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Subtype-selective Electroporation of Cortical Interneurons
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Genetically Defined Subtypes of Somatostatin-Containing Cortical Interneurons
Rachel E Hostetler1, Hang Hu1, Ariel Agmon1
1Dept. of Neuroscience, West Virginia University School of Medicine, WV Rockefeller Neuroscience Institute, Morgantown, WV 26506, USA.
Biorxiv : the Preprint Server for Biology
|February 13, 2023
Summary
Researchers developed new genetic tools to study diverse somatostatin-containing (SOM) interneurons in the cerebral cortex. This work identifies three distinct SOM subtypes, enabling future research into their roles in brain function and behavior.
Area of Science:
- Neuroscience
- Cell Biology
Background:
- Inhibitory interneurons are vital for mammalian cerebral cortex development and function.
- Somatostatin-containing (SOM) interneurons represent the most diverse subclass of inhibitory neurons.
- Previous classification schemes for SOM interneurons, including morpho-electro-transcriptomic (MET) types, lack clear interrelations and experimental access.
Approach:
- Developed novel genetic tools by crossing Flp and Cre driver mouse lines with a dual-color reporter for precise genetic targeting of SOM interneuron subsets.
- Utilized retrograde dye labeling from the pial surface to identify layer 1-projecting neurons.
- Performed ex-vivo whole-cell recordings and immunostaining to correlate genetic identity, axonal targets, and marker protein expression with electrophysiological properties.
Key Points:
- Identified two novel layer 1-targeting SOM interneuron subsets with distinct marker expression and electrophysiological profiles.
- These identified subsets, along with a known layer 4-targeting subtype, constitute approximately half of layer 5 SOM cells and over 40% of all SOM cells.
- The identified subtypes appear to correspond to 5 of the 13 previously defined MET types.
Conclusions:
- The developed genetic tools provide unprecedented experimental access to specific SOM interneuron subtypes.
- Characterized three distinct SOM subtypes in deep cortical layers based on anatomical, neurochemical, and electrophysiological properties.
- These tools will facilitate future investigations into the circuit integration and functional roles of specific SOM interneuron subtypes in behavior.
