Balancing memory fidelity and representational stability in the female mouse accessory olfactory bulb

Sensory systems must balance the value of efficient coding schemes against the need to update specific memorized representations without perturbing other memories. Here we describe a unique solution to this challenge that is implemented by the vomeronasal system (VNS) to encode and remember multiple conspecific individuals as part of the Bruce Effect (BE). In the BE, exposure of a pregnant female mouse to the odors of an unfamiliar male leads to failure of the pregnancy (pregnancy block) via the VNS. Following mating and sensory exposure, however, the female becomes protected from a pregnancy block by the stud individual. While this form of natural learning has been proposed to depend on changes in the representation of his odors in her accessory olfactory bulb (AOB), a key VNS structure, there are no direct comparisons of in vivo sensory responses before and after imprinting. It has further been suggested that these changes simply render the AOB insensitive to stud odors. However, the combinatorial odor code used by the AOB and the significant overlap in the odor composition of different males means that silencing responses to one individual is likely to degrade responses to others, posing potential problems for more general sensory encoding. To identify the neuronal correlates of learning in the context of the BE, we recorded extracellular responses of AOB neurons in vivo in mated and unmated female mice upon controlled presentation of urinary chemosignals, including urine from both the stud and males of a distinct strain. We find that while initial sensory responses in the AOB (within a timescale required to guide social interactions) remain stable, responses to extended stimulation (as required for eliciting the pregnancy block) display selective attenuation of stud-responsive neurons. Based on our results, we propose a model that reconciles the formation of strong, selective memories with the need to sustain robust representational bandwidth by noting a distinction between the representations of brief and extended stimuli. This temporal disassociation allows attenuation of slow-acting endocrine processes in a stimulus-specific manner, without compromising consistent ongoing representations of stimuli that guide behavior.

Molecular and Structural Basis of Olfactory Sensory Neuron Coalescence by Kirrel Receptors

ABSTRACTProjections from sensory neurons of olfactory systems coalesce into glomeruli in the brain. The Kirrel receptors are believed to homodimerize via their ectodomains and help separate sensory neuron axons into Kirrel2- or Kirrel3-expressing glomeruli. Here we present the crystal structures of homodimeric Kirrel receptors and show that the closely related Kirrel2 and Kirrel3 have evolved specific sets of polar and hydrophobic interactions, respectively, disallowing heterodimerization while preserving homodimerization, likely resulting in proper segregation and coalescence of Kirrel-expressing axons into glomeruli. We show that the dimerization interface at the N-terminal IG domains is necessary and sufficient to create homodimers, and fail to find evidence for a secondary interaction site in Kirrel ectodomains. Furthermore, we show that abolishing dimerization of Kirrel3 in vivo leads to improper formation of glomeruli in the mouse accessory olfactory bulb as observed in Kirrel3-/- animals. Our results provide strong evidence for Kirrel3 homodimerization controlling axonal coalescence.