Metabotropic signaling within somatostatin interneurons controls transient thalamocortical inputs during development

Deepanjali Dwivedi, Dimitri Dumontier, Mia Sherer, Sherry Lin, Andrea M. C. Mirow, Yanjie Qiu, Qing Xu, Samuel A. Liebman, Djeckby Joseph, Sandeep R. Datta, Gord Fishell () and Gabrielle Pouchelon ()
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Deepanjali Dwivedi: Department of Neurobiology
Dimitri Dumontier: Cold Spring Harbor
Mia Sherer: Department of Neurobiology
Sherry Lin: Department of Neurobiology
Andrea M. C. Mirow: Department of Neurobiology
Yanjie Qiu: Department of Neurobiology
Qing Xu: Department of Neurobiology
Samuel A. Liebman: Cold Spring Harbor
Djeckby Joseph: Cold Spring Harbor
Sandeep R. Datta: Department of Neurobiology
Gord Fishell: Department of Neurobiology
Gabrielle Pouchelon: Department of Neurobiology

Nature Communications, 2024, vol. 15, issue 1, 1-17

Abstract: Abstract During brain development, neural circuits undergo major activity-dependent restructuring. Circuit wiring mainly occurs through synaptic strengthening following the Hebbian “fire together, wire together” precept. However, select connections, essential for circuit development, are transient. They are effectively connected early in development, but strongly diminish during maturation. The mechanisms by which transient connectivity recedes are unknown. To investigate this process, we characterize transient thalamocortical inputs, which depress onto somatostatin inhibitory interneurons during development, by employing optogenetics, chemogenetics, transcriptomics and CRISPR-based strategies in mice. We demonstrate that in contrast to typical activity-dependent mechanisms, transient thalamocortical connectivity onto somatostatin interneurons is non-canonical and involves metabotropic signaling. Specifically, metabotropic-mediated transcription, of guidance molecules in particular, supports the elimination of this connectivity. Remarkably, we found that this process impacts the development of normal exploratory behaviors of adult mice.

Date: 2024
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DOI: 10.1038/s41467-024-49732-w

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