GABAergic neurons in the olfactory cortex projecting to the lateral hypothalamus in mice

Koshi Murata,Hiroyuki Okuno,Kazuto Kobayashi,Tomoki Kinoshita,Masahiro Yamaguchi,Kazunari Miyamichi,Yugo Fukazawa,Kenta Kobayashi,Haruhiko Bito,Yoshio Sakurai,Hiroyuki Manabe,Kensaku Mori

doi:10.1038/s41598-019-43580-1

Abstract

Olfaction guides goal-directed behaviours including feeding. To investigate how central olfactory neural circuits control feeding behaviour in mice, we performed retrograde tracing from the lateral hypothalamus (LH), an important feeding centre. We observed a cluster of retrogradely labelled cells distributed in the posteroventral region of the olfactory peduncle. Histochemical analyses revealed that the majority of these retrogradely labelled projection neurons expressed glutamic acid decarboxylase 65/67 (GAD65/67), but not vesicular glutamate transporter 1 (VGluT1). We named this region containing GABAergic projection neurons the ventral olfactory nucleus (VON) to differentiate it from the conventional olfactory peduncle. VON neurons were less immunoreactive for DARPP-32, a striatal neuron marker, compared to neurons in the olfactory tubercle and nucleus accumbens, which distinguished the VON from the ventral striatum. Fluorescent labelling confirmed putative synaptic contacts between VON neurons and olfactory bulb projection neurons. Rabies-virus-mediated trans-synaptic labelling revealed that VON neurons received synaptic inputs from the olfactory bulb, other olfactory cortices, horizontal limb of the diagonal band, and prefrontal cortex. Collectively, these results identify novel GABAergic projection neurons in the olfactory cortex that may integrate olfactory sensory and top-down inputs and send inhibitory output to the LH, which may modulate odour-guided LH-related behaviours.

Highlights

The central olfactory system translates odour information into motivated behaviours, including appetite-based food approach and eating behaviours[1]
In agreement with previous findings indicating that the lateral hypothalamus (LH) receives inputs from the anterior olfactory nucleus (AON), ventral tenia tecta (VTT), APC, and OT8, we observed a subset of retrogradely labelled cells clustered in a postero-ventral region of the olfactory peduncle
We targeted an area of the LH containing orexin neurons and melanin-concentrating hormone (MCH) neurons (Fig. 1a), as both these neuronal subpopulations are involved in feeding behaviours[9,10]

Summary

Introduction

The central olfactory system translates odour information into motivated behaviours, including appetite-based food approach and eating behaviours[1]. Recent studies have revealed neuronal circuit mechanisms by which odorants evoke specific behaviours, such as fear responses to predator odours[2,3] and attractive responses to social odours[4]. It is still unclear how central olfactory neural circuits control feeding-related behaviours in mammals. Mitral cells and tufted cells (M/ TCs) are projection neurons in the OB They convey odour information to several areas in the olfactory cortex which is composed of the anterior olfactory nucleus (AON), tenia tecta, dorsal peduncular cortex, anterior www.nature.com/scientificreports/.

Methods

Results

Conclusion