John P. Andrews, Jinghui Geng, Kateryna Voitiuk, Matthew A. T. Elliott, David Shin, Ash Robbins, Alex Spaeth, Albert Wang, Lin Li, Daniel Solis, Matthew G. Keefe, Jessica L. Sevetson, Julio A. Rivera de Jesús, Kevin C. Donohue, H. Hanh Larson, Drew Ehrlich, Kurtis I. Auguste, Sofie Salama, Vikaas Sohal, Tal Sharf, David Haussler, Cathryn R. Cadwell, David V. Schaffer, Edward F. Chang, Mircea Teodorescu, Tomasz Jan Nowakowski
{"title":"对人类海马切片的网络活动和光遗传干预进行多模式评估","authors":"John P. Andrews, Jinghui Geng, Kateryna Voitiuk, Matthew A. T. Elliott, David Shin, Ash Robbins, Alex Spaeth, Albert Wang, Lin Li, Daniel Solis, Matthew G. Keefe, Jessica L. Sevetson, Julio A. Rivera de Jesús, Kevin C. Donohue, H. Hanh Larson, Drew Ehrlich, Kurtis I. Auguste, Sofie Salama, Vikaas Sohal, Tal Sharf, David Haussler, Cathryn R. Cadwell, David V. Schaffer, Edward F. Chang, Mircea Teodorescu, Tomasz Jan Nowakowski","doi":"10.1038/s41593-024-01782-5","DOIUrl":null,"url":null,"abstract":"Seizures are made up of the coordinated activity of networks of neurons, suggesting that control of neurons in the pathologic circuits of epilepsy could allow for control of the disease. Optogenetics has been effective at stopping seizure-like activity in non-human disease models by increasing inhibitory tone or decreasing excitation, although this effect has not been shown in human brain tissue. Many of the genetic means for achieving channelrhodopsin expression in non-human models are not possible in humans, and vector-mediated methods are susceptible to species-specific tropism that may affect translational potential. Here we demonstrate adeno-associated virus–mediated, optogenetic reductions in network firing rates of human hippocampal slices recorded on high-density microelectrode arrays under several hyperactivity-provoking conditions. This platform can serve to bridge the gap between human and animal studies by exploring genetic interventions on network activity in human brain tissue. Brain slices offer an experimental window into human neurophysiology. Using high-density microelectrode array recordings and adeno-associated virus–mediated optogenetics, the authors demonstrate that optogenetic targeting of CAMK2A+ neurons can affect network activity in human hippocampal slices.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"27 12","pages":"2487-2499"},"PeriodicalIF":21.2000,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Multimodal evaluation of network activity and optogenetic interventions in human hippocampal slices\",\"authors\":\"John P. Andrews, Jinghui Geng, Kateryna Voitiuk, Matthew A. T. Elliott, David Shin, Ash Robbins, Alex Spaeth, Albert Wang, Lin Li, Daniel Solis, Matthew G. Keefe, Jessica L. Sevetson, Julio A. Rivera de Jesús, Kevin C. Donohue, H. Hanh Larson, Drew Ehrlich, Kurtis I. Auguste, Sofie Salama, Vikaas Sohal, Tal Sharf, David Haussler, Cathryn R. 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Multimodal evaluation of network activity and optogenetic interventions in human hippocampal slices
Seizures are made up of the coordinated activity of networks of neurons, suggesting that control of neurons in the pathologic circuits of epilepsy could allow for control of the disease. Optogenetics has been effective at stopping seizure-like activity in non-human disease models by increasing inhibitory tone or decreasing excitation, although this effect has not been shown in human brain tissue. Many of the genetic means for achieving channelrhodopsin expression in non-human models are not possible in humans, and vector-mediated methods are susceptible to species-specific tropism that may affect translational potential. Here we demonstrate adeno-associated virus–mediated, optogenetic reductions in network firing rates of human hippocampal slices recorded on high-density microelectrode arrays under several hyperactivity-provoking conditions. This platform can serve to bridge the gap between human and animal studies by exploring genetic interventions on network activity in human brain tissue. Brain slices offer an experimental window into human neurophysiology. Using high-density microelectrode array recordings and adeno-associated virus–mediated optogenetics, the authors demonstrate that optogenetic targeting of CAMK2A+ neurons can affect network activity in human hippocampal slices.
期刊介绍:
Nature Neuroscience, a multidisciplinary journal, publishes papers of the utmost quality and significance across all realms of neuroscience. The editors welcome contributions spanning molecular, cellular, systems, and cognitive neuroscience, along with psychophysics, computational modeling, and nervous system disorders. While no area is off-limits, studies offering fundamental insights into nervous system function receive priority.
The journal offers high visibility to both readers and authors, fostering interdisciplinary communication and accessibility to a broad audience. It maintains high standards of copy editing and production, rigorous peer review, rapid publication, and operates independently from academic societies and other vested interests.
In addition to primary research, Nature Neuroscience features news and views, reviews, editorials, commentaries, perspectives, book reviews, and correspondence, aiming to serve as the voice of the global neuroscience community.