Hasiera » Seminars » Virus delivered, brain circuit targetable, tightly-controlled inducible gene expression system in the mammalian brain

Virus delivered, brain circuit targetable, tightly-controlled inducible gene expression system in the mammalian brain

Gorka Kortabarria Pérez

Laboratories of Brain Circuits Therapeutics & Neurogenesis, Neuroinflammation and Network Dynamics, ACHUCARRO

30 May 2025 13:00

Aketxe Room (Ground floor), Sede Building, Science Park of UPV/EHU, Leioa

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Inducing controlled gene expression in precisely targeted brain circuits is crucial for understanding the role of brain circuits in fundamental neurobiological processes and brain disorders. In this study, we characterized a virus-delivered tetracycline (Tet)-controlled system. This system incorporates genetic modules that utilize silencer and activator proteins to minimize baseline gene activity while enhancing Tet-induced gene expression with specificity for brain regions and cell types. We evaluated the genetic technology across various models, including primary neuronal cultures, hippocampal organotypic slices, and live mice. Currently, we are conducting fluorescence imaging with miniature microscopes (miniscopes) to determine the in vivo activation and inactivation time courses. Additionally, we have investigated its applicability in biological processes such as eyeblink conditioning. Our results demonstrate robust suppression of basal activity, highlighting the system’s potential for safe gene-based therapies for neurological disorders.
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