Design, Surface Treatment, Cellular Plating, and Culturing of Modular Neuronal Networks Composed of Functionally Inter-connected Circuits

The brain operates through the coordinated activation and the dynamic communication of neuronal assemblies. A major open question is how a vast repertoire ...

Tel-Aviv University

The growing recognition that brain pathologies do not affect neurons only but rather are, to a large extent, pathologies of glial cells as well as of the vasculature opens to new perspectives in our understanding of genetic disorders of the CNS. To validate the role of the neuron-glial-vascular unit in the etiology of genome instability disorders, we report about cell death and morphological aspects of neuroglia networks and the associated vasculature in a mouse model of Ataxia Telangiectasia (A-T), a human genetic disorder that induces severe motor impairment. We found that A-T-mutated protein deficiency was consistent with aberrant astrocytic morphology and alterations of the vasculature, often accompanied by reactive gliosis. Interestingly similar findings could also be reported in the case of other genetic disorders. These observations bolster the notion that astrocyte-specific pathologies, hampered vascularization and astrocyte-endothelium interactions in the CNS could play a crucial role in the etiology of genome instability brain disorders and could underlie neurodegeneration.

The role of the neuro-astro-vascular unit in the etiology of ataxia telangiectasia.

Brain-machine interfaces (BMI) were born to control "actions from thoughts" in order to recover motor capability of patients with impaired functional connectivity between the central and peripheral nervous system. The final goal of our studies is the development of a new proof-of-concept BMI-a neuromorphic chip for brain repair-to reproduce the functional organization of a damaged part of the central nervous system. To reach this ambitious goal, we implemented a multidisciplinary "bottom-up" approach in which in vitro networks are the paradigm for the development of an in silico model to be incorporated into a neuromorphic device. In this paper we present the overall strategy and focus on the different building blocks of our studies: (i) the experimental characterization and modeling of "finite size networks" which represent the smallest and most general self-organized circuits capable of generating spontaneous collective dynamics; (ii) the induction of lesions in neuronal networks and the whole brain preparation with special attention on the impact on the functional organization of the circuits; (iii) the first production of a neuromorphic chip able to implement a real-time model of neuronal networks. A dynamical characterization of the finite size circuits with single cell resolution is provided. A neural network model based on Izhikevich neurons was able to replicate the experimental observations. Changes in the dynamics of the neuronal circuits induced by optical and ischemic lesions are presented respectively for in vitro neuronal networks and for a whole brain preparation. Finally the implementation of a neuromorphic chip reproducing the network dynamics in quasi-real time (10 ns precision) is presented.

In vitro large-scale experimental and theoretical studies for the realization of bi-directional brain-prostheses.

Les interfaces cerveau-machine (IMC) sont n&eacute;s au contr&ocirc;le &laquo; des actions de pens&eacute;es &raquo; afin de r&eacute;cup&eacute;rer le moteur capacit&eacute; des patients avec une d&eacute;ficience connectivit&eacute; fonctionnelle entre le syst&egrave;me nerveux central et p&eacute;riph&eacute;rique. L&#39;objectif final de nos travaux est l&#39;&eacute;laboration d&#39;une nouvelle puce de validation, un IMC neuromorphic pour cerveau-r&eacute;paration &agrave; reproduire l&#39;organisation fonctionnelle d&#39;une partie endommag&eacute;e du syst&egrave;me nerveux central. Pour atteindre cet objectif ambitieux, nous avons impl&eacute;ment&eacute; une approche multidisciplinaire de la &laquo; bottom-up &raquo; dans laquelle les r&eacute;seaux in vitro sont le paradigme pour le d&eacute;veloppement d&#39;un in silico mod&egrave;le &ecirc;tre int&eacute;gr&eacute;e &agrave; un dispositif neuromorphic. Dans cet article, nous pr&eacute;sentons la strat&eacute;gie globale et mettre l&#39;accent sur les diff&eacute;rents &eacute;l&eacute;ments constitutifs de nos &eacute;tudes: (i) l&#39;exp&eacute;rimental caract&eacute;risation et mod&eacute;lisation des &laquo; r&eacute;seaux de taille finie &raquo;, qui repr&eacute;sentent les circuits auto-organis&eacute;e plus petits et plus g&eacute;n&eacute;rales capables de g&eacute;n&eacute;rer une dynamique collective spontan&eacute;e ; (ii) l&#39;induction des l&eacute;sions dans les r&eacute;seaux de neurones et la pr&eacute;paration du cerveau entier avec une attention particuli&egrave;re sur l&#39;impact sur l&#39;organisation fonctionnelle des circuits ; (iii) la premi&egrave;re production d&#39;une puce neuromorphic capable d&#39;appliquer un mod&egrave;le en temps r&eacute;el des r&eacute;seaux neurones. Une caract&eacute;risation dynamique des circuits taille finie avec r&eacute;solution unicellulaire est fournie. Un mod&egrave;le de r&eacute;seau neuronal bas&eacute; sur neurones d&#39;izhikevich a &eacute;t&eacute; en mesure de reproduire les observations exp&eacute;rimentales. Changements dans la dynamique des circuits neuronaux induits par des l&eacute;sions isch&eacute;miques et optiques sont pr&eacute;sent&eacute;s respectivement pour les r&eacute;seaux de neurones in vitro et pour une pr&eacute;paration de tout le cerveau. Enfin, la mise en &oelig;uvre d&#39;une puce neuromorphic reproduisant la dynamique du r&eacute;seau en temps quasi r&eacute;el (pr&eacute;cision de 10 ns) est pr&eacute;sent&eacute;.

&Eacute;tudes in vitro &agrave; grande &eacute;chelle exp&eacute;rimentales et th&eacute;oriques pour la r&eacute;alisation de bi-directional cerveau-proth&egrave;ses.

Interfacce cervello-macchina (BMI) sono nati a controllo &quot;azioni da pensieri&quot; al fine di recuperare la motricit&agrave; dei pazienti con alterata connettivit&agrave; funzionale tra il sistema nervoso centrale e periferico. L&#39;obiettivo finale dei nostri studi &egrave; lo sviluppo di un nuovo chip di proof-of-concept, un BMI neuromorphic per riparazione di cervello-a riprodurre l&#39;organizzazione funzionale di una parte danneggiata del sistema nervoso centrale. Per raggiungere questo ambizioso obiettivo, abbiamo implementato un approccio &quot;bottom-up&quot; multidisciplinare in cui le reti in vitro sono il paradigma per lo sviluppo di un in silico modello ad essere incorporati in un dispositivo di neuromorphic. In questo libro ci presenta la strategia complessiva e concentrarsi sui diversi blocchi dei nostri studi: (i) la sperimentale caratterizzazione e modellazione delle &quot;reti di dimensione finita&quot;, che rappresentano i circuiti auto-organizzati pi&ugrave; piccoli e pi&ugrave; generali in grado di generare dinamiche collettive spontanee; (ii) l&#39;induzione di lesioni in reti neuronali e la preparazione del cervello intero con speciale attenzione all&#39;impatto sull&#39;organizzazione funzionale dei circuiti; (iii) la prima produzione di un chip di neuromorphic in grado di implementare un modello in tempo reale delle reti neuronali. Viene fornita una caratterizzazione dinamica dei circuiti di dimensione finita con risoluzione della singola cella. Un modello di rete neurale basato su neuroni Izhikevich era in grado di replicare alle osservazioni sperimentali. Cambiamenti nella dinamica dei circuiti neuronali indotti da lesioni ischemiche e ottiche sono presentati rispettivamente per le reti neuronali in vitro e per una preparazione intero cervello. Infine l&#39;implementazione di un chip neuromorphic riproducendo le dinamiche di rete in tempo quasi-real (precisione 10 ns) &egrave; presentato.

Sivan Kanner

Department of Neurobiology,
George S. Wise Faculty of Life Sciences,
Department of Neurobiology, George S. Wise Faculty of Life Sciences

Tel-Aviv University

Design, Surface Treatment, Cellular Plating, and Culturing of Modular Neuronal Networks Composed of Functionally Inter-connected Circuits

Sivan Kanner

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}Department of Neurobiology,George S. Wise Faculty of Life Sciences,Department of Neurobiology, George S. Wise Faculty of Life Sciences

Tel-Aviv University

Design, Surface Treatment, Cellular Plating, and Culturing of Modular Neuronal Networks Composed of Functionally Inter-connected Circuits

Department of Neurobiology,
George S. Wise Faculty of Life Sciences,
Department of Neurobiology, George S. Wise Faculty of Life Sciences