Extrinsic and intrinsic stress signals influence nervous systems to undergo plastic changes, including alteration of gene expression, modulation of synaptic structure and ultimately leads to behavioral adaptation. Under adverse environmental conditions, nematodes develop into hibernation-like diapause states like, the dauer and the L1-diapause states, which show altered responsiveness to various environmental cues and a strikingly different locomotory behavior, suggesting a wide scale rewiring of the nervous system. However, a system wide understanding of the circuit in the diapause state or the molecular mechanisms responsible underneath the possible circuit plasticity are lacking. I focused my study on the electrical synapse or gap-junction network. I took an entire nervous system wide approach to understand the dynamics of innexin (inx) gene expression, the family of 25 genes that encodes the building blocks invertebrate electrical synapses. Using fosmid-based fluorescent transcriptional reporter transgenes, I identified several of the inx genes show altered expression in the dauer nervous system. Among them, inx-6 showed the most striking expression plasticity in dauer and in L1-diapause states. Under favorable condition, inx-6 is expressed only in a subset of pharyngeal muscle cells. In diapause states, inx-6 expression is additionally turned on in the interneuron pair AIB, which regulates reversals and turns. inx-6 expression in AIB is reversible. As animals exit the diapause states, inx-6 expression turns off in AIB. I found that a transcriptional activator-repressor combination provides the cellular specificity of expression while integrating the environmental information. This diapause specific INX-6 expression in AIB leads to de-novo gap-junction formation between CO2-sencing sensory neuron BAG and AIB. INX-6 acts in a heterotypic gap junction complex with CHE-7, another innexin that is expressed in BAG, albeit constitutively. INX-6 expression in AIB also leads to formation of auto-synapses between AIBL and AIBR. Nematodes show opposing chemotaxis preference towards CO2 in dauer state. While non-dauer animals are repelled by CO2, dauers are attracted to CO2. I found animals in L1-diapause are also attracted by CO2. Using an AIB-specific inx-6 mutant allele, generated by CRISPR/Cas9 mediated genome editing, I identified that the loss of INX-6 activity in AIB leads to defects in CO2-attraction in diapause states. Loss of che-7 also has similar effects on CO2-attraction. INX-6 activity in AIB is also required to control locomotion speed and locomotory quiescence, specifically in diapause stage. My studies provide novel insights into the process of stress induced nervous system plasticity at different levels of gene regulation, circuit plasticity and behavior.

Affiliations:
- Department of Biological Sciences, Columbia University, New York, NY
- Howard Hughes Medical Institute