BIG-2 Mediates Olfactory Axon Convergence to Target Glomeruli

Laboratory for Neurobiology of Synapse, RIKEN Brain Science Institute, Saitama 351-0198, Japan.
Neuron (Impact Factor: 15.98). 04/2008; 57(6):834-46. DOI: 10.1016/j.neuron.2008.01.023
Source: PubMed

ABSTRACT Olfactory sensory neurons expressing a given odorant receptor converge axons onto a few topographically fixed glomeruli in the olfactory bulb, leading to establishment of the odor map. Here, we report that BIG-2/contactin-4, an axonal glycoprotein belonging to the immunoglobulin superfamily, is expressed in a subpopulation of mouse olfactory sensory neurons. A mosaic pattern of glomerular arrangement is observed with strongly BIG-2-positive, weakly positive, and negative axon terminals in the olfactory bulb, which is overlapping but not identical with those of Kirrel2 and ephrin-A5. There is a close correlation between the BIG-2 expression level and the odorant receptor choice in individual sensory neurons. In BIG-2-deficient mice, olfactory sensory neurons expressing a given odorant receptor frequently innervate multiple glomeruli at ectopic locations. These results suggest that BIG-2 is one of the axon guidance molecules crucial for the formation and maintenance of functional odor map in the olfactory bulb.

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These patterns of IEG expression in medial amygdala may provide glimpses of a higher-level processing of chemosensory signals beyond the primary-level selectivity of chemosensory neurons, the secondary sorting in main and accessory olfactory bulbs and the tertiary sorting by the medial amygdala into “biologically relevant and non-relevant” categories. Both non-volatile and volatile chemical-communication signals may be detected by the vomeronasal organ, which sends projections to the accessory olfactory bulb and on to the medial amygdala. Results of the first experiment (above) argue that the mouse medial amygdala sorts complex chemosensory information categorically, according to its biological relevance (salience). In order to determine the role of AOS in categorization, male mice underwent vomeronasal removal surgery (VNX) or a sham-operation (SHAM) and then were exposed to conspecific (male and female mouse urine) or heterospecific (hamster vaginal fluid and worn cat collar) chemical stimuli. As with the mice in the above experiment, SHAM mice exhibited different IEG expression patterns in the medial amygdala dependent upon the biological relevance of the chemical stimuli. However, regardless of biological relevance, vomeronasal organ removal eliminated the different IEG response patterns in the medial amygdala to any of the chemical stimuli. Interestingly, VNX also disrupted the avoidance of (an unfamiliar) predator odor, worn cat collar. These experiments show that the medial amygdala response to these tested chemical signals is dependent upon an intact vomeronasal organ. Normal function of the neuropeptide oxytocin (OT) in the medial amygdala is necessary for social recognition. In the final set of experiments, male mice having undergone intracerebroventricular cannulation (i.c.v.) were injected with either PBS (control) or oxytocin antagonist (OTA) and exposed to conspecific (female mouse urine) and heterospecific (steer urine and worn cat collar) chemical stimuli. As in the above experiments, PBS-injected mice exhibited different IEG expression patterns in the medial amygdala dependent upon the biological relevance of the chemical stimuli. However, OTA injection eliminated the increase in IEG expression in the medial amygdala to all of the tested conspecific or heterospecific stimuli. Importantly, OTA injection disrupted defensive and non-defensive behaviors after exposure to the unfamiliar predator odor, worn cat collar. The disruption of the social/individual recognition behavior in male mice deficient in OT may be due to the inability of the medial amygdala to process all biologically relevant chemical-communication signals.
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