MECHANISMS OF SENSORY PLASTICITY IN C. ELEGANS

Brandeis University, Waltham MA

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Abstract

DESCRIPTION (provided by applicant): Animals alter their behavior in response to experience, and environmental and developmental cues. Long-term changes in behavioral circuits arise from modulation of gene expression in neuronal components. However, the contribution of changes in the expression of signaling genes in sensory neurons to sensory behavioral plasticity has not been fully explored. Expression of a set of chemo- and thermosensory neuron-specific genes is regulated by neuronal activity and developmental cues in C elegans. The specific aims of this proposal are: 1) To investigate plasticity in chemoreceptor gene expression and chemosensory neuron function. The role of TGF-beta signaling in the developmental plasticity of chemoreceptor gene expression will be explored. Mechanisms of neuronal activity in acute environmental regulation of chemoreceptor gene expression will be investigated. Genes required for regulation of chemoreceptors in response to environmental signals will be identified using genetic and genomic techniques. 2) To analyze the role of the CMK-1 calcium calmodulin-dependent kinase 1 enzyme in sensory neuron-specific gene expression and sensory plasticity. Mutations in CMK-1 result in defects in thermosensory neuron specific gene expression and in thermosensory and olfactory behavioral plasticity. Mechanisms required for activation of CMK-1 in response to neuronal activity will be identified. Direct and indirect targets of CMK-1 phosphorylation in vivo will be identified using genetic methods. The long-term goals of this proposal are to identify and analyze the signaling pathways required for modulation of sensory gene expression, and to explore the consequences of altered gene expression in sensory plasticity. Misregulation of gene expression in response to external cues underlies multiple abnormalities such as cognitive disorders and cancer. Experiments in this proposal will yield new insights into the mechanisms by which cellular function is regulated by extracellular signals, thereby suggesting targets for therapeutic intervention.