Short-term synaptic depression and stochastic vesicle dynamics reduce and shape neuronal correlations

Abstract

Rosenbaum R, Rubin JE, Doiron B. Short-term synaptic depression and stochastic vesicle dynamics reduce and shape neuronal correlations. J Neurophysiol 109: 475-484, 2013. First published October 31, 2012 doi:10.1152/jn.00733.2012.-Correlated neuronal activity is an important feature in many neural codes, a neural correlate of a variety of cognitive states, as well as a signature of several disease states in the nervous system. The cellular and circuit mechanics of neural correlations is a vibrant area of research. Synapses throughout the cortex exhibit a form of short-term depression where increased presynaptic firing rates deplete neurotransmitter vesicles, which transiently reduces synaptic efficacy. The release and recovery of these vesicles are inherently stochastic, and this stochasticity introduces variability into the conductance elicited by depressing synapses. The impact of spiking and subthreshold membrane dynamics on the transfer of neuronal correlations has been studied intensively, but an investigation of the impact of short-term synaptic depression and stochastic vesicle dynamics on correlation transfer is lacking. We find that short-term synaptic depression and stochastic vesicle dynamics can substantially reduce correlations, shape the timescale over which these correlations occur, and alter the dependence of spiking correlations on firing rate. Our results show that short-term depression and stochastic vesicle dynamics need to be taken into account when modeling correlations in neuronal populations. Synaptic neurotransmitter vesicles are released probabilistically in response to a presynaptic spike, and released vesicles are recovered stochastically over a timescale of several hundred milliseconds (Vere-Jones 1966;Wang 1999;Fuhrmann et al. 2002;Goldman 2004;Rosenbaum et al. 2012). The depletion of neurotransmitter vesicles by trains of presynaptic action potentials gives rise to a form of short-term synaptic depression that is pervasive in the cortex (Zucker and Regehr 2002). We find that when two postsynaptic neurons receive correlated input through depressing synapses, the correlation between the synaptic conductances across the neurons' membranes, as well as the neurons' spike trains, are drastically smaller than the correlations predicted by a nondepressing, static synapse model. This reduction in correlation is especially prevalent at higher presynaptic firing rates that more effectively deplete neurotransmitter vesicles. Coupled with the fact that cellular dynamics suppress correlations at low firing rates (de la Rocha et al. 2007), these results show that a population of neurons with depressing synapses exhibit small correlations over a broad range of firing rates, even when their inputs are strongly correlated. Our conclusions reveal an important, yet often ignored, mechanism that promotes asynchronous spiking activity in densely connected neuronal populations. METHODSWe begin by describing the statistical measures used to quantify correlations in this study. We then describe the presyn...

Axonal and synaptic failure suppress the transfer of firing rate oscillations, synchrony and information during high frequency deep brain stimulation

“…We propose that this question is answered by recent studies showing that increased activation of STN axons during DBS elicits a form of short term depression believed to arise from a combination of axonal and synaptic failures [65,78,55,2], consistent with similar findings during high frequency stimulation in other brain regions [4,35,3,46,19,51,10,37,21]. Theoretical studies and empirical studies in other brain systems show that short term depression can suppress the synaptic transfer of low frequency oscillations, information and synchrony during periods of increased presynaptic spiking [1,27,29,44,50,63,62], and experimental evidence suggests these effects can suppress the synaptic transfer of parkinsonian activity patterns during DBS [3,2]. In this article, we systematically explore the hypothesis that DBS-induced axonal and synaptic failure produce short term depression that can suppress the synaptic transfer of pathological spiking patterns from STN to basal ganglia output nuclei while still producing an increase of total STN synaptic output during DBS.…”

The mechanics of state-dependent neural correlations

“…Previous studies focused on the impact of such synaptic variability on the information transmission across a synapse 77,75 . Here we follow our past study 78 and show how input correlations are diluted by synaptic variability in a firing rate dependent manner (see also 79 ).…”

“…One way to distinguish the mechanisms underlying correlation modulation is to consider spiking correlations ρ as a function of the time window ( T ) over which they are computed, because different mechanism modulate correlations on different timescales 89,78,101 . In general, ρ increases with the time window 106 , as in the case of the feedforward model with non-plastic synapses (Fig.…”

Kv7 channels regulate pairwise spiking covariability in health and disease

“…The reduction of firing rates by both of these mechanisms is well understood. More recently, synaptic depression has been predicted to reduce pairwise correlations by causing failures in shared, correlating inputs (Rosenbaum et al 2013). Previous theoretical investigations of the intrinsic mechanisms of adaptation and population coding have focused on how spike-driven processes shape the variability of uncorrelated neurons (Naud and Gerstner 2012;Farkhooi et al 2011).…”