Scott Ginebaugh

  • 5th Year Graduate Student

Dissertation Research

The release of neurotransmitter occurs at specialized sites, called active zones (AZs), within the presynaptic nerve terminals. AZs contain all the components necessary for the control of calcium-triggered release of neurotransmitter, including synaptic vesicles, voltage-gated calcium channels (VGCCs), and calcium-activated potassium (BK) channels. However, our understanding of how the organization and relationships of these components impact calcium spatiotemporal dynamics and synaptic function remains superficial because few experimental approaches allow for the high resolution necessary to investigate the structure and function of the small components of the AZ. Furthermore, the organization of the AZ in the presynaptic neuromuscular junction (NMJ) is altered by the neuromuscular disease Lambert-Eaton Myasthenic Syndrome (LEMS), which causes severe muscle weakness by decreasing transmitter release from the AZs in the NMJ. Also, symptomatic treatments for LEMS are known to impact the calcium spatiotemporal profile and relationships between the AZ components, but exactly how this occurs is unclear.

My research involves developing a novel Monte Carlo computational model of the AZ in the NMJ which will allow us to investigate the presynaptic calcium spatiotemporal profile, the structure-function relationships between components in the AZ, and the impact of LEMS and LEMS treatments on these relationships and the calcium spatiotemporal profile. To generate new experimental data which will constrain our computational model (and answer some long-standing questions about the physiology of the NMJ), I have performed a variety of voltage-imaging experiments which allow us to measure the AP waveform at the NMJ (traditional electrophysiology techniques cannot be used here because the axon of the mammalian motoneuron is too small to impale with an electrode). Voltage-imaging will allow us to measure the AP waveform at the NMJ and to determine the impact of BK channels and various LEMS drug treatments on the AP waveform.

The results from the voltage-imaging experiments will allow us to develop our new AZ computational model. This model will then be used to answer questions about the physiology of transmitter release at the NMJ, determine the impact of LEMS on the AZ structure, and test potential drug combinations for the treatment of LEMS in silico.

Dissertation Mentor

Dr. Stephen D. Meriney

Education & Training

  • B.S. in Mathematics, Wayne State University, 2016

Research Categories

Representative Publications

Infinite Products for Powers of e^{1/k}, The American Mathematical Monthly 124 (2017) 161-165

Scott P. Ginebaugh, Eric D. Cyphers, Viswanath Lanka, Gloria Ortiz, Evan W. Miller, Rozita Laghaei and Stephen D. Meriney. The frog motor nerve terminal has very brief action potentials and three electrical regions predicted to differentially control transmitter release. Journal of Neuroscience 7 April 2020,JN-RM-2415-19.