Using rAAV2-retro in rhesus macaques: Promise and caveats for circuit manipulation.
J Neurosci Methods
; 345: 108859, 2020 11 01.
Article
em En
| MEDLINE
| ID: mdl-32668316
ABSTRACT
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. NEWMETHOD:
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.Palavras-chave
Texto completo:
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Encéfalo
/
Neurônios
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article