Shape-Induced Asymmetric Diffusion in Dendritic Spines Allows Efficient Synaptic AMPA Receptor Trapping

Abstract

Dendritic spines are the primary postsynaptic sites of excitatory neurotransmission in the brain. They exhibit a remarkable morphological variety, ranging from thin protrusions, to stubby shapes, to bulbous mushroom shapes. The remodeling of spines is thought to regulate the strength of the synaptic connection, which depends vitally on the number and the spatial distribution of AMPA-type glutamate receptors (AMPARs). We present numerical and analytical analyses demonstrating that this shape strongly affects AMPAR diffusion. We report a pronounced suppression of the receptor exit rate out of spines with decreasing neck radius. Thus, mushroomlike spines become highly effective at retaining receptors in the spine head. Moreover, we show that the postsynaptic density further enhances receptor trapping, particularly in mushroomlike spines local exocytosis in the spine head, in contrast to release at the base, provides rapid and specific regulatory control of AMPAR concentration at synapses.

Psychiatric Risk Factor ANK3/Ankyrin-G Nanodomains Regulate the Structure and Function of Glutamatergic Synapses

“…Ankyrin-G may act as a barrier in the spine neck, limiting the mobility of GluA1 out of the spine, promoting the retention of AMPARs in the spine head and thereby maintaining synaptic function. This proposed mechanism is supported by experimental data and mathematical models that indicate that the spine neck plays an essential role in limiting diffusion (Ashby et al, 2006; Kusters et al, 2013; Simon et al, 2014). …”

“…Our GFPAnkG190 overexpression experiments show that ankyrin-G can alter spine neck width in addition to head size; when overexpressed in the spine head, only spine head area increased, however when overexpressed in the spine head and neck concurrently, head area increased even more and was accompanied by neck thickening. Spine neck changes have recently been shown to be a critical parameter of spine plasticity (Tonnesen et al 2014) and it is emerging that spine necks are essential for myriad spine functions, including modulating AMPAR diffusion (Ashby et al, 2006; Kusters et al, 2013; Simon et al, 2014), compartmentalization of signalling (Grunditz et al, 2008; Murakoshi et al, 2011; Noguchi et al, 2005), and regulating diffusion across the neck during activity (Bloodgood and Sabatini, 2005). The presence of the leading psychiatric risk gene, ankyrin-G within the spine neck places it at a critical crossroads for influencing synaptic functions.…”

Synaptic receptor dynamics: From theoretical concepts to deep quantification and chemistry in cellulo

“…The model also emphasizes the importance of obstacles to diffusion (apparent viscosity) and the geometry of the structure on which the receptor diffuses, since these factors greatly influence receptor fluxes. Shape is of particular importance in the case of dendritic spines, where the thin spine neck represents a bottleneck that limits the exchange of synaptic components including neurotransmitter receptors (Kusters et al, 2013;Simon et al, 2014). Also the shape of spines can be modulated by synaptic activity (e.g.…”

Impact of morphology on diffusive dynamics on curved surfaces

“…In this paper, we focus on geometrical compartmentalization, where out-of-plane curvature is used to create relatively isolated microenvironments in the membrane. This is a common motif in cells: Among the many examples of biological systems in which morphology creates small microdomains within a membrane are cristea in mitochondria [9,10], dendritic spines in synapses [11][12][13][14], and grana thylakoids in choroplasts [15,16] (see Fig. 1).…”