Spatiotemporal recruitment of inhibition and excitation in the mammalian cortex during electrical stimulation

Abstract

Electrical stimulation has emerged as a powerful and precise treatment in which to modulate aberrant neural activity patterns common in neural dysfunction and disease; however, the physiological process involved in microstimulation is poorly understood, particularly regarding the contributions of inhibitory neurons to shaping stimulation-evoked activity. To address this issue, we used 2-photon imaging of transgenic mice to measure the widespread responses of inhibitory and excitatory neurons to electrical stimulation through a chronically-implanted cortical microelectrode. We found that increasing stimulation amplitude both raised the fraction of neurons that responded to a stimulus and increased the distance at which inhibitory and excitatory neurons were significantly modulated by stimulation; however, the lateral spread of inhibitory activity preceded that of excitatory activity. By 50 micro-Amps, a significantly larger fraction of inhibitory neurons vs. excitatory neurons were modulated by stimulation. Increasing amplitude also shifted the temporal response properties of the population --- towards longer-latency excitation close to the electrode tip and strong inhibition of more distant neurons. Animal behavior, specifically their locomotion patterns, strongly correlated with trial-to-trial variability in stimulation evoked responses. We conclude that changing electrical stimulation amplitude can shift the balance of excitation to inhibition in the brain in a manner that interact with ongoing animal behavior.

Biomimetic microstimulation of sensory cortices

“…Here, higher amplitudes and frequencies drove more rapid adaptation of neurons, agreeing with previous results [31], [32], [36], [66]. Higher frequencies and amplitudes then may result in increased recruitment of inhibitory neurons [35] at onset, driving strong rapid adaptation. RA neurons were significantly farther from the electrode than SS neurons.…”

Biomimetic multi-channel microstimulation of somatosensory cortex conveys high resolution force feedback for bionic hands

“…In the experiments described above, ICMS consisted of pulse trains of constant amplitude (flat trains). Such pulse trains typically evoke an abrupt rise in the activation of neurons around the electrode, followed by a slow decrease (22) . In contrast, interactions with objects evoke phasic responses at the onset and offset of contact and much weaker responses (< 10%) during maintained contact, a property inherited from the periphery (11) .…”

Neural mechanisms of the temporal response of cortical neurons to intracortical microstimulation

“…Despite this understanding, no computational model exists that reproduces the stereotyped temporal effects of ICMS. Further, current experimental techniques used to quantify the neural responses to ICMS, such as 2-photon calcium imaging and microelectrode recordings, have limitations including limited temporal resolution, and short latency responses may be obscured by stimulation artifacts [ 1 , 24 - 26 ]. The relative contribution of various biophysical mechanisms including after-hyperpolarization (AHP) currents, short-term synaptic depression, and GABAergic synaptic transmission to the ICMS-induced inhibitory response are not known.…”