In many mammalian species, the accessory olfactory system plays a central role in guiding behavioral and physiological responses to social and reproductive interactions. Because of its relatively compact structure and its direct access to amygdalar and hypothalamic nuclei, the accessory olfactory pathway provides an ideal system to study sensory control of complex mammalian behavior. During the last several years, many studies employing molecular, behavioral, and physiological approaches have significantly expanded and enhanced our understanding of this system. The purpose of the current review is to integrate older and newer studies to present an updated and comprehensive picture of vomeronasal signaling and coding with an emphasis on early accessory olfactory system processing stages. These include vomeronasal sensory neurons in the vomeronasal organ, and the circuitry of the accessory olfactory bulb. Because the overwhelming majority of studies on accessory olfactory system function employ rodents, this review is largely focused on this phylogenetic order, and on mice in particular. Taken together, the emerging view from both older literature and more recent studies is that the molecular, cellular, and circuit properties of chemosensory signaling along the accessory olfactory pathway are in many ways unique. Yet, it has also become evident that, like the main olfactory system, the accessory olfactory system also has the capacity for adaptive learning, experience, and state-dependent plasticity. In addition to describing what is currently known about accessory olfactory system function and physiology, we highlight what we believe are important gaps in our knowledge, which thus define exciting directions for future investigation.

The striatum comprises multiple subdivisions and neural circuits that differentially control motor output. The islands of Calleja (IC) contain clusters of densely-packed granule cells situated in the ventral striatum, predominantly in the olfactory tubercle (OT). Characterized by expression of the D3 dopamine receptor, the IC are evolutionally conserved, but have undefined functions. Here we show that optogenetic activation of OT D3 neurons robustly initiates self-grooming in mice while suppressing other ongoing behaviors. Conversely, optogenetic inhibition of these neurons halts ongoing grooming, and genetic ablation reduces spontaneous grooming. Furthermore, OT D3 neurons show increased activity before and during grooming and influence local striatal output via synaptic connections with neighboring OT neurons (primarily spiny projection neurons, SPNs), whose firing rates display grooming-related modulation. Our study uncovers a novel role of the ventral striatum’s IC in regulating motor output and has important implications for the neural control of grooming.

The influence of the sex steroid hormones progesterone and estradiol on physiology and behavior during menstrual cycles and pregnancy is well known. Several studies indicate that olfactory performance changes with cyclically fluctuating steroid hormone levels in females. Knowledge of the exact mechanisms behind how female sex steroids modulate olfactory signaling is limited. A number of different known genomic and non-genomic actions that are mediated by progesterone and estradiol via interactions with different receptors may be responsible for this modulation. Next generation sequencing-based RNA-Seq transcriptome data from the murine olfactory epithelium (OE) and olfactory receptor neurons (ORNs) revealed the expression of several membrane progestin receptors and the estradiol receptor Gpr30. These receptors are known to mediate rapid non-genomic effects through interactions with G proteins. RT-PCR and immunohistochemical staining results provide evidence for progestin and estradiol receptors in the ORNs. These data support the hypothesis that steroid hormones are capable of modulating the odorant-evoked activity of ORNs. Here, we validated this hypothesis through the investigation of steroid hormone effects by submerged electro-olfactogram and whole cell patch-clamp recordings of ORNs. For the first time, we demonstrate that the sex steroid hormones progesterone and estradiol decrease odorant-evoked signals in the OE and ORNs of mice at low nanomolar concentrations. Thus, both of these sex steroids can rapidly modulate the odor responsiveness of ORNs through membrane progestin receptors and the estradiol receptor Gpr30.

Mammalian odor reception is achieved by highly specialized olfactory sensory neurons (OSNs) located in the nasal cavity. Despite their importance for the daily survival of most mammals, the gene expression and regulatory profiles of these single neurons are poorly understood. Here, we report the isolation of individual GFP-labeled OSNs from Olfr73-GFP mice at different developmental stages followed by Next Generation Sequencing, thereby analyzing the detailed transcriptome for the first time. We characterized the repertoire of olfactory receptors (ORs) and found that in addition to the highly and predominant detectable Olfr73, 20 additional ORs were stably detectable at lower transcript levels in adult mice. Additionally, OSNs collected from mice of earlier developmental stages did not show any stable OR patterns. However, more than one predominant OR per OSN was detectable.