Abstract

Modulation of gap junction-mediated electrical synapses is a common form of neural plasticity. However, the behavioral consequence of the modulation and the underlying molecular cellular mechanisms are not understood. Here, using a C. elegans circuit of interneurons that are connected by gap junctions, we show that modulation of the gap junctions facilitates olfactory learning. Learning experience weakens the gap junctions and induces a repulsive sensory response to the training odorants, which together decouple the responses of the interneurons to the training odorants to generate learned olfactory behavior. The weakening of the gap junctions results from downregulation of the abundance of a gap junction molecule, which is regulated by cell-autonomous function of the worm homologs of a NMDAR subunit and CaMKII. Thus, our findings identify the function of a gap junction modulation in an in vivo model of learning and a conserved regulatory pathway underlying the modulation.

Highlights

  • Modulation of gap junction-mediated electrical synapses is a common form of neural plasticity

  • We show that training-dependent weakening of RIM-gap junctions is regulated by the worm homolog of a mammalian NMDA-type glutamate receptors (NMDAR) subunit, NMR-1, and its downstream effector CaMKII in RIM, which reduce the abundance of the gap junction molecule INX-4 after training

  • Our results demonstrate the function of modulating gap junctions in an in vivo model of learning and identify the NMDAR- and CaMKII-mediated cellautonomous downregulation of gap junction molecules as the mechanism underlying the modulation

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Summary

Introduction

Modulation of gap junction-mediated electrical synapses is a common form of neural plasticity. We address these questions using Caenorhabditis elegans, taking advantage of the wiring diagram of its small nervous system (302 neurons)[15] and the knowledge of the genes encoding the synaptic or gap junction components in many of the neurons[16,17,18,19,20] This system allows us to examine in vivo the function of conserved molecules in regulating the activity and connectivity of neural circuits with genetics and imaging tools and to mechanistically dissect the molecular and cellular bases for the dynamics of circuit activity and their function in behavior. Our results demonstrate the function of modulating gap junctions in an in vivo model of learning and identify the NMDAR- and CaMKII-mediated cellautonomous downregulation of gap junction molecules as the mechanism underlying the modulation

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