Dendritic NMDA receptors in parvalbumin neurons enable strong and stable neuronal assemblies
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
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
© 2019, Cornford et al.
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.
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