Tuft dendrites in frontal motor cortex enable flexible learning

Flexible learning relies on integrating sensory and contextual information to adjust behavioral output in different environments. The anterolateral motor cortex (ALM) is a frontal area critical for action selection in rodents. We found that inputs critical to decision-making converge on the apical tuft dendrites of layer 5b pyramidal neurons in ALM. We therefore investigated the role of these dendrites in a rule-switching paradigm. Activation of dendrite-inhibiting layer 1 interneurons impaired relearning, without affecting previously learned behavior. This inhibition profoundly suppressed global calcium activity in dendritic shafts but not local transients in spines, while additionally reducing burst firing. Moreover, excitatory synaptic inputs to tuft dendrites exhibited rule-dependent clustering. We conclude that dendritic calcium signaling is a key computational component of flexible learning.