Sensory Adaptation to Chemical Cues by Vomeronasal Sensory Neurons

Abstract

Sensory adaptation is a source of experience-dependent feedback that impacts responses to environmental cues. In the mammalian main olfactory system (MOS), adaptation influences sensory coding at its earliest processing stages. Sensory adaptation in the accessory olfactory system (AOS) remains incompletely explored, leaving many aspects of the phenomenon unclear. We investigated sensory adaptation in vomeronasal sensory neurons (VSNs) using a combination of in situ Ca2+ imaging and electrophysiology. Parallel studies revealed prominent short-term sensory adaptation in VSNs upon repeated stimulation with mouse urine and monomolecular bile acid ligands at interstimulus intervals (ISIs) less than 30 s. In such conditions, Ca2+ signals and spike rates were often reduced by more than 50%, leading to dramatically reduced chemosensory sensitivity. Short-term adaptation was reversible over the course of minutes. Population Ca2+ imaging experiments revealed the presence of a slower form of VSN adaptation that accumulated over dozens of stimulus presentations delivered over tens of minutes. Most VSNs showed strong adaptation, but in a substantial VSN subpopulation adaptation was diminished or absent. Investigation of same- and opposite-sex urine responses in male and female VSNs revealed that adaptation to same-sex cues occurred at ISIs up to 180 s, conditions that did not induce adaptation to opposite-sex cues. This result suggests that VSN sensory adaptation can be modulated by sensory experience. These studies comprehensively establish the presence of VSN sensory adaptation and provide a foundation for future inquiries into the molecular and cellular mechanisms of this phenomenon and its impact on mammalian behavior.

Signal Detection and Coding in the Accessory Olfactory System

“…Another mechanism for experience-driven feedback in the AOS is peripheral sensory adaptation in VSNs. Although the existence of such peripheral adaptation has long remained subject of some debate ( Holy et al 2000 ; Nodari et al 2008 ; Spehr et al 2009 ), recent evidence shows both short- and long-term adaptation upon repeated VSN stimulation ( Wong et al 2018 ).…”

Physiology-forward identification of bile acid sensitive vomeronasal receptors

“…Even though BAs were previously shown to reliably elicit AOS activation in the AOB (Doyle et al, 2016) and VNO (Wong et al, 2018), there has been relatively limited information about the sensitivity and selectivity of VSNs to BAs. Other monomolecular AOS steroid ligands have been found to be highly potent VSN activatorssome at subnanomolar concentrationsso we sought to thoroughly evaluate VSN BA tuning using OCPI microscopy ( Figs.…”

“…1-4). Volumetric Ca 2+ imaging via OCPI microscopy remains one of the most robust methods for evaluating VSN ligand sensitivity because it enables the unbiased sampling of hundreds to thousands of VSNs per animal Turaga and Holy, 2012;Wong et al, 2018;Xu et al, 2016). Concentration-response experiments using OCPI in pairs of BAs revealed the presence of BA-specialist and BA-generalist VSNs (Figs.…”

“…Volumetric VNO Ca 2+ imaging. Following deep isofluorane anesthesia and rapid decapitation, VNOs were dissected and the vomeronasal epithelium carefully removed under a dissection microscope (Leica Microsystems, Buffalo Grove, IL, USA) similar to previous studies (Turaga and Holy, 2012;Wong et al, 2018). The vomeronasal epithelium was mounted onto nitrocellulose paper (Fisher Scientific, Atlanta, GA, USA) before placement into a custom imaging chamber.…”

“…The vomeronasal epithelium was mounted onto nitrocellulose paper (Fisher Scientific, Atlanta, GA, USA) before placement into a custom imaging chamber. Volumetric Ca 2+ imaging was performed using a custom objective-coupled planar illumination (OCPI) microscope with refinements described previously (Wong et al, 2018). GCaMP6s/f fluorescence was acquired using custom software that synchronized imaging with stimulus delivery via a randomized, interleaved stimulus delivery system (Automate Scientific).…”