Fig. 5.

Model depicting the spatiotemporal integration of MAPK and PKA signaling cascades in mediating synaptic facilitation. Repeated TNS triggers the release of endogenous 5-HT, which binds to 5-HT receptors on the membranes of SN soma and SN-MN synapses to activate adenylate cyclase (AC)-dependent intracellular signaling cascades, including MAPK and PKA. At the synapse, transient PKA activation leads to STF (red arrows). In addition, synaptic MAPK activation resulting from repeated TNS is required to sustain synaptic PKA activation, resulting in ITF (green arrows). Repeated TNS also induced persistent somatic MAPK activation and delayed somatic PKA activation, which we posit converge on regulation of transcriptional machinery that leads to LTF (blue arrows).