Rewiring neural circuits by the insertion of ectopic electrical synapses in transgenic C. elegans

Ithai Rabinowitch, Marios Chatzigeorgiou, Buyun Zhao, Millet Treinin, William R. Schafer*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

Abstract

Neural circuits are functional ensembles of neurons that are selectively interconnected by chemical or electrical synapses. Here we describe a synthetic biology approach to the study of neural circuits, whereby new electrical synapses can be introduced in novel sites in the neuronal circuitry to reprogram behaviour. We added electrical synapses composed of the vertebrate gap junction protein Cx36 between Caenorhabditis elegans chemosensory neurons with opposite intrinsic responses to salt. Connecting these neurons by an ectopic electrical synapse led to a loss of lateral asymmetry and altered chemotaxis behaviour. In a second example, introducing Cx36 into an inhibitory chemical synapse between an olfactory receptor neuron and an interneuron changed the sign of the connection from negative to positive, and abolished the animal' s behavioural response to benzaldehyde. These data demonstrate a synthetic strategy to rewire behavioural circuits by engineering synaptic connectivity in C. elegans.

Original languageEnglish
Article number4442
JournalNature Communications
Volume5
DOIs
StatePublished - 16 Jul 2014

Bibliographical note

Funding Information:
We thank C.I. Bargmann for strains, N. Chronis for the microfluidic device and for help in setting it up, Y. Tanizawa and K.E. Busch for reagents, H. Bringmann for help with the codon optimizing, and J. Bai, R.S. Branicky, A.E.X. Brown, M. Ezcurra and R. Straussman for helpful discussions and comments on the manuscript. This work was supported by the MRC grant MC-A022-5PB91. I.R. was also supported by postdoctoral fellowships granted by the Israeli Science Foundation Bikura program, the Edmond and Lily Safra Center for Brain Sciences (ELSC), and the Institute for Medical Research Israel-Canada (IMRIC).

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