This research project is designed to take a CaM kinase-dependent plastic behavior and define the neuronal circuits that generate that behavior. We will manipulate kinase substrate activity genetically and monitor the effects of these manipulations on whole animal and synaptic behavior. These experiments will provide a well defined, genetically and physiologically accessible model for learning and memory, define biochemical pathways downstream of CaM kinase required for generation of this behavior and correlate specific changes in the properties of synapses with alterations in behavior.
Specific aims i nclude: 1. Identification of neuronal circuits requiring CaM kinase for plastic behavior. We will use GAL4/UAS expression of modulators of CaM kinase activity to define the neural substrates of courtship conditioning. We will investigate long-term memory in this paradigm. A neural network model will be generated to allow qualitative and quantitative predictions of the effects of manipulation of the circuit on behavior. 2. Characterization of plastic behavior in animals with altered CaM kinase-dependent biochemical pathways. We will investigate the role of the CaM kinase substrates Eag and Adf-1 in the production of plasticity in the courtship conditioning assay. Dominant mutant transgenic strains will be constructed to test the function of phosphorylation of these substrates in behavior. 3. Characterization of the effects of alterations in CaM kinase and its substrates on synaptic plasticity at the larval neuromuscular junction. We will use the third instar neuromuscular junction (NMJ) to investigate synaptic plasticity in animals with alterations in CaM kinase and its substrates. Genetic methods allowing expression of transgenes in either the pre- or postsynaptic cell will allow definitive assignment of aspects of CaM kinase function to one side of the synapse. Cognitive function such as learning and memory are impaired in many disease states. Understanding the biochemical basis of normal changes in neuronal properties is an important first step in understanding how pathological processes can disrupt brain function. CaM kinase has been proposed to play a role in many plastic process, from long-term potentiation to whole animal behavior. The proposed experiments are directed at allowing the first direct correlation between a biochemical activity, cell excitability and a whole animal behavioral output.
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