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

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

doi:10.1016/j.jneumeth.2020.108859

Cited by 30 publications

(29 citation statements)

References 134 publications

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“…In this study, we have evaluated the suitability of the recently‐described rAAV2‐retro vector for labeling striatal inputs in rats and NHPs. As reported previously in mice (Tervo et al., 2016) and macaques (Cushnie et al., 2020; Weiss et al., 2020), we found that intra‐striatal injections of rAAV2‐retro resulted in abundant labeling in numerous cortical and subcortical regions (summarized in Figure 6). Within the basal ganglia, retrograde transport was observed in the GPe and STN, regions known to project to the striatum, in both species.…”

Section: Discussionsupporting

confidence: 87%

“…Recently, a study reported viral transduction patterns following intra‐striatal infusions of rAAV2‐retro in rhesus macaques (Weiss et al., 2020; see also Cushnie et al., 2020). The transgene (GFP) labeling patterns described by Weiss et al are similar to those reported here, which is remarkable given some important differences in viral injection parameters.…”

Section: Discussionmentioning

confidence: 99%

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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

Albaugh

Smith

Galván

2020

Eur J of Neuroscience

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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. | 4825

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Section: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Comparative analyses of transgene expression patterns after intra‐striatal injections of rAAV2‐retro in rats and rhesus monkeys: A light and electron microscopic study

Albaugh

Smith

Galván

2020

Eur J of Neuroscience

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“…While our results establish the causal dependence of CDh neuronal activity on intact SC output, they do not reveal the specific circuits or networks responsible. Experiments to determine the mechanism(s) by which SC can influence CDh will be facilitated by the development of primate optogenetic tools, particularly those suited for subcortical applications (Cushnie et al, 2020). Specifically, such tools will allow manipulation of neuronal activity with fine spatial and temporal precision, making it possible to target specific area-to-area projections on the timescale of milliseconds.…”

Section: A Reversal Of the Classic Subcortical Hierarchymentioning

confidence: 99%

Attention-related modulation of caudate neurons depends on superior colliculus activity

Herman

Arcizet

Krauzlis

2020

eLife

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Recent work has implicated the primate basal ganglia in visual perception and attention, in addition to their traditional role in motor control. The basal ganglia, especially the caudate nucleus 'head' (CDh) of the striatum, receive indirect anatomical connections from the superior colliculus, a midbrain structure that is known to play a crucial role in the control of visual attention. To test the possible functional relationship between these subcortical structures, we recorded CDh neuronal activity of macaque monkeys before and during unilateral superior colliculus (SC) inactivation in a spatial attention task. SC inactivation significantly altered the attention-related modulation of CDh neurons and strongly impaired the classification of task epochs based on CDh activity. Only inactivation of SC on the same side of the brain as recorded CDh neurons, not the opposite side, had these effects. These results demonstrate a novel interaction between SC activity and attention-related visual processing in the basal ganglia.

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“…Neuroanatomists of the 20 th century devoted considerable effort to developing methods for precisely determining region-to-region connectivity in the brain Gygax, 1951, 1954;Fink and Heimer, 1967;Heimer, 1970;Wouterlood and Groenewegen, 1991;Nauta, 1993). Modern day tract-tracing techniques rely on dyes (or, more recently, viruses, Cushnie et al, 2020;Lanciego and Wouterlood, 2020) that are taken up by cells and/or terminating axons and actively transported retrogradely (from the terminal field to the cell body) or anterogradely (from the cell body to terminal fields). This reliance on active transport means that most tract-tracing requires a delay period of days to weeks during which the tracer remains in the live brain.…”

Section: Tract-tracingmentioning

confidence: 99%

A taxonomy of the brain’s white matter: Twenty-one major tracts for the twenty-first century

Bullock¹,

Ea²,

Grier³

et al. 2021

Preprint

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The functional and computational properties of brain areas are determined, in large part, by their connectivity profiles. Advances in neuroimaging and network neuroscience allow us to characterize the human brain noninvasively and in vivo, but a comprehensive understanding of the human brain demands an account of the anatomy of brain connections. Long-range anatomical connections are instantiated by white matter and organized into tracts. Here, we aim to characterize the connections, morphology, traversal, and functions of the major white matter tracts in the brain. It is clear that there are significant discrepancies across different accounts of white matter tract anatomy, hindering our attempts to accurately map the connectivity of the human brain. We thoroughly synthesize accounts from multiple methods, but especially nonhuman primate tract-tracing and human diffusion tractography. Ultimately, we suggest that our synthesis provides an essential reference for neuroscientists and clinicians interested in brain connectivity and anatomy, allowing for the study of the association of white matter’s macro and microstructural properties with behavior, development, and disordered processes.

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

Cited by 30 publications

References 134 publications

Comparative analyses of transgene expression patterns after intra‐striatal injections of rAAV2‐retro in rats and rhesus monkeys: A light and electron microscopic study

Comparative analyses of transgene expression patterns after intra‐striatal injections of rAAV2‐retro in rats and rhesus monkeys: A light and electron microscopic study

Attention-related modulation of caudate neurons depends on superior colliculus activity

A taxonomy of the brain’s white matter: Twenty-one major tracts for the twenty-first century

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