SPARKS, Garrett; COOPER, Robin; DUDEL, Josef: Serotonin offsets saturation of synaptic release in crayfish motor nerve terminals

With repetitive stimulation of the crayfish walking leg opener motor nerve terminal, in short pulse trains at given frequency, the excitatory postsynaptic potentials (EPSP) facilitate and reach a plateau in amplitude, an effect known as short term facilitation (STF). With higher stimulation frequencies, the EPSP responses increase in amplitude, reaching a new plateau. Even though the electrochemical driving gradient for the EPSP is sufficient to produce larger potentials, they are limited presynaptically by the amount of transmitter being released. During stimulation, presynaptic [Ca²⁺]_i increases, and an equilibrium is reached with continual influx, buffering, and exchange mechanisms, resulting in a steady state of transmitter release. Upon increasing the frequency of stimulation, a new equilibrium is established at a higher [Ca²⁺]_i, while the latter may enhance Ca/Na exchange affecting the steady state. The number of vesicles that can be released at the active zone may also be limited. Such anatomical limitations may also explain why higher-output terminals associated with phasic motor nerves terminals do not facilitate as much as lower-output tonic motor nerve terminals. This idea may also explain the differences in low- and high-output tonic terminals. The neuromodulator serotonin greatly enhances transmitter release by increasing the probability of vesicular fusion. Testing showed the release process is saturated during the plateau phase in the presence of high frequency stimulation when further increases in stimulation frequency failed to enhance transmission significantly. Serotonin (5-HT) was used to further enhance release during this maximized plateau phase, showing that depletion of releasable vesicles does not limit release under these conditions.