Quantum Tunneling in Synaptic Enzymes as a Source of Genuine Neural Variability

We propose that proton quantum tunneling in presynaptic enzymes constitutes a source of genuine synaptic variability, qualitatively distinct from classical thermal noise and detectable via the kinetic isotope effect (KIE). The central prediction is that H→D isotopic substitution in neuronal cultures should reduce the coefficient of variation of interspike intervals (CV of ISI) by a factor KIEₙet in the range 1. 5–3. 5×, derived from a quantitative three-scale model (molecular → vesicular → network). The prediction rests on documented proton tunneling in enzymes (KIE up to 100×), a PCET-mediated vesicle fusion model, and experimental evidence that heavy water modulates hippocampal synaptic transmission. The hypothesis requires no macroscopic quantum coherence or new physics. The falsification threshold is explicit: KIEₙet < 1. 5× under controlled conditions with adequate statistical power (N ≥ 15 per group, α = 0. 0125) refutes the hypothesis in its current formulation. The protocol includes explicit controls for osmotic, viscous, and thermal confounds of heavy water.