An enhancer-AAV toolbox to target and manipulate distinct interneuron subtypes.

Neuron
Authors
Keywords
Abstract

In recent years, we and others have identified a number of enhancers that, when incorporated into rAAV vectors, can restrict the transgene expression to particular neuronal populations. Yet, viral tools to access and manipulate specific neuronal subtypes are still limited. Here, we performed systematic analysis of single-cell genomic data to identify enhancer candidates for each of the telencephalic interneuron subtypes. We established a set of enhancer-AAV tools that are highly specific for distinct cortical interneuron populations and striatal cholinergic interneurons. These enhancers, when used in the context of different effectors, can target (fluorescent proteins), observe activity (GCaMP), and manipulate (opto-genetics) specific neuronal subtypes. We also validated our enhancer-AAV tools across species. Thus, we provide the field with a powerful set of tools to study neural circuits and functions and to develop precise and targeted therapy.

Year of Publication
2025
Journal
Neuron
Volume
113
Issue
10
Pages
1525-1547.e15
Date Published
05/2025
ISSN
1097-4199
DOI
10.1016/j.neuron.2025.05.002
PubMed ID
40403705
Links