Presynaptic NMDARs cooperate with local spikes toward GABA release from the reciprocal olfactory bulb granule cell spine.

Vanessa Lage-Rupprecht,Max Mueller,Marco Sassoè-Pognetto,Li Zhou,S Sara Aghvami,Veronica Egger,Balázs Rózsa,Gaia Bianchini

doi:10.7554/elife.63737

Abstract

In the rodent olfactory bulb the smooth dendrites of the principal glutamatergic mitral cells (MCs) form reciprocal dendrodendritic synapses with large spines on GABAergic granule cells (GC), where unitary release of glutamate can trigger postsynaptic local activation of voltage-gated Na+-channels (Navs), that is a spine spike. Can such single MC input evoke reciprocal release? We find that unitary-like activation via two-photon uncaging of glutamate causes GC spines to release GABA both synchronously and asynchronously onto MC dendrites. This release indeed requires activation of Navs and high-voltage-activated Ca2+-channels (HVACCs), but also of NMDA receptors (NMDAR). Simulations show temporally overlapping HVACC- and NMDAR-mediated Ca2+-currents during the spine spike, and ultrastructural data prove NMDAR presence within the GABAergic presynapse. This cooperative action of presynaptic NMDARs allows to implement synapse-specific, activity-dependent lateral inhibition, and thus could provide an efficient solution to combinatorial percept synthesis in a sensory system with many receptor channels.

Highlights

Reciprocal dendrodendritic microcircuits can be found in several parts of the nervous system and are especially abundant in the vertebrate olfactory bulb (Crespo et al, 2013), where the dendrites of the principal mitral and tufted cells (MTCs) engage in such interactions with several major subtypes of local GABAergic neurons
Wash-in of 1 mM DNI-caged glutamate (DNI) further increased the basal frequency by on average 1.9 ± 1.2 times, due to the disinhibition resulting from a partial blockade of GABAARs by DNI, which reduced the mean spontaneous IPSC amplitude to a fraction of 0.47 ± 0.16 of control (n = 14 mitral cells (MCs), p
two-photon uncaging (TPU)-evoked signals can be expected to be localized to the stimulated granule cell (GC) spine: there is no Ca2+ influx into the adjacent dendritic shaft upon TPU, as we have shown in GC Ca2+ imaging experiments that were performed previously and interleaved with the MC recordings in this study, using a low-affinity dye (100 mM OGB-6F, ratio DF/F spine:dendrite 24:2, Ona Jodar et al, 2020)

Summary

Introduction

Reciprocal dendrodendritic microcircuits can be found in several parts of the nervous system and are especially abundant in the vertebrate olfactory bulb (Crespo et al, 2013), where the dendrites of the principal mitral and tufted cells (MTCs) engage in such interactions with several major subtypes of local GABAergic neurons. In the external plexiform layer, the long MC lateral dendrites are densely covered with GABAergic synapses that mostly originate from reciprocal arrangements (Bartel et al, 2015; Sailor et al, 2016; Matsuno et al, 2017). While proximal circuits are thought to be mostly formed by granule cell (GC) spines (Miyamichi et al, 2013), there are reciprocal dendrodendritic interactions with other GABAergic cell types such as SOM+ neurons, CRH+ neurons and most prominently parvalbumin/PV+ neurons that all feature aspiny, smooth dendrites (partially overlapping populations; Toida et al, 1994; Lepousez et al, 2010; Huang et al, 2013; Kato et al, 2013; Miyamichi et al, 2013)

Objectives

Methods

Results

Discussion

Conclusion