Associative Learning Via the Vomeronasal System

Behavioral and physiological responses can be broadly classified as innate or learned. The former are most appropriate in critical and predictable contexts when particular stimuli require a clear and often automatic response. The latter are required in novel situations in which proper mapping between stimuli and responses must be learned through association. In many cases, distinct neuronal pathways mediate these two types of responses, even within a given sensory modality and even for a given stimulus. Many animals heavily rely on their chemical senses to guide both innate and learned behaviors, and in most mammals, multiple olfactory subsystems are used to accomplish this. The two most prominent sub-systems are the main olfactory system (MOS) and the vomeronasal system (VNS). A common view holds that the MOS is a generalist system with advanced associative capabilities, while the VNS is dedicated to mediating innate responses to a confined set of well-defined sensory cues. Although particular hardwired VNS-mediated behaviors can show flexibility in the strength of coupling between stimulus and response, it remains unknown whether the VNS can map arbitrary cues into entirely new behavioral outputs. Indeed, the designation of the VNS as a pheromone processing system suggests that responses mediated by this system will be hardwired, stereotyped, and even involuntary. The goal of the present study was to experimentally challenge this notion by testing the capacity of the VNS to support associative learning. Using various strategies for selective optogenetic activation of vomeronasal pathways, we show that mice can exploit VNS activity to form novel behavioral associations. These findings call for a revised view of the VNS as a hardwired system, and suggest that it has a significant capacity for associative learning.