Using rAAV2-retro in rhesus macaques: Promise and caveats for circuit manipulation

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...
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Gespeichert in:

Autor*in:	Cushnie, Adriana K. [verfasserIn] El-Nahal, Hala G. [verfasserIn] Bohlen, Martin O. [verfasserIn] May, Paul J. [verfasserIn] Basso, Michele A. [verfasserIn] Grimaldi, Piercesare [verfasserIn] Wang, Maya Zhe [verfasserIn] de Velasco Ezequiel, Marron Fernandez [verfasserIn] Sommer, Marc A. [verfasserIn] Heilbronner, Sarah R. [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2020

Schlagwörter:	Nonhuman primate rAAV2-retro DREADDs Optogenetics Chemogenetics

Übergeordnetes Werk:	Enthalten in: Journal of neuroscience methods - Amsterdam [u.a.] : Elsevier Science, 1979, 345
Übergeordnetes Werk:	volume:345

DOI / URN:	10.1016/j.jneumeth.2020.108859

Katalog-ID:	ELV004646371

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520			\|a 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.
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650		4	\|a rAAV2-retro
650		4	\|a DREADDs
650		4	\|a Optogenetics
650		4	\|a Chemogenetics
700	1		\|a El-Nahal, Hala G. \|e verfasserin \|4 aut
700	1		\|a Bohlen, Martin O. \|e verfasserin \|4 aut
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700	1		\|a Basso, Michele A. \|e verfasserin \|4 aut
700	1		\|a Grimaldi, Piercesare \|e verfasserin \|4 aut
700	1		\|a Wang, Maya Zhe \|e verfasserin \|0 (orcid)0000-0002-5915-7008 \|4 aut
700	1		\|a de Velasco Ezequiel, Marron Fernandez \|e verfasserin \|4 aut
700	1		\|a Sommer, Marc A. \|e verfasserin \|0 (orcid)0000-0001-5061-763X \|4 aut
700	1		\|a Heilbronner, Sarah R. \|e verfasserin \|0 (orcid)0000-0003-0893-5364 \|4 aut
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allfields	10.1016/j.jneumeth.2020.108859 doi (DE-627)ELV004646371 (ELSEVIER)S0165-0270(20)30282-X DE-627 ger DE-627 rda eng 610 DE-600 44.90 bkl Cushnie, Adriana K. verfasserin aut Using rAAV2-retro in rhesus macaques: Promise and caveats for circuit manipulation 2020 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. Nonhuman primate rAAV2-retro DREADDs Optogenetics Chemogenetics El-Nahal, Hala G. verfasserin aut Bohlen, Martin O. verfasserin aut May, Paul J. verfasserin aut Basso, Michele A. verfasserin aut Grimaldi, Piercesare verfasserin aut Wang, Maya Zhe verfasserin (orcid)0000-0002-5915-7008 aut de Velasco Ezequiel, Marron Fernandez verfasserin aut Sommer, Marc A. verfasserin (orcid)0000-0001-5061-763X aut Heilbronner, Sarah R. verfasserin (orcid)0000-0003-0893-5364 aut Enthalten in Journal of neuroscience methods Amsterdam [u.a.] : Elsevier Science, 1979 345 Online-Ressource (DE-627)306659786 (DE-600)1500499-5 (DE-576)081986416 1872-678X nnns volume:345 GBV_USEFLAG_U SYSFLAG_U GBV_ELV SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_224 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2034 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2336 GBV_ILN_4037 GBV_ILN_4242 GBV_ILN_4251 GBV_ILN_4313 GBV_ILN_4326 GBV_ILN_4334 GBV_ILN_4338 44.90 Neurologie AR 345
spelling	10.1016/j.jneumeth.2020.108859 doi (DE-627)ELV004646371 (ELSEVIER)S0165-0270(20)30282-X DE-627 ger DE-627 rda eng 610 DE-600 44.90 bkl Cushnie, Adriana K. verfasserin aut Using rAAV2-retro in rhesus macaques: Promise and caveats for circuit manipulation 2020 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. Nonhuman primate rAAV2-retro DREADDs Optogenetics Chemogenetics El-Nahal, Hala G. verfasserin aut Bohlen, Martin O. verfasserin aut May, Paul J. verfasserin aut Basso, Michele A. verfasserin aut Grimaldi, Piercesare verfasserin aut Wang, Maya Zhe verfasserin (orcid)0000-0002-5915-7008 aut de Velasco Ezequiel, Marron Fernandez verfasserin aut Sommer, Marc A. verfasserin (orcid)0000-0001-5061-763X aut Heilbronner, Sarah R. verfasserin (orcid)0000-0003-0893-5364 aut Enthalten in Journal of neuroscience methods Amsterdam [u.a.] : Elsevier Science, 1979 345 Online-Ressource (DE-627)306659786 (DE-600)1500499-5 (DE-576)081986416 1872-678X nnns volume:345 GBV_USEFLAG_U SYSFLAG_U GBV_ELV SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_224 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2034 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2336 GBV_ILN_4037 GBV_ILN_4242 GBV_ILN_4251 GBV_ILN_4313 GBV_ILN_4326 GBV_ILN_4334 GBV_ILN_4338 44.90 Neurologie AR 345
allfields_unstemmed	10.1016/j.jneumeth.2020.108859 doi (DE-627)ELV004646371 (ELSEVIER)S0165-0270(20)30282-X DE-627 ger DE-627 rda eng 610 DE-600 44.90 bkl Cushnie, Adriana K. verfasserin aut Using rAAV2-retro in rhesus macaques: Promise and caveats for circuit manipulation 2020 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. Nonhuman primate rAAV2-retro DREADDs Optogenetics Chemogenetics El-Nahal, Hala G. verfasserin aut Bohlen, Martin O. verfasserin aut May, Paul J. verfasserin aut Basso, Michele A. verfasserin aut Grimaldi, Piercesare verfasserin aut Wang, Maya Zhe verfasserin (orcid)0000-0002-5915-7008 aut de Velasco Ezequiel, Marron Fernandez verfasserin aut Sommer, Marc A. verfasserin (orcid)0000-0001-5061-763X aut Heilbronner, Sarah R. verfasserin (orcid)0000-0003-0893-5364 aut Enthalten in Journal of neuroscience methods Amsterdam [u.a.] : Elsevier Science, 1979 345 Online-Ressource (DE-627)306659786 (DE-600)1500499-5 (DE-576)081986416 1872-678X nnns volume:345 GBV_USEFLAG_U SYSFLAG_U GBV_ELV SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_224 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2034 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2336 GBV_ILN_4037 GBV_ILN_4242 GBV_ILN_4251 GBV_ILN_4313 GBV_ILN_4326 GBV_ILN_4334 GBV_ILN_4338 44.90 Neurologie AR 345
allfieldsGer	10.1016/j.jneumeth.2020.108859 doi (DE-627)ELV004646371 (ELSEVIER)S0165-0270(20)30282-X DE-627 ger DE-627 rda eng 610 DE-600 44.90 bkl Cushnie, Adriana K. verfasserin aut Using rAAV2-retro in rhesus macaques: Promise and caveats for circuit manipulation 2020 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. Nonhuman primate rAAV2-retro DREADDs Optogenetics Chemogenetics El-Nahal, Hala G. verfasserin aut Bohlen, Martin O. verfasserin aut May, Paul J. verfasserin aut Basso, Michele A. verfasserin aut Grimaldi, Piercesare verfasserin aut Wang, Maya Zhe verfasserin (orcid)0000-0002-5915-7008 aut de Velasco Ezequiel, Marron Fernandez verfasserin aut Sommer, Marc A. verfasserin (orcid)0000-0001-5061-763X aut Heilbronner, Sarah R. verfasserin (orcid)0000-0003-0893-5364 aut Enthalten in Journal of neuroscience methods Amsterdam [u.a.] : Elsevier Science, 1979 345 Online-Ressource (DE-627)306659786 (DE-600)1500499-5 (DE-576)081986416 1872-678X nnns volume:345 GBV_USEFLAG_U SYSFLAG_U GBV_ELV SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_224 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2034 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2336 GBV_ILN_4037 GBV_ILN_4242 GBV_ILN_4251 GBV_ILN_4313 GBV_ILN_4326 GBV_ILN_4334 GBV_ILN_4338 44.90 Neurologie AR 345
allfieldsSound	10.1016/j.jneumeth.2020.108859 doi (DE-627)ELV004646371 (ELSEVIER)S0165-0270(20)30282-X DE-627 ger DE-627 rda eng 610 DE-600 44.90 bkl Cushnie, Adriana K. verfasserin aut Using rAAV2-retro in rhesus macaques: Promise and caveats for circuit manipulation 2020 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. Nonhuman primate rAAV2-retro DREADDs Optogenetics Chemogenetics El-Nahal, Hala G. verfasserin aut Bohlen, Martin O. verfasserin aut May, Paul J. verfasserin aut Basso, Michele A. verfasserin aut Grimaldi, Piercesare verfasserin aut Wang, Maya Zhe verfasserin (orcid)0000-0002-5915-7008 aut de Velasco Ezequiel, Marron Fernandez verfasserin aut Sommer, Marc A. verfasserin (orcid)0000-0001-5061-763X aut Heilbronner, Sarah R. verfasserin (orcid)0000-0003-0893-5364 aut Enthalten in Journal of neuroscience methods Amsterdam [u.a.] : Elsevier Science, 1979 345 Online-Ressource (DE-627)306659786 (DE-600)1500499-5 (DE-576)081986416 1872-678X nnns volume:345 GBV_USEFLAG_U SYSFLAG_U GBV_ELV SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_224 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2034 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2336 GBV_ILN_4037 GBV_ILN_4242 GBV_ILN_4251 GBV_ILN_4313 GBV_ILN_4326 GBV_ILN_4334 GBV_ILN_4338 44.90 Neurologie AR 345
language	English
source	Enthalten in Journal of neuroscience methods 345 volume:345
sourceStr	Enthalten in Journal of neuroscience methods 345 volume:345
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authorswithroles_txt_mv	Cushnie, Adriana K. @@aut@@ El-Nahal, Hala G. @@aut@@ Bohlen, Martin O. @@aut@@ May, Paul J. @@aut@@ Basso, Michele A. @@aut@@ Grimaldi, Piercesare @@aut@@ Wang, Maya Zhe @@aut@@ de Velasco Ezequiel, Marron Fernandez @@aut@@ Sommer, Marc A. @@aut@@ Heilbronner, Sarah R. @@aut@@
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author	Cushnie, Adriana K.
spellingShingle	Cushnie, Adriana K. ddc 610 bkl 44.90 misc Nonhuman primate misc rAAV2-retro misc DREADDs misc Optogenetics misc Chemogenetics Using rAAV2-retro in rhesus macaques: Promise and caveats for circuit manipulation
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title	Using rAAV2-retro in rhesus macaques: Promise and caveats for circuit manipulation
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author_browse	Cushnie, Adriana K. El-Nahal, Hala G. Bohlen, Martin O. May, Paul J. Basso, Michele A. Grimaldi, Piercesare Wang, Maya Zhe de Velasco Ezequiel, Marron Fernandez Sommer, Marc A. Heilbronner, Sarah R.
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title_sort	using raav2-retro in rhesus macaques: promise and caveats for circuit manipulation
title_auth	Using rAAV2-retro in rhesus macaques: Promise and caveats for circuit manipulation
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.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.
abstractGer	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.
abstract_unstemmed	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.
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title_short	Using rAAV2-retro in rhesus macaques: Promise and caveats for circuit manipulation
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author2	El-Nahal, Hala G. Bohlen, Martin O. May, Paul J. Basso, Michele A. Grimaldi, Piercesare Wang, Maya Zhe de Velasco Ezequiel, Marron Fernandez Sommer, Marc A. Heilbronner, Sarah R.
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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.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Nonhuman primate</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">rAAV2-retro</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">DREADDs</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Optogenetics</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Chemogenetics</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">El-Nahal, Hala G.</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Bohlen, Martin O.</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield 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Using rAAV2-retro in rhesus macaques: Promise and caveats for circuit manipulation

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