Spatiotemporal modelling reveals geometric dependence of AMPAR dynamics on dendritic spine morphology
Abstract
The modification of neural circuits depends on the strengthening and weakening of synaptic connections. Synaptic strength is often correlated to the density of the ionotropic, glutamatergic receptors, AMPARs, (α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid receptors) at the postsynaptic density (PSD). While AMPAR density is known to change based on complex biological signalling cascades, the effect of geometric factors such as dendritic spine shape, size and curvature remain poorly understood. In this work, we developed a deterministic, spatiotemporal model to study the dynamics of AMPARs during long‐term potentiation (LTP). This model includes a minimal set of biochemical events that represent the upstream signalling events, trafficking of AMPARs to and from the PSD, lateral diffusion in the plane of the spine membrane, and the presence of an extrasynaptic AMPAR pool. Using idealized and realistic spine geometries, we show that the dynamics and increase of bound AMPARs at the PSD depends on a combination of endo‐ and exocytosis, membrane diffusion, the availability of free AMPARs and intracellular signalling interactions. We also found non‐monotonic relationships between spine volume and the change in AMPARs at the PSD, suggesting that spines restrict changes in AMPARs to optimize resources and prevent runaway potentiation. image
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Nov 23, 2022
- Source ID
- 10.1113/jp283407
Entities
People
- Christopher T Lee
- Miriam Bell
- Padmini Rangamani
Organizations
- Air Force Office of Scientific Research
- University of California, San Diego