Activity induced GEM-4/Copine expression inhibits gap junctions and promotes thermosensory plasticity

Activity regulated transcription modifies the intrinsic excitability of cells, which is proposed to promote neuronal and behavioral plasticity; however, the transcriptional targets involved have not been identified. Here, we identify a single MEF-2 and CRH-1/CREB transcriptional target, gem-4/Copine, whose expression in C. elegans body muscles inhibits gap junction coupling, thereby increasing excitability. We show that gem-4 also promotes a form of experience and CRH-1 dependent neuronal plasticity. Inactivating gem-4 diminishes the ability of AFD thermosensory neurons to adjust their sensory response threshold following shifts in cultivation temperature. These results describe a mechanism linking activity regulated gem-4 expression to the plasticity of intrinsic excitability and sensory responses. Significance StatementActivity induced gene expression (e.g. that produced by activating the transcription factors CREB and MEF-2) is required for behavioral plasticity, including several forms of learning and memory. The effects of activity-induced gene expression on behavior are thought to be mediated by changes in synaptic connectivity and by changes in the intrinsic excitability of neurons. The role of altered excitability on behavioral plasticity has been difficult to assess because specific transcriptional targets regulating excitability have not been identified. Here we identify the gem-4 Copine gene as a MEF-2 and CREB transcriptional target that regulates intrinsic excitability by inhibiting gap junction coupling.