Complementary roles of cell-type-specific plasticity in shaping neocortical dynamics for learning action timing

AI Summary

CaMKII activity in premotor cortex is necessary for learning a motor timing task but not for execution of already learned actions.
Cell-type-specific CaMKII-dependent plasticity in two pyramidal tract neuron subtypes is required for learning, whereas intratelencephalic neuron plasticity is not.
PT subtype plasticity sculpts distinct premotor cortical dynamics that anticipate motor timing; IT neuron plasticity reduces cortical activity dimensionality.

Nat Commun. 2026 Jul 6. doi: 10.1038/s41467-026-74869-1. Online ahead of print.

ABSTRACT

Neocortical spiking dynamics underlie voluntary behavior and are thought to emerge through synaptic plasticity during learning. However, the causal role of plasticity across cortical cell types in shaping population dynamics remains unclear. To address this, we manipulated Ca²⁺/calmodulin-dependent protein kinase II (CaMKII), a key mediator of plasticity, in mice learning a motor timing task. Transient CaMKII inactivation in the premotor cortex impaired learning without affecting execution of learned actions. Cell-type-specific manipulations revealed that CaMKII-dependent plasticity in two pyramidal tract (PT) neuron subtypes-but not intratelencephalic (IT) neurons-was required for learning. Concurrent large-scale electrophysiology showed that CaMKII activity in the two PT subtypes was necessary to shape distinct aspects of premotor cortical dynamics that jointly anticipate motor timing, whereas IT neuron plasticity was required to reduce the dimensionality of cortical activity. Together, synaptic plasticity in major cortical cell types plays specialized and complementary roles in sculpting cortical dynamics during learning.

PMID:42409803 | DOI:10.1038/s41467-026-74869-1

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