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Comparative analyses of transgene expression patterns after intra‐striatal injections of rAAV2‐retro in rats and rhesus monkeys: A light and electron microscopic study
Author(s) -
Albaugh Daniel L.,
Smith Yoland,
Galvan Adriana
Publication year - 2020
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/ejn.15027
Subject(s) - transduction (biophysics) , biology , transgene , striatum , neuroscience , basal ganglia , axoplasmic transport , green fluorescent protein , postsynaptic potential , putamen , direct pathway of movement , viral vector , microbiology and biotechnology , anatomy , central nervous system , genetics , gene , biophysics , receptor , dopamine , recombinant dna
Retrogradely‐transducing viral vectors are versatile tools for anatomical and functional interrogations of neural circuits. These vectors can be applied in nonhuman primates (NHPs), powerful model species for neuroscientific studies with limited genetic tractability, but limited data are available regarding the tropism and transgene expression patterns of such viruses after injections in NHP brains. Consequently, NHP researchers must often rely on related data available from other species for experimental planning. To evaluate the suitability of rAAV2‐retro in the NHP basal ganglia, we studied the transgene expression patterns at the light and electron microscope level after injections of rAAV2‐retro vector encoding the opsin Jaws conjugated to a green fluorescent protein (GFP) in the putamen of rhesus macaques. For inter‐species comparison, we injected the same vector in the rat dorsal striatum. In both species, GFP expression was observed in numerous cortical and subcortical regions with known striatal projections. However, important inter‐species differences in pathway transduction were seen, including labeling of the intralaminar thalamostriatal projection in rats, but not monkeys. Electron microscopic ultrastructural observations within the basal ganglia revealed GFP labeling in both postsynaptic dendrites and presynaptic axonal terminals; the latter likely derived from anterograde transgene transport in neurons that project to the striatum, and from collaterals of these neurons. Our results suggest that certain neural pathways may be refractory to transduction by retrograde vectors in a species‐specific manner, highlighting the need for caution when determining the suitability of a retrograde vector for NHP studies based solely on rodent data.