Layer 5 myelination gates corticothalamic coincidence detection

Myelin is essential for rapid saltatory propagation of action potentials (APs) to decrease the temporal delays between distant brain regions. Whether myelination plays a role in the long-range computational processing of disparate inputs is not well understood. Using a cell-type specific approach with retrograde AAV targeting in the layer 5 (L5) Cre-driver mouse line (Rbp4-Cre), we studied optogenetically evoked L5 pyramidal neuron responses and made in vivo juxtacellular recordings to determine the spike transfer to the posteromedial nucleus (POm) of the thalamus. Cuprizone-induced demyelination caused milliseconds of temporal delays and jitter of conduction times as well as failures in the high-frequency burst code. Computational models of the corticothalamic projection pathway revealed that grey matter myelin loss alone sufficed to account for the failure in burst propagation. Finally, pairing optically evoked spikes with whisker stimulation demonstrated that L5–POm myelination is critical for gating coincidence detection in the thalamus.