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.
Highlights
Neural circuits are functional ensembles of neurons that are selectively interconnected by chemical or electrical synapses
To test whether connexin 36 (Cx36) expression could generate ectopic gap junctions linking ASEL and ASER, we performed calciumimaging experiments to investigate the effects of ASERCx36 and ASELCx36 on neuronal responses to chemosensory stimulation
We observed that in wild-type, ASELCx36 and ASERCx36 animals, salt upsteps led to a calcium increase in ASEL and a calcium decrease in ASER (Fig. 1e,h,i)
Summary
Neural circuits are functional ensembles of neurons that are selectively interconnected by chemical or electrical synapses. 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. In ASERCx36ASELCx36 animals (Fig. 1e, red), ASER showed a calcium increase in response to a salt upstep, as expected if the depolarizing current in ASEL depolarized ASER through an electrical connetion These alterations in ASE activity correlated with a significant defect in the ability of the animals to navigate in a point-source gradient of NaCl (Supplementary Fig. 2a). Together, these results indicate that functional electrical synapses were successfully inserted between ASEL and ASER
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