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, yet the cellular mechanisms enabling behavioral adaptation remain poorly understood. Using anatomical tracing, 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 using two-photon calcium imaging combined with optogenetic manipulation. Activation of dendrite-inhibiting NDNF-positive layer 1 interneurons selectively impaired the acquisition of new rules, without affecting previously learned behavior. This inhibition profoundly suppressed global calcium activity in dendritic shafts but left local calcium transients in spines largely intact, while additionally reducing somatic burst firing. These findings suggest that shaft calcium signals, presumably induced by calcium spikes, rather than spine-specific inputs, are impaired by NDNF interneuron inhibition. Furthermore, we observed that excitatory synaptic inputs to tuft dendrites exhibited rule-dependent spatial clustering, indicating that the organization of synaptic inputs dynamically restructures according to task demands. Together, our results demonstrate that active dendritic integration in layer 5b pyramidal neurons is a key computational component of flexible learning, providing a cellular substrate for context-dependent behavioral adaptation.