Invited reviewNMDA receptor-dependent function and plasticity in inhibitory circuits

- We review the impact of NMDA receptors on interneuron function and plasticity.
- Glutamatergic synapses on interneurons and GABAergic synapses on principal cells are highly plastic.
- Different forms of LTP and LTD have been identified in distinct interneuron subtypes.
- Both post- and presynaptic NMDA receptors are involved in inhibitory circuit plasticity.
- Decreased NMDA function in specific interneuron populations has been proposed to play a central role in schizophrenia.

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'.