TrkC-dependent regulation of dendritic branching shapes dendritic bundle architecture in the rat granular retrosplenial cortex.

Abstract

Cortical modules are thought to provide anatomical frameworks for local microcircuits. However, the mechanisms regulating the morphological organization of these modules during development remain poorly understood. In the rat granular retrosplenial cortex, layer 1 contains prominent dendritic bundle-centered modules formed by the apical dendrites of layer 2 neurons and aligned with specific afferent inputs. I investigated the molecular mechanisms regulating the architecture of these dendritic bundles, focusing on TrkC, a high-affinity receptor for neurotrophin-3. Reanalysis of developmental gene expression data showed that neurotrophin-3 was transiently enriched in layer 2 before dendritic bundle formation, whereas TrkC expression was maintained at above-average levels and became modestly elevated after bundle formation. Pathway analysis further suggested developmental changes in neurotrophin pathways. To examine whether perturbation of TrkC-related signaling affects dendritic bundle architecture, I overexpressed a truncated TrkC construct lacking the intracellular tyrosine kinase domain in layer 2 neurons via in utero electroporation. Overexpression of this construct expanded dendritic bundle territories in upper layer 1. Sparse single-cell labeling revealed that this bundle-level phenotype was accompanied by increased branching of the apical dendrites of individual layer 2 neurons. These findings suggest that TrkC-related signaling may regulate the morphology of dendritic bundles by restricting excessive branching of apical dendrites during development. Thus, regulation of dendritic branching may contribute to the refinement of the distinctive dendritic bundle architecture of the granular retrosplenial cortex.