Various neuromodulation approaches have been employed to alter neuronal spiking activity and thus regulate brain functions and alleviate neurological disorders. Infrared neural stimulation (INS) could be a potential approach for neuromodulation because it requires no tissue contact and possesses a high spatial resolution. However, the risk of overheating and an unclear mechanism hamper its application. Here we show that midinfrared stimulation (MIRS) with a specific wavelength exerts nonthermal, long-distance, and reversible modulatory effects on ion channel activity, neuronal signaling, and sensorimotor behavior. Patch-clamp recording from mouse neocortical pyramidal cells revealed that MIRS readily provides gain control over spiking activities, inhibiting spiking responses to weak inputs but enhancing those to strong inputs. MIRS also shortens action potential (AP) waveforms by accelerating its repolarization, through an increase in voltage-gated K+ (but not Na+) currents. Molecular dynamics simulations further revealed that MIRS-induced resonance vibration of –C=O bonds at the K+ channel ion selectivity filter contributes to the K+ current increase. Importantly, these effects are readily reversible and independent of temperature increase. At the behavioral level in larval zebrafish, MIRS modulates startle responses by sharply increasing the slope of the sensorimotor input–output curve. Therefore, MIRS represents a promising neuromodulation approach suitable for clinical application.

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A deficiency of Ca2+ fluxes arising from dysfunctional voltage-gated calcium channels has been associated with a list of calcium channelopathies such as epilepsy, hypokalemic periodic paralysis, episodic ataxia, etc. Apart from analyzing the pathogenic channel mutations, understanding how the channel regulates the ion conduction would be instructive to the treatment as well. In the present work, in relating the free energetics of Ca2+ transport to the calcium channel, we demonstrate the importance of bridging Ca2+ hydration waters, which form hydrogen bonds with channel −COO– and −CO groups and enable a long-distance effect on the Ca2+ permeation. By firing a terahertz wave which resonates with the stretching mode of either the −COO– or the −CO group, we obtain significantly enhanced selectivity and conductance of Ca2+. The Ca2+ free energy negatively grows nearly 5-fold. The direct evidence is the reinforced hydrogen bonds. In addition, thanks to forced vibrations, −COO– contributes to raised permeation as well even under a field in resonance with −CO, and vice versa. Since the resonant terahertz field could manipulate the conduction of calcium channels, it has potential applications in therapeutic intervention such as rectifying a Ca2+ deficiency in degraded calcium channels, inducing apoptosis of tumor cells with overloaded calcium etc.

The myelin sheath enables dramatic speed enhancement for signal propagation in nerves. In this work, myelinated nerve structure is experimentally and theoretically studied using synchrotron-radiation-based Fourier-transform infrared microspectroscopy. It is found that, with a certain mid-infrared to terahertz spectral range, the myelin sheath possesses a ≈2-fold higher refraction index compared to the outer medium or the inner axon, suggesting that myelin can serve as an infrared dielectric waveguide. By calculating the correlation between the material characteristics of myelin and the radical energy distribution in myelinated nerves, it is demonstrated that the sheath, with a normal thickness (≈2 µm) and dielectric constant in nature, can confine the infrared field energy within the sheath and enable the propagation of an infrared signal at the millimeter scale without dramatic energy loss. The energy of signal propagation is supplied and amplified when crossing the nodes of Ranvier via periodic relay. These findings provide the first model for explaining the mechanism of infrared and terahertz neurotransmission through myelinated nerves, which may promote the development of biological-tissue label-free detection, biomaterial-based sensors, neural information, and noninvasive brain-machine interfaces.

Excellent permeation of one-dimensional (1-D) confined water across membrane channels is implicated in physiological processes and widely inspires the design of novel nanodevices and materials. Here, through molecular dynamics simulations, we proposed a phase transition to superpermeation (approximately 1 order of magnitude enhancement) of confined water across a 1-D water channel caused by a terahertz electromagnetic stimulus with a limited thermal effect. The underlying mechanism is revealed to be a combination of strength matching and frequency resonance between a relatively weak stimulus and the hydrogen bond network of 1-D confined water, rather than the bulk water outside. This combination causes an anomalously structural phase transition of only the confined water while efficiently limiting the thermal effect of bulk water. Our findings are promising for promoting the developments of advanced nanofluidic systems and terahertz technology and even physiological research.

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.

Unwinding the double helix of the DNA molecule is the basis of gene duplication and gene editing, and the acceleration of this unwinding process is crucial to the rapid detection of genetic information. Based on the unwinding of six-base-pair DNA duplexes, we demonstrate that a terahertz stimulus at a characteristic frequency (44.0 THz) can serve as an efficient, nonthermal, and long-range method to accelerate the unwinding process of DNA duplexes. The average speed of the unwinding process increased by 20 times at least, and its temperature was significantly reduced. The mechanism was revealed to be the resonance between the terahertz stimulus and the vibration of purine connected by the weak hydrogen bond and the consequent break in hydrogen bond connections between these base pairs. Our findings potentially provide a promising application of terahertz technology for the rapid detection of nucleic acids, biomedicine, and therapy.

Static magnetic undulators used by x-ray light sources are fundamentally too limited to achieve shorter undulator periods and dynamic control. To overcome these limitations, we report experimental demonstration of a novel short-period microwave undulator, essentially a Thomson scattering device, that has yielded tunable spontaneous emission and seeded coherent radiation. Its equivalent undulator period (λ u) is 13.9 mm while it has achieved an equivalent magnetic field of 0.65 T. For future-generation light sources, this device promises a shorter undulator period, a large aperture, and fast dynamic control.