A Thermal–Quantum Crossover Model for Mid-Infrared Modulation of Neuronal Excitability

Voltage-gated ion channels in neurons open when a gating coordinate crosses a free-energy barrier
that is sharply sensitive to the local transmembrane voltage, typically over tens to hundreds of
millivolts of effective bias. We model the channel pore as a nanoscale dielectric cavity that supports
electromagnetic field modes whose voltage fluctuations include both classical (thermal) and quantum
(zero-point) contributions. We show that these contributions are separated by a single thermal–
quantum crossover frequency ωc = 2kB T /ℏ, which at physiological temperature lies in the long-
wavelength mid-infrared (∼ 23 μm). Above ωc, the zero-point (quantum) contribution dominates
the voltage variance across the pore. In a simple barrier-limited WKB picture of channel gating, this
enhanced variance lowers the effective barrier and produces an exponential increase in the predicted
channel opening probability.

We carry this crossover scale consistently from a finite-temperature field-theoretic description,
through an effective gating Hamiltonian that couples a voltage-sensitive coordinate to electromagnetic
fluctuations, and into an experimentally testable prediction at the cellular level. Specifically, the
framework predicts that neuronal firing thresholds (rheobase current and spike-initiation voltage) will
exhibit a localized dip under two complementary conditions: (i) during absorbed-dose–equalized
mid-infrared stimulation, as a function of illumination frequency; and (ii) at a fixed long-wavelength
illumination near 23 μm while the bath temperature is swept, precisely at the temperature T* where
the illumination frequency matches ωc(T*) = 2kB T*/ℏ. We outline whole-cell patch-clamp and
infrared neural stimulation protocols — including fast membrane thermometry, TTX block, and
power normalization to control for bulk heating — that can falsify these predictions. Our analysis
links nanoscale electromagnetic fluctuations to macroscopic neuronal excitability in a way that is, in
principle, testable with existing mid-/far-infrared neuromodulation hardware.