Two-photon imaging of GABAergic and non-GABAergic neuronal calcium activity induced by infrared neural stimulation in awake mouse cortex

Infrared neural stimulation (INS, 1875 nm) is an emerging neuromodulation technology that holds promise for clinical application. However, little is known about its effect on excitatory and inhibitory cell types in the cerebral cortex. Here, using two-photon calcium imaging in the awake mouse somatosensory cortex, we have examined the effect of INS pulse train application on non-GABAergic (hSyn) excitatory neurons and GABAergic (mDlx) inhibitory neurons tagged with GCaMP6s. We find that each INS pulse train reliably induces a robust response in both excitatory and inhibitory neurons characterized by an initial decrease in intracellular calcium signal followed by a positive rebound; cessation of the several pulse trains leads to a large positive rebound, most prominently seen in non-GABAergic neurons. Quantification using indices of correlation, oscillation amplitude, and size of post-stimulation rebound illustrates responses are intensity-dependent and distance-dependent. Estimates of summed population response timecourses provide a potential basis for neural and hemodynamic signals described in other studies.