Interneuron-specific plasticity at parvalbumin and somatostatin inhibitory synapses onto CA1 pyramidal neurons shapes hippocampal output

Matt Udakis,Sophie E L Chamberlain,Jack R Mellor,Claudia Clopath,Victor Pedrosa

doi:10.1038/s41467-020-18074-8

Matt Udakis, Sophie E L Chamberlain + Show 3 more

Open Access

https://doi.org/10.1038/s41467-020-18074-8

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Abstract

The formation and maintenance of spatial representations within hippocampal cell assemblies is strongly dictated by patterns of inhibition from diverse interneuron populations. Although it is known that inhibitory synaptic strength is malleable, induction of long-term plasticity at distinct inhibitory synapses and its regulation of hippocampal network activity is not well understood. Here, we show that inhibitory synapses from parvalbumin and somatostatin expressing interneurons undergo long-term depression and potentiation respectively (PV-iLTD and SST-iLTP) during physiological activity patterns. Both forms of plasticity rely on T-type calcium channel activation to confer synapse specificity but otherwise employ distinct mechanisms. Since parvalbumin and somatostatin interneurons preferentially target perisomatic and distal dendritic regions respectively of CA1 pyramidal cells, PV-iLTD and SST-iLTP coordinate a reprioritisation of excitatory inputs from entorhinal cortex and CA3. Furthermore, circuit-level modelling reveals that PV-iLTD and SST-iLTP cooperate to stabilise place cells while facilitating representation of multiple unique environments within the hippocampal network.

Highlights

The formation and maintenance of spatial representations within hippocampal cell assemblies is strongly dictated by patterns of inhibition from diverse interneuron populations
Immunohistochemisty confirmed that ChR2 expression was highest in the stratum pyramidal (SP) and stratum oriens (SO) layers for PV-ChR2 mice with cell bodies principally located in SP (Fig. 1a)
ChR2 expression was highest in the SO and stratum lacunosum moleculare (SLM) layers for SST-ChR2 mice with cell bodies principally located in SO (Fig. 1b)

Summary

Introduction

The formation and maintenance of spatial representations within hippocampal cell assemblies is strongly dictated by patterns of inhibition from diverse interneuron populations. Individual CA1 pyramidal neurons can encode distinct place fields in different environments[22] presumably driven by ongoing excitatory synaptic plasticity This feature of place cells and the persistent plasticity of their synaptic connections present fundamental problems for hippocampal networks balancing flexibility versus stability of representations[23]. Synapses from PV and SST interneurons can undergo unique forms of plasticity[38,41], whilst in the hippocampus, recent evidence suggests that interneuron subtype-specific inhibitory synapses are regulated in distinct ways[15,42] It is not clear whether long-term plasticity of inhibitory synapses is differentially engaged between interneuron subtypes during physiologically relevant activity and, what the consequences of such plasticity would be for hippocampal network activity and place cell representations

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