NMDA receptor-dependent function and plasticity in inhibitory circuits

Neuropharmacology. 2013 Nov;74:23-31. doi: 10.1016/j.neuropharm.2013.03.004. Epub 2013 Mar 26.


NMDA receptors have been known to play a central role in long-term potentiation at glutamatergic synapses in principal cells for thirty years. In contrast, their roles in the development and activity-dependent plasticity of synapses in inhibitory circuits have only recently begun to be understood. Progress has, to a great extent, been hampered by the extensive diversity of GABAergic cell types in the CNS. However, anatomical, immunohistochemical and electrophysiological methods have allowed distinct types to be identified, with the result that consistent patterns of synaptic plasticity have begun to emerge. This review summarizes recent evidence on the role of NMDA receptors in the development and plasticity of GABAergic synapses on principal cells and of glutamatergic synapses on identified interneurons. A major challenge is to understand how NMDA receptors affect the routing of information in healthy inhibitory circuits, and how changes in NMDA receptor function may contribute to altered circuit function in disorders such as schizophrenia. This article is part of the Special Issue entitled 'Glutamate Receptor-Dependent Synaptic Plasticity'.

Keywords: Inhibitory circuits; Interneurons; NMDA receptors; Plasticity; Schizophrenia.

Publication types

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

MeSH terms

  • Animals
  • Brain / metabolism
  • Brain / physiology
  • Brain / physiopathology
  • GABAergic Neurons / physiology*
  • Glutamic Acid / physiology
  • Humans
  • Interneurons / metabolism
  • Interneurons / physiology
  • Models, Neurological
  • Neural Inhibition / physiology*
  • Neuronal Plasticity / physiology*
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Receptors, N-Methyl-D-Aspartate / physiology*
  • Schizophrenia / physiopathology
  • Synaptic Transmission / physiology


  • Receptors, N-Methyl-D-Aspartate
  • Glutamic Acid