Research Fellow Max Fletcher Wins $450K Grant


August 26, 2015

Dept of Neurobiology and Anatomy Research Fellow Max Fletcher, Ph.D., has been awarded a $450,000 three year grant by the National Institutes of Health for a project titled, “In Vivo Optical Imaging Of Experience-Induced Olfactory Bulb Glomerular Plasticity.”

From The Abstract

The long-term goal of this project is to understand how learning can influence olfactory odorant representations at the first level of processing within the olfactory bulb. While the mammalian olfactory system has been shown to have a remarkable capability for undergoing experience-dependent plasticity, how such odor memories are imprinted in the adult olfactory neural circuit remains unclear.

Although this process most likely involves changes at multiple stages in the olfactory pathway, one interesting site for plasticity is the olfactory glomerular layer. Within this layer, the anatomical organization of receptor neuron input allows odorant information to be transformed into an odorant-specific topographical map of glomerular activity. This activity pattern can be visualized in vivo using a newly-developed transgenic mouse with a GFP-based calcium indicator (GCaMP2) expressed exclusively in olfactory bulb output neurons immediately postsynaptic to receptor input.

Unlike previous imaging methods, this mouse allows us to observe purely postsynaptic odor maps in the glomerular layer for the first time. Using this mouse model we can directly test the hypothesis that olfactory learning significantly alters olfactory bulb postsynaptic glomerular odorant representations for the trained odorant. This will be accomplished by comparing odorant-evoked glomerular activity patterns in the same animal before and after associative conditioning.

Preliminary data suggests that conditioning with a given odorant significantly alters glomerular responses to that odorant following training. Based on this, we plan to extend our findings by testing the hypothesis that these changes will serve to reduce the representational overlap between the trained odorant and similar odorants. Together, these studies will have a significant impact on our understanding of the neural basis of odor coding and role plasticity plays in shaping neural responses to sensory stimuli.