Abstract
Neurostimulant drugs or magnetic/electrical stimulation techniques can overcome attention deficits, but these drugs or techniques are weakly beneficial in boosting the learning capabilities of healthy subjects. Here, we report a stimulation technique, mid-infrared modulation (MIM), that delivers mid-infrared light energy through the opened skull or even non-invasively through a thinned intact skull and can activate brain neurons in vivo without introducing any exogeneous gene. Using c-Fos immunohistochemistry, in vivo single-cell electrophysiology and two-photon Ca2+ imaging in mice, we demonstrate that MIM significantly induces firing activities of neurons in the targeted cortical area. Moreover, mice that receive MIM targeting to the auditory cortex during an auditory associative learning task exhibit a faster learning speed (~50% faster) than control mice. Together, this non-invasive, opsin-free MIM technique is demonstrated with potential for modulating neuronal activity.
Highlights
Neurostimulant drugs or magnetic/electrical stimulation techniques can overcome attention deficits, but these drugs or techniques are weakly beneficial in boosting the learning capabilities of healthy subjects
mid-infrared modulation (MIM) induces neuronal firing in complete absence of any exogeneous gene
We demonstrate that MIM application in the auditory cortex of healthy adult mice during a sound-licking associative learning task boosts learning speed by ~50%
Summary
We used a pulsed quantum cascade laser as the MIR light source for MIM in this study (see “Methods” for details). MIM through thinned intact skull (irradiation time of 20 s) induced neuronal activation (Fig. 1e, “Thinned 20 s”, c-Fos cell proportion: 12.3/9.5–21.0 %, n = 8 slices from 4 mice), albeit with a lower efficacy than that through opened skull (P = 0.012 comparing to “Opened 20 s”, two-sided Wilcoxon rank-sum test). There have been studies on photostimulation or photomodulation using light in the near-infrared spectrum[7,19] (typically 1–3 μm wavelength), for which heat-related mechanisms could account for the activation of nerve cells[20,21] To test this hypothesis, we measured the cortical tissue temperature under MIR or VIS light irradiation in vivo (Fig. 1i and Supplementary Fig. 1) with the same configuration as that described above for the c-Fos experiment.
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