Mechanisms of Supralinear Calcium Integration in Dendrites of Hippocampal CA1 Fast-Spiking Cells.

Olivier Camiré,Lisa Topolnik,Ivan Lazarevich,Tommy Gilbert

doi:10.3389/fnsyn.2018.00047

Abstract

In fast-spiking (FS), parvalbumin-expressing interneurons of the CA1 hippocampus, activation of the GluA2-lacking Ca2+-permeable AMPA receptors (CP-AMPARs) in basal dendrites is coupled to Ca2+-induced Ca2+-release (CICR), and can result in a supralinear summation of postsynaptic Ca2+-transients (post-CaTs). While this mechanism is important in controlling the direction of long-term plasticity, it is still unknown whether it can operate at all excitatory synapses converging onto FS cells or at a set of synapses receiving a particular input. Using a combination of patch-clamp recordings and two-photon Ca2+ imaging in acute mouse hippocampal slices with computational simulations, here we compared the generation of supralinear post-CaTs between apical and basal dendrites of FS cells. We found that, similar to basal dendrites, apical post-CaTs summated supralinearly and relied mainly on the activation of the CP-AMPARs, with a variable contribution of other Ca2+ sources, such as NMDA receptors, L-type voltage-gated Ca2+-channels and Ca2+ release. In addition, supralinear post-CaTs generated in apical dendrites had a slower decay time and a larger cumulative charge than those in basal, and were associated with a stronger level of somatic depolarization. The model predicted that modulation of ryanodine receptors and of the Ca2+ extrusion mechanisms, such as the Na+/Ca2+-exchanger and SERCA pump, had a major impact on the magnitude of supralinear post-CaTs. These data reveal that supralinear Ca2+ summation is a common mechanism of Ca2+ signaling at CP-AMPAR-containing synapses. Shaped in a location-specific manner through modulation of ryanodine receptors and Ca2+ extrusion mechanisms, CP-AMPAR/CICR signaling is suitable for synapse-specific bidirectional modification of incoming inputs in the absence of active dendritic conductances.

Highlights

In cortical networks, GABAergic inhibitory interneurons play a crucial role in the development and maturation of neural circuits, regulation of synaptic plasticity and rhythmogenesis (Cossart, 2011; Lehmann et al, 2012; Allen and Monyer, 2014)
We found no correlation between the peak amplitude of post-CaTs and that of postsynaptic depolarization for both inputs (Figure 1I), consistent with the local nature of post-CaTs generated in distal dendrites of FS cells
Compared with other types of cortical interneurons, FS PV+ cells exhibit the highest levels of GluA1, GluA3, and GluA4 mRNAs (Paul et al, 2017), pointing to the relative abundance of CP-AMPARs at their excitatory synapses

Summary

Introduction

GABAergic inhibitory interneurons play a crucial role in the development and maturation of neural circuits, regulation of synaptic plasticity and rhythmogenesis (Cossart, 2011; Lehmann et al, 2012; Allen and Monyer, 2014) These cells form a highly heterogeneous population with distinct gene expression as well as morphological, molecular, and physiological properties that. Increasing activity levels during synchronous theta-bursting of CA1 pyramidal cells leads to additional activation of Ca2+ -induced Ca2+ release (CICR) via ryanodine receptors (RyRs) and generation of supralinear Ca2+ signals in dendritic microdomains (Camiré and Topolnik, 2014) As a result, this CP-AMPAR-triggered CICR is involved in the induction of long-term depression (LTD) (Camiré and Topolnik, 2014). CP-AMPARs are able to play a dual role as the triggering factor in both LTP and LTD induction, which was observed in different cell types and synapses (Nissen et al, 2010; Hainmuller et al, 2014)

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Conclusion