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Front. Cell. Neurosci. | doi: 10.3389/fncel.2018.00047

Cannabinoid Receptors Modulate Excitation of an Olfactory Bulb Local Circuit by Cortical Feedback

  • 1Physiology and Biophysics, University of Colorado Denver School of Medicine, United States

Recent studies have provided evidence that corticofugal feedback (CFF) from the olfactory cortex to the olfactory bulb can significantly impact the state of excitation of output mitral cells (MCs) and tufted cells (TCs) and also modulate neural synchrony. Interpreting these effects however has been complicated by the large number of cell targets of CFF axons in the bulb. Within the granule cell layer alone, CFF axons target both GABAergic granule cells (GCs) as well as GABAergic deep short-axon cells (dSACs) that inhibit GCs. Because GCs are a major source of inhibition of MCs/TCs, CFF feedback could be inhibitory to MCs (by exciting GCs) or disinhibitory (by exciting dSACs that inhibit GCs). In this study, we used patch-clamp recordings combined with optogenetic and electrical stimulation methods to investigate the role of presynaptic cannabinoid receptors in regulating CFF pathways, which could alter the weights of inhibition and disinhibition. Recording first from dSACs, we found that the cannabinoid receptor (CB-R) agonist WIN-55212.2 (WIN) reduced excitatory post-synaptic currents (CFF-EPSCs) driven by stimulation of CFF axons. The effects were reversed by the Type 1 CB-R (CB1-R)-specific antagonist SR-141716A. Furthermore, prolonged 5-second depolarizations applied to postsynaptic dSACs effectively reduced CFF-EPSCs in a CB1-R-dependent fashion, providing evidence for depolarization-induced suppression of excitation (DSE) at CFF-to-dSAC synapses. Further analysis indicated that CB1-Rs mediate widespread suppressive effects on synaptic transmission, occurring at CFF synapses onto different dSAC subtypes and CFF synapses onto GCs. Feedforward excitation of dSACs, mediated by MCs/TCs, however, was not impacted by CB1-Rs. In recordings from MCs, performed to examine the net effect of CB1-R activation on GC-to-MC transmission, we found that WIN could both increase and decrease disynaptic inhibition evoked by CFF axon stimulation. The exact effect depended on the size of the inhibitory response, reflecting the local balance of dSAC versus GC activation. Our results taken together indicate that CB1-Rs can bidirectionally alter the weighting of inhibition and disinhibition of MCs through their effects on CFF pathways.

Keywords: Olfaction, Olfactory Bulb, granule cell, mitral cell, corticofugal, Cannabinoids

Received: 02 Dec 2017; Accepted: 15 Feb 2018.

Edited by:

Qi Yuan, Memorial University of Newfoundland, Canada

Reviewed by:

Veronica Egger, University of Regensburg, Germany
SOURAV GHOSH, INSERM U1215 Neurocentre Magendie, France  

Copyright: © 2018 Schoppa and Pouille. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Nathan Schoppa, University of Colorado Denver School of Medicine, Physiology and Biophysics, 12800 East 19th Ave, Campus Box 8307, Aurora, CO, United States,