Formation and Stability of Synaptic Receptor Domains

Neurotransmitter receptor molecules, concentrated in postsynaptic domains along with scaffold and a number of other molecules, are key regulators of signal transmission across synapses. Combining experiment and theory, we develop a quantitative description of synaptic receptor domains in terms of a reaction-diffusion model. We show that interactions between only receptors and scaffolds, together with the rapid diffusion of receptors on the cell membrane, are sufficient for the formation and stable characteristic size of synaptic receptor domains. Our work reconciles long-term stability of synaptic receptor domains with rapid turnover and diffusion of individual receptors, and suggests novel mechanisms for a form of short-term, postsynaptic plasticity.

Figure 1

Experimental results on the formation and stable characteristic size of RSDs composed of glycine receptors and gephyrin scaffolds [14]. (a) Example of a transfected COS-7 cell with domains on its membrane: Receptor (R, red) and scaffold (S, green) concentration and overlay (codomains in yellow). A fraction of the apparent green-labeled scaffolds is endoplasmic. (In the print version of this Letter, codomains are in light gray.) Scale bar, $5\mu \mathrm{m}$. (b) Examples of selected RSDs at higher resolution. For ease of visualization, the concentration maps of the two molecular species were slightly shifted with respect to one another in the color panel. Scale bars, $0.5\mu \mathrm{m}$. (c) Mean RSD (cluster) area and number of RSDs (clusters) per cell versus time. Error bars: standard errors; $n>10$ cells from two independent experiments for each point.

Figure 2

Model results on the formation and stable characteristic size of RSDs [14]. (a) Irregular patterns of stable RSDs, with an area of approximately 0.2 to $0.3\mu {\mathrm{m}}^2$ each, emerge on a time scale of hours. The distributions of receptors (upper panel) and scaffolds (middle panel) are overlayed (lower panel), and the domain shapes and patterns are stable. (b) Formation and (c) shape of RSDs at higher resolution. The fields $r$ and $s$ in panel (c) are scaled with respect to their maximum values inside RSDs. Scale bars, $0.5\mu \mathrm{m}$.

Figure 3

Model results on the regulation of mature RSDs [14]. Left panel: temporal profiles of step stimulations. Inset: receptor concentration profiles at times of maximum domain size. Right panel: time course of the in-domain receptor population size, $R$, following stimulation, normalized by the in-domain receptor population size in the absence of any stimulation, $R_0$.