Activity-dependent increases in [Ca2+]i contribute to digital-analog plasticity at a molluscan synapse

Abstract

In a type of short-term plasticity that is observed in a number of systems, synaptic transmission is potentiated by depolarizing changes in the membrane potential of the presynaptic neuron before spike initiation. This digital-analog form of plasticity is graded. The more depolarized the neuron, the greater the increase in the efficacy of synaptic transmission. In a number of systems, including the system presently under investigation, this type of modulation is calcium dependent, and its graded nature is presumably a consequence of a direct relationship between the intracellular calcium concentration ([Ca²⁺]_i) and the effect on synaptic transmission. It is therefore of interest to identify factors that determine the magnitude of this type of calcium signal. We studied a synapse in Aplysia and demonstrate that there can be a contribution from currents activated during spiking. When neurons spike, there are localized increases in [Ca²⁺]_i that directly trigger neurotransmitter release. Additionally, spiking can lead to global increases in [Ca²⁺]_i that are reminiscent of those induced by subthreshold depolarization. We demonstrate that these spike-induced increases in [Ca²⁺]_i result from the activation of a current not activated by subthreshold depolarization. Importantly, they decay with a relatively slow time constant. Consequently, with repeated spiking, even at a low frequency, they readily summate to become larger than increases in [Ca²⁺]_i induced by subthreshold depolarization alone. When this occurs, global increases in [Ca²⁺]_i induced by spiking play the predominant role in determining the efficacy of synaptic transmission.NEW & NOTEWORTHY We demonstrate that spiking can induce global increases in the intracellular calcium concentration ([Ca²⁺]_i) that decay with a relatively long time constant. Consequently, summation of the calcium signal occurs even at low firing frequencies. As a result there is significant, persistent potentiation of synaptic transmission.

Keywords: Aplysia; calcium; invertebrate; synaptic plasticity; transmitter release.