Research Projects

Locomotion is a crucial process for organisms' survival and is regulated by a network of neuronal circuits, including cell adhesion molecules (CAMs) like Calsyntenins (CASY-1). CASY-1 is present in Caenorhabditis elegans (C. elegans) and is required for coordinating locomotion by maintaining E-I balance at the neuromuscular junction (NMJ). CASY-11/CLSTN is expressed in three isoforms: CASY-1A, CASY-1B, and CASY-1C. CASY-1A is the full-length isoform and is expressed in sensory and interneurons, while CASY-1B/C is expressed in motor neurons. Casy-1 mutants display accelerated motor activity and paralysis in response to Aldicarb, suggesting an increase in cholinergic signaling. This is mediated by elevated glutamate release from sensory neurons, indicating that CASY-1A is the negative regulator of glutamate release. However, the exact mechanism by which CASY-1A acts at the sensory and interneuron level to regulate cholinergic signaling in motor neurons is not understood. Previous studies have reported the role of several neuropeptides in modulating the excitation-inhibition balance in the locomotory circuit. Preliminary experiments show that mutants in the neuropeptide Y receptor, npr-1, show a similar hypersensitivity to Aldicarb as casy-1 mutants. This suggests that CASY-1A may act through neuropeptidergic signaling to regulate sensorimotor signaling. C. elegans serves as a model system to understand the intricate neuromodulatory mechanisms operating in the locomotory circuit. The C. elegans NMJ allows for various manipulations, allowing for well-defined readouts to decipher mechanisms coordinating motor output.Locomotion is a crucial process for organisms' survival and is regulated by a network of neuronal circuits, including cell adhesion molecules (CAMs) like Calsyntenins (CASY-1). CASY-1 is present in Caenorhabditis elegans (C. elegans) and is required for coordinating locomotion by maintaining E-I balance at the neuromuscular junction (NMJ). CASY-11/CLSTN is expressed in three isoforms: CASY-1A, CASY-1B, and CASY-1C. CASY-1A is the full-length isoform and is expressed in sensory and interneurons, while CASY-1B/C is expressed in motor neurons. Casy-1 mutants display accelerated motor activity and paralysis in response to Aldicarb, suggesting an increase in cholinergic signaling. This is mediated by elevated glutamate release from sensory neurons, indicating that CASY-1A is the negative regulator of glutamate release. However, the exact mechanism by which CASY-1A acts at the sensory and interneuron level to regulate cholinergic signaling in motor neurons is not understood. Previous studies have reported the role of several neuropeptides in modulating the excitation-inhibition balance in the locomotory circuit. Preliminary experiments show that mutants in the neuropeptide Y receptor, npr-1, show a similar hypersensitivity to Aldicarb as casy-1 mutants. This suggests that CASY-1A may act through neuropeptidergic signaling to regulate sensorimotor signaling. C. elegans serves as a model system to understand the intricate neuromodulatory mechanisms operating in the locomotory circuit. The C. elegans NMJ allows for various manipulations, allowing for well-defined readouts to decipher mechanisms coordinating motor output.