Closed-Loop and Activity-Guided Optogenetic Control

Grosenick, Logan; Marshel, James H.; Deisseroth, Karl

doi:10.1016/j.neuron.2015.03.034

Cited by 345 publications

(341 citation statements)

References 331 publications

(620 reference statements)

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“…Closing the loop between optical readouts and the generation of these stimuli (i.e. by real-time generation of stimuli based on live image analysis) will provide a powerful strategy to study cause-andeffect relationships in neural circuitry 115 . Although this discussion was limited to calcium imaging of in vitro neuronal networks, obviously such measurements can be expanded to live animals.…”

Section: Discussionmentioning

confidence: 99%

Image Informatics Strategies for Deciphering Neuronal Network Connectivity

Detrez

Verstraelen

Gebuis

et al. 2016

Focus on Bio-Image Informatics

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Brain function relies on an intricate network of highly dynamic neuronal connections that rewires dramatically under the impulse of various external cues and pathological conditions. Among the neuronal structures that show morphological plasticity are neurites, synapses, dendritic spines and even nuclei. This structural remodelling is directly connected with functional changes such as intercellular communication and the associated calcium-bursting behaviour. In vitro cultured neuronal networks are valuable models for studying these morpho-functional changes. Owing to the automation and standardisation of both image acquisition and image analysis, it has become possible to extract statistically relevant readout from such networks. Here, we focus on the current state-of-the-art in image informatics that enables quantitative microscopic interrogation of neuronal networks. We describe the major correlates of neuronal connectivity and present workflows for analysing them. Finally, we provide an outlook on the challenges that remain to be addressed, and discuss how imaging algorithms can be extended beyond in vitro imaging studies.2

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Section: Discussionmentioning

confidence: 99%

Image Informatics Strategies for Deciphering Neuronal Network Connectivity

Detrez

Verstraelen

Gebuis

et al. 2016

Focus on Bio-Image Informatics

View full text Add to dashboard Cite

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“…An interesting alternative would be to couple the iM1 neural activity readout as feedback to modulate cM1 stimulation. Such closed-loop and activityguided control of neural circuit dynamics can be powerful while studying behaving mice [133].…”

Section: What We Can Learn From Using Optogenetics To Investigate Neumentioning

confidence: 99%

Optogenetic Approaches to Target Specific Neural Circuits in Post-stroke Recovery

2016

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Stroke is a leading cause of death and disability in the USA, yet treatment options are very limited. Functional recovery can occur after stroke and is attributed, in part, to rewiring of neural connections in areas adjacent to or remotely connected to the infarct. A better understanding of neural circuit rewiring is thus an important step toward developing future therapeutic strategies for stroke recovery. Because stroke disrupts functional connections in peri-infarct and remotely connected regions, it is important to investigate brain-wide network dynamics during post-stroke recovery. Optogenetics is a revolutionary neuroscience tool that uses bioengineered lightsensitive proteins to selectively activate or inhibit specific cell types and neural circuits within milliseconds, allowing greater specificity and temporal precision for dissecting neural circuit mechanisms in diseases. In this review, we discuss the current view of post-stroke remapping and recovery, including recent studies that use optogenetics to investigate neural circuit remapping after stroke, as well as optogenetic stimulation to enhance stroke recovery. Multimodal approaches employing optogenetics in conjunction with other readouts (e.g., in vivo neuroimaging techniques, behavior assays, and next-generation sequencing) will advance our understanding of neural circuit reorganization during post-stroke recovery, as well as provide important insights into which brain circuits to target when designing brain stimulation strategies for future clinical studies.

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“…Therefore, we used a small but non-zero value for d c2 , i.e. d c2 = 1 ms, which is close to the overall closed-loop delay introduced by current technologies [31,32]. A crucial advantage of differential DFC is that no additional rate compensation is required, because the mean contribution of the control signal vanishes…”

Section: Differential Controlmentioning

confidence: 99%

Recovery of dynamics and function in spiking neural networks by closed-loop control

Vlachos

Taşkın

Aertsen

et al. 2015

Preprint

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There is a growing interest in developing novel brain stimulation methods to control disease--related aberrant neural activity and to address basic neuroscience questions. Conventional methods for manipulating brain activity rely on open-loop approaches that usually lead to excessive stimulation and, crucially, do not restore the original computations performed by the network. Thus, they are often accompanied by undesired side-effects. Here, we introduce delayed feedback control (DFC), a conceptually simple but effective method, to control pathological oscillations in spiking neural networks (SNNs). Using mathematical analysis and numerical simulations we show that DFC can restore a wide range of aberrant network dynamics either by suppressing or enhancing synchronous irregular activity. Importantly, DFC, besides steering the system back to a healthy state, also recovers the computations performed by the underlying network. Finally, using our theory we identify the role of single neuron and synapse properties in determining the stability of the closed-loop system. Author SummaryBrain stimulation is being used to ease symptoms in several neurological disorders in cases where pharmacological treatment is not effective (anymore). The most common way for stimulation so far has been to apply a fixed, predetermined stimulus irrespective of the actual state of the brain or the condition of the patient. Recently, alternative strategies such as event-triggered stimulation protocols have attracted the interest of researchers. In these protocols the state of the affected brain area is continuously monitored, but the stimulus is only applied if certain criteria are met. Here we go one step further and present a truly closed-loop stimulation protocol. That is, a stimulus is being continuously provided and the magnitude of the stimulus depends, at any point in time, on the ongoing neural activity dynamics of the affected brain area. This results not only in suppression of the pathological activity, but also in a partial recovery of the transfer function of the activity dynamics. Thus, the ability of the lesioned brain area to carry out relevant computations is restored up to a point as well. PLOS Computational Biology |

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Closed-Loop and Activity-Guided Optogenetic Control

Cited by 345 publications

References 331 publications

Image Informatics Strategies for Deciphering Neuronal Network Connectivity

Image Informatics Strategies for Deciphering Neuronal Network Connectivity

Optogenetic Approaches to Target Specific Neural Circuits in Post-stroke Recovery

Recovery of dynamics and function in spiking neural networks by closed-loop control

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