Methods for mechanical delivery of viral vectors into rhesus monkey brain

Fredericks, J. Megan; Dash, Kiana; Jaskot, Emilia M.; Bennett, T. W.; Lerchner, Walter; Dold, George; Ide, David C.; Cummins, Alexander; Minassian, Violette H. Der; Turchi, Janita; Richmond, Barry J.; Eldridge, Mark

doi:10.1016/j.jneumeth.2020.108730

Cited by 39 publications

(35 citation statements)

References 39 publications

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“…For further development of CED techniques, it is practical to first develop an MRI phantom for infusion testing prior to MRI-guided neurosurgery (Chen et al, 2004) and to consider the use of a step reflux cannula to avoid the solution diffusing upwards (Krauze et al, 2005). Some groups have also developed procedures for mass injections using multi-channel injection devices (Fredericks et al, 2020).…”

Section: Neural Transfectionmentioning

confidence: 99%

“…The pharmacological and viral injection site and substance spread can be assessed with co-injection of an MRI contrast agent. Paramagnetic substances based on Gadolinium (Gd) (Heiss et al, 2010;Yazdan-Shahmorad et al, 2016), such as Gadovist or Dotarem, and Manganese (Mn) (Chen et al, 2016;Fredericks et al, 2020) are typically used. Mn is also used for in vivo visualization of trans-synaptic spread .…”

Section: Box 1: Targeting Brain Regions For Perturbationmentioning

confidence: 99%

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Combining Brain Perturbation and Neuroimaging in Non-human Primates

Klink¹,

jean-francois.aubry@espci.fr²,

Ferrera³

et al. 2020

Preprint

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Brain perturbation studies allow detailed causal inferences of behavioral and neural processes. Because the combination of brain perturbation methods and neural measurement techniques is inherently challenging, research in humans has predominantly focused on non-invasive, indirect brain perturbations, or neurological lesions. Non-human primates have been indispensable as a neurobiological system that is highly similar to humans while simultaneously being more experimentally tractable, allowing visualization of the functional and structural impact of systematic brain perturbation. This review considers the state-of-the-art in non-human primate brain perturbation with a focus on approaches that can be combined with neuroimaging. We consider both non-reversible (lesions) and reversible or temporary perturbations such as electrical, pharmacological, optical, optogenetic, chemogenetic, pathway-selective, and ultrasound based interference methods. Method-specific considerations from the research and development community are offered to facilitate research in this field and support further innovations. We conclude by identifying novel avenues for further research and innovation and by highlighting the clinical translational potential of the methods.

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Section: Neural Transfectionmentioning

confidence: 99%

Section: Box 1: Targeting Brain Regions For Perturbationmentioning

confidence: 99%

Combining Brain Perturbation and Neuroimaging in Non-human Primates

Klink¹,

jean-francois.aubry@espci.fr²,

Ferrera³

et al. 2020

Preprint

View full text Add to dashboard Cite

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“…A similar problem arises in optogenetics when pathway selectivity is achieved by photo-stimulation of local axon terminals. To overcome this kind of problem, the development of a method that can simultaneously deliver the ligand to a wide range of areas 87 or the development of a widespread photostimulation device with a sheet-like LED array 88 will be required.…”

Section: Discussionmentioning

confidence: 99%

Chemogenetic inactivation reveals the inhibitory control function of the prefronto-striatal pathway in the macaque brain

et al. 2021

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The lateral prefrontal cortex (LPFC) has a strong monosynaptic connection with the caudate nucleus (CdN) of the striatum. Previous human MRI studies have suggested that this LPFC-CdN pathway plays an important role in inhibitory control and working memory. We aimed to validate the function of this pathway at a causal level by pathway-selective manipulation of neural activity in non-human primates. To this end, we trained macaque monkeys on a delayed oculomotor response task with reward asymmetry and expressed an inhibitory type of chemogenetic receptors selectively to LPFC neurons that project to the CdN. Ligand administration reduced the inhibitory control of impulsive behavior, as well as the task-related neuronal responses observed in the local field potentials from the LPFC and CdN. These results show that we successfully suppressed pathway-selective neural activity in the macaque brain, and the resulting behavioral changes suggest that the LPFC-CdN pathway is involved in inhibitory control.

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“…in NHPs. Recently, a multi-channel injection device was developed to deliver AAV vectors uniformly to large NHP cortical regions 16 . Similar results can be obtained using convection-enhanced delivery 17 , 18 .…”

Section: Several Other Aav Injection Techniques Have Been Usedmentioning

confidence: 99%

Injections of AAV Vectors for Optogenetics in Anesthetized and Awake Behaving Non-Human Primate Brain

Kojima

Ting

Soetedjo

et al. 2021

JoVE

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Optogenetic techniques have revolutionized neuroscience research and are poised to do the same for neurological gene therapy. The clinical use of optogenetics, however, requires that safety and efficacy be demonstrated in animal models, ideally in nonhuman primates (NHPs), because of their neurological similarity to humans. The number of candidate vectors that are potentially useful for neuroscience and medicine is vast, and no high-throughput means to test these vectors yet exists. Thus, there is a need for techniques to make multiple spatially and volumetrically accurate injections of viral vectors into NHP brain that can be identified unambiguously through postmortem histology. Described herein is such a method. Injection cannulas are constructed from coupled polytetrafluoroethylene and stainless-steel tubes. These cannulas are autoclavable, disposable, and have low minimal-loading volumes, making them ideal for the injection of expensive, highly concentrated viral vector solutions. An inert, reddyed mineral oil fills the dead space and forms a visible meniscus with the vector solution, allowing instantaneous and accurate measurement of injection rates and volumes. The oil is loaded into the rear of the cannula, reducing the risk of co-injection with the vector. Cannulas can be loaded in 10 min, and injections can be made in 20 min. This procedure is well suited for injections into awake or anesthetized animals. When used to deliver high-quality viral vectors, this procedure can produce robust expression of optogenetic proteins, allowing optical control of neural activity and behavior in NHPs.

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Methods for mechanical delivery of viral vectors into rhesus monkey brain

Cited by 39 publications

References 39 publications

Combining Brain Perturbation and Neuroimaging in Non-human Primates

Combining Brain Perturbation and Neuroimaging in Non-human Primates

Chemogenetic inactivation reveals the inhibitory control function of the prefronto-striatal pathway in the macaque brain

Injections of AAV Vectors for Optogenetics in Anesthetized and Awake Behaving Non-Human Primate Brain

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