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<!DOCTYPE HTML> <!-- HTML v5 -->
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<title>SfN Poster Rosch et al 2019</title>
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<h1>Whole brain seizure networks in zebrafish models of <em>GABRA1</em> and <em>GABRG2</em> related epilepsies</h1>
<h2> R. E. Rosch<sup>1,2,3 *</sup>, D. R. W. Burrows<sup>1 *</sup>, É. Samarut<sup>4</sup>, M. P. Meyer<sup>1</sup></h2>
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<p style="color:#BEE4DA; font-style: italic;" >
1 - MRC Centre for Neurodevelopmental Disorders, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK;
2 - Complex Systems Group, Department of Bioengineering, University of Pennsylvania, Philadelphia PA, USA;
3 - Department of Paediatric Neurology, Great Ormond Street Hospital NHS Foundation Trust, London, UK;
4 - Department of Neurosciences, Research Centre of the University of Montreal Hospital Center, Montreal QC, Canada; <br /><br />
<b>* These authors contributed equally</b>
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<h3 class = "boxhead"> Knock-outs of <em>gabra1</em> and <em>gabrg2</em> cause epileptic phenotypes in zebrafish </h3>
<ul class = "normtext">
<li> GABA-A receptors are the predominant fast inhibitory neurotransmitters in the brain and are implicated in epilepsy </li>
<li> Zebrafish have emerged as novel a novel model organism for epilepsy research, with an increasing number of genetic lines now in development </li>
<li> Zebrafish lines of two human genetic epilepsies <em>GABRA1</em> and <em>GABRG2</em> show evidence of reflex convulsive seizures </li>
<li> <strong> Loss of function in different GABA-A subunits is associated with behaviourally distinct phenotypes in zebrafish models of the disorder </strong>
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<video loop autoplay height=325px style="margin-top:25px" >
<source src="https://www.dropbox.com/s/u8nmsjcjt4w5yth/fish_seizure.mov?raw=1" type="video/mp4">
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<h3 class = "boxhead">There are persistent genotype-specific functional brain network differences</h3>
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<li>We estimate time varying interregional functional connectivity over a five minute time window following light stimulation</li>
<li>After initial response to the light stimulation, functional connectivity reaches a steady state</li>
<li>The steady state is dominated by distinct, genotype specific steady state connectivity patterns</li>
<li> <strong> The different KO zebrafish lines show distinct differences in functional connectivity, extending beyond ictal stimulus responses
</strong></li>
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<source src="https://www.dropbox.com/s/ncvgzqt12i3l3he/Correlation_matrix.mov?raw=1" type="video/mp4">
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<h3 class = "boxhead"> Neuronal responses to visual stimuli show genotype-specific signatures</h3>
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<li> We performed light sheet imaging of 3-4 PTU-raised wildtype, <em>gabra1 -/-</em>, and <em>gabrg2 -/-</em> larvae at 6-8dpf</li>
<li> Both <em>gabra1 -/-</em>, and <em>gabrg2 -/-</em> larvae show patterns of hyuperexcitability in response to light stimulation</li>
<li> The predominant different in overall activity distribution occurs early after light exposure </li>
<li> <strong> Brain-wide light-induced responses in the different lines are separable in even a low dimensional representation </strong></li>
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<h3 class = "boxhead">GABA subunit knockouts affect distinct parts of synaptic network coupling</h3>
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<li> distributed difference in functional connectivity may result from more localised differences in effective connectivity </li>
<li> dynamic causal modelling (DCM) allows us to estimate parameters of a biophysical population model based on the observed data</li>
<li> we find genotype specific differences in network connectivity of these model descriptions </li>
<li> <strong> GABA subunit knockouts may target anatomically or physiologically defined subsets of GABAergic synapses</strong></li>
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<!-- <div id = "box"; style="background:#ccc;"> Introduction </div>
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<p style = "font-size:12pt; text-align:left; color:white">
<b> Richard E Rosch </b> <br /> <em>MD PhD</em>
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<img src = "Images/email.png" class = "icon"> <a href = "mailto:richard.rosch@kcl.ac.uk"> richard.rosch@kcl.ac.uk</a> <br>
<img src = "Images/url.png" class = "icon"> <a href = "http://www.dynamic-brains.com"> dynamic-brains.com </a> <br>
<img src = "Images/github.png" class = "icon"> <a href = "https://github.com/roschkoenig/Zebrafish_Seizures"> github.com/roschkoenig </a><br>
<img src = "Images/twitter.png" class = "icon"> <a href = "http://www.twitter.com/roschkoenig"> @roschkoenig</a> <br>
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<img src = "Images/Liao_et_al.png" height = 65 style = "margin-top: 0px">
<p class=smaller style="text-align:center; color:white; margin-top:2px">
<b>Liao et al 2019</b><br />
<em>GABRG2 characterisation</em>
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<img src = "Images/Samarut_et_al.png" height = 65 style = "margin-top: 0px">
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<b>Samarut et al 2018</b><br />
<em>GABRA1 characterisation</em>
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<img src = "Images/Rosch_et_al.png" height = 65 style = "margin-top: 0px">
<p class=smaller style="text-align:center; color:white; margin-top:2px">
<b>Rosch et al 2018</b><br />
<em>Network Analysis</em>
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