Thermosensory Neurons Mediate Tactile-Dependent Locomotion Modulation in C. elegans

Abstract

Behavioral plasticity is the ability of animals to modify their behavior, a capacity essential for survival in constantly changing environments. This flexibility arises from experience-dependent changes in neuronal activity that modulate the flow of information through neural circuits. These changes are supported by molecular and circuit mechanisms that promote behavioral adaptation by modulating a wide range of neuronal functions, including excitability, synaptic strength, and connectivity. Disruption of these mechanisms can contribute to a wide range of neurological and psychiatric disorders that severely impair behavior. Despite their importance, the fundamental cellular and molecular principles of neuronal function and behavioral plasticity remain poorly understood, partly because the complexity of mammalian systems makes it difficult to dissect these mechanisms at the cellular and molecular levels. To bypass these limitations, neuroscientists have turned to simpler vertebrate and invertebrate animal models to gain insight into the molecular and circuit mechanisms that enable behavioral plasticity. One such model is the nematode Caenorhabditis elegans, which offers powerful genetic tools, and a well-mapped nervous system ideally suited for dissecting these mechanisms. In this dissertation, I investigated the molecular and circuit mechanisms that enable context-dependent behavioral plasticity in the nematode C. elegans. Using behavioral assays and genetic tools, I uncovered a novel role for the thermosensory neuron AFD in modulating locomotion based on tactile experience across different contexts. Genes in a cGMP signaling pathway are required in AFD for tactile-dependent modulation. Although these genes have previously been implicated in AFD's role in thermosensation, our findings indicate that they function in tactile modulation independently of thermal signaling. This conclusion is supported by the observation that tactile-dependent modulation persists even in the absence of AFD's thermosensory apparatus, suggesting that AFD does not act as a sensory neuron in this context. Rather, its function appears to depend on electrical synapses with the AIB interneuron, indicating that AFD's connectivity is essential for its role in tactile-dependent behavior. Together, these findings reveal a previously unrecognized circuit logic in which AFD contributes to behavioral plasticity by integrating information from other sensory modalities. This work advances our understanding of how molecular signaling and circuit architecture shape behavior and highlights C. elegans as a powerful model for dissecting the molecular basis of neuronal plasticity.