Blueprints for Smell: Defining the Architecture of the Necklace Olfactory System

Abstract

Animals must extract salient information from complex environments in order to generate adaptive behaviors. Mice have evolved multiple olfactory subsystems that enable detection and discrimination of a vast range of chemical stimuli. Although distinct olfactory subsystems detect overlapping subsets of odor space, the specific perceptual functions of each subsystem – and how subsystems interact with one another – remains largely unknown. The GC-D “necklace” olfactory subsystem detects odorants from mates, predators, and food, suggesting it may play an important role in mediating innate behaviors. However, this subsystem is also required for a specific form of olfactory social learning. Olfactory sensory neurons (OSNs) of the GC-D subsystem detect odorants via molecular mechanisms distinct from those of conventional OSNs. Consistent with a specialized role in olfactory processing, the GC-D subsystem also exhibits atypical anatomical organization: GC-D OSNs are concentrated within isolated regions of the nasal epithelium, and unlike canonical OSNs – whose axons converge onto a small number of isolated foci (called glomeruli) within the olfactory bulb (OB) – GC-D neurons project axons to a “necklace” of 25-40 seemingly interconnected glomeruli that encircle the caudal OB. The neural circuitry beyond the OB that decodes information from necklace glomeruli is completely unknown. To define the organizing principles by which this subsystem processes olfactory information, we combined novel surgical approaches and an electroporation cell-labeling technique with retrograde and trans-synaptic viral reagents to trace the connectivity of the necklace glomeruli. We find that individual GC-D glomeruli are presynaptically innervated by spatially dispersed OSN populations and postsynaptically are heavily interconnected with both GC-D and other atypical glomeruli within the OB; these features define physical substrates for integration of peripheral olfactory signals both within the GC-D necklace system and between multiple olfactory subsystems. Centrally, the GC-D subsystem projects to canonical brain targets of the main (but not the accessory) olfactory system; however, it also projects to unique septal targets within the basal forebrain, in part synapsing with cholinergic neurons. The GC-D subsystem is therefore – through peripheral mechanisms to broadly sample sensory channels and privileged access to central behavioral circuits – uniquely poised to direct behavioral responses to ethologically salient cues.