Astrocyte GluN2C NMDA receptors control basal synaptic strengths of hippocampal CA1 pyramidal neurons in the stratum radiatum.

Peter H Chipman,Chi Chung Alan Fung,Manabu Abe,Abhilash Sawant,Alejandra Pazo Fernandez,Kenji Sakimura,Yukiko Goda,Mizuki Kurosawa,Angelo Tedoldi,Tomoki Fukai,Atsushi Kawai,Sunita Ghimire Gautam

doi:10.7554/elife.70818

Abstract

Experience-dependent plasticity is a key feature of brain synapses for which neuronal N-Methyl-D-Aspartate receptors (NMDARs) play a major role, from developmental circuit refinement to learning and memory. Astrocytes also express NMDARs, although their exact function has remained controversial. Here, we identify in mouse hippocampus, a circuit function for GluN2C NMDAR, a subtype highly expressed in astrocytes, in layer-specific tuning of synaptic strengths in CA1 pyramidal neurons. Interfering with astrocyte NMDAR or GluN2C NMDAR activity reduces the range of presynaptic strength distribution specifically in the stratum radiatum inputs without an appreciable change in the mean presynaptic strength. Mathematical modeling shows that narrowing of the width of presynaptic release probability distribution compromises the expression of long-term synaptic plasticity. Our findings suggest a novel feedback signaling system that uses astrocyte GluN2C NMDARs to adjust basal synaptic weight distribution of Schaffer collateral inputs, which in turn impacts computations performed by the CA1 pyramidal neuron.

Highlights

Plasticity is a fundamental feature of neuronal connections in the brain, where experiencedependent changes in synaptic strengths over different time scales are crucial for a variety of processes ranging from neural circuit development, circuit computations to learning and memory (Feldman and Brecht, 2005; Bliss and Collingridge, 1993; Abbott and Regehr, 2004; Collingridge et al, 2010; Nicoll, 2017)
Summary 22 Experience-dependent plasticity is a key feature of brain synapses for which neuronal N-Methyl23 D-Aspartate receptors (NMDARs) play a major role, from developmental circuit refinement to 24 learning and memory
We identify in mouse hippocampus, a circuit function for GluN2C NMDAR, a subtype highly expressed in astrocytes, in layer-specific tuning of synaptic strengths in CA1 pyramidal neurons

Summary

Introduction

Plasticity is a fundamental feature of neuronal connections in the brain, where experiencedependent changes in synaptic strengths over different time scales are crucial for a variety of processes ranging from neural circuit development, circuit computations to learning and memory (Feldman and Brecht, 2005; Bliss and Collingridge, 1993; Abbott and Regehr, 2004; Collingridge et al, 2010; Nicoll, 2017). Deciphering how neurons dynamically express different forms of synaptic plasticity while ensuring the optimal performance of the circuit remains a key challenge (Vitureira and Goda, 2013; Turrigiano, 2017; Nicoll, 2017; Brunel, 2016). NMDARs that are typically composed of two GluN1 and two GluN2 subunits and are present postsynaptically have been extensively studied for their role in memory mechanisms (Paoletti et al, 2013; Sanz-Clemente et al, 2013; Nicoll 2017). The precise function for astrocyte NMDARs, has remained a matter of debate (e.g. Kirchhoff, 2017), and the role for astrocyte GluN2C has not yet been identified

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Conclusion