Synapsin is not involved in the potentiation of spontaneous synaptic release by forskolin

Synaptic vesicles (SVs) mediate neural transmission by
fusing with the membrane at the active zone and releasing
neurotransmitter into the synaptic cleft. Synapsin is the
most abundant group of phosphoproteins associated with
the SV membrane. They tether SVs to each other and to the
actin-based cytoskeleton, thus creating the reserve pool
(RP) of vesicles. Synapsin-synapsin interactions control the
association of SVs within the RP, and thereby regulate the
supply of vesicles from the reserve pool to the active zone.
The N-terminal A domain of all major synapsin isoforms
J Mol Neurosci (2011) 45 (Suppl 1):S1–S137 S113
contains a phosphorylation site (site 1) recognized by
cAMP-dependent protein kinase (PKA) and CaM Kinase
I. Phosphorylation of synapsin at this site during neurotransmission causes declustering of the reserve pool,
releasing SVs to migrate to the active zone.
By activating adenylyl cyclase, forskolin induces phosphorylation of synapsin at site 1. In addition, the frequency
of spontaneous synaptic release is significantly elevated by
forskolin.
We examined whether synapsin phosphorylation participates in elevating the frequency of spontaneous postsynaptic events after forskolin application. For this purpose,
intracellular recording of spontaneous events were performed in dense cultures of hippocampal neurons. The
effect of forskolin on cultures from wildtype and synapsin
triple knockout (TKO) mice was compared. We observed
that the initial rate of spontaneous events in both cultures
was not different. Moreover, forskolin induced a significant
but similar increase in the frequency of spontaneous
release. These results suggest that synapsin does not play
an important role in determining the effect of forskolin.
Thus, other mechanisms, perhaps phosphorylation of Epac,
are involved in increasing the probability of spontaneous
release by forskolin, rather than the availability of mobilized vesicles.