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

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.

The Pre-synaptic Landscape of Mitral/Tufted Cells of the Main Olfactory Bulb.

In olfaction, all volatile odor information is tunneled through the main olfactory bulb (OB). Odor information is then processed before it is transferred to higher brain centers. Odor processing in the OB is carried out by numerous local inhibitory circuits and modulated by top-down input. Top-down modulation of OB function has been shown to act via interneurons but evidence also exists for its direct impact onto the principle mitral and tufted cells (M/Ts). Here, we used monosynaptic rabies trans-synaptic tracing from the OB to map and quantify the local and top-down pre-synaptic landscape of M/Ts and local inhibitory interneurons. We found that M/Ts receive a significant amount of top-down inputs from various brain regions that match qualitatively but not quantitatively those that synapse onto local inhibitory inter-neurons. These results show that M/Ts are direct targets of top-down inputs.