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Nonequivalent release sites govern synaptic depression.

ABSTRACT: Synaptic depression is prominent among synapses, but the underlying mechanisms remain uncertain. Here, we use paired patch clamp recording to study neuromuscular transmission between the caudal primary motor neuron and target skeletal muscle in zebrafish. This synapse has an unusually low number of release sites, all with high probabilities of release in response to low-frequency stimulation. During high-frequency stimulation, the synapse undergoes short-term depression and reaches steady-state levels of transmission that sustain the swimming behavior. To determine the release parameters underlying this steady state, we applied variance analysis. Our analysis revealed two functionally distinct subclasses of release sites differing by over 60-fold in rates of vesicle reloading. A slow reloading class requires seconds to recover and contributes to depression onset but not the steady-state transmission. By contrast, a fast reloading class recovers within tens of milliseconds and is solely responsible for steady-state transmission. Thus, in contrast to most current models that assign levels of steady-state depression to vesicle availability, our findings instead assign this function to nonuniform release site kinetics. The duality of active-site properties accounts for the highly nonlinear dependence of steady-state depression levels on frequency.

SUBMITTER: Wen H

PROVIDER: S-EPMC4725501 | biostudies-other | 2016 Jan

REPOSITORIES: biostudies-other

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Project description:The release of neurotransmitters from synapses obeys complex and stochastic dynamics. Depending on the recent history of synaptic activation, many synapses depress the probability of releasing more neurotransmitter, which is known as synaptic depression. Our understanding of how synaptic depression affects the information efficacy, however, is limited. Here we propose a mathematically tractable model of both synchronous spike-evoked release and asynchronous release that permits us to quantify the information conveyed by a synapse. The model transits between discrete states of a communication channel, with the present state depending on many past time steps, emulating the gradual depression and exponential recovery of the synapse. Asynchronous and spontaneous releases play a critical role in shaping the information efficacy of the synapse. We prove that depression can enhance both the information rate and the information rate per unit energy expended, provided that synchronous spike-evoked release depresses less (or recovers faster) than asynchronous release. Furthermore, we explore the theoretical implications of short-term synaptic depression adapting on longer time scales, as part of the phenomenon of metaplasticity. In particular, we show that a synapse can adjust its energy expenditure by changing the dynamics of short-term synaptic depression without affecting the net information conveyed by each successful release. Moreover, the optimal input spike rate is independent of the amplitude or time constant of synaptic depression. We analyze the information efficacy of three types of synapses for which the short-term dynamics of both synchronous and asynchronous release have been experimentally measured. In hippocampal autaptic synapses, the persistence of asynchronous release during depression cannot compensate for the reduction of synchronous release, so that the rate of information transmission declines with synaptic depression. In the calyx of Held, the information rate per release remains constant despite large variations in the measured asynchronous release rate. Lastly, we show that dopamine, by controlling asynchronous release in corticostriatal synapses, increases the synaptic information efficacy in nucleus accumbens.

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Nonequivalent release sites govern synaptic depression.

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