NMDAR-Regulated Dynamics of Layer 4 Neuronal Dendrites during Thalamocortical Reorganization in Neonates

• A general method for single-cell labeling/gene KO was developed
• Layer 4 neuronal dendrites and TC axons were simultaneously visualized in neonates
• Layer 4 neuronal dendrites are highly motile during TC circuit refinement
• NMDARs cell autonomously regulate dendritic motility during TC circuit refinement

SummaryThalamocortical (TC) connectivity is reorganized by thalamic inputs during postnatal development; however, the dynamic characteristics of TC reorganization and the underlying mechanisms remain unexplored. We addressed this question using dendritic refinement of layer 4 (L4) stellate neurons in mouse barrel cortex (barrel cells) as a model; dendritic refinement of L4 neurons is a critical component of TC reorganization through which postsynaptic L4 neurons acquire their dendritic orientation toward presynaptic TC axon termini. Simultaneous labeling of TC axons and individual barrel cell dendrites allowed in vivo time-lapse imaging of dendritic refinement in the neonatal cortex. The barrel cells reinforced the dendritic orientation toward TC axons by dynamically moving their branches. In N-methyl-D-aspartate receptor (NMDAR)-deficient barrel cells, this dendritic motility was enhanced, and the orientation bias was not reinforced. Our data suggest that L4 neurons have “fluctuating” dendrites during TC reorganization and that NMDARs cell autonomously regulate these dynamics to establish fine-tuned circuits.