The role of nicotinic receptors in shaping and functioning of the glutamatergic system: a window into cognitive pathology

Neurosci Biobehav Rev. 2014 Oct:46 Pt 2:315-25. doi: 10.1016/j.neubiorev.2014.05.012. Epub 2014 May 29.

Abstract

The involvement of the cholinergic system in learning, memory and attention has long been recognized, although its neurobiological mechanisms are not fully understood. Recent evidence identifies the endogenous cholinergic signaling via nicotinic acetylcholine receptors (nAChRs) as key players in determining the morphological and functional maturation of the glutamatergic system. Here, we review the available experimental and clinical evidence of nAChRs contribution to the establishment of the glutamatergic system, and therefore to cognitive function. We provide some clues of the putative underlying molecular mechanisms and discuss recent human studies that associate genetic variability of the genes encoding nAChR subunits with cognitive disorders. Finally, we discuss the new avenues to therapeutically targeting nAChRs in persons with cognitive dysfunction for which the α7-nAChR subunit is an important etiological mechanism.

Keywords: Intellectual disability; Neuronal plasticity; Nicotinic receptors; nAChRs.

Publication types

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

MeSH terms

  • Cognition Disorders / drug therapy
  • Cognition Disorders / genetics
  • Cognition Disorders / metabolism
  • Cognition Disorders / physiopathology*
  • Glutamic Acid / metabolism*
  • Humans
  • Molecular Targeted Therapy / methods
  • Neuronal Plasticity / physiology
  • Neurons / physiology
  • Protein Subunits / metabolism
  • Receptors, Nicotinic / genetics
  • Receptors, Nicotinic / physiology*
  • Synaptic Transmission / physiology

Substances

  • Protein Subunits
  • Receptors, Nicotinic
  • Glutamic Acid