The olfactory system is emerging as an attractive model for studying neuronal wiring and information processing in the mammalian brain. This system represents information about molecular stimuli, in part, as spatial patterns of activation in the olfactory bulb of the brain. The molecular basis for these odor representations is being elucidated by studies on the genetic basis of olfactory function. In mammals, olfaction is mediated by a large family of odorant receptors expressed in chemosensory neurons. The current hypothesis is that odorant receptors have two distinct roles in olfactory function: mediating odorant responsiveness and influencing the wiring of axonal projections to the olfactory bulb. This idea raises important questions as to what information is mapped onto the surface of the brain. The objective of these studies is to begin to elucidate the relationship between these two roles.
The first aim i s to determine whether the distinct functions of ORs (ligand binding and axon guidance) can be separated. This will be done by creating mouse strains with targeted genetic mutations in a defined endogenous odorant receptor locus, assaying the odorant specificity of fluorescently tagged neurons expressing defined receptors, and correlating these data with observed axon pathfinding behavior in vivo.
The second aim i s to determine whether odorant specificity or receptor sequence correlate with the location of neuronal projections dictated by a set of odorant receptors expressed from a defined genetic locus. Odorant response profiles will be measured, and expressed receptors sequenced from afferents projecting to local regions of the olfactory bulb defined by the projections of genetically tagged neurons. Addressing these issues provides a first step towards understanding how the mammalian nervous system represents chemical information. The combination of gene targeting and optical imaging of neuronal activity provides powerful tools for investigating information coding in the mammalian olfactory system. The general approach of targeting expression of exogenous proteins (e.g., genetically encoded optical indicators) to defined neuronal populations could provide new methods to monitor neuronal activity in intact neuronal circuits.
