Immobility responses are induced by photoactivation of single glomerular species responsive to fox odour TMT

Harumi Saito,Nao Ieki,Hideo Yokota,Hirofumi Nishizumi,Satoshi Suzuki,Kensaku Mori,Hideyuki Matsumoto,Takefumi Kikusui,Hitoshi Sakano,Hiroshi Kiyonari,Takaya Abe,Masahiko Morita,Nozomi Hirayama,Takahiro Yamazaki

doi:10.1038/ncomms16011

Abstract

Fox odour 2,4,5-trimethyl thiazoline (TMT) is known to activate multiple glomeruli in the mouse olfactory bulb (OB) and elicits strong fear responses. In this study, we screened TMT-reactive odourant receptors and identified Olfr1019 with high ligand reactivity and selectivity, whose glomeruli are located in the posterodorsal OB. In the channelrhodopsin knock-in mice for Olfr1019, TMT-responsive olfactory-cortical regions were activated by photostimulation, leading to the induction of immobility, but not aversive behaviour. Distribution of photoactivation signals was overlapped with that of TMT-induced signals, but restricted to the narrower regions. In the knockout mice, immobility responses were reduced, but not entirely abolished likely due to the compensatory function of other TMT-responsive glomeruli. Our results demonstrate that the activation of a single glomerular species in the posterodorsal OB is sufficient to elicit immobility responses and that TMT-induced fear may be separated into at least two different components of immobility and aversion.

Highlights

Fox odour 2,4,5-trimethyl thiazoline (TMT) is known to activate multiple glomeruli in the mouse olfactory bulb (OB) and elicits strong fear responses
To clone the odourant receptor (OR) genes associated with these glomeruli, we retrogradely labelled the connecting OSNs15,16 by injecting DiI solution into the single glomeruli activated by TMT, but not by 4MT
To examine whether TMT-responsive brain regions are activated by photostimulation of Olfr1019 glomeruli in the KI mouse, we studied the expression of Egr[1], an immediate-early protein induced by neuronal activity, in the OB and in the following brain regions: anterior olfactory nucleus (AON), anterior piriform cortex, olfactory tubercle (OT), cortical amygdala (CoA), medial amygdala (MeA) and bed nucleus of stria terminals (BNST) (Fig. 4a–c and Supplementary Fig. 4a–h)

Summary

Introduction

Fox odour 2,4,5-trimethyl thiazoline (TMT) is known to activate multiple glomeruli in the mouse olfactory bulb (OB) and elicits strong fear responses. Multiple glomeruli are activated in both dorsal and ventral domains by TMT, it was uncertain whether individual glomeruli are functionally specialized to instruct particular responses, or whether a pattern of activated glomeruli as a whole is recognized to mediate behavioural decisions It was unclear whether the TMT-induced fear responses can be further divided into different categories, such as immobility and avoidance. To address these questions, we performed loss-offunction and gain-of-function experiments to determine the effect on mouse behaviour when a single glomerular species, responsive to the fox odourant TMT, is deleted or photoactivated

Methods

Results

Conclusion