Cerebellar nicotinic cholinergic receptors are intrinsic to the cerebellum: Implications for diverse functional roles

Jill R. Turner, Pavel I. Ortinski, Rachel M. Sherrard, Kenneth J. Kellar

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Although recent studies have delineated the specific nicotinic subtypes present in the mammalian cerebellum, very little is known about their location or function within the cerebellum. This is of increased interest since nicotinic receptors (nAChRs) in the cerebellum have recently been implicated in the pathology of autism spectrum disorders. To begin to better understand the roles of these heteromeric nAChRs in the cerebellar circuitry and their therapeutic potential as targets for drug development, we used various chemical and stereotaxic lesion models in conjunction with slice electrophysiology to examine how specific heteromeric nAChR subtypes may influence the surrounding cerebellar circuitry. Using subunit-specific immunoprecipitation of radiolabeled nAChRs in the cerebella following N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride, p-chloroamphetamine, and pendunculotomy lesions, we show that most, if not all, cerebellar nicotinic receptors are present in cells within the cerebellum itself and not in extracerebellar afferents. Furthermore, we demonstrate that the β4-containing, but not the β2-containing, nAChRs intrinsic to the cerebellum can regulate inhibitory synaptic efficacy at two major classes of cerebellar neurons. These tandem findings suggest that nAChRs may present a potential drug target for disorders involving the cerebellum.

Original languageEnglish
Pages (from-to)748-757
Number of pages10
JournalCerebellum
Volume10
Issue number4
DOIs
StatePublished - Dec 2011

Bibliographical note

Funding Information:
Acknowledgments We thank Dr. Stefano Vicini for helpful discussions about the data presented here. We also thank Drs. Scott Rogers and Lorise Gahring (University of Utah, USA) and Drs. Barry Wolfe and Robert Yasuda (Georgetown University, USA) for providing us with antisera to several nicotinic receptor subunits. This study was supported by NIH grant DA012976 and NIH Training grant NIH-T32-NS41218.

Keywords

  • Cerebellum
  • Electrophysiology
  • Immunoprecipitation
  • Lesion
  • Nicotinic receptor
  • Rat

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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