Shape-induced asymmetric diffusion in dendritic spines allows efficient synaptic AMPA receptor trapping

More recent modeling studies report that shape should also affect lateral diffusion of proteins embedded in the plasma membrane.

“In addition, more recent modeling studies report that shape should also affect lateral diffusion of proteins embedded in the plasma membrane (Kusters et al., 2013).”

Trapping of receptors may be facilitated by the curvature of plasma membrane in spines.

“In addition, trapping of receptors may be facilitated by the curvature of plasma membrane in spines (Kusters et al., 2013), as discussed in detail below.”

Decreasing neck radius and increasing neck length effectively increase the confinement of receptors at the synapse.

“In combination with an exocytic event in the head of the spine, a decreasing neck radius and increasing neck length effectively increase the confinement of receptors at the synapse, as can be seen in Figure 3B showing the time-evolution of receptor concentration after the release of 1000 receptors at the top of the spine (Kusters et al., 2013).”

The mean escape time of receptors through the neck of a typical mushroom-shaped spine follows a power-law dependence on neck radius r and neck length l.

“More specifically, the characteristic timescale for retention, the mean escape time of receptors through the neck of a typical mushroom-shaped spines follows a power-law dependence on neck radius r, τescape~(rneck)−λ”

Mushroom shaped spines with an exocytosis site adjacent to the synapse are privileged over others, because they can rapidly and specifically regulate the synaptic AMPA receptor level.

“Altogether, this modeling study concluded that mushroom shaped spines with an exocytosis site adjacent to the synapse are privileged over others, because they can rapidly and specifically regulate the synaptic AMPA receptor level (Kusters et al., 2013).”

The timescale for an AMPA receptor reaching the synapse may be up to an order of magnitude faster than the time it takes for a receptor to exit through the neck of the spine.

“The timescale for an AMPA receptor reaching the synapse may be up to an order of magnitude faster that the time it takes for a receptor to exit through the neck of the spine.”

Modeling studies show that typical mushroom-like morphology strongly alters lateral diffusion of AMPA receptors, with pronounced suppression of receptor exit rate out of spines with decreasing neck radius and increasing neck length.

“These observations have been rationalized by several modeling studies, which showed that the typical mushroom-like morphology of dendritic spines strongly alters the lateral diffusion of AMPA receptors, demonstrating a pronounced suppression of the receptor exit rate out of spines with decreasing neck radius as well as increasing neck length (Holcman and Schuss, 2011; Kusters et al., 2013; Kusters”