magnified scene by clicking image Fig. 1 WGA transgene method for selective labeling of neural pathways of interest By using WGA cDNA as a transgene in combination with a neuron type-specific promotor element, anatomically-connected and functionally-related neural pathways can be clearly visualized with great accuracy and high reproducibility.

Systematic single-unit recordings, and more recently optical imaging of intrinsic signals1), by Mori and colleagues have established the functional organization of the olfactory bulb2). Identification of the 1000 gene repertoire of mammalian odorant receptors has further made this sensory system accessible to molecular analysis and manipulation. Sensory neurons expressing a given olfactory receptor converge their axons onto topographically fixed glomeruli in the target bulb and make synaptic contact with a specific set of principal neurons, mitral and tufted cells. The overriding mystery remains how such a precise wiring scheme can be established and maintained. The Laboratory for Neurobiology of Synapse (Y. Yoshihara, head) will continue to tackle this question in two ways. First, the ongoing identification of recognition molecules that may guide individual odorant receptor cell axons to specific glomerular targets will be expanded. To date, Yoshihara et al. have described several novel cell-adhesion molecules expressed in robust patterns within olfactory bulb (e.g. OCAM, BIG-1, telencephalin), as well as the rest of the brain2). Tissue culture and gene targeting in mice are clarifying their functional role in neurite outgrowth. A complementary approach using mutant screens in zebrafish will further characterize molecules underlying olfactory axon pathfinding. Second, an innovative anatomical tract-tracing technique pioneered by this laboratory aims to elucidate the multiple processing stages downstream of any given odorant receptor3). Cell type-specific promoters have been coupled to the gene encoding wheat-germ agglutinin (WGA) to successfully visualize neuronal circuits emanating from those source neurons in transgenic mice (Fig. 1). Trans-synaptic transport of WGA expressed in individual odorant receptor cells is expected to reveal the fine-tuning of connectivity through olfactory bulb and beyond into cortex during development and plasticity.