Short-Term Plasticity in Cortical GABAergic Synapses on Olfactory Bulb Granule Cells Is Modulated by Endocannabinoids

Fu-Wen Zhou,Adam C Puche

doi:10.3389/fncel.2021.629052

Abstract

Olfactory bulb and higher processing areas are synaptically interconnected, providing rapid regulation of olfactory bulb circuit dynamics and sensory processing. Short-term plasticity changes at any of these synapses could modulate sensory processing and potentially short-term sensory memory. A key olfactory bulb circuit for mediating cortical feedback modulation is granule cells, which are targeted by multiple cortical regions including both glutamatergic excitatory inputs and GABAergic inhibitory inputs. There is robust endocannabinoid modulation of excitatory inputs to granule cells and here we explored whether there was also endocannabinoid modulation of the inhibitory cortical inputs to granule cells. We expressed light-gated cation channel channelrhodopsin-2 (ChR2) in GABAergic neurons in the horizontal limb of the diagonal band of Broca (HDB) and their projections to granule cells in olfactory bulb. Selective optical activation of ChR2 positive axons/terminals generated strong, frequency-dependent short-term depression of GABAA-mediated-IPSC in granule cells. As cannabinoid type 1 (CB1) receptor is heavily expressed in olfactory bulb granule cell layer (GCL) and there is endogenous endocannabinoid release in GCL, we investigated whether activation of CB1 receptor modulated the HDB IPSC and short-term depression at the HDB→granule cell synapse. Activation of the CB1 receptor by the exogenous agonist Win 55,212-2 significantly decreased the peak amplitude of individual IPSC and decreased short-term depression, while blockade of the CB1 receptor by AM 251 slightly increased individual IPSCs and increased short-term depression. Thus, we conclude that there is tonic endocannabinoid activation of the GABAergic projections of the HDB to granule cells, similar to the modulation observed with glutamatergic projections to granule cells. Modulation of inhibitory synaptic currents and frequency-dependent short-term depression could regulate the precise balance of cortical feedback excitation and inhibition of granule cells leading to changes in granule cell mediated inhibition of olfactory bulb output to higher processing areas.

Highlights

Reciprocal projections between olfactory bulb and brain higher processing areas form a feedback/feedforward circuit that can rapidly regulate the olfactory bulb circuit dynamics and sensory processing (Rothermel et al, 2014; Soria-Gómez et al, 2014; Mazo et al, 2016; In ’t Zandt et al, 2019)
ChR2 labeled axons emanating from HDB GABAergic neurons terminated in all layers of olfactory bulb (Figure 1A)
The densest labeling was found in granule cell layer (GCL) and glomerular layer (GL), lower density labeling in mitral cell layer (ML) and only scattered fibers labeling in external plexiform layer (EPL, Figure 1B)

Summary

Introduction

Reciprocal projections between olfactory bulb and brain higher processing areas form a feedback/feedforward circuit that can rapidly regulate the olfactory bulb circuit dynamics and sensory processing (Rothermel et al, 2014; Soria-Gómez et al, 2014; Mazo et al, 2016; In ’t Zandt et al, 2019) These higher processing areas include primary olfactory cortex (piriform cortex, anterior olfactory nucleus, tenia tecta, olfactory tubercle, and entorhinal cortex – all glutamatergic), hippocampal structures (glutamatergic), locus coeruleus (noradrenergic), raphe nucleus (serotonergic), and basal forebrain (cholinergic and GABAergic neurons) (Luskin and Price, 1983; Záborszky et al, 1986; Shipley and Ennis, 1996; Nunez-Parra et al, 2013; Ennis et al, 2015; Sanz Diez et al, 2019). Projections of HDB neurons to olfactory bulb have been shown to influence olfactory processing (Paolini and McKenzie, 1993; Roman et al, 1993; Linster and Hasselmo, 2000; Nunez-Parra et al, 2013; Devore et al, 2016), but the underlying circuit mechanisms are unclear

Methods

Results

Conclusion