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

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

doi:10.7554/elife.49872

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 and 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 potential 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.

Highlights

Interactions among cell assemblies underlie information representation and processing in the brain (Buzsáki, 2010)
PV+ interneurons are equipped with NMDA receptors (NMDARs) whose slow kinetics and nonlinear voltage dependence do not appear well-aligned with fast inhibition of principal cells
The present study shows that clustered excitatory synapses on stratum oriens dendrites of CA1 PV+ interneurons interact supralinearly, challenging the view that they act as linear integrators of synaptic inputs (see (Tzilivaki et al, 2019))

Summary

Introduction

Interactions among cell assemblies underlie information representation and processing in the brain (Buzsáki, 2010). The biophysical properties of PV+ cells that make them suited to fast inhibition of target neurons are well established (Jonas et al, 2004) These properties are critical for functions such as the enforcement of narrow temporal integration, input normalization, and sparsification of neuronal assemblies (de Almeida et al, 2009; Pouille et al, 2009; Pouille and Scanziani, 2001). We show that NMDARs at feedback synapses mediate integrative dendritic nonlinearities in PV+ interneurons. This mechanism can be exploited to promote the formation of robust cell assemblies that are stable in the face of distracting noise

Results

Discussion

Materials and Methods