Transient Receptor Potential (TRP) channels: Quantitative biophysical correlates of cognitive function across brain...

Transient Receptor Potential (TRP) channels represent a diverse superfamily of polymodal cation channels that serve as critical molecular integrators linking sensory stimuli, cellular metabolism, and synaptic signaling to higher-order cognitive processes. This comprehensive review synthesizes quantitative biophysical properties of TRP channels across 24 distinct parameters, examining their region-specific expression patterns and functional correlates in the hippocampus, prefrontal cortex, amygdala, thalamus, and hypothalamus. Through integration of electrophysiological, transcriptomic, and neuroimaging data, we demonstrate robust correlations between TRP channel properties-including ion selectivity (PCa/PNa ratios of 1.5-6.5), single-channel conductance (40-120 pS), activation kinetics (50-200 ms), and modulatory sensitivity-and cognitive functions such as learning, memory consolidation, working memory, emotional processing, and sensory integration. Particular emphasis is placed on TRPV1, TRPM2, TRPC5, TRPA1, and related subfamily members that exhibit quantifiable relationships with synaptic plasticity mechanisms including long-term potentiation (LTP) and calcium-dependent signaling cascades. Spearman correlation analyses reveal significant associations (ρ = 0.62-0.83, p < 0.05) between channel expression levels (weighted nTPM) and cognitive performance metrics across brain regions. This work establishes TRP channels as quantifiable molecular bridges between ionic dynamics and systems-level cognition, with implications for understanding cognitive disorders and developing targeted therapeutic interventions.