Form Of Short-term Depression Research Articles

Short term synaptic depression with stochastic vesicle dynamics imposes a high-pass filter on presynaptic information

The filtering properties of synapses are modulated by a form of short term depression arising from the depletion of neurotransmitter vesicles. The uptake and release of these vesicles is stochastic in nature, but a widely used model of synaptic depression does not take this stochasticity into account. While this model of synaptic depression accurately captures the trial-averaged synaptic response to a presynaptic spike train [1], it fails to capture variability introduced by stochastic vesicle dynamics [2]. Our goal is to understand the impact of stochastic vesicle dynamics on filtering and information transfer in depressing synapses. We derive compact, closed-form expressions for the synaptic filter induced by short term synaptic depression when stochastic vesicle dynamics are taken into account and when they are not. We find that stochasticity in vesicle uptake and release fundamentally alters the way in which a synapse filters presynaptic information. Predictably, the variability introduced by this stochasticity reduces the rate at which information is transmitted through a synapse. Additionally, this variability introduces frequency-dependence to the transfer of information through a synapse: a model that ignores synaptic variability transmits slowly varying signals with the same fidelity as faster varying signals [3,4], but a model that takes this variability into account transmits faster varying signals with higher fidelity than slower signals (Figure ​(Figure1).1). Differences between the models persist even when the presynaptic cell makes many contacts onto the postsynaptic cell. We extend our analysis to the population level and conclude that a slowly varying signal must be encoded by a large presynaptic population if it is to be reliably transmitted through depressing synapses, but faster varying signals can be reliably encoded by smaller populations. Our results provide useful analytical tools for understanding the filtering properties of depressing synapses and have important consequences for neural coding in the presence of short term synaptic depression. Figure 1 The linear information rate, IL(g;s), which represents the information per unit time available to an optimal linear decoder that estimates a rate-coded presynaptic signal, s(t), by observing a postsynaptic conductance, g(t). The linear information rate ...

Short term synaptic depression imposes a frequency dependent filter on synaptic information transfer.

Depletion of synaptic neurotransmitter vesicles induces a form of short term depression in synapses throughout the nervous system. This plasticity affects how synapses filter presynaptic spike trains. The filtering properties of short term depression are often studied using a deterministic synapse model that predicts the mean synaptic response to a presynaptic spike train, but ignores variability introduced by the probabilistic nature of vesicle release and stochasticity in synaptic recovery time. We show that this additional variability has important consequences for the synaptic filtering of presynaptic information. In particular, a synapse model with stochastic vesicle dynamics suppresses information encoded at lower frequencies more than information encoded at higher frequencies, while a model that ignores this stochasticity transfers information encoded at any frequency equally well. This distinction between the two models persists even when large numbers of synaptic contacts are considered. Our study provides strong evidence that the stochastic nature neurotransmitter vesicle dynamics must be considered when analyzing the information flow across a synapse.

Kinetic Isolation of a Slowly Recovering Component of Short-Term Depression During Exhaustive Use at Excitatory Hippocampal Synapses

This study examines the kinetics of the longest lasting form of short-term depression at excitatory hippocampal synapses. After initial depletion of the readily releasable pool (RRP), continued 20-Hz stimulation was found to be fast enough to maximally drive presynaptic neurotransmitter exocytosis; maximal is defined here as the rate needed to maintain the RRP in a nearly empty steady state. Induction of depression proceeded in two distinct phases. The first was caused by RRP depletion, whereas the second is shown to reflect the progressive reduction of the overall rate at which new vesicles are supplied to the RRP and is termed "supply-rate depression." Supply-rate depression is identified further with the emergence, during heavy use, of a rate-limiting vesicle trafficking step that slows the timing of RRP replenishment by switching from a fast (tau congruent with 7 s) to a slow (tau congruent with 1 min) vesicle supply mechanism. Both mechanisms apparently follow first-order kinetics. After the induction of the maximum amount of depression, individual synapses were able to output only <1 quantum of neurotransmitter per synapse per second, matching previous predictions based on cell biological measurements of synaptic vesicle cycling. Surprisingly, the onset of supply-rate depression occurred with a marked delay, not having a detectable impact on synaptic function until after several seconds of continuous use. The delayed onset is not consistent with traditional vesicle trafficking models, but may be important for limiting the impact of supply-rate depression to pathological episodes and might function as a native antiepilepsy device.

Post-hypoxic frequency decline characterized in the rat working heart brainstem preparation.

The respiratory response to brief episodes of hypoxia is dynamic, i.e., the breathing pattern changes progressively both during and following an hypoxic episode1. The initial response in breathing with hypoxic exposure includes a sharp and acute increase in breathing frequency (F). Subsequently, F decreases as exposure to hypoxia continues. This decrease in F is a form of short-term depression that is referred to as “hypoxic ventilatory decline.” Immediately after the cessation of hypoxia and return to hyperoxic gas, F decreases further below the baseline frequency; the latter may be a form of short-term depression which is called post-hypoxic frequency decline (PHFD)1,2.