TY - JOUR
T1 - Using rAAV2-retro in rhesus macaques
T2 - Promise and caveats for circuit manipulation
AU - Cushnie, Adriana K.
AU - El-Nahal, Hala G.
AU - Bohlen, Martin O.
AU - May, Paul J.
AU - Basso, Michele A.
AU - Grimaldi, Piercesare
AU - Wang, Maya Zhe
AU - de Velasco, Ezequiel Marron Fernandez
AU - Sommer, Marc A.
AU - Heilbronner, Sarah R.
N1 - Publisher Copyright:
© 2020
PY - 2020/11/1
Y1 - 2020/11/1
N2 - Background: Recent genetic technologies such as opto- and chemogenetics allow for the manipulation of brain circuits with unprecedented precision. Most studies employing these techniques have been undertaken in rodents, but a more human-homologous model for studying the brain is the nonhuman primate (NHP). Optimizing viral delivery of transgenes encoding actuator proteins could revolutionize the way we study neuronal circuits in NHPs. New method: rAAV2-retro, a popular new capsid variant, produces robust retrograde labeling in rodents. Whether rAAV2-retro's highly efficient retrograde transport would translate to NHPs was unknown. Here, we characterized the anatomical distribution of labeling following injections of rAAV2-retro encoding opsins or DREADDs in the cortico-basal ganglia and oculomotor circuits of rhesus macaques. Results: rAAV2-retro injections in striatum, frontal eye field, and superior colliculus produced local labeling at injection sites and robust retrograde labeling in many afferent regions. In every case, however, a few brain regions with well-established projections to the injected structure lacked retrogradely labeled cells. We also observed robust terminal field labeling in downstream structures. Comparison with existing method(s): Patterns of labeling were similar to those obtained with traditional tract-tracers, except for some afferent labeling that was noticeably absent. Conclusions: rAAV2-retro promises to be useful for circuit manipulation via retrograde transduction in NHPs, but caveats were revealed by our findings. Some afferently connected regions lacked retrogradely labeled cells, showed robust axon terminal labeling, or both. This highlights the importance of anatomically characterizing rAAV2-retro's expression in target circuits in NHPs before moving to manipulation studies.
AB - Background: Recent genetic technologies such as opto- and chemogenetics allow for the manipulation of brain circuits with unprecedented precision. Most studies employing these techniques have been undertaken in rodents, but a more human-homologous model for studying the brain is the nonhuman primate (NHP). Optimizing viral delivery of transgenes encoding actuator proteins could revolutionize the way we study neuronal circuits in NHPs. New method: rAAV2-retro, a popular new capsid variant, produces robust retrograde labeling in rodents. Whether rAAV2-retro's highly efficient retrograde transport would translate to NHPs was unknown. Here, we characterized the anatomical distribution of labeling following injections of rAAV2-retro encoding opsins or DREADDs in the cortico-basal ganglia and oculomotor circuits of rhesus macaques. Results: rAAV2-retro injections in striatum, frontal eye field, and superior colliculus produced local labeling at injection sites and robust retrograde labeling in many afferent regions. In every case, however, a few brain regions with well-established projections to the injected structure lacked retrogradely labeled cells. We also observed robust terminal field labeling in downstream structures. Comparison with existing method(s): Patterns of labeling were similar to those obtained with traditional tract-tracers, except for some afferent labeling that was noticeably absent. Conclusions: rAAV2-retro promises to be useful for circuit manipulation via retrograde transduction in NHPs, but caveats were revealed by our findings. Some afferently connected regions lacked retrogradely labeled cells, showed robust axon terminal labeling, or both. This highlights the importance of anatomically characterizing rAAV2-retro's expression in target circuits in NHPs before moving to manipulation studies.
KW - Chemogenetics
KW - DREADDs
KW - Nonhuman primate
KW - Optogenetics
KW - rAAV2-retro
UR - http://www.scopus.com/inward/record.url?scp=85089278725&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85089278725&partnerID=8YFLogxK
U2 - 10.1016/j.jneumeth.2020.108859
DO - 10.1016/j.jneumeth.2020.108859
M3 - Review article
C2 - 32668316
AN - SCOPUS:85089278725
SN - 0165-0270
VL - 345
JO - Journal of Neuroscience Methods
JF - Journal of Neuroscience Methods
M1 - 108859
ER -