DREADD-Induced Silencing of the Medial Olfactory Tubercle Disrupts the Preference of Female Mice for Opposite-Sex Chemosignals(1,2,3).

Michael J. Baum,Brett T. DiBenedictis,James A. Cherry,Adaeze O. Olugbemi

doi:10.1523/eneuro.0078-15.2015

Michael J. Baum, Brett T. DiBenedictis

Open Access

https://doi.org/10.1523/eneuro.0078-15.2015

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Journal: eNeuro	Publication Date: Sep 1, 2015
Citations: 64	License type: cc-by

Affiliation: Boston University

Abstract

Attraction to opposite-sex pheromones during rodent courtship involves a pathway that includes inputs to the medial amygdala (Me) from the main and accessory olfactory bulbs, and projections from the Me to nuclei in the medial hypothalamus that control reproduction. However, the consideration of circuitry that attributes hedonic properties to opposite-sex odors has been lacking. The medial olfactory tubercle (mOT) has been implicated in the reinforcing effects of natural stimuli and drugs of abuse. We performed a tract-tracing study wherein estrous female mice that had received injections of the retrograde tracer, cholera toxin B, into the mOT were exposed to volatile odors from soiled bedding. Both the anterior Me and ventral tegmental area sent direct projections to the mOT, of which a significant subset was selectively activated (expressed Fos protein) by testes-intact male (but not female) volatile odors from soiled bedding. Next, the inhibitory DREADD (designer receptors exclusively activated by designer drugs) receptor hM4Di was bilaterally expressed in the mOT of female mice. Urinary preferences were then assessed after intraperitoneal injection of either saline or clozapine-N-oxide (CNO), which binds to the hM4Di receptor to hyperpolarize infected neurons. After receiving CNO, estrous females lost their preference for male over female urinary odors, whereas the ability to discriminate these odors remained intact. Male odor preference returned after vehicle treatment in counterbalanced tests. There were no deficits in locomotor activity or preference for food odors when subject mice received CNO injections prior to testing. The mOT appears to be a critical segment in the pheromone–reward pathway of female mice.

Highlights

The processing of social chemosignals in the rodent brain occurs via hardwired circuitry involving either or both the main and accessory olfactory systems
Experiment 1 To determine whether medial olfactory tubercle (mOT) neurons are activated by volatile odors in estrous female mice, E2 plus P-treated subject mice were exposed to volatiles from clean bedding, estrous female bedding, or intact male bedding; and forebrains were immunostained for Fos protein (Fig. 2A–C)
The present results indicate that neuronal activity in the mOT plays an essential role in motivating female mice to investigate male odors, providing evidence that the mOT is part of a circuit that regulates the innate attraction of mice for urinary odors

Summary

Introduction

The processing of social chemosignals (or “pheromones”) in the rodent brain occurs via hardwired circuitry involving either or both the main and accessory olfactory systems. Additional evidence implicates the medial olfactory tubercle (mOT) in both drug-induced as well as natural reinforcement (Ikemoto, 2003; Ikemoto et al, 2005; FitzGerald et al, 2014). The mOT receives direct input from the main olfactory bulb, and recent evidence suggests that the mOT is an important center for encoding odor valence (White, 1965; Schwob and Price, 1984a; Wesson and Wilson 2011; Gadziola et al, 2015). Tract-tracing studies in female mice have shown that the mOT receives dense monosynaptic input from the Me (Pardo-Bellver et al, 2012; DiBenedictis et al, 2014a), and other results suggest that the preference of female mice to investigate opposite-sex chemosignals may involve the mOT (Agustín-Pavón et al, 2014).

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