Widespread optogenetic expression in macaque cortex obtained with MR-guided, convection enhanced delivery (CED) of AAV vector to the thalamus

Yazdan-Shahmorad, Azadeh; Tian, Nan; Kharazia, Viktor; Samaranch, Lluı́s; Kells, Adrian P.; Bringas, John; He, Jiwen; Bankiewicz, Krystof; Sabes, Philip N.

doi:10.1016/j.jneumeth.2017.10.009

Cited by 46 publications

(55 citation statements)

References 29 publications

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“…hM4Di) can interfere with expression at the plasma membrane. Consistent with this idea, fusion of mCherry with the opsin ChR2 results in a lower expression level of the opsin than were observed upon ChR2 fusion to yellow fluorescent protein (Yazdan‐Shahmorad et al., ).…”

Section: Discussionmentioning

confidence: 73%

Ultrastructural localization of DREADDs in monkeys

Galván

Raper

et al. 2019

Eur J of Neuroscience

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Designer receptors exclusively activated by designer drugs (DREADDs) are extensively used to modulate neuronal activity in rodents, but their use in primates remains limited. An essential need that remains is the demonstration that DREADDs are efficiently expressed on the plasma membrane of primate neurons. To address this issue, electron microscopy immunogold was used to determine the subcellular localization of the AAV vector‐induced DREADDs hM4Di and hM3Dq fused to different tags in various brain areas of rhesus monkeys and mice. When hM4Di was fused to mCherry, the immunogold labelling was mostly confined to the intracellular space, and poorly expressed at the plasma membrane in monkey dendrites. In contrast, the hM4Di‐mCherry labelling was mostly localized to the dendritic plasma membrane in mouse neurons, suggesting species differences in the plasma membrane expression of these exogenous proteins. The lack of hM4Di plasma membrane expression may limit the functional effects of systemic administration of DREADD‐actuators in monkey neurons. Removing the mCherry and fusing of hM4Di with the haemagglutinin (HA) tag resulted in strong neuronal plasma membrane immunogold labelling in both monkeys and mice neurons. Finally, hM3Dq‐mCherry was expressed mostly at the plasma membrane in monkey neurons, indicating that the fusion of mCherry with hM3Dq does not hamper membrane incorporation of this specific DREADD. Our results suggest that the pattern of ultrastructural expression of DREADDs in monkey neurons depends on the DREADD/tag combination. Therefore, a preliminary characterization of plasma membrane expression of specific DREADD/tag combinations is recommended when using chemogenetic approaches in primates.

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Section: Discussionmentioning

confidence: 73%

Ultrastructural localization of DREADDs in monkeys

Galván

Raper

et al. 2019

Eur J of Neuroscience

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“…Our MMAD in combination with our previously presented chronic interfaces (Yazdan-Shahmorad et al ., 2015, 2016; Griggs et al ., 2019) equip us for a variety of research pursuits. Moving forward, we plan to capitalize on our previous optogenetic (Ledochowitsch et al ., 2015; Yazdan-Shahmorad et al ., 2015, 2016, 2018b, 2018a, 2018c; Khateeb et al ., 2019a; Ojemann et al ., 2020; Tremblay et al ., 2020) and imaging (Khateeb et al ., 2019b; Macknik et al ., 2019) experience as we pioneer the experimental spaces unveiled by the merging of large-scale ECoG and large-scale optical access to the NHP cortex. The synergistic power of these technologies poise us to build on our past work investigating neural plasticity (Yazdan-Shahmorad et al ., 2018a; Bloch et al ., 2019) as we study large-scale, chronic neural phenomena including neural disease, damage, and recovery.…”

Section: Discussionmentioning

confidence: 99%

Multi-modal artificial dura for simultaneous large-scale optical access and large-scale electrophysiology in non-human primate cortex

Griggs

Khateeb

Zhou

et al. 2021

Preprint

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Objective. Non-human primates (NHPs) are critical for development of translational neural technologies because of their neurological and neuroanatomical similarities to humans. Large-scale neural interfaces in NHPs with multiple modalities for stimulation and data collection poise us to unveil network-scale dynamics of both healthy and unhealthy neural systems. We aim to develop a large-scale multi-modal interface for NHPs for the purpose of studying large-scale neural phenomena including neural disease, damage, and recovery. Approach. We present a multi-modal artificial dura (MMAD) composed of flexible conductive traces printed into transparent medical grade polymer. Our MMAD provides simultaneous neurophysiological recordings and optical access to large areas of the cortex (~3 cm2) and is designed to mitigate photo-induced electrical artifacts. The MMAD is the centerpiece of the interfaces we have designed to support electrocorticographic recording and stimulation, cortical imaging, and optogenetic experiments, all at the large-scales afforded by the brains of NHPs. We performed electrical and optical experiments bench-side and in vivo with macaques to validate the utility of our MMAD. Main results. Using our MMAD we present large-scale electrocorticography from sensorimotor cortex of three macaques. Furthermore, we validated surface electrical stimulation in one of our animals. Our bench-side testing showed up to 90% reduction of photo-induced artifacts with our MMAD. The transparency of our MMAD was confirmed both via bench-side testing (87% transmittance) and via in vivo imaging of blood flow from the underlying microvasculature using optical coherence tomography angiography. Significance. Our results indicate that our MMAD supports large-scale electrocorticography, large-scale cortical imaging, and, by extension, large-scale optical stimulation. The MMAD prepares the way for both acute and long-term chronic experiments with complimentary data collection and stimulation modalities. When paired with the complex behaviors and cognitive abilities of NHPs, these assets prepare us to study large-scale neural phenomena including neural disease, damage, and recovery.

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“…The primary motor cortex (M1) and the motor thalamus are reciprocally connected. To study the projection from thalamus to cortex, Yazdan-Shahmorad et al (27) injected an AAV vector carrying the gene for ChR2 into the motor thalamus of macaques. Thalamic transduction was extensive, due to the high-volume, high-pressure injection method (28).…”

Section: Interareal Signalingmentioning

confidence: 99%

“…Optogenetic investigations of neural circuits in monkeys are at a relatively early stage but have already started to yield valuable new data. Neurons in the monkey basal ganglia, motor cortex, and motor thalamus have all been successfully transduced with viral vectors and stimulated optogenetically (23,27,30,42,55,(145)(146)(147). These are necessary first steps toward the functional interrogation of these structures in parkinsonian and nonparkinsonian animals.…”

Section: Clinical Applicationsmentioning

confidence: 99%

Primate optogenetics: Progress and prognosis

El-Shamayleh

Horwitz

2019

Proc. Natl. Acad. Sci. U.S.A.

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Monkeys are a premier model organism for neuroscience research. Activity in the central nervous systems of monkeys can be recorded and manipulated while they perform complex perceptual, motor, or cognitive tasks. Conventional techniques for manipulating neural activity in monkeys are too coarse to address many of the outstanding questions in primate neuroscience, but optogenetics holds the promise to overcome this hurdle. In this article, we review the progress that has been made in primate optogenetics over the past 5 years. We emphasize the use of gene regulatory sequences in viral vectors to target specific neuronal types, and we present data on vectors that we engineered to target parvalbumin-expressing neurons. We conclude with a discussion of the utility of optogenetics for treating sensorimotor hearing loss and Parkinson’s disease, areas of translational neuroscience in which monkeys provide unique leverage for basic science and medicine.

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Widespread optogenetic expression in macaque cortex obtained with MR-guided, convection enhanced delivery (CED) of AAV vector to the thalamus

Abstract: MR-guided CED infusion into thalamus provides a simplified approach to transduce large cortical areas by thalamo-cortico-thalamic projections in primate brain.

Cited by 46 publications

References 29 publications

Ultrastructural localization of DREADDs in monkeys

Ultrastructural localization of DREADDs in monkeys

Multi-modal artificial dura for simultaneous large-scale optical access and large-scale electrophysiology in non-human primate cortex

Primate optogenetics: Progress and prognosis

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