{"id":61729,"date":"2023-12-14T11:10:34","date_gmt":"2023-12-14T09:10:34","guid":{"rendered":"https:\/\/www.iemn.fr\/?p=61729"},"modified":"2024-01-31T09:25:17","modified_gmt":"2024-01-31T07:25:17","slug":"these-nathan-schoojans-etablissement-dune-boucle-de-communication-bidirectionnelle-entre-des-neurones-vivants-et-des-neurones-artificiels-analogiques-pour-la-conception-de-neurobiohybrides","status":"publish","type":"post","link":"https:\/\/www.iemn.fr\/en\/agenda\/these-nathan-schoojans-etablissement-dune-boucle-de-communication-bidirectionnelle-entre-des-neurones-vivants-et-des-neurones-artificiels-analogiques-pour-la-conception-de-neurobiohybrides.html","title":{"rendered":"Th\u00e8se Nathan SCHOOJANS :\u00a0\u00bb\u00c9tablissement d\u2019une boucle de communication bidirectionnelle entre des neurones vivants et des neurones artificiels analogiques pour la conception de neurobiohybrides de nouvelle g\u00e9n\u00e9ration \u00bb"},"content":{"rendered":"<div id='layer_slider_1'  class='avia-layerslider main_color avia-shadow  avia-builder-el-0  el_before_av_heading  avia-builder-el-first  container_wrap sidebar_right'  style='height: 261px;'  ><div id=\"layerslider_58_10jwx73wbemep\" data-ls-slug=\"homepageslider\" class=\"ls-wp-container fitvidsignore ls-selectable\" style=\"width:1140px;height:260px;margin:0 auto;margin-bottom: 0px;\"><div class=\"ls-slide\" data-ls=\"duration:6000;transition2d:5;\"><img loading=\"lazy\" decoding=\"async\" width=\"2600\" height=\"270\" src=\"https:\/\/www.iemn.fr\/wp-content\/uploads\/2019\/01\/sliders_news1.jpg\" class=\"ls-bg\" alt=\"\" srcset=\"https:\/\/www.iemn.fr\/wp-content\/uploads\/2019\/01\/sliders_news1.jpg 2600w, https:\/\/www.iemn.fr\/wp-content\/uploads\/2019\/01\/sliders_news1-300x31.jpg 300w, https:\/\/www.iemn.fr\/wp-content\/uploads\/2019\/01\/sliders_news1-768x80.jpg 768w, https:\/\/www.iemn.fr\/wp-content\/uploads\/2019\/01\/sliders_news1-1030x107.jpg 1030w, https:\/\/www.iemn.fr\/wp-content\/uploads\/2019\/01\/sliders_news1-1500x156.jpg 1500w, https:\/\/www.iemn.fr\/wp-content\/uploads\/2019\/01\/sliders_news1-705x73.jpg 705w\" sizes=\"auto, (max-width: 2600px) 100vw, 2600px\" \/><ls-layer style=\"font-size:14px;text-align:left;font-style:normal;text-decoration:none;text-transform:none;font-weight:700;letter-spacing:0px;border-style:solid;border-color:#000;background-position:0% 0%;background-repeat:no-repeat;width:180px;height:30px;left:0px;top:231px;line-height:32px;color:#ffffff;border-radius:6px 6px 6px 6px;padding-left:50px;background-color:rgba(0, 0, 0, 0.57);\" class=\"ls-l ls-ib-icon ls-text-layer\" data-ls=\"minfontsize:0;minmobilefontsize:0;\"><i class=\"fa fa-quote-right\" style=\"color:#ffffff;margin-right:0.8em;font-size:1em;transform:translateY( -0.125em );\"><\/i>ACTUALITES<\/ls-layer><\/div><\/div><\/div><div id='after_layer_slider_1'  class='main_color av_default_container_wrap container_wrap sidebar_right'  ><div class='container av-section-cont-open' ><div class='template-page content  av-content-small alpha units'><div class='post-entry post-entry-type-page post-entry-61729'><div class='entry-content-wrapper clearfix'>\n\n<style type=\"text\/css\" data-created_by=\"avia_inline_auto\" id=\"style-css-av-ls1gq7cr-5940dbee044fc0f21207ae7469647311\">\n#top .av-special-heading.av-ls1gq7cr-5940dbee044fc0f21207ae7469647311{\nmargin:0 0 10px 0;\npadding-bottom:4px;\n}\nbody .av-special-heading.av-ls1gq7cr-5940dbee044fc0f21207ae7469647311 .av-special-heading-tag .heading-char{\nfont-size:25px;\n}\n.av-special-heading.av-ls1gq7cr-5940dbee044fc0f21207ae7469647311 .av-subheading{\nfont-size:15px;\n}\n<\/style>\n<div  class='av-special-heading av-ls1gq7cr-5940dbee044fc0f21207ae7469647311 av-special-heading-h2  avia-builder-el-1  el_after_av_layerslider  el_before_av_hr  avia-builder-el-first'><h2 class='av-special-heading-tag'  itemprop=\"headline\"  >Th\u00e8se Nathan SCHOONJANS :\u00a0\u00bb \u00c9tablissement d\u2019une boucle de communication bidirectionnelle entre des neurones vivants et des neurones artificiels analogiques pour la conception de neurobiohybrides de nouvelle g\u00e9n\u00e9ration \u00ab\u00a0<\/h2><div class=\"special-heading-border\"><div class=\"special-heading-inner-border\"><\/div><\/div><\/div>\n\n<style type=\"text\/css\" data-created_by=\"avia_inline_auto\" id=\"style-css-av-18u73nj-dad6a947580930e400fc42ba200e80f1\">\n#top .hr.av-18u73nj-dad6a947580930e400fc42ba200e80f1{\nmargin-top:5px;\nmargin-bottom:5px;\n}\n.hr.av-18u73nj-dad6a947580930e400fc42ba200e80f1 .hr-inner{\nwidth:100%;\n}\n<\/style>\n<div  class='hr av-18u73nj-dad6a947580930e400fc42ba200e80f1 hr-custom  avia-builder-el-2  el_after_av_heading  el_before_av_textblock  hr-left hr-icon-no'><span class='hr-inner inner-border-av-border-thin'><span class=\"hr-inner-style\"><\/span><\/span><\/div>\n<section  class='av_textblock_section av-jriy64i8-2f4600354c0449b610997916bbd9b6bc'   itemscope=\"itemscope\" itemtype=\"https:\/\/schema.org\/BlogPosting\" itemprop=\"blogPost\" ><div class='avia_textblock'  itemprop=\"text\" >\n<style type=\"text\/css\" data-created_by=\"avia_inline_auto\" id=\"style-css-av-13ewzjw-68e036126b913e5028f77311dc66b825\">\n.av_font_icon.av-13ewzjw-68e036126b913e5028f77311dc66b825{\ncolor:#bfbfbf;\nborder-color:#bfbfbf;\n}\n.av_font_icon.av-13ewzjw-68e036126b913e5028f77311dc66b825 .av-icon-char{\nfont-size:60px;\nline-height:60px;\n}\n<\/style>\n<span  class='av_font_icon av-13ewzjw-68e036126b913e5028f77311dc66b825 avia_animate_when_visible av-icon-style- avia-icon-pos-left avia-icon-animate'><span class='av-icon-char' aria-hidden='true' data-av_icon='\ue8c9' data-av_iconfont='entypo-fontello' ><\/span><\/span>\n<p><strong>Nathan SCHOOJANS<\/strong><\/p>\n<p>Soutenance : 13 d\u00e9cembre 2023 \u00e0 10h30<strong><br \/>\n<\/strong>IEMN Amphitheatre - Central Laboratory - Villeneuve d'Ascq<\/p>\n<\/div><\/section>\n<section  class='av_textblock_section av-jtefqx33-628129dba2299b2ecd65ebfc92eac29d'   itemscope=\"itemscope\" itemtype=\"https:\/\/schema.org\/BlogPosting\" itemprop=\"blogPost\" ><div class='avia_textblock'  itemprop=\"text\" ><div  class='hr av-kjh3zw-4dff888f744b728a1aca9b3a0971493a hr-default  avia-builder-el-6  avia-builder-el-no-sibling'><span class='hr-inner'><span class=\"hr-inner-style\"><\/span><\/span><\/div>\n<h5><strong><span style=\"color: #800000;\">Jury :<\/span><\/strong><\/h5>\n<ul>\n<li>&#8211; Rapporteurs : M. Fr\u00e9d\u00e9ric SARRY : Professeur (Universit\u00e9 de Lorraine)<br \/>\nM. Matthieu RAOUX :Ma\u00eetre de Conf\u00e9rences (Universit\u00e9 de Bordeaux-Examinateurs :<br \/>\n&#8211; M. Pierre VEINANTE : Professeur (Universit\u00e9 de Strasbourg)<br \/>\nM. Michael BAUDOIN : Professeur (Universit\u00e9 de Lille)<br \/>\nM. Guillaume PERRY : Ma\u00eetre de Conf\u00e9rences (Sorbonne Universit\u00e9)<\/p>\n<p>Membres invit\u00e9s :<br \/>\nMme C\u00e9cile DELACOUR : Charg\u00e9e de Recherche (Institut N\u00e9el &#8211; CNRS)<br \/>\nM. Pascal MARIOT : Ma\u00eetre de Conf\u00e9rences (Universit\u00e9 de Lille)<\/p>\n<p>Directrices de th\u00e8se :<br \/>\nMme Virginie HOEL : Professeure (Universit\u00e9 de Lille)<br \/>\nMme Christel VANBESIEN-MAILLIOT : Ma\u00eetre de Conf\u00e9rences (Universit\u00e9 de Lille)<\/p>\n<p>Co-encadrant :<br \/>\nM. Alexis VLANDAS : Charg\u00e9 de Recherche (IEMN &#8211; CNRS)<\/li>\n<\/ul>\n<h5>Summary:<\/h5>\n<p>Les neurobiohybrides sont des syst\u00e8mes compos\u00e9s d\u2019un \u00e9l\u00e9ment artificiel, d\u2019une composante vivante et de l\u2019interface qui les relie. Ces puissants outils permettent de connecter de mani\u00e8re fonctionnelle des \u00e9l\u00e9ments \u00e9lectroniques et des structures neuronales in vitro comme in vivo. De nombreux syst\u00e8mes neurobiohybrides, plus commun\u00e9ment appel\u00e9s neuroproth\u00e8ses, sont utilis\u00e9s en m\u00e9decine pour am\u00e9liorer la qualit\u00e9 de vie de patients atteints de handicaps (surdit\u00e9, d\u00e9ficits visuels, paralysie) en leur permettant de recouvrer partiellement les fonctions physiologiques perdues. Les neuroproth\u00e8ses actuelles sont unidirectionnelles (elles stimulent OU enregistrent l\u2019activit\u00e9 des neurones cibl\u00e9s) et sont particuli\u00e8rement \u00e9nergivores. Int\u00e9grer une boucle de r\u00e9troaction de sorte que ces syst\u00e8mes communiquent en temps r\u00e9el de mani\u00e8re bidirectionnelle avec le tissu nerveux am\u00e9liorerait leur efficacit\u00e9 tout en \u00e9largissant leur potentiel th\u00e9rapeutique \u00e0 d\u2019autres conditions pathologiques. La principale difficult\u00e9 \u00e0 lever pour permettre l\u2019\u00e9tablissement d\u2019une telle boucle consiste \u00e0 trouver un syst\u00e8me de traitement de signal autonome et suffisamment miniaturis\u00e9. En 2017, le groupe Circuits Syst\u00e8mes Applications des Micro-ondes (CSAM) de l\u2019Institut d\u2019Electronique, de Micro\u00e9lectronique et de Nanotechnologies (IEMN) de Lille a publi\u00e9 un neurone artificiel ultra-efficace en termes de consommation \u00e9nerg\u00e9tique qui pourrait r\u00e9pondre \u00e0 ces besoins. Ce neurone \u00e9met des potentiels d\u2019action biomim\u00e9tiques en termes de forme, d\u2019amplitude et de fr\u00e9quence des signaux \u00e9mis, et fonctionne de mani\u00e8re enti\u00e8rement analogique. Dans un pr\u00e9c\u00e9dent doctorat, il a \u00e9t\u00e9 d\u00e9montr\u00e9 que ces potentiels d\u2019action biomim\u00e9tiques permettent bien de stimuler l\u2019activit\u00e9 \u00e9lectrique de neurones vivants. Les travaux pr\u00e9sent\u00e9s ici font suite \u00e0 cette d\u00e9monstration et visent \u00e0 \u00e9tablir une boucle de communication bidirectionnelle compl\u00e8te entre des neurones vivants et ces neurones artificiels. Dans cet objectif, trois axes principaux de travail ont \u00e9t\u00e9 d\u00e9finis : 1- Optimiser le design et la technologie d&rsquo;une interface neurobiohybride ; 2- S\u00e9lectionner et caract\u00e9riser de mani\u00e8re morphologique et fonctionnelle des mod\u00e8les cellulaires vivants maintenus in vitro ; 3- Etablir une premi\u00e8re boucle de communication bidirectionnelle entre ces neurones vivants et les neurones artificiels par le biais de l\u2019interface neurobiohybride. Ce manuscrit pr\u00e9sente les \u00e9tapes de fabrication et d\u2019optimisation de l\u2019interface dont la surface a \u00e9t\u00e9 travaill\u00e9e pour optimiser les conditions d\u2019enregistrement en milieu \u00e9lectrolytique, notamment par l\u2019ajout d\u2019une couche de passivation isolant les lignes d\u2019acc\u00e8s et un d\u00e9veloppement de m\u00e9thodes afin d\u2019optimiser le positionnement des cellules sur les \u00e9lectrodes. Les Les cellules \u00e9lectriquement actives choisies pour cette d\u00e9monstration (cellules endocrines hypophysaires murines GH4C1 (lign\u00e9e \u00e9tablie) et neurones glutamatergiques humains d\u00e9riv\u00e9s de cellules souches pluripotentes induites) ont \u00e9t\u00e9 caract\u00e9ris\u00e9es par patch-clamp, imagerie par fluorescence et imagerie calcique. Les premiers enregistrements de l\u2019activit\u00e9 \u00e9lectrique de cellules GH4C1 cultiv\u00e9es dans une interface neurobiohybride ont \u00e9t\u00e9 r\u00e9alis\u00e9s sur un banc d\u2019enregistrement \u00e9lectronique con\u00e7u et optimis\u00e9 au sein du laboratoire pour une d\u00e9tection de signaux de tr\u00e8s faible amplitude. Ces travaux sont accompagn\u00e9s par le d\u00e9veloppement d\u2019un mod\u00e8le \u00e9lectrique impl\u00e9ment\u00e9 sous le logiciel LTSPICE int\u00e9grant le signal \u00e9lectrique \u00e9mis par des cellules GH4C1 et enregistr\u00e9 via l\u2019interface neurobiohybride. Ce faisant, il est possible d\u2019\u00e9tablir une boucle de communication bidirectionnelle entre des neurones vivants et artificiels. En conclusion, ce travail permet d\u2019ouvrir la voie vers une nouvelle g\u00e9n\u00e9ration de neuroproth\u00e8ses bidirectionnelles<\/p>\n<h5>Abstract:<\/h5>\n<p>Neurobiohybrids are systems composed of an artificial element, a living component and their interface. These powerful tools enable the functional connection of electronic elements and neuronal structures both in vitro and in vivo. Many neurobiohybrid systems, more commonly known as neuroprostheses, are used in medicine to improve the quality of life of patients with disabilities (deafness, visual impairment, paralysis) by enabling them to recover, at least partly, lost physiological functions. Current neuroprostheses are unidirectional (they stimulate OR record the activity of targeted neurons) and are particularly energy-intensive. Integrating a feedback loop into these systems so that they could communicate bidirectionally in real time with nerve tissues would improve their efficiency and effectiveness, while broadening the range of their therapeutic potential. The main difficulty to overcome for enabling such a loop is to find an autonomous and sufficiently miniaturized signal processing system. In 2017, the Circuits Syst\u00e8mes Applications des Micro-ondes (CSAM) group at Lille&rsquo;s Institute of Electronics, Microelectronics and Nanotechnologies (IEMN) published an ultra-efficient artificial neuron in terms of energy consumption that could meet these needs. This neuron generates biomimetic action potentials of similar shape, amplitude and frequency compared to living neurons, and is entirely analog. In a previous PhD work, it was shown that such biomimetic action potentials can trigger electric activity in living neurons. Following this demonstration, the present work aims to establish the proof-of-concept of the complete bidirectional communication loop between living neurons and these artificial neurons. To reach this goal, three main objectives were set: 1- Optimize the design and technology of a neurobiohybrid interface; 2- Select living cells for in vitro use and characterize them both morphologically and functionally; 3- Establish a first bidirectional communication loop between these living neurons and artificial neurons through the neurobiohybrid interface. This manuscript presents the manufacturing and optimization steps of the interface, whose surface has been enhanced to optimize recording conditions in an electrolytic environment, notably by adding a passivation layer to isolate the access lines and by developing methods to optimize cell position on the electrodes. The electrically active cells chosen for this demonstration (murine pituitary endocrine GH4C1 cells, an established cell line, and human glutamatergic neurons derived from induced pluripotent stem cells) were characterized by patch-clamp, fluorescence imaging and calcium imaging. The first recordings of the electrical activity of GH4C1 cells grown in a neurobiohybrid interface were carried out on an electronic recording bench designed and optimized in-house for detecting very low amplitude signals. This work also led to the development of an electrical model implemented in LTSPICE software, integrating electrical signals emitted by GH4C1 cells as recorded through the neurobiohybrid interface. This enabled the establishment of a bidirectional communication loop between living and artificial neurons. To conclude, this work opens the way to a new generation of bidirectional neuroprostheses.<\/p>\n<\/div><\/section>","protected":false},"excerpt":{"rendered":"","protected":false},"author":20,"featured_media":61748,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[87,65,84,187,318],"tags":[],"class_list":["post-61729","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-agenda-en","category-agenda","category-agenda-en-en","category-annonces-these","category-these-2023"],"_links":{"self":[{"href":"https:\/\/www.iemn.fr\/en\/wp-json\/wp\/v2\/posts\/61729","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.iemn.fr\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.iemn.fr\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.iemn.fr\/en\/wp-json\/wp\/v2\/users\/20"}],"replies":[{"embeddable":true,"href":"https:\/\/www.iemn.fr\/en\/wp-json\/wp\/v2\/comments?post=61729"}],"version-history":[{"count":0,"href":"https:\/\/www.iemn.fr\/en\/wp-json\/wp\/v2\/posts\/61729\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.iemn.fr\/en\/wp-json\/wp\/v2\/media\/61748"}],"wp:attachment":[{"href":"https:\/\/www.iemn.fr\/en\/wp-json\/wp\/v2\/media?parent=61729"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.iemn.fr\/en\/wp-json\/wp\/v2\/categories?post=61729"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.iemn.fr\/en\/wp-json\/wp\/v2\/tags?post=61729"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}