Afferent specific role of NMDA receptors for the circuit integration of hippocampal neurogliaform cells

Chittajallu, R. et al. (2017) Afferent specific role of NMDA receptors for the circuit integration of hippocampal neurogliaform cells. Nature Communications, 8, 152. (doi: 10.1038/s41467-017-00218-y) (PMID:28751664) (PMCID:PMC5532276)

Abstract

Appropriate integration of GABAergic interneurons into nascent cortical circuits is critical for ensuring normal information processing within the brain. Network and cognitive deficits associated with neurological disorders, such as schizophrenia, that result from NMDA receptor-hypofunction have been mainly attributed to dysfunction of parvalbumin-expressing interneurons that paradoxically express low levels of synaptic NMDA receptors. Here, we reveal that throughout postnatal development, thalamic, and entorhinal cortical inputs onto hippocampal neurogliaform cells are characterized by a large NMDA receptor-mediated component. This NMDA receptor-signaling is prerequisite for developmental programs ultimately responsible for the appropriate long-range AMPAR-mediated recruitment of neurogliaform cells. In contrast, AMPAR-mediated input at local Schaffer-collateral synapses on neurogliaform cells remains normal following NMDA receptor-ablation. These afferent specific deficits potentially impact neurogliaform cell mediated inhibition within the hippocampus and our findings reveal circuit loci implicating this relatively understudied interneuron subtype in the etiology of neurodevelopmental disorders characterized by NMDA receptor-hypofunction.

• Item Type: Articles
• Additional Information: This work was supported by an intramural award to C.J.M. from the Eunice Kennedy–Shriver National Institute of Child Health and Human Development and a Competitive Fellowship Award to J.C.W. from the National Institute of Neurological Disorders and Stroke.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Craig, Dr Mick
• Authors: Chittajallu, R., Wester, J.C., Craig, M.T., Barksdale, E., Yuan, X.Q., Akgül, G., Fang, C., Collins, D., Hunt, S., Pelkey, K.A., and McBain, C.J.
• College/School: College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience
• Journal Name: Nature Communications
• Publisher: Nature Research
• ISSN: 2041-1723
• ISSN (Online): 2041-1723
• Copyright Holders: Copyright © 2017 The Authors
• First Published: First published in Nature Communications 8: 152
• Publisher Policy: Reproduced under a Creative Commons License