VISUAL EXPERIENCE SHAPES TOP-DOWN CONNECTIVITY ONTO NDNF+ INTERNEURONS IN THE PRIMARY VISUAL CORTEX

Top-down cortical signals conveying contextual and predictive information critically shape visual perception, yet how they are integrated in the primary visual cortex (V1) remains unclear. These projections predominantly target layer 1, where NDNF+ inhibitory interneurons are ideally positioned to mediate their integration.
We investigated the structural organization and developmental refinement of top-down inputs from the anterior cingulate cortex (ACC) and retrosplenial cortex (RSP) onto NDNF+ interneurons in mouse V1. Using dual-color eGRASP labeling, confocal imaging, and three-dimensional reconstructions, we quantified synaptic distribution, clustering, and compartment-specific targeting across development and following sensory deprivation (enucleation).
Preliminary results indicate that ACC and RSP provide convergent and balanced synaptic inputs onto individual NDNF+ neurons, with a modest enrichment of RSP inputs at the soma in the mature circuit. Both projections underwent compartment-specific refinement but followed distinct developmental trajectories. ACC inputs showed pronounced pruning and spatial reorganization that were strongly dependent on visual experience. In contrast, RSP projections exhibited somatic pruning and dendritic reorganization that occurred even in the absence of visual input.
These results suggest that NDNF+ interneurons integrate multiple top-down streams and follow pathway-specific developmental programs for contextual modulation in V1.