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An Intersectional Approach to Target Neural Circuits With Cell- and Projection-Type Specificity: Validation in the
Nefeli Kakava-Georgiadou1, Maria M Zwartkruis1,2, Clara Bullich-Vilarrubias1,2
1Division of Neuroscience, Department of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, Netherlands.
Frontiers in Molecular Neuroscience
|March 16, 2019
Summary
Researchers developed a novel viral vector system to precisely control specific neuron activity. This tool enables subtype- and projection-specific neuronal manipulation for advanced neuroscience research.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Dissecting neural circuit function requires tools to manipulate specific neuron activity.
- Existing methods target neuronal subtypes by region or projection, but few combine both.
- A need exists for tools enabling precise targeting of neuronal subtypes within specific projections.
Purpose of the Study:
- To develop and validate a viral vector system for subtype- and projection-specific neuronal manipulation.
- To demonstrate the system's ability to target dopamine neurons in the mesolimbic projection.
- To enable chemogenetic control of targeted neurons for in vivo studies.
Main Methods:
- Utilized a canine adenovirus type 2 (CavFlexFlp) expressing Cre-dependent Flp recombinase.
- Employed an adeno-associated viral (AAV) vector expressing a Flp-dependent cDNA.
- Targeted Designer Receptor Exclusively Activated by Designer Drugs (DREADD) to mesolimbic dopamine neurons.
Main Results:
- The viral vector system successfully targeted dopamine neurons in a subtype- and projection-specific manner.
- Chemogenetic activation using Clozapine-N-Oxide (CNO) resulted in increased locomotor activity.
- Validated the system's efficacy for in vivo neuronal activation.
Conclusions:
- A novel viral vector system provides precise control over neuronal activity.
- This tool allows for subtype- and projection-specific manipulation of neural circuits.
- The validated system is valuable for studying neural circuit function and behavior.
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