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Synapses change on multiple timescales, ranging from milliseconds to minutes, due to a combination of both short- and long-term plasticity. Here we develop an extension of the common generalized linear model to infer both short- and long-term changes in the coupling between a pre- and postsynaptic neuron based on observed spiking activity. We model short-term synaptic plasticity using additive effects that depend on the presynaptic spike timing, and we model long-term changes in both synaptic weight and baseline firing rate using point process adaptive smoothing. Using simulations, we first show that this model can accurately recover time-varying synaptic weights (1) for both depressing and facilitating synapses, (2) with a variety of long-term changes (including realistic changes, such as due to STDP), (3) with a range of pre and postsynaptic firing rates, and (4) for both excitatory and inhibitory synapses. We then apply our model to two experimentally recorded putative synaptic connections. We find that simultaneously tracking fast changes in synaptic weights, slow changes in synaptic weights, and unexplained variations in baseline firing is essential. Omitting any one of these factors can lead to spurious inferences for the others. Altogether, this model provides a flexible framework for tracking short- and long-term variation in spike transmission.
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Predictable Fluctuations in Excitatory Synaptic Strength Due to Natural Variation in Presynaptic Firing Rate
Many controlledin vitrostudies have demonstrated how postsynaptic responses to presynaptic spikes are not constant but depend on short-term synaptic plasticity (STP) and the detailed timing of presynaptic spikes. However, the effects of short-term plasticity (depression and facilitation) are not limited to short, subsecond timescales. The effects of STP appear on long timescales as changes in presynaptic firing rates lead to changes in steady-state synaptic transmission. Here, we examine the relationship between natural variations in the presynaptic firing rates and spike transmissionin vivo. Using large-scale spike recordings in awake male and female mice from the Allen Institute Neuropixels dataset, we first detect putative excitatory synaptic connections based on cross-correlations between the spike trains of millions of pairs of neurons. For the subset of pairs where a transient, excitatory effect was detected, we use a model-based approach to track fluctuations in synaptic efficacy and find that efficacy varies substantially on slow (∼1 min) timescales over the course of these recordings. For many connections, the efficacy fluctuations are correlated with fluctuations in the presynaptic firing rate. To understand the potential mechanisms underlying this relationship, we then model the detailed probability of postsynaptic spiking on a millisecond timescale, including both slow changes in postsynaptic excitability and monosynaptic inputs with short-term plasticity. The detailed model reproduces the slow efficacy fluctuations observed with many putative excitatory connections, suggesting that these fluctuations can be both directly predicted based on the time-varying presynaptic firing rate and, at least partly, explained by the cumulative effects of STP. SIGNIFICANCE STATEMENTThe firing rates of individual neurons naturally vary because of stimuli, movement, and brain state. Models of synaptic transmission predict that these variations in firing rates should be accompanied by slow fluctuations in synaptic strength because of short-term depression and facilitation. Here, we characterize the magnitude and predictability of fluctuations in synaptic strengthin vivousing large-scale spike recordings. For putative excitatory connections from a wide range of brain areas, we find that typical synaptic efficacy varies as much as ∼70%, and in many cases the fluctuations are well described by models of short-term synaptic plasticity. These results highlight the dynamic nature ofin vivosynaptic transmission and the interplay between synaptic strength and firing rates in awake animals.
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- Award ID(s):
- 1651396
- PAR ID:
- 10407337
- Publisher / Repository:
- DOI PREFIX: 10.1523
- Date Published:
- Journal Name:
- The Journal of Neuroscience
- Volume:
- 42
- Issue:
- 46
- ISSN:
- 0270-6474
- Page Range / eLocation ID:
- p. 8608-8620
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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