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B.S. in Medicine at Dalian Med. Univ., 1992 Ph.D. in Neurophysiology at Dalian Med. Univ., 2000 Zhuo has been charactering the genomic responses to altered neuronal activity in the Drosophila brain. Neurons perform a host of activity-dependent and independent processes, including pathfinding, synapse formation, and regulation of membrane excitability and synaptic strength. Within the basic framework of circuit function, neurons adapt to changes in innervation patterns and synaptic input via homeostatic compensation mechanisms that maintain neurotransmission within appropriate levels of excitation. Experience also alters neuronal output through various short- and long-term plastic changes that occur in the context of learning and memory. Studies of long-term synaptic plasticity have focused on the activation of intermediate early genes (IEGs) and the requirement for CREB-mediated transcriptional regulation for behavioral plasticity. However, the downstream target genes that underlie activity-dependent modification in neuronal circuits are largely unknown. In addition, the cellular mechanisms that differentiate homeostatic adaptation to chronic changes in neuronal activity from experience-driven acute changes are unclear. To explore changes in neuronal function that occur downstream of altered activity, Zhuo performed an expression analysis in Drosophila mutants with acute or chronic alterations in neuronal activity. Zhuo found that seizure induction leads to an overproliferation of synaptic connections, indicating activity-dependent neuronal rewiring occurs in Drosophila. To analyze transcriptional recoding during altered neuronal activity, Zhuo performed genome-wide DNA microarray analysis following multiple seizure induction and recovery paradigms. Approximately 250 genes implicated in cell adhesion, membrane excitability, and cellular signaling are differentially regulated, including the Kek 2 neuronal cell adhesion protein, which we demonstrate functions as a regulator of synaptic growth. These data identify a collection of activity-regulated transcripts that may link changes in neuronal firing patterns to transcription-dependent modulation of brain function, including activity-dependent synaptic rewiring. |
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