Diversity of native nicotinic receptor subtypes in mammalian brain

• nAChRs are a heterogeneous family of pentameric ion channels ubiquitously expressed in the brain.
• Each subtype has distinct pharmacological properties determined by its subunit composition.
• Changes in nAChR expression or dysfunction are involved in various neuropsychiatric diseases.
• In some neuronal circuits nAChR subtypes are remarkably conserved from rodents to primates.

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’.