Local Postsynaptic Signaling on Slow Time Scales in Reciprocal Olfactory Bulb Granule Cell Spines Matches Asynchronous Release.

Tiffany Ona Jodar,Vanessa Lage-Rupprecht,Nixon M Abraham,Veronica Egger,Christine R Rose

doi:10.3389/fnsyn.2020.551691

Abstract

In the vertebrate olfactory bulb (OB), axonless granule cells (GC) mediate self- and lateral inhibitory interactions between mitral/tufted cells via reciprocal dendrodendritic synapses. Locally triggered release of GABA from the large reciprocal GC spines occurs on both fast and slow time scales, possibly enabling parallel processing during olfactory perception. Here we investigate local mechanisms for asynchronous spine output. To reveal the temporal and spatial characteristics of postsynaptic ion transients, we imaged spine and adjacent dendrite Ca2 +- and Na+-signals with minimal exogenous buffering by the respective fluorescent indicator dyes upon two-photon uncaging of DNI-glutamate in OB slices from juvenile rats. Both postsynaptic fluorescence signals decayed slowly, with average half durations in the spine head of t1/2_Δ[Ca2 +]i ∼500 ms and t1/2_Δ[Na+]i ∼1,000 ms. We also analyzed the kinetics of already existing data of postsynaptic spine Ca2 +-signals in response to glomerular stimulation in OB slices from adult mice, either WT or animals with partial GC glutamate receptor deletions (NMDAR: GluN1 subunit; AMPAR: GluA2 subunit). In a large subset of spines the fluorescence signal had a protracted rise time (average time to peak ∼400 ms, range 20 to >1,000 ms). This slow rise was independent of Ca2 + entry via NMDARs, since similarly slow signals occurred in ΔGluN1 GCs. Additional Ca2 + entry in ΔGluA2 GCs (with AMPARs rendered Ca2 +-permeable), however, resulted in larger ΔF/Fs that rose yet more slowly. Thus GC spines appear to dispose of several local mechanisms to promote asynchronous GABA release, which are reflected in the time course of mitral/tufted cell recurrent inhibition.

Highlights

In the vertebrate olfactory bulb (OB), the lateral dendrites of the principal mitral and tufted cells are interconnected via local GABAergic interneurons
Since as in other synapses reciprocal release of GABA is Ca2+-dependent (Isaacson and Strowbridge, 1998), how could spine Ca2+ signals mediate asynchronous release? To answer this question, we explored several potential local mechanisms that might be involved in slow spine Ca2+ signaling and are directly related to the biophysical properties of individual spines
To investigate the local mechanisms underlying the asynchronous component of reciprocal GABA release, we aimed to detect local postsynaptic Ca2+ signaling in granule cells (GC) spines with as little exogenous buffering as possible, since sluggish extrusion of Ca2+ might contribute to delayed release (Egger and Stroh, 2009)

Summary

Introduction

In the vertebrate olfactory bulb (OB), the lateral dendrites of the principal mitral and tufted cells are interconnected via local GABAergic interneurons. The most abundant class of these local neurons, the axonless granule cells (GC), mediate self- and lateral inhibitory interactions between mitral/tufted cells via reciprocal dendrodendritic synapses that on the GC dendrite are housed in large spines (Shepherd, 2004) These reciprocal synapses have been directly demonstrated to play. Early IPSCs will occur with a very short latency (below 10 ms), but recurrent activity takes several hundreds of milliseconds to subside While this long tail of recurrent inhibition is unlikely to directly contribute to odor discrimination itself (Uchida and Mainen, 2003; Abraham et al, 2004, 2010), it may well play a role in learning and memory formation (Gschwend et al, 2015; see section “Discussion”)

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