Circadian Regulation of Neuronal Membrane Capacitance-Mechanisms and Implications for Neural Computation and Behavior.

Neuronal membrane capacitance (Cm) has traditionally been viewed as a static biophysical property determined solely by the geometric and dielectric characteristics of the lipid bilayer. Recent discoveries have fundamentally challenged this perspective, revealing that Cm exhibits robust circadian oscillations that profoundly influence neural computation and behavior. These rhythmic fluctuations in membrane capacitance are orchestrated by intrinsic cellular clocks through coordinated regulation of molecular processes including transcriptional control of membrane proteins, lipid metabolism, ion channel trafficking, and glial-mediated extracellular matrix remodeling. The dynamic modulation of Cm directly impacts the membrane time constant (τm = RmCm), thereby altering synaptic integration windows, action potential dynamics, and network synchronization across the 24 h cycle. At the computational level, circadian Cm oscillations enable neurons to shift between temporal summation and coincidence detection modes, optimizing information processing according to behavioral demands throughout the day-night cycle. These biophysical rhythms influence critical aspects of cognition including memory consolidation, attention, working memory, and sensory processing. Disruptions in normal Cm rhythmicity are increasingly implicated in neuropsychiatric and neurodegenerative disorders, including depression, schizophrenia, Alzheimer's disease, and epilepsy, where altered membrane dynamics compromise neural circuit stability and information transfer. The integration of circadian biophysics with chronomedicine offers promising therapeutic avenues, including chronotherapeutic strategies that target membrane properties, personalized interventions based on individual chronotypes, and environmental modifications that restore healthy biophysical rhythms. This review synthesizes evidence from molecular chronobiology, cellular electrophysiology, and systems neuroscience to establish circadian Cm regulation as a fundamental mechanism linking molecular timekeeping to neural computation and behavior.