Spatiotemporal properties of cortical excitatory and inhibitory neuron activation by sustained and bursting electrical microstimulation

Intracortical microstimulation (ICMS) of sensory cortices produces artificial sensation yet the neural mechanisms underlying evoked responses, particularly among inhibitory subpopulations, remain unclear. We investigated how long durations (30 s) of ICMS shape spatiotemporal patterns in excitatory and inhibitory network activation using two-photon imaging of visual cortex in transgenic mice. Inhibitory neurons were more likely to facilitate (increase in activation) across 30 s of ICMS, whereas excitatory neurons were more likely to adapt (decrease in activation) and exhibit post-ICMS depression. Different temporal profiles led to preferential activation of excitatory or inhibitory neurons, with theta-burst stimulation driving the strongest inhibitory response and 10-Hz burst patterns driving the strongest peak excitatory response. Neurons located farther from the electrode exhibited more diverse responses to ICMS, highlighting synaptic recruitment dynamics such as inhibition and disinhibition. This study reveals how ICMS differentially influences excitatory and inhibitory neuron activity across long durations of ICMS and suggests temporal patterning can be used to potentially target neuronal subpopulations and drive desirable activity patterns.