Complexity and Computation at the Synapse: Multilayer Architecture and Role of Diffusion in Shaping Synaptic Activity and Computation - Bioinspired Approaches for Human-Centric Technologies - page 284

Fig. 9.6 Functional role of lateral diffusion in the fast modulation of synaptic response. (a)
Diagram of fast AMPA receptor exchange at synapses during synaptic transmission: following
glutamate release ( left panel ), some AMPA receptors undergo desensitization ( middle panel ).
After 50 ms, due to lateral mobility, desensitized receptors are partially replaced by na¨ve
extrasynaptic receptors, thus limiting the depression of synaptic current due to accumulation of
desensitization ( right panel ). (b) Hypothetical redistribution of desensitized receptors at inhibitory
synapses after GABA release. GABAA receptors possess long-living desensitized states that can
persist up to 1 s. In these conditions, GABAA receptors in the desensitized state may diffuse to
neighboring GABAergic synapses determining “functional cross talk”

synapses. This finding emphasizes the crucial importance of receptor diffusion in
synaptic transmission and adds a further level of complexity in the modulation of
postsynaptic signal at sub-millisecond time scale. Indeed, in particular during
sustained synaptic activity, the level of the steady-state current will be influenced
not only by the equilibrium between desensitized and non-desensitized state (dic-
tated by presynaptic release and receptor gating) but also from the rate of exchange
between postsynaptic and extrasynaptic receptors. Receptor diffusion, thus, is a key
player in modulating the fidelity of synaptic transmission with crucial implications
in the neuronal signal processing.

9.5.3 Implications of Receptor Diffusion in Long-Term

Plasticity

Besides its role in the fast tuning of receptor availability at synapses, at longer time
scale, lateral diffusion has been extensively implicated in setting the number of
postsynaptic receptors expressed at postsynaptic sites in response to external
stimuli, thus representing an important determinant for postsynaptic long-term
plasticity. As demonstrated in the first studies describing the diffusion of receptors
at single-molecule level (Meier et al. 2001 ; Borgdorff and Choquet 2002 ), the