Optogenetic control of human neurons in organotypic brain cultures

Andersson, My; Avaliani, Natalia; Svensson, Andreas; Wickham, Jenny; Pinborg, Lars H.; Jespersen, Bo; Christiansen, Søren H.; Bengzon, Johan; Woldbye, David P. D.; Kokaia, Mérab

doi:10.1038/srep24818

Cited by 62 publications

(53 citation statements)

References 22 publications

(23 reference statements)

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“…This is particularly relevant considering that slices cultured on membranes are known to undergo flattening and synaptic re-organization upon long-term cultivation in newborn rodent brain-derived cultures (Humpel, 2015;Gilbride, 2016), and changes in gene/ protein expression in the rodent mature brain (Staal and Alexander, 2011). Therefore, although flattening has not been reported in recent works using long-term adult human brain-derived slice cultures (Eugene and Cluzeaud, 2014;Andersson and Avaliani, 2016), morphofunctional alterations triggered by plasticity-like events associated to the adaptation to the in vitro environment should not be completely ruled out. Supporting this notion is the observation by Eugene and Cluzeaud (2014) of a slight difference in electrophysiological patterns between slices at 9DIV and 24DIV.…”

Section: Resultsmentioning

confidence: 99%

Free-floating adult human brain-derived slice cultures as a model to study the neuronal impact of Alzheimer’s disease-associated Aβ oligomers

Mendes

Fernandes

Almeida

et al. 2018

Journal of Neuroscience Methods

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Section: Resultsmentioning

confidence: 99%

Free-floating adult human brain-derived slice cultures as a model to study the neuronal impact of Alzheimer’s disease-associated Aβ oligomers

Mendes

Fernandes

Almeida

et al. 2018

Journal of Neuroscience Methods

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“…Despite recent technological advances in long-term recording equipment for animal studies (Okun et al, 2016), obtaining stable intracranial recordings over such durations remains challenging in animals (Blake et al, 2006; Kato et al, 2015) and was, until recently, impossible in humans (Brumberg et al, 2010; Kennedy et al, 2011). As a result, studies of long-term neuroplasticity in humans have employed non-invasive imaging (Sala-Llonch et al, 2015; Zatorre et al, 2012) or brain stimulation (Freitas et al, 2011), ex vivo physiology (Andersson et al, 2016), and cross-sectional study design (Freitas et al, 2011; Skoe et al, 2015). …”

Section: Discussionmentioning

confidence: 99%

Chronic ambulatory electrocorticography from human speech cortex

et al. 2017

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Direct intracranial recording of human brain activity is an important approach for deciphering neural mechanisms of cognition. Such recordings, usually made in patients with epilepsy undergoing inpatient monitoring for seizure localization, are limited in duration and depend on patients’ tolerance for the challenges associated with recovering from brain surgery. Thus, typical intracranial recordings, similar to most non-invasive approaches in humans, provide snapshots of brain activity in acute, highly constrained settings, limiting opportunities to understand long timescale and natural, real-world phenomena. A new device for treating some forms of drug-resistant epilepsy, the NeuroPace RNS® System, includes a cranially-implanted neurostimulator and intracranial electrodes that continuously monitor brain activity and respond to incipient seizures with electrical counterstimulation. The RNS System can record epileptic brain activity over years, but whether it can record meaningful, behavior-related physiological responses has not been demonstrated. Here, in a human subject with electrodes implanted over high-level speech-auditory cortex (Wernicke’s area; posterior superior temporal gyrus), we report that cortical evoked responses to spoken sentences are robust, selective to phonetic features, and stable over nearly 1.5 years. In a second subject with RNS System electrodes implanted over frontal cortex (Broca’s area, posterior inferior frontal gyrus), we found that word production during a naming task reliably evokes cortical responses preceding speech onset. The spatiotemporal resolution, high signal-to-noise, and wireless nature of this system’s intracranial recordings make it a powerful new approach to investigate the neural correlates of human cognition over long timescales in natural ambulatory settings.

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“…The in-vitro application of optogenetics in human-derived cells, provided the important evidence that this method could be applied to humans [134,135]. However, critical issues in optogenetic therapy remain the expression of optogenetic sensors in the human cell membrane and the current produced by individual actuators, properties that balance the possibility of improving a pathological condition with the risk of further neuronal damage [136].…”

Section: The Future Of Optogeneticsmentioning

confidence: 99%

Optogenetics in Brain Research: From a Strategy to Investigate Physiological Function to a Therapeutic Tool

et al. 2019

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Dissecting the functional roles of neuronal circuits and their interaction is a crucial step in basic neuroscience and in all the biomedical field. Optogenetics is well-suited to this purpose since it allows us to study the functionality of neuronal networks on multiple scales in living organisms. This tool was recently used in a plethora of studies to investigate physiological neuronal circuit function in addition to dysfunctional or pathological conditions. Moreover, optogenetics is emerging as a crucial technique to develop new rehabilitative and therapeutic strategies for many neurodegenerative diseases in pre-clinical models. In this review, we discuss recent applications of optogenetics, starting from fundamental research to pre-clinical applications. Firstly, we described the fundamental components of optogenetics, from light-activated proteins to light delivery systems. Secondly, we showed its applications to study neuronal circuits in physiological or pathological conditions at the cortical and subcortical level, in vivo. Furthermore, the interesting findings achieved using optogenetics as a therapeutic and rehabilitative tool highlighted the potential of this technique for understanding and treating neurological diseases in pre-clinical models. Finally, we showed encouraging results recently obtained by applying optogenetics in human neuronal cells in-vitro.

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Optogenetic control of human neurons in organotypic brain cultures

Cited by 62 publications

References 22 publications

Free-floating adult human brain-derived slice cultures as a model to study the neuronal impact of Alzheimer’s disease-associated Aβ oligomers

Free-floating adult human brain-derived slice cultures as a model to study the neuronal impact of Alzheimer’s disease-associated Aβ oligomers

Chronic ambulatory electrocorticography from human speech cortex

Optogenetics in Brain Research: From a Strategy to Investigate Physiological Function to a Therapeutic Tool

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