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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Further reading
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When navigating environments with changing rules, human brain circuits flexibly adapt how and where we retain information to help us achieve our immediate goals.
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Human-specific cognitive abilities depend on information processing in the cerebral cortex, where the neurons are significantly larger and their processes longer and sparser compared to rodents. We found that, in synaptically connected layer 2/3 pyramidal cells (L2/3 PCs), the delay in signal propagation from soma to soma is similar in humans and rodents. To compensate for the longer processes of neurons, membrane potential changes in human axons and/or dendrites must propagate faster. Axonal and dendritic recordings show that the propagation speed of action potentials (APs) is similar in human and rat axons, but the forward propagation of excitatory postsynaptic potentials (EPSPs) and the backward propagation of APs are 26 and 47% faster in human dendrites, respectively. Experimentally-based detailed biophysical models have shown that the key factor responsible for the accelerated EPSP propagation in human cortical dendrites is the large conductance load imposed at the soma by the large basal dendritic tree. Additionally, larger dendritic diameters and differences in cable and ion channel properties in humans contribute to enhanced signal propagation. Our integrative experimental and modeling study provides new insights into the scaling rules that help maintain information processing speed albeit the large and sparse neurons in the human cortex.