Differences in peripheral sensory input to the olfactory bulb between male and female mice

Abstract

Female mammals generally have a superior sense of smell than males, but the biological basis of this difference is unknown. Here, we demonstrate sexually dimorphic neural coding of odorants by olfactory sensory neurons (OSNs), primary sensory neurons that physically contact odor molecules in the nose and provide the initial sensory input to the brain’s olfactory bulb. We performed in vivo optical neurophysiology to visualize odorant-evoked OSN synaptic output into olfactory bub glomeruli in unmanipulated (gonad-intact) adult mice from both sexes, and found that in females odorant presentation evoked more rapid OSN signaling over a broader range of OSNs than in males. These spatiotemporal differences enhanced the contrast between the neural representations of chemically related odorants in females compared to males during stimulus presentation. Removing circulating sex hormones makes these signals slower and less discriminable in females, while in males they become faster and more discriminable, suggesting opposite roles for gonadal hormones in influencing male and female olfactory function. These results demonstrate that the famous sex difference in olfactory abilities likely originates in the primary sensory neurons, and suggest that hormonal modulation of the peripheral olfactory system could underlie differences in how males and females experience the olfactory world.

Persistent, generalized hypersensitivity of olfactory bulb interneurons after olfactory fear generalization

“…In vivo optical imaging was performed (Czarnecki, Moberly, Rubinstein, Turkel, Pottackal, & McGann, 2011; Czarnecki, Moberly, Turkel, Rubinstein, Pottackal, Rosenthal et al, 2012; Fast & McGann, 2017; Kass, Czarnecki, Moberly, & McGann, 2017; Kass, Guang, Moberly, & McGann, 2016; Kass, Moberly, & McGann, 2013a; Kass, Moberly, Rosenthal, Guang, & McGann, 2013b; Kass, Pottackal, Turkel, & McGann, 2013c; Kass et al, 2013d) to visualize odor-evoked GCaMP signals from GAD65-expressing PG interneurons (Figure 1G–I) before and after conditioning (Figure 1A). Vapor dilution olfactometry was used during imaging (Czarnecki et al, 2011; Czarnecki et al, 2012; Kass et al, 2017; Kass et al, 2016; Kass et al, 2013a; Kass et al, 2013b; Kass et al, 2013c; Kass et al, 2013d) to present up to 3 concentrations of up to 5 monomolecular odorants that have no known innate valence.…”

“…Vapor dilution olfactometry was used during imaging (Czarnecki et al, 2011; Czarnecki et al, 2012; Kass et al, 2017; Kass et al, 2016; Kass et al, 2013a; Kass et al, 2013b; Kass et al, 2013c; Kass et al, 2013d) to present up to 3 concentrations of up to 5 monomolecular odorants that have no known innate valence. The odor-panel was selected based on previous experiments (Kass et al, 2013b; Kass et al, 2013d), and included 3 esters (MV, which was used as the CS, EV, and BA), 1 ketone (2H), and 1 aldehyde (t rans -2-methyl-2-butenal, 2M2B), yielding 3 odor categories for paired and odor-alone subjects (training ester, unexposed esters, and unexposed “other”) and 1 odor category for shock-alone subjects (unexposed odors).…”

“…Blocks of 3–6 trials (20-sec/trial, 60-sec ITI) were presented to anesthetized subjects. Respiration was monitored (Kass et al, 2017; Kass et al, 2013d), and odor presentations (6-sec/presentation) were timed to begin during the exhalation phase of the respiration cycle to ensure reliable odor concentrations during the first inhalation of odor.…”

“…Optical signals were analyzed as previously reported (Czarnecki et al, 2011; Czarnecki et al, 2012; Fast & McGann, 2017; Kass et al, 2017; Kass et al, 2016; Kass et al, 2013a; Kass et al, 2013b; Kass et al, 2013c; Kass et al, 2013d). Odor-evoked response amplitudes (ΔF/Fs) were quantified as the change in fluorescence during the first inhalation of odor and as the integrated change from baseline fluorescence during the 6-sec odor presentation.…”

Sex differences in main olfactory system pathways involved in psychosexual function

“…Despite the lack of clear sex differences in the MOE, a recent study 89 in mice comparing the OSN response to a variety of monomolecular odorants showed that odor-induced signaling was more rapid and affected more MOB glomeruli in females than males. Curiously, these responses were decreased by gonadectomy in females, but increased in males.…”