4.7 Article

Circumventing neural damage in a C. elegans chemosensory circuit using genetically engineered synapses

Journal

CELL SYSTEMS
Volume 12, Issue 3, Pages 263-+

Publisher

CELL PRESS
DOI: 10.1016/j.cels.2020.12.003

Keywords

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Funding

  1. Hartwell Innovation Fund grant
  2. NIH [R21DC016158, R01GM127857]
  3. Israel Science Foundation [1465/20]
  4. NIH Office of Research Infrastructure Programs [P40 OD010440]

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Loss of neurons can impair neural circuit function, but in this study, genetically engineered electrical synapses were used to reroute information flow in a damaged chemosensory circuit, restoring organism behavior. Additional electrical synapses were found to help restore circuit function by amplifying weakened neuronal signals and emulating the wild-type circuit.
Neuronal loss can considerably diminish neural circuit function, impairing normal behavior by disrupting information flow in the circuit. Here, we use genetically engineered electrical synapses to reroute the flow of information in a C. elegans damaged chemosensory circuit in order to restore organism behavior. We impaired chemotaxis by removing one pair of interneurons from the circuit then artificially coupled two other adjacent neuron pairs by ectopically expressing the gap junction protein, connexin, in them. This restored chemotaxis in the animals. We expected to observe linear and direct information flow between the connexin-coupled neurons in the recovered circuit but also revealed the formation of new potent left-right lateral electrical connections within the connexin-expressing neuron pairs. Our analysis suggests that these additional electrical synapses help restore circuit function by amplifying weakened neuronal signals in the damaged circuit in addition to emulating the wild-type circuit. A record of this paper's transparent peer review process is included in the Supplemental Information.

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