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 267

Fig. 9.1 Schematic
representation of the
multilayer architecture of
synaptic transmission and of
the parallel processes
occurring at the various
levels through diffusion.
For further details, see text
for fusion and constitute the readily releasable pool (RRP) (Jahn and Fasshauer
2012 ). Based on their release probability, these SVs can be immediately released in
response to the action potential and in general are completely discharged after 1-2 s
at 20-40 Hz or by a hypertonic stimulus (sucrose; Fatt and Katz 1952 ) that
destabilizes the bilayer in a Ca 2+ -independent fashion. Depleted RRP is refilled
by a second pool of SVs, the recycling pool (RP) that represents a large reserve of
SV that are not immediately releasable. This pool is maintained by endocytosis of
released SVs and is responsible for the continued release occurring after complete
RRP depletion. RRP and RP represent all SVs capable of undergoing release and
constitute the so-called total recycling pool (TRP) (Alabi and Tsien 2012 ) that
serves evoked neurotransmitter release. In hippocampal synapses, 5-9 SVs form the
RRP, while the TRP can represent at most 60-70 % of the total SV population and
the RP is about 3-5-fold the RRP size (Murthy and Stevens 1999 ). The transition of
SVs from the RP to the RRP is a rate-limiting reaction during sustained activity, and
its kinetics impacts synaptic transmission. The time constant of RRP replenishment
under basal conditions is in the order of seconds, and its speed and extent can be
significantly modulated by activity (von Gersdorff and Matthews 1997 ).
The interplay of SVs between functional pools represents a mechanism of
paramount importance to adapt the response of the nerve terminal to the action
potential on the basis of the previous history of the neuron and the parallel activity
of signal transduction pathways. Transitions of SVs in and out of the various pools
are fueled by second messengers and phosphorylation/dephosphorylation of spe-
cific SV substrates that favor association/dissociation of the SVs with the cyto-
skeleton and the active zone scaffold components, as well as their mobility within
the terminal. Phosphorylation of synapsin I by Ca 2+ /calmodulin-dependent kinases
I and II, as well as by protein kinase A and neurotrophin-dependent extracellular-
regulated kinase (MAPK/Erk), increases the availability of SVs for refilling the
RRP and therefore contributes to the expression of short-term plasticity phenomena
by enhancing post-tetanic potentiation and limiting depression through a positive
effect on the quantal content (Cesca et al. 2010 ; Valente et al. 2012 ), while
phosphorylation of synapsin I by the tyrosine kinase Src or by cyclin-dependent