Connectivity in the mouse olfactory system

The mammalian olfactory system consists of the main olfactory system that discriminates between thousands of volatile odorants, and the accessory olfactory system that mediates behavioral and hormonal changes in response to pheromones. This thesis describes various approaches to analyze neuronal connectivity in the olfactory system.; The first chapter involves the development of a genetic transneuronal tracer methodology which may later be applied to analyzing the organization of sensory information derived from a given odorant receptor in the olfactory cortex. Transgenic mice were generated in which a plant lectin, barley lectin, is expressed in neurons of the olfactory epithelium and vomeronasal organ using an olfactory specific promoter. We showed that the lectin protein is transferred transneuronally, anterogradely to neurons of the olfactory bulb and their axons in the olfactory cortex, and probably retrogradely to neurons that innervate the olfactory bulb. We found that during development, lectin transneuronal transfer occurs prenatally in the main olfactory system, but only postnatally in the accessory olfactory system. In ongoing experiments, we are using gene targeting in embryonic stem cells to obtain mice in which the lectin is coexpressed with a single odorant receptor gene.; The second chapter describes experiments looking for differences in the projection from the dorsal versus ventral olfactory bulb to the olfactory cortex. Previous studies by others have indicated that sensory information in the olfactory epithelium and in the olfactory bulb is segregated along the dorsal-ventral axis. Using two different colored fluorescent dyes in the dorsal and ventral olfactory bulb, we saw some segregation of fibers in the connections of the olfactory bulb to restricted areas of olfactory cortex.; The last chapter presents experiments that ask how the odorant receptor genes themselves may affect the targeting of olfactory sensory neuron axons to specific locations in the olfactory bulb. We are generating mice in which the coding region of one odorant receptor gene has been exchanged with that of another. Preliminary results suggest that the alteration of an odorant receptor gene affects axon targeting, and also suggest that a critical number of sensory neuron axons may be required to form a distinct glomerulus.