in these neurons. Furthermore, both nicotine and endogenous acetylcholine enhance the frequency of sIPSCs. Moreover, endogenous acetylcholine tonically facilitates sIPSC frequency, primarily by activating the α4Β2 nAChRs on the GABAergic terminals. Conclusion: Nicotine facilitates GABA release onto SNc dopaminergic neurons mainly via the activation of presynaptic α4Β2 nAChRs. © 2009 CPS and SIMM.

Publication Date

6-1-2009

Publication Title

Acta Pharmacologica Sinica

ISSN

16714083

Volume

30

Issue

6

First Page

851

Last Page

858

Digital Object Identifier (DOI)

10.1038/aps.2009.65

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