Diversity of native nicotinic receptor subtypes in mammalian brain

Neuropharmacology. 2015 Sep;96(Pt B):302-11. doi: 10.1016/j.neuropharm.2014.11.003. Epub 2014 Nov 25.


Neuronal nicotinic acetylcholine receptors (nAChRs) are a heterogeneous family of pentameric ligand-gated cation channels that are expressed throughout the brain and involved in a wide range of physiological and pathophysiological processes. The nAChR subtypes share a common basic structure, but their biophysical and pharmacological properties depend on their subunit composition, which is therefore central to understanding their function in the nervous system and discovering new subtype selective drugs. The development of new technologies and the generation of mice carrying deletions or the expression of gain-of-function nAChR subunits, or GFP-tagged receptor genes has allowed the in vivo identification of complex subtypes and to study the role of individual subtypes in specific cells and complex neurobiological systems but much less is known about which native nAChR subtypes are involved in specific physiological functions and pathophysiological conditions in human brain. We briefly review some recent findings concerning the structure and function of native nAChRs, focussing on the subtypes identified in the rodent habenulo-interpeduncular pathway, a pathway involved in nicotine reinforcement and withdrawal. We also discuss recent findings concerning the expression of native subtypes in primate brain. This article is part of the Special Issue entitled 'The Nicotinic Acetylcholine Receptor: From Molecular Biology to Cognition'.

Keywords: Habenulo-interpeduncular pathway; Neuronal nicotinic receptors; Primate; Stoichiometry; Subtypes; Subunit composition.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Acetylcholine / metabolism
  • Allosteric Site
  • Animals
  • Brain / drug effects
  • Brain / metabolism*
  • Habenula / drug effects
  • Habenula / metabolism
  • Humans
  • Interpeduncular Nucleus / drug effects
  • Interpeduncular Nucleus / metabolism
  • Macaca mulatta
  • Mice
  • Neurons / drug effects
  • Neurons / metabolism*
  • Nicotine / pharmacology
  • Nicotinic Agonists / pharmacology
  • Protein Structure, Tertiary
  • Protein Subunits / chemistry*
  • Protein Subunits / metabolism*
  • Rats
  • Receptors, Nicotinic / chemistry*
  • Receptors, Nicotinic / metabolism*


  • Nicotinic Agonists
  • Protein Subunits
  • Receptors, Nicotinic
  • Nicotine
  • Acetylcholine