Sensory systems process incoming information via multiple, parallel pathways that break the complex representation of the external environment into distinct processing streams. These parallel pathways encode a subset of stimulus features and contribute to specific aspects of a unified sensory percept - for example, motion and form in vision. While well-described and recognized as fundamental to sensory processing in other modalities such as vision, parallel pathways in the olfactory system remain poorly understood. This project will characterize for the first time how outputs from the olfactory bulb - the first synaptic level of processing in the olfactory system - differ in their representation of odor information as a function of their projection target. The project uses recently-developed optical, genetic and molecular tools to enable recording activity from individual olfactory bulb output neurons tagged according to their axonal projection to specific regions of primary olfactory cortex. To accomplish this, genetically-encoded Ca2+ reporter proteins (GCaMP) or light-activated channels (ChR2) will be expressed in olfactory bulb projection neurons using a viral vector driving Cre-recombinase dependent expression of the transgene and a mouse line expressing Cre-recombinase selectively in mitral and tufted cells of the olfactory bulb. The experiments take advantage of the fact - newly established by our laboratory - that these neurons can be infected through their axons, allowing expression in only those neurons projecting to specific areas of olfactory cortex. Odor responses in such target-defined neurons will then be recorded with in vivo imaging or with electrophysiology in both anesthetized and awake mice. All aspects of this methodology have recently been developed and work robustly in our laboratory. Using this approach we will ask how neurons projecting to distinct olfactory cortical areas differ with respect to their odorant- evoked response properties and their degree of modulation in the awake, behaving animal. The experiments will address important questions regarding the nature of olfactory processing streams that emerge from the olfactory bulb: Do projections to different cortical targets carry distinct representations of sensory information - a occurs, for example, in the parallel representations of motion and form in the visual system? If so, what is the nature of these differences in the context of odor coding and odor perception? In addition, do the different classes of olfactory bulb output neurons - classically identified by ther dendritic morphology and somatic location - map to distinct anatomical pathways according to their cortical targets or to distinct functional coding streams according to their odor response properties? Together the proposed experiments should lead to a significant advance in understanding parallel olfactory processing streams in a functional and behavioral context.
The sense of smell presents unique problems to the nervous system in terms of stimulus detection, neural encoding and recognition of complex stimuli;understanding how the brain solves these problems will likely lead to general insights into how the brain processes information. This project will characterize in new detail the functional differences between olfactory processing streams originating in the olfactory bulb and projecting to different cortical targets, using newly-developed genetic and optical tools. Understanding how different processing pathways contribute to odor perception and odor-guided behaviors could lead to a greater understanding of the nature of olfactory deficits that occur from injury or disease and point towards more successful therapeutic approaches.
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