Optogenetic stimulus-triggered acquisition of seizure resistance

Shimoda, Yoshiteru; Beppu, Kiichiro; Ikoma, Yoko; Morizawa, Yosuke; Zuguchi, Satoshi; Hino, Utaro; Yano, Ryutaro; Moritoh, Satoru; Fukazawa, Yugo; Suematsu, Makoto; Mushiake, Hajime; Nakasato, Nobukazu; Iwasaki, Masaki; Tanaka, Kenji F.; Tominaga, Teiji; Matsui, Kosuke

doi:10.1016/j.nbd.2021.105602

Cited by 16 publications

(16 citation statements)

References 75 publications

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“…1). As previously demonstrated in the hippocampus, 7,[17][18][19][20] optogenetic stimulation of CA1 excitatory neurons reliably evoked focal hypersynchronous activity that had a high probability of inducing convulsive seizures up to 154 days post-virus injection (Supplementary Table 1).…”

Section: Focal Activation Of Area Ca1 Induced Seizuressupporting

confidence: 69%

“…Most interestingly, we found conserved EEG patterns on both micro-and macro-timescales (millisecond and second, respectively) among nonseizure responses to stimulation and seizure responses. By using computational techniques and building on recent discoveries, 7,[17][18][19][20][21][22][23][24][25] we presented a novel method of analyzing the local field potential (LFP) recordings for investigating local electrographic changes leading to a seizure. Our results identified stepwise and discrete phases of neuronal activity underlying ictogenesis that were demarcated by key transition points.…”

Section: Introductionmentioning

confidence: 99%

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Ictogenesis Proceeds Through Discrete Phases in Hippocampal CA1 Seizures

Mueller

Tescarollo

Huynh

et al. 2023

Preprint

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Epilepsy is characterized by spontaneous non-provoked seizures, yet the mechanisms that trigger a seizure and allow its evolution remain underexplored. To dissect out phases implicated in the development of a seizure, we evoked hypersynchronous activity with optogenetic stimulation. Focal optogenetic activation of putative excitatory neurons in the mouse hippocampal CA1 reliably evoked convulsive seizures in awake mice. A novel time-vs-time “pulsogram” plot characterized the evolution of the EEG pulse response from a light evoked response to induced seizure activity. Our results depict ictogenesis as a stepwiseprocess comprised of three distinctive phases demarcated by two transition points. The induction phase undergoes the first transition to reverberant phase activity, followed by the second transition into the paroxysmal phase or a seizure. Non-seizure responses are confined to either induction or reverberant phases, suggesting ictogenesis can be stopped at these stages, thus offering novel therapeutic perspectives to abort a seizure before it develops.

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Section: Focal Activation Of Area Ca1 Induced Seizuressupporting

confidence: 69%

Section: Introductionmentioning

confidence: 99%

Ictogenesis Proceeds Through Discrete Phases in Hippocampal CA1 Seizures

Mueller

Tescarollo

Huynh

et al. 2023

Preprint

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“…Depending on the opsin used, targeted neurons can be activated or inhibited (or even both) using light stimulation to precisely control neuronal activity. Optogenetics can trigger or prevention of epileptic activity (196) with millisecond temporal precision, enabling the assessment of how specific firing patterns affect brain cells and networks (197). Optogenetics can be applied invasively and non-invasively (198) and can be combined with electrophysiological recordings and imaging techniques.…”

Section: Techniques To Study Network Interaction Involved In Sudepmentioning

confidence: 99%

Autonomic dysfunction in epilepsy mouse models with implications for SUDEP research

et al. 2023

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Epilepsy has a high prevalence and can severely impair quality of life and increase the risk of premature death. Sudden unexpected death in epilepsy (SUDEP) is the leading cause of death in drug-resistant epilepsy and most often results from respiratory and cardiac impairments due to brainstem dysfunction. Epileptic activity can spread widely, influencing neuronal activity in regions outside the epileptic network. The brainstem controls cardiorespiratory activity and arousal and reciprocally connects to cortical, diencephalic, and spinal cord areas. Epileptic activity can propagate trans-synaptically or via spreading depression (SD) to alter brainstem functions and cause cardiorespiratory dysfunction. The mechanisms by which seizures propagate to or otherwise impair brainstem function and trigger the cascading effects that cause SUDEP are poorly understood. We review insights from mouse models combined with new techniques to understand the pathophysiology of epilepsy and SUDEP. These techniques include in vivo, ex vivo, invasive and non-invasive methods in anesthetized and awake mice. Optogenetics combined with electrophysiological and optical manipulation and recording methods offer unique opportunities to study neuronal mechanisms under normal conditions, during and after non-fatal seizures, and in SUDEP. These combined approaches can advance our understanding of brainstem pathophysiology associated with seizures and SUDEP and may suggest strategies to prevent SUDEP.

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“…The proposed system, as shown in Figure 1 (8)(9)(10)(11)(12)(13), theta (4-7 Hz)), and gamma band oscillations can be considered as a biomarker of MDD [30]. Once an abnormal class is identified, a trigger signal is sent the control algorithm to set the stimulation parameters.…”

Section: Overview Of the Closed-loop Optogenetic Stimulation Devicementioning

confidence: 99%

“…In optogenetics, light-sensitive proteins called opsins are genetically encoded into the neurons, and the neuronal activity is modulated by delivering light [6]. Recently, optogenetics has been intensively studied in animal disease models for identifying the role of specific neuronal populations in various neurological conditions including Parkinson's disease (PD) [7], major depressive disorder (MDD), epilepsy [8], Alzheimer's disease (AD) [9], among others.…”

Section: Introductionmentioning

confidence: 99%

A Miniaturized Closed-Loop Optogenetic Brain Stimulation Device

Kumari

Kouzani

2022

Electronics

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This paper presents a tetherless and miniaturized closed-loop optogenetic brain stimulation device, designed as a back mountable device for laboratory mice. The device has the ability to sense the biomarkers corresponding to major depressive disorder (MDD) from local field potential (LFP), and produces a feedback signal to control the closed-loop operation after on-device processing of the sensed signals. MDD is a chronic neurological disorder and there are still many unanswered questions about the underlying neurological mechanisms behind its occurrence. Along with other brain stimulation paradigms, optogenetics has recently proved effective in the study of MDD. Most of these experiments have used tethered and connected devices. However, the use of tethered devices in optogenetic brain stimulation experiments has the drawback of hindering the free movement of the laboratory animal subjects undergoing stimulation. To address this issue, the proposed device is small, light-weight, untethered, and back-mountable. The device consists of: (i) an optrode which houses an electrode for collecting neural signals, an optical source for delivering light stimulations, and a temperature sensor for monitoring the temperature increase at the stimulation site, (ii) a neural sensor for acquisition and pre-processing of the neural signals to obtain LFP signals in the frequency range of 4 to 200 Hz, as electrophysiological biomarkers of MDD (iii) a classifier for classification of the signal into four classes: normal, abnormal alpha, abnormal theta, and abnormal gamma oscillations, (iv) a control algorithm to select stimulation parameters based on the input class, and (v) a stimulator for generating light stimulations. The design, implementation, and evaluation of the device are presented, and the results are discussed. The neural sensor and the stimulator are circular in shape with a radius of 8 mm. Pre-recorded neural signals from the mouse hippocampus are used for the evaluation of the device.

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Optogenetic stimulus-triggered acquisition of seizure resistance

Cited by 16 publications

References 75 publications

Ictogenesis Proceeds Through Discrete Phases in Hippocampal CA1 Seizures

Ictogenesis Proceeds Through Discrete Phases in Hippocampal CA1 Seizures

Autonomic dysfunction in epilepsy mouse models with implications for SUDEP research

A Miniaturized Closed-Loop Optogenetic Brain Stimulation Device

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