Reciprocal interaction between cortical SST and PV interneurons in top-down regulation of retinothalamic refinement.

Proceedings of the National Academy of Sciences of the United States of America
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Abstract

Refinement of thalamic circuits is crucial for the proper maturation of sensory circuits. In the visual system, this process is regulated by corticothalamic feedback during the experience-dependent phase of development. Yet the cortical circuits modulating this feedback remain elusive. Here, we demonstrate opposing roles for cortical somatostatin (SST) and parvalbumin (PV) interneurons in shaping retinogeniculate connectivity during the thalamic sensitive period (P20-30). Early in the refinement process, SST interneurons promote the strengthening and pruning of retinal inputs in the thalamus, as evidenced by disrupted synaptic refinement following their ablation. In contrast, PV interneurons, which mature later, act as a brake on this refinement, with their ablation leading to enhanced pruning of retinogeniculate connections. Notably, manipulating the relative balance between these inhibitory circuits can regulate sensory deprivation-induced retinogeniculate remodeling. Taken together, our findings show that cortical SST and PV interneuron circuits drive experience-dependent reciprocal antagonism that gates cortical feedback regulation of feedforward thalamic refinement.

Year of Publication
2025
Journal
Proceedings of the National Academy of Sciences of the United States of America
Volume
122
Issue
25
Pages
e2504224122
Date Published
06/2025
ISSN
1091-6490
DOI
10.1073/pnas.2504224122
PubMed ID
40531875
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