A unique olfactory bulb microcircuit driven by neurons expressing the precursor to glucagon-like peptide 1

Nicolas Thiebaud,Frank Reimann,Stefan Trapp,Debra Ann Fadool,Fiona Gribble

doi:10.1038/s41598-019-51880-9

Abstract

The presence of large numbers of local interneurons in the olfactory bulb has demonstrated an extensive local signaling process, yet the identification and purpose of olfactory microcircuits is poorly explored. Because the discrimination of odors in a complex environment is highly dependent on the tuning of information by local interneurons, we studied for the first time the role of preproglucagon (PPG) neurons in the granule cell layer of the olfactory bulb. Combining electrophysiological recordings and confocal microscopy, we discovered that the PPG neurons are a population of cells expressing the precursor of glucagon-like peptide 1 and are glutamatergic; able to modulate the firing pattern of the mitral cells (M/TCs). Optogenetic activation of PPG neurons resulted in a mixed excitation and inhibition that created a multiphasic response shaping the M/TCs firing pattern. This suggests that PPG neurons could drive neuromodulation of the olfactory output and change the synaptic map regulating olfactory coding.

Highlights

The presence of large numbers of local interneurons in the olfactory bulb has demonstrated an extensive local signaling process, yet the identification and purpose of olfactory microcircuits is poorly explored
Morphological analysis demonstrated that the PPG neuron cell bodies were larger than granule cells (10.2 ± 0.2 μm, n = 73 from 3 mice) and were predominantly concentrated in the inner part of the granule cell layer (GCL) with axons projecting towards the mitral cell layer (MCL) and the internal plexiform layer (IPL) (Figs 1a, 3a,b)
Our study provides the first evidence that terminations of some glucagon-like peptide 1 (GLP-1) producing neurons in the inner part of the granule cell layer (GCL) are capable of providing a fine tuning of mitral cells (M/TCs) output by activating both excitatory glutamatergic synapses and an inhibitory GABAergic response

Summary

Introduction

The presence of large numbers of local interneurons in the olfactory bulb has demonstrated an extensive local signaling process, yet the identification and purpose of olfactory microcircuits is poorly explored. Optogenetic activation of PPG neurons resulted in a mixed excitation and inhibition that created a multiphasic response shaping the M/TCs firing pattern This suggests that PPG neurons could drive neuromodulation of the olfactory output and change the synaptic map regulating olfactory coding. We reported a subclass of deep short-axon cells (dSACs) located in the GCL, which we speculated to be responsible for the secretion of the traditional gut peptide, glucagon-like peptide 1 (GLP-1) We subsequently called these cells preproglucagon (PPG) neurons[4]. Recording under current-clamp conditions, a biphasic inhibition-excitation control of action potential firing in M/TCs was found as a result of light-activation of the PPG neurons Taken together, these results demonstrate that PPG neurons constitute a unique population of glutamatergic neurons within the GCL that form a local microcircuit controlling M/TC activity. Subsequent confocal imaging microscopy confirmed the expression of the vesicular glutamate transporter in PPG neurons

Methods

Results

Conclusion