Drueke, M. | bioRxiv Science

bioRxiv2025

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. Here we show that inputs critical to decision-making converge on the apical tuft dendrites of L5b 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. Remarkably, this inhibition profoundly suppressed calcium activity selectively in dendritic shafts but not spines while reducing burst firing. Moreover, excitatory synaptic inputs to tuft dendrites exhibited rule-dependent clustering. We conclude that active dendritic integration is a key computational component of flexible learning.

neuroscience↗

bioRxiv2019

Perirhinal input to neocortical layer 1 controls learning

Signals sent back to the neocortex from the hippocampus control the long-term storage of memories in the neocortex1,2, but the cellular mechanisms underlying this process remain elusive. Here, we show that learning is controlled by specific medial-temporal input to neocortical layer 1. To show this we used direct cortical microstimulation detection task that allowed the precise region of learning to be examined and manipulated. Chemogenetically suppressing the last stage of the medial temporal loop, i.e. perirhinal cortex input to neocortical layer 1, profoundly disrupted early memory formation but had no effect on behavior in trained animals. The learning involved the emergence of a small population of layer 5 pyramidal neurons (~10%) with significantly increased firing involving high-frequency bursts of action potentials that were also blocked by suppression of perirhinal input. Moreover, we found that dendritic excitability was correspondingly enhanced in a similarly-sized population of pyramidal neurons and suppression of dendritic activity via optogenetic activation of dendrite-targeting inhibitory neurons also suppressed learning. Finally, single-cell stimulation of cortical layer 5 pyramidal neurons showed that burst but not regular firing retrieved previously learned behavior. We conclude that the medial temporal input to the neocortex controls learning through a process in L1 that elevates dendritic calcium and promotes burst firing.

neuroscience↗