JournalNeural Excitability, Synapses, and GliaTechniques

A viral strategy for targeting and manipulating interneurons across vertebrate species

Representative example of colocalization between dTomato and HA-tagged Gq-DREADD in somatosensory cortex layer VI. Note the membrane localization of the Gq-DREADD.

A fundamental impediment to understanding the brain is the availability of inexpensive and robust methods for targeting and manipulating specific neuronal populations. The need to overcome this barrier is pressing because there are considerable anatomical, physiological, cognitive and behavioral differences between mice and higher mammalian species in which it is difficult to specifically target and manipulate genetically defined functional cell types. In particular, it is unclear the degree to which insights from mouse models can shed light on the neural mechanisms that mediate cognitive functions in higher species, including humans. Here we describe a novel recombinant adeno-associated virus that restricts gene expression to GABAergic interneurons within the telencephalon. We demonstrate that the viral expression is specific and robust, allowing for morphological visualization, activity monitoring and functional manipulation of interneurons in both mice and non-genetically tractable species, thus opening the possibility to study GABAergic function in virtually any vertebrate species.

Dimidschstein, J., Chen, Q., Tremblay, R., Rogers, S.L., Saldi, G.-A., Guo, L., Xu, Q., Liu, R., Lu, C., Chu, J., et al. (2016). A viral strategy for targeting and manipulating interneurons across vertebrate species. Nat Neurosci advance online publication.