Computational Analysis of Acetylcholine Dynamics at the Neuromuscular Junction
Session Number
3
Advisor(s)
Dr. Ashwin Mohan, Synapse Lab, IMSA
Location
A131
Discipline
Medical and Health Sciences
Start Date
15-4-2026 2:15 PM
End Date
15-4-2026 3:00 PM
Abstract
Neuromuscular transmission, critical for muscle contraction, depends on acetylcholine (ACh) rapidly diffusing across the synaptic cleft and binding to clustered nicotinic receptors on the postsynaptic membrane. Disruptions in this process underlie diseases like myasthenia gravis and muscular dystrophies. While synaptic geometry, receptor distribution, and kinetics have been studied separately, their combined influence on ACh signaling dynamics is poorly understood. This project investigates how synaptic fold morphology and receptor clustering affect local ACh concentration, receptor activation, and desensitization under physiological conditions, aiming to reveal mechanisms that maintain synaptic reliability and inform therapeutic approaches. A three-dimensional reaction-diffusion computational model of the neuromuscular junction was developed, integrating curved synaptic folds, clustered receptor distributions, and receptor state transitions with biological parameters. Simulations tracked ACh diffusion and receptor interactions over time to measure changes in local neurotransmitter concentration and receptor activation/desensitization. Results show that the combination of synaptic folds and receptor clustering enhances local ACh retention and prolongs receptor activation, suggesting a structural mechanism that improves neuromuscular transmission reliability. This model provides new insights into how synaptic microarchitecture modulates function and offers a platform to study how pathological changes in synaptic structure may impair signaling, supporting the development of targeted treatments for neuromuscular diseases.
Computational Analysis of Acetylcholine Dynamics at the Neuromuscular Junction
A131
Neuromuscular transmission, critical for muscle contraction, depends on acetylcholine (ACh) rapidly diffusing across the synaptic cleft and binding to clustered nicotinic receptors on the postsynaptic membrane. Disruptions in this process underlie diseases like myasthenia gravis and muscular dystrophies. While synaptic geometry, receptor distribution, and kinetics have been studied separately, their combined influence on ACh signaling dynamics is poorly understood. This project investigates how synaptic fold morphology and receptor clustering affect local ACh concentration, receptor activation, and desensitization under physiological conditions, aiming to reveal mechanisms that maintain synaptic reliability and inform therapeutic approaches. A three-dimensional reaction-diffusion computational model of the neuromuscular junction was developed, integrating curved synaptic folds, clustered receptor distributions, and receptor state transitions with biological parameters. Simulations tracked ACh diffusion and receptor interactions over time to measure changes in local neurotransmitter concentration and receptor activation/desensitization. Results show that the combination of synaptic folds and receptor clustering enhances local ACh retention and prolongs receptor activation, suggesting a structural mechanism that improves neuromuscular transmission reliability. This model provides new insights into how synaptic microarchitecture modulates function and offers a platform to study how pathological changes in synaptic structure may impair signaling, supporting the development of targeted treatments for neuromuscular diseases.