Date of Award
Jennifer R. Kowalski
euronal communication (synaptic transmission) is critical for nervous system function. This communication occurs at specialized junctions called synapses where chemical neurotransmitters signal from presynaptic to postsynaptic cells. Additional signaling via neuropeptide activated G protein-coupled receptors (GPCRs) fine-tunes synaptic communication. GPCRs are a large family of transmembrane receptor proteins that bind extracellular neurotransmitters and neuropeptides to activate intracellular signaling pathways. My project investigated the function of FSHR-l, a GPCR and potential neuropeptide receptor, in regulating synaptic transmission at the neuromuscular junction (NMJ) in Caenorhabditis elegans roundworms, which share conservation of nervous system structure and function with humans. Worms lacking the fshr-I gene have reduced muscle contraction at the NMJ; however, the mechanism by which FSHR-l controls signaling at this synapse is unknown. I hypothesized that FSHR-l is a neuropeptide receptor for one or more unknown neuropeptides that acts in presynaptic motor neurons to modulate NMJ transmission. Initial genetic and behavioral analyses of/shr-l and neuropeptide signaling mutants indicate that.f~·hr-l does not interact with neuropeptide signaling; however future studies are needed to fully explore a potential interaction. With regard to downstream targets of FSHR-l signaling at the NMJ, behavioral results indicate that the adenylyl cyclase enzyme ACY -1, may work in the same signaling pathway as FSHR-l to control muscle contraction. I currently am exploring other downstream targets of FSHR-l, as well as quantifying synaptic vesicles in cholinergic and GABAergic motor neurons ofJshr-1 mutants using imaging techniques. To date, I have found that there is an increase in synaptic vesicle accumulation in presynaptic cholinergic motor neurons in fshr-I mutants suggestive of decreased synaptic vesicle release from these cells. Together these results provide information regarding the potential neuronal function of FSHR -1 in synaptic transmission, which may provide insight into human neurological diseases that involve in altered neurotransmission.
Kolnik, Julie Christine, "Investigation of FSHR-l Protein Function in Regulating Synaptic Transmission at the Neuromuscular Junction in C. elegans" (2014). Undergraduate Honors Thesis Collection. 241.