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Selective targeting of striatal parvalbumin-expressing interneurons for transgene delivery.

Research paper by Marcelo Duarte MD Azevedo, Sibilla S Sander, Cheryl C Jeanneret, Soophie S Olfat, Liliane L Tenenbaum

Indexed on: 03 Mar '21Published on: 03 Mar '21Published in: Journal of Neuroscience Methods



Abstract

PV mice combined with AAV-FLEX vectors allowed efficient and specific targeting of PV interneurons in the striatum. However, diffusion of viral particles to the globus pallidus caused massive transduction of PV projection neurons and subsequent anterograde transport of the transgene product to the subthalamic nucleus and the substantia nigra pars reticulata. Different AAV serotypes (1 and 9) and promoters (CBA and human synapsin) were evaluated. The combination of AAV1, a moderate expression level (human synapsin promoter) and a precise adjustement of the stereotaxic coordinates in the anterior and dorsolateral part of the striatum were necessary to avoid transduction of PV GP projection neurons. Even in the absence of direct transduction due to diffusion of viral particles, GP PV projection neurons could be retrogradely transduced via their terminals present in the dorsal striatum. However, in the absence of diffusion, GP-Str PV projection neurons were poorly (AAV9) or not (AAV1) transduced suggesting that retrograde transduction did not significantly impair the selective targeting of striatal PV neurons. Finally, a prominent (about 50%) toxicity of the Cre recombinase toward the striatal PV interneurons was evidenced suggesting that functional effects of AAV-mediated transgene expression in PV striatal interneurons in PV mice should be analyzed with caution. Copyright © 2021. Published by Elsevier B.V.