Molecular membrane dynamics: Insights into synaptic function and neuropathological disease

The fluid mosaic model states that molecules in the plasma membrane can freely undergo lateral diffusion; however, in neurons and glia, specific membrane molecules are concentrated in cellular microdomains to overcome the randomizing effects of free diffusion. This specialized distribution of membrane molecules is crucial for various cell functions; one example is the accumulation of neurotransmitter receptors at the postsynaptic neuronal membrane, which enables efficient synaptic transmission. Quantum dot-single particle tracking (QD-SPT) is a super-resolution imaging technique that uses semiconductor nanocrystal quantum dots as fluorescent probes, and is a powerful tool for analyzing protein and lipid behavior in the plasma membrane. In this article, we review studies implementing QD-SPT in neuroscience research and important data gleaned using this technology. Recent QD-SPT experiments have provided critical insights into the mechanism and physiological relevance of membrane self-organization in neurons and astrocytes in the brain. The mobility of some membrane molecules may become abnormal in cellular models of epilepsy and Alzheimer's disease. Based on these findings, we propose that the behavior of membrane molecules reflects the condition of neurons in pathological disease states.