Supplementary MaterialsTable S1. fields results in a prominent electric field envelope

Supplementary MaterialsTable S1. fields results in a prominent electric field envelope modulated at the difference frequency. We validated this temporal interference (TI) concept via modeling and physics experiments, and verified that neurons in?the living mouse brain could follow the electric field?envelope. We demonstrate the power of TI stimulation by stimulating neurons in the hippocampus of living mice without recruiting neurons of the overlying cortex. Finally, we show that by altering the currents delivered to a set of immobile electrodes, we can steerably evoke different motor patterns in living mice. that fall outside the range of normal neural operation, but which differ by a small amount, (Physique?1B). The amplitude of the envelope modulation at a particular location depends on the vectorial sum of the two applied field vectors at that point and as a result can have a maximum at a point distant from the electrodes, potentially even deep in the brain (Physique?1C). The location of this envelope maximum depends on the electrode configuration, as well as properties of the applied waveforms. For GRS the trapezoidal configuration shown in Physique?1A, the low-frequency envelope oscillates at a frequency of 40?Hz, with waveforms in Physique?1B plotted at Argatroban inhibitor the two specific points highlighted by Roman numerals in Determine?1A. For example, Figure?1Bi shows a large envelope modulation amplitude at a location where the two fields are aligned and huge, whereas Body?1Bii shows a little envelope modulation amplitude at a spot where in fact the two areas are less aligned. Open up in another window Body?1 Idea of TI Excitement and Validation of Neural Activation in Intact Mouse Human brain (ACC) TI idea. (A) Electric powered field vectors and (grey and blue arrows respectively) caused by alternating currents and (once again normalized to optimum) in the locations indicated by containers within a and indicated by Roman numerals ((grey) and (blue) along the path, aswell as the envelope caused by the superposition of both areas, i.e., (reddish colored). may be Argatroban inhibitor the envelope modulation waveform along the path (dark dashed range). (C) Color map (normalized to optimum) from the spatial distribution from the envelope modulation amplitude along the path (as plotted for just two factors in B), for the modeled configuration shown in A. (DCJ) TI effects on neural activity, assessed with in?vivo whole cell patch clamp in anesthetized mouse. (DCF) Representative neural responses from a single patched neuron in the somatosensory cortex undergoing TI activation (D) (gray waveform, activation at 2.01 kHz, 100?A amplitude, 0.25?s ramp-up, 1.75?s period, 0.25?s delay; blue waveform, 2 kHz, 100?A amplitude, 0.25?s ramp up, 2?s period, no delay), 10?Hz activation (E) (blue waveform, Argatroban inhibitor 10?Hz, 200?A amplitude, 0.25?s ramp-up period, 2?s period) and high-frequency activation (F) (blue waveform, 2 kHz, 200?A amplitude, 0.25?s ramp-up, 2?s period). Showing (i) spike raster plots, (ii) traces of current-clamp recording and (iii) magnified views of the trace regions indicated by boxes in (ii). Traces were filtered using a fifth-order Butterworth band-stop filter Argatroban inhibitor with cutoff frequencies of 1 1 kHz and 15 kHz and with a third order Butterworth high-pass filter with a cutoff frequency of 100?Hz to remove 10?Hz and 2 kHz activation artifacts; see Figures S1ACS1I for non-filtered traces. (G and H) Representative neural responses from a single patched neuron in hippocampus undergoing TI activation (G); gray waveform, activation at 2.01 kHz, 400?A amplitude, 0.5?s ramp-up, 2?s period, 0.5?s ramp-down; blue waveform, 2 kHz, 400?A amplitude, 0.5?s ramp up, 2?s period, 0.5?s ramp-down; shown are (i) traces of current-clamp recording and (ii) magnified views of the trace regions indicated by boxes in (i) and high-frequency activation (H); gray waveform, 2?kHz, 400?A amplitude, 0.5?s ramp-up, 2?s period, 0.5?s ramp-down; blue waveform, 2 kHz, 400?A amplitude, 0.5?s ramp-up, 2?s period, 0.5?s ramp-down). Traces were filtered using a fifth order Butterworth band-stop filter with cutoff frequencies of 1 1 kHz and 15 kHz to remove 2 kHz activation artifacts. (I) Spike frequency in neurons undergoing stimulation, as assessed by whole patch clamp in anesthetized mice (plotted are imply SD). (i) Neurons in somatosensory cortex, from left to right: 10?Hz activation (200?A, n?= 7 cells Argatroban inhibitor from 4 mice), TI activation with 1 kHz?+.