TY - JOUR T1 - DREADD-induced silencing of the medial olfactory tubercle disrupts the preference of female mice for opposite-sex chemosignals JF - eneuro JO - eneuro DO - 10.1523/ENEURO.0078-15.2015 SP - ENEURO.0078-15.2015 AU - Brett T. DiBenedictis AU - Adaeze O. Olugbemi AU - Michael J. Baum AU - James A. Cherry Y1 - 2015/09/08 UR - http://www.eneuro.org/content/early/2015/09/08/ENEURO.0078-15.2015.abstract N2 - 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, 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, CTb, into the mOT were exposed to volatile odors from soiled bedding. Both the anterior Me and ventral tegmental area (VTA) 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 receptor, hM4Di, was bilaterally expressed in the mOT of female mice. Urinary preferences were then assessed after i.p. 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 subjects received CNO injections prior to testing. The mOT appears to be a critical segment in the pheromone-reward pathway of female mice.Significance Statement: This work adds to a growing body of evidence that the medial olfactory tubercle (often thought of as solely an olfactory cortical structure) encodes natural, reinforcing hedonic behaviors. Females’ innate preference for male urinary odors was abolished when the mOT was silenced using DREADD methodology, but persisted under control conditions wherein the mOT was not silenced. Importantly, this effect was not due to a deficit in olfactory processing (i.e. an inability to discriminate between male and female urinary odors). Moreover, the female mOT is selectively activated by male urinary odors, and this activation appears to be driven mainly by MeA and VTA efferents. The mOT is a key node in the pheromone-reward pathway in mice. ER -