Synapse Geometry and Receptor Dynamics Modulate Synaptic Strength

Abstract

Synaptic transmission relies on several processes, such as the location of a released vesicle, the number and type of receptors, trafficking between the postsynaptic density (PSD) and extrasynaptic compartment, as well as the synapse organization. To study the impact of these parameters on excitatory synaptic transmission, we present a computational model for the fast AMPA-receptor mediated synaptic current. We show that in addition to the vesicular release probability, due to variations in their release locations and the AMPAR distribution, the postsynaptic current amplitude has a large variance, making a synapse an intrinsic unreliable device. We use our model to examine our experimental data recorded from CA1 mice hippocampal slices to study the differences between mEPSC and evoked EPSC variance. The synaptic current but not the coefficient of variation is maximal when the active zone where vesicles are released is apposed to the PSD. Moreover, we find that for certain type of synapses, receptor trafficking can affect the magnitude of synaptic depression. Finally, we demonstrate that perisynaptic microdomains located outside the PSD impacts synaptic transmission by regulating the number of desensitized receptors and their trafficking to the PSD. We conclude that geometrical modifications, reorganization of the PSD or perisynaptic microdomains modulate synaptic strength, as the mechanisms underlying long-term plasticity.

Stochastic models of intracellular transport

“…One major simplification of the diffusing-trapping model is that it neglects the detailed structure of a spine and the associated PSD. A more comprehensive model would need to take into the complex organization of the PSD, interactions with scaffolding proteins, and the geometry of the spine (Freche et al, 2011;Kerr and Blanpied, 2012;MacGillavry et al, 2011;Sekimoto and Triller, 2009). Finally, note that the coupling between exocytosis and endocytosis during AMPA receptor recycling is one example of a more general transport mechanism that occurs in neurons (and other secretory cells) via the so-called endocytic pathway (Gundelfinger et al, 2003).…”

The Narrow Escape Problem

“…The models and simulations of synaptic transmission are given in Freche et al (2011); Taflia and Holcman (2011);and Holcman and Triller (2006). The microscopic model of reaction and diffusion follows Holcman and Schuss (2005) and Dao Duc and Holcman (2010).…”

“…Applications to the calculation of the synaptic current, as described in Kandel, Schwartz, and Jessell (2000), are given in Taflia and Holcman (2011) and Freche et al (2011). This current plays a fundamental role in neuronal communication: it is the direct and fast signal of synaptic transmission.…”

Computer simulations of synchrony and oscillations evoked by two coherent inputs

“…Thus the standard deviation of synaptic weight will decrease to 10 -1 . Although each synaptic weight is unreliable device (Freche et al 2011), we approximate each unit weight as a mean value. Thus, the present study focuses on, so to speak, mesoscopic phenomena of oscillatory neuronal activities (Foster et al 2008;Guo 2011;Schütt et al 2012).…”