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1.
Nat Nanotechnol ; 18(6): 667-676, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37012508

RESUMO

Remote and precisely controlled activation of the brain is a fundamental challenge in the development of brain-machine interfaces for neurological treatments. Low-frequency ultrasound stimulation can be used to modulate neuronal activity deep in the brain, especially after expressing ultrasound-sensitive proteins. But so far, no study has described an ultrasound-mediated activation strategy whose spatiotemporal resolution and acoustic intensity are compatible with the mandatory needs of brain-machine interfaces, particularly for visual restoration. Here we combined the expression of large-conductance mechanosensitive ion channels with uncustomary high-frequency ultrasonic stimulation to activate retinal or cortical neurons over millisecond durations at a spatiotemporal resolution and acoustic energy deposit compatible with vision restoration. The in vivo sonogenetic activation of the visual cortex generated a behaviour associated with light perception. Our findings demonstrate that sonogenetics can deliver millisecond pattern presentations via an approach less invasive than current brain-machine interfaces for visual restoration.


Assuntos
Expressão Ectópica do Gene , Córtex Visual , Neurônios/metabolismo , Retina , Visão Ocular
2.
Cell Rep ; 42(4): 112369, 2023 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-37043356

RESUMO

To better understand how the brain allows primates to perform various sets of tasks, the ability to simultaneously record neural activity at multiple spatiotemporal scales is challenging but necessary. However, the contribution of single-unit activities (SUAs) to neurovascular activity remains to be fully understood. Here, we combine functional ultrasound imaging of cerebral blood volume (CBV) and SUA recordings in visual and fronto-medial cortices of behaving macaques. We show that SUA provides a significant estimate of the neurovascular response below the typical fMRI spatial resolution of 2mm3. Furthermore, our results also show that SUAs and CBV activities are statistically uncorrelated during the resting state but correlate during tasks. These results have important implications for interpreting functional imaging findings while one constructs inferences of SUA during resting state or tasks.


Assuntos
Volume Sanguíneo Cerebral , Circulação Cerebrovascular , Animais , Circulação Cerebrovascular/fisiologia , Encéfalo/fisiologia , Mapeamento Encefálico/métodos , Primatas , Imageamento por Ressonância Magnética/métodos , Neurônios/fisiologia , Cognição
3.
Transl Vis Sci Technol ; 11(1): 18, 2022 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-35024784

RESUMO

After revolutionizing neuroscience, optogenetic therapy has entered successfully in clinical trials for restoring vision to blind people with degenerative eye diseases, such as retinitis pigmentosa. These clinical trials still have to evaluate the visual acuity achieved by patients and to determine if it reaches its theoretical limit extrapolated from ex vivo experiments. Different strategies are developed in parallel to reduce required light levels and improve information processing by targeting various cell types. For patients with vision loss due to optic atrophy, as in the case of glaucoma, optogenetic cortical stimulation is hampered by light absorption and scattering by the brain tissue. By contrast, ultrasound waves can diffuse widely through the dura mater and the brain tissue as indicated by ultrasound imaging. Based on our recent results in rodents, we propose the sonogenetic therapy relying on activation of the mechanosensitive channel as a very promising vision restoration strategy with a suitable spatiotemporal resolution. Genomic approaches may thus provide efficient brain machine interfaces for sight restoration.


Assuntos
Optogenética , Retinose Pigmentar , Humanos , Transtornos da Visão , Visão Ocular , Acuidade Visual
4.
Mol Ther Methods Clin Dev ; 24: 1-10, 2022 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-34977267

RESUMO

Over the last 15 years, optogenetics has changed fundamental research in neuroscience and is now reaching toward therapeutic applications. Vision restoration strategies using optogenetics are now at the forefront of these new clinical opportunities. But applications to human patients suffering from retinal diseases leading to blindness raise important concerns on the long-term functional expression of optogenes and the efficient signal transmission to higher visual centers. Here, we demonstrate in non-human primates continued expression and functionality at the retina level ∼20 months after delivery of our construct. We also performed in vivo recordings of visually evoked potentials in the primary visual cortex of anesthetized animals. Using synaptic blockers, we isolated the in vivo cortical activation resulting from the direct optogenetic stimulation of primate retina. In conclusion, our work indicates long-term transgene expression and transmission of the signal generated in the macaque retina to the visual cortex, two important features for future clinical applications.

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