Dendritic NMDA receptors in parvalbumin neurons enable strong and stable neuronal assemblies

Abstract
Data availability
Article and author information
Metrics

Abstract

Parvalbumin-expressing (PV+) GABAergic interneurons mediate feedforward and feedback inhibition and have a key role in gamma oscillations and information processing. The importance of fast synaptic recruitment, action potential initiation and repolarization, and rapid synchronous GABA release by PV+ cells is well established. In contrast, the functional significance of PV+ cell NMDA receptors (NMDARs), which generate relatively slow postsynaptic currents, is unclear. Underlining their importance, several studies implicate PV+ cell NMDAR disruption in impaired network function and circuit pathologies. Here, we show that dendritic NMDARs underlie supralinear integration of feedback excitation from local pyramidal neurons onto mouse CA1 PV+ cells. Furthermore, by incorporating NMDARs at feedback connections onto PV+ cells in spiking networks, we show that these receptors enable cooperative recruitment of PV+ interneurons, strengthening and stabilising principal cell assemblies. Failure of this phenomenon provides a parsimonious explanation for cognitive and sensory gating deficits in pathologies with impaired PV+ NMDAR signalling.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files.

Article and author information

Author details

Jonathan H Cornford

UCL Institute of Neurology, University College London, London, United Kingdom

For correspondence
jonathan.cornford.12@ucl.ac.uk

Competing interests
The authors declare that no competing interests exist.
Marion S Mercier

UCL Institute of Neurology, University College London, London, United Kingdom

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-3929-8118
Marco Leite

UCL Institute of Neurology, University College London, London, United Kingdom

Competing interests
The authors declare that no competing interests exist.
Vincent Magloire

UCL Institute of Neurology, University College London, London, United Kingdom

Competing interests
The authors declare that no competing interests exist.
Michael Häusser

Wolfson Institute for Biomedical Research, Department of Neuroscience, Physiology and Pharmacology, University College London, London, United Kingdom

Competing interests
The authors declare that no competing interests exist.
Dimitri Michael Kullmann

UCL Institute of Neurology, University College London, London, United Kingdom

For correspondence
d.kullmann@ucl.ac.uk

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0001-6696-3545

Funding

Wellcome (095580/Z/11/Z)

Jonathan H Cornford
Marion S Mercier
Marco Leite
Vincent Magloire
Dimitri Michael Kullmann

Wellcome (212285/Z/18/Z)

Dimitri Michael Kullmann

Medical Research Council (MR/L01095X/1)

Vincent Magloire

Brain Research Trust

Jonathan H Cornford

Wellcome

Michael Häusser

Epilepsy Research UK (P1702)

Vincent Magloire

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: The study was performed in accordance with the Animals (Scientific Procedures) Act 1986 and reviewed by the Animal Welfare and Ethical Review Body (AWERB) of the UCL Queen Square Institute of Neurology.

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.