Maximally selective single-cell target for circuit control in epilepsy models

Hadjiabadi, Darian; Lovett-Barron, Matthew; Raikov, Ivan; Sparks, Fraser T.; Liao, Zhenrui; Baraban, Scott C.; Leskovec, Jure; Losonczy, Attila; Deisseroth, Karl

doi:10.1016/j.neuron.2021.06.007

Cited by 36 publications

(60 citation statements)

References 75 publications

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“…Next, we analyzed photic-evoked neural activity recorded by two-photon calcium imaging. We explored how the brain circuits evolved during various seizure-inducing perturbations (35). Photic stimulation elicited an initial elevated neural state.…”

Section: Discussionmentioning

confidence: 99%

Elevated photic response is followed by a rapid decay and depressed state in ictogenic networks

Myren‐Svelstad

Jamali

Ophus

et al. 2022

Preprint

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The switch between non-seizure and seizure states involves profound alterations in network excitability and synchrony. Both increased and decreased excitability may underlie the state transitions, as shown in epilepsy patients and animal models. Inspired by video-electroencephalography recordings in patients, we developed a framework to study spontaneous and photic-evoked neural and locomotor activity in zebrafish larvae. We combined high-throughput behavioral tracking and whole-brain in vivo two-photon calcium imaging to perform side-by-side comparison of multiple zebrafish seizure and epilepsy models. Our setup allowed us to dissect behavioral and physiological features that are divergent or convergent across multiple seizure models. We observed that locomotor and neural activity during interictal and spontaneous ictal periods exhibit great diversity across seizure models. Yet, during photic stimulation, hyperexcitability and rapid response dynamics was well conserved across multiple seizure models, highlighting the reliability of photic-evoked seizure activity for high-throughput assays. Intriguingly, in several seizure models, we observed that the initial elevated photic response is often followed by fast decay of neural activity and a prominent depressed state. We argue that such depressed states are likely due to homeostatic mechanisms triggered by excessive neural activity. An improved understanding of the interplay between elevated and depressed excitability states might suggest tailored epilepsy therapies.

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Section: Discussionmentioning

confidence: 99%

Elevated photic response is followed by a rapid decay and depressed state in ictogenic networks

Myren‐Svelstad

Jamali

Ophus

et al. 2022

Preprint

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“…At the level of neuronal connectivity, computational modeling studies have shown that the presence of certain motifs relates to sustained neural activity (Bojanek et al, 2020). Additionally, recent modeling work identified the presence of superhubs – highly connected neurons that drive network activity through feedforward motifs – in epileptic networks (Hadjiabadi et al, 2021). Thus, the reorganization and increase of motif coherence in the T1 subgroup suggests that this subgroup might be expected to experience a change in brain activity, such as synchronization, as well.…”

Section: Discussionmentioning

confidence: 99%

Differential patterns of change in brain connectivity resulting from severe traumatic brain injury

Nakuci

McGuire

Schweser

et al. 2021

Preprint

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BackgroundTraumatic brain injury (TBI) damages white matter tracts, disrupting brain network structure and communication. There exists a wide heterogeneity in the pattern of structural damage associated with injury, as well as a large heterogeneity in behavioral outcomes. However, little is known about the relationship between changes in network connectivity and clinical outcomes.MethodsWe utilize the rat lateral fluid-percussion injury (FPI) model of severe TBI to study differences in brain connectivity in 8 animals that received the insult and 11 animals that received only a craniectomy. Diffusion Tensor Imaging (DTI) is performed 5 weeks after the injury and network theory is used to investigate changes in white matter connectivity.ResultsWe find that 1) global network measures are not able to distinguish between healthy and injured animals; 2) injury induced alterations predominantly exist in a subset of connections (subnetworks) distributed throughout the brain; and 3) injured animals can be divided into subgroups based on changes in network motifs – measures of local structural connectivity. Additionally, alterations in predicted functional connectivity indicate that the subgroups have different propensities to synchronize brain activity, which could relate to the heterogeneity of clinical outcomes such as the risk of developing post-traumatic epilepsy.DiscussionThese results suggest that network measures can be used to quantify progressive changes in brain connectivity due to injury and differentiate among subpopulations with similar injuries but different pathological trajectories.Impact StatementWhite matter tracts are important for efficient communication between brain regions and their connectivity pattern underlies proper brain function. Traumatic brain injury (TBI) damages white matter tracts and changes brain connectivity, but how specific changes relate to differences in clinical/behavioral outcomes is not known. Using network theory to study injury related changes in structural connectivity, we find that local measures of network structure can identify subgroups of injured rats with different types of changes in brain structure. Our results suggest that these different patterns of change could relate to differences in clinical outcomes such as the propensity to develop epilepsy.

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“…This paradigm has proved to be able to control the excitability of the epileptic circuits and block the surge of a frank epileptic attack [ 199 , 200 , 201 ]. Although these experiments targeted specific groups of neurons, recent studies reached an even higher level of cellular specificity identifying a distinct type of cell and the superhubs that appear to control network excitability [ 202 ]. This cell type was identified by looking at new patterns of cell–cell connectivity and communication in the data set obtained by whole-brain functional imaging, with cellular resolution, in a validated acute model of epilepsy in zebrafish.…”

Section: Light-based Brain Circuit Analysis and Modulation In Patholo...mentioning

confidence: 99%

Optogenetic Methods to Investigate Brain Alterations in Preclinical Models

Brondi

Bruzzone

Lodovichi

et al. 2022

Cells

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Investigating the neuronal dynamics supporting brain functions and understanding how the alterations in these mechanisms result in pathological conditions represents a fundamental challenge. Preclinical research on model organisms allows for a multiscale and multiparametric analysis in vivo of the neuronal mechanisms and holds the potential for better linking the symptoms of a neurological disorder to the underlying cellular and circuit alterations, eventually leading to the identification of therapeutic/rescue strategies. In recent years, brain research in model organisms has taken advantage, along with other techniques, of the development and continuous refinement of methods that use light and optical approaches to reconstruct the activity of brain circuits at the cellular and system levels, and to probe the impact of the different neuronal components in the observed dynamics. These tools, combining low-invasiveness of optical approaches with the power of genetic engineering, are currently revolutionizing the way, the scale and the perspective of investigating brain diseases. The aim of this review is to describe how brain functions can be investigated with optical approaches currently available and to illustrate how these techniques have been adopted to study pathological alterations of brain physiology.

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Maximally selective single-cell target for circuit control in epilepsy models

Cited by 36 publications

References 75 publications

Elevated photic response is followed by a rapid decay and depressed state in ictogenic networks

Elevated photic response is followed by a rapid decay and depressed state in ictogenic networks

Differential patterns of change in brain connectivity resulting from severe traumatic brain injury

Optogenetic Methods to Investigate Brain Alterations in Preclinical Models

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