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Publication : A single-vector intersectional AAV strategy for interrogating cellular diversity and brain function.

First Author  Hughes AC Year  2024
Journal  Nat Neurosci Volume  27
Issue  7 Pages  1400-1410
PubMed ID  38802592 Mgi Jnum  J:354296
Mgi Id  MGI:7730983 Doi  10.1038/s41593-024-01659-7
Citation  Hughes AC, et al. (2024) A single-vector intersectional AAV strategy for interrogating cellular diversity and brain function. Nat Neurosci 27(7):1400-1410
abstractText  As discovery of cellular diversity in the brain accelerates, so does the need for tools that target cells based on multiple features. Here we developed Conditional Viral Expression by Ribozyme Guided Degradation (ConVERGD), an adeno-associated virus-based, single-construct, intersectional targeting strategy that combines a self-cleaving ribozyme with traditional FLEx switches to deliver molecular cargo to specific neuronal subtypes. ConVERGD offers benefits over existing intersectional expression platforms, such as expanded intersectional targeting with up to five recombinase-based features, accommodation of larger and more complex payloads and a vector that is easy to modify for rapid toolkit expansion. In the present report we employed ConVERGD to characterize an unexplored subpopulation of norepinephrine (NE)-producing neurons within the rodent locus coeruleus that co-express the endogenous opioid gene prodynorphin (Pdyn). These studies showcase ConVERGD as a versatile tool for targeting diverse cell types and reveal Pdyn-expressing NE(+) locus coeruleus neurons as a small neuronal subpopulation capable of driving anxiogenic behavioral responses in rodents.
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