Abstract
Neuromodulation is often thought to have a static, gain-setting function in neural circuits. We found that biphasic-bidirectional neuromodulatory actions of serotonergic neurons in the mollusc, Tritonia diomedea, arise from the dynamics of two independent intracellular events, and further investigated the mechanism underlying such neuromodulatory actions that we termed spike timing-dependent neuromodulation (STDN). The Dorsal Swim Interneurons (DSIs) are serotonergic neurons intrinsic to the Tritonia swim central pattern generator (CPG). When stimulated at physiological rates, they alter the size of synaptic currents evoked by another CPG neuron, Ventral Swim Interneuron B (VSI), in a time-varying manner; there is an initial potentiation phase lasting 15 seconds, followed by a depression phase lasting up to 2 min. We have determined that STDN is caused by two independent responses of VSI to serotonin (5-HT) released from DSI. The depression phase is caused by a serotonergic enhancement of a 4-aminopyridine (4-AP)-sensitive, voltage-gated outward current ( I A). The depression phase, but not the potentiation is blocked by 4-AP. Pharmacological experiments show that this synaptic potentiation is dependent upon intracellular stores of Ca 2+. Thus, the dynamic neuromodulatory change in synaptic strength is caused by independent mechanisms within VSI: an enhancement of vesicle release and an enhancement of I A. The dynamics of neuromodulation may play a role in production of the motor pattern by the CPG.
