Mild Focal Cooling Decouples Dendrites to Reconfigure Cortical Output

ABSTRACT Focal cooling modulates cortical computations, yet how principal neurons respond remains unclear. We demonstrate that mild focal cooling of the barrel cortex (S1) while impacting behavior creates a steep translaminar temperature gradient with ∼4°C drop in layer 5 (L5)—a range where conduction velocity changes are minimal. L5 neurons integrate self‐motion and touch by encoding whisker dynamics, and because their apical tuft dendrites lie proximal to the cooled surface, the gradient implicates possible dendritic mechanisms in mediating behavioral disruption. In vitro experiments confirm this: focal cooling (100 µm radius) selectively increases impedance and input‐output transformations in L5 tuft but not basal dendrites, yet paradoxically impairs recovery from inactivation of apical dendritic Na + channels, reducing somato‐dendritic coupling. These results challenge the view that cooling acts mainly through slowed conduction. Instead, suggesting that cooling decouples basal‐tuft integration and dynamically regulates cortical gain, revealing a potent neuromodulatory mechanism with implications for sensory‐motor computation.