Pyramidal neuron excitability correlates with behavioral measures of recovery of function. A, Linear correlations with recovery of function were found for adaptation ratio at low-amplitude (20 pA shown here) and high-amplitude (180 pA) current stimuli, such that greater adaptation (lower ratio) at low-amplitude stimuli is associated with fewer days to recover preoperative grasp but lower adaptation at high-amplitude stimuli is associated with faster latency. B, Linear correlations with recovery of function were found for EPSC frequency and E:I ratio, such that the greater excitation relative to inhibition, the greater the recovery. C-F, Linear correlations between recovery of function and measures of c-fos⁺ activation of neurons during HDT as follows: (C) the total density of c-fos⁺ cells and the subpopulation of CB⁺/c-fos⁺ cells were significantly correlated with days to return to preoperative grasp level; (D) days to return to preoperative latency; and (E) postoperative mean latencies during the final 5 d of testing.F, The density of PV⁺/c-fos⁺ cells and % cfos unlabeled with inhibitory neuron markers were significantly correlated with mean latencies during the final 5 d of testing. G, Linear correlations between MAP2 optical density (% area labeled) and number of days to recover preoperative grasp level and mean latencies (final 5 d of testing). H, Summary of lesion-associated changes and the effects of MSC-EVs on pyramidal neuron cellular structure and function in perilesional vPMC. Based on our evidence here and from our previous work (Go et al., 2020; Moore et al., 2019), we propose two possible mechanisms of action of EV treatment to either limit initial acute damage and dampen lesion-associated compensatory changes in firing and synaptic current properties, or enhance neurite remodeling during the chronic recovery phase after injury.