A new strategy for the viral manipulation of interneurons in mice and other mammals

A new strategy for the viral manipulation of interneurons in mice and other mammals
High-resolution confocal image of a fast-spiking interneuron in the cortex of a macaque. As a consequence of its exposure to the AAV-E2-GFP described in the study, this neuron expresses a green viral reporter that fills his membrane, revealing its proximal morphology. The red signal confirms the presence of parvalbumin, a gene expressed exclusively in this subtype of interneurons. The ability to target and manipulate specific types of neurons is crucial for understanding brain function and develop novel therapeutic approaches to treat CNS disorders. The work from the Dimidschstein laboratory describes a series of novel gene regulatory sequences that restrict expression of viral transgenes to specific interneuron subtypes, allowing for precise visualization and manipulation of their neuronal activity from mice to humans. Credit: Jessica Lin.

Large-scale studies examining RNA transcripts produced by genomes under specific circumstances or in specific cell populations, also known as transcriptomic studies, have recently led to fascinating new observations. These observations could help to understand where and when genes associated with specific neuropsychiatric disorders are expressed within different types of cells.

To devise effective treatments for neuropsychiatric disorders, medical specialists first need to be able to gain a better picture of the neural and associated with them. This can be achieved by targeting and manipulating specific neuronal subtypes in the brains of humans, and other mammals in order to study the animals’ behavior and identify cells that may play a role in specific neuropsychiatric disorders.

Researchers at the Stanley Center for Psychiatric Research (Broad Institute) and other institutes in the United States have recently devised a new viral tool for manipulating interneurons in mice, non-human primates and humans. Their method, outlined in a paper published in Nature Neuroscience, entails the use of viral vectors that were developed by identifying short sequences of DNA restricting the expression of a virus onto the desired target cell type.

“We focused our efforts on a particular type of cell: fast-spiking interneurons,” Jordane Dimidschstein, head of the team who led the study, told Medical Xpress. “These neurons exert a strong level of inhibitory control over local networks, and their dysfunction has been directly implicated in neurological and neuropsychiatric disorders, including Dravet syndrome, focal epilepsy, ASD and schizophrenia. As such, gaining control over their activity is of particular interest for both fundamental research and clinical applications.”

The main objective of the study carried out by Dimidschstein and his colleagues was to develop a viral tool that could be used to study the neural underpinnings of different neuropsychiatric disorders in a broad range of settings. To do this, the researchers used a class of viral vectors known as adeno-associated viruses, which can be used both to conduct research and to implement gene-th