Many controlled, in vitro studies 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, sub-second 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 transmission in 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 ...