Project

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Network dynamics underlying learning in embodied cortical brain cells grown over an 11,011-electrode CMOS circuit

Applicant Bakkum Douglas
Number 132245
Funding scheme Ambizione
Research institution Computational Systems Biology Department of Biosystems, D-BSSE ETH Zürich
Institution of higher education ETH Zurich - ETHZ
Main discipline Neurophysiology and Brain Research
Start/End 01.06.2011 - 31.05.2014
Approved amount 539'407.00
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All Disciplines (4)

Discipline
Neurophysiology and Brain Research
Other disciplines of Engineering Sciences
Microelectronics. Optoelectronics
Biomedical Engineering

Keywords (9)

CMOS; plasticity; multi-electrode array; brain; learning and memory; MEA; embodyment; cortex; in vitro

Lay Summary (English)

Lead
Lay summary
The brain is arguably the most complex system studied in science. A human brain contains about one hundred billion brain cells (neurons), each of which communicate electrically and chemically with tens of thousands of other neurons and make up about a quadrillion interconnections. The patterns and strengths of connections constantly change with experience and no two brains are alike. Neurons use voltage spikes (action potentials) to relay sensations of the world, filtered through the connections in the brain, into commands for muscles to move the body and produce speech. Their manipulation gives rise to perceptions, memories, consciousness, imagination, language, and adaptive behavior. Such manipulations are thought to emerge from the collective activity of ensembles of neurons, but much remains unknown about the fundamental rules governing information processing in the brain. With this in mind, individual neurons have been studied extensively at the cellular and molecular levels. However, mainly due to technological limitations, little is yet known about how the activity of individual neurons can combine to produce behavior, learning, and memory.

Therefore, to investigate the population dynamics and plasticity of neural networks, a state-of-the-art 11,011-electrode complementary metal oxide semiconductor (CMOS) array was developed in our laboratory. The densely packed electrodes allow for the first time 2-way access to any neuron grown over the array. Electrodes can both detect signals from multiple neurons in parallel and electrically evoke new signals, allowing a months-long communication between a neural network and a computer. Recording channels can be routed within milliseconds to connect to nearly any arbitrary set of 126 of the electrodes, and any electrode can supply stimulation. By then embodying the neurons with a simulated body situated within an artificial environment, we can observe in detail the population dynamics while the networks are expressing behaviors: recorded action potentials would determine movement while behavior would determine the subsequent feedback of electrical stimuli.

We seek to address both scientific and engineering issues. What is the capacity of neural tissue to encode and store information? What network and cellular dynamics are responsible for this? Can we then find basic computational rules to create new types of artificial (or even biological) control systems? Could a better understanding of the electrode-neuron interface help inform the design of future sensory and motor neuroprosthetics? These are but a few of the questions that could be addressed with the CMOS array.
Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Employees

Publications

Publication
Parameters for burst detection.
Bakkum Douglas J, Radivojevic Milos, Frey Urs, Franke Felix, Hierlemann Andreas, Takahashi Hirokazu (2013), Parameters for burst detection., in Frontiers in computational neuroscience, 7, 193-193.
Tracking axonal action potential propagation on a high-density microelectrode array across hundreds of sites.
Bakkum Douglas J, Frey Urs, Radivojevic Milos, Russell Thomas L, Müller Jan, Fiscella Michele, Takahashi Hirokazu, Hierlemann Andreas (2013), Tracking axonal action potential propagation on a high-density microelectrode array across hundreds of sites., in Nature communications, 4, 2181-2181.
High-density microelectrode array recordings and real-time spike sorting for closed-loop experiments: an emerging technology to study neural plasticity.
Franke Felix, Jäckel David, Dragas Jelena, Müller Jan, Radivojevic Milos, Bakkum Douglas, Hierlemann Andreas (2012), High-density microelectrode array recordings and real-time spike sorting for closed-loop experiments: an emerging technology to study neural plasticity., in Frontiers in neural circuits, 6, 105-105.
Sub-millisecond closed-loop feedback stimulation between arbitrary sets of individual neurons.
Müller Jan, Bakkum Douglas J, Hierlemann Andreas (2012), Sub-millisecond closed-loop feedback stimulation between arbitrary sets of individual neurons., in Frontiers in neural circuits, 6, 121-121.

Collaboration

Group / person Country
Types of collaboration
University of Tokyo Japan (Asia)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Exchange of personnel
University of Bordeaux France (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
Georgia Institute of Technology United States of America (North America)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Exchange of personnel
University of Freiburg Germany (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
RIKEN Kobe Japan (Asia)
- in-depth/constructive exchanges on approaches, methods or results
- Publication

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
9th International Meeting on Substrate-Integrated Micro Electrode Arrays (SIMEA) Poster 3D Finite Element Modeling of Single Neurons and the Microelectrode Array Microenvironment 01.07.2014 Reutlingen, Germany Radivojevic Milos; Bakkum Douglas;
9th International Meeting on Substrate-Integrated Micro Electrode Arrays (SIMEA) Poster Finding the most effective site for extracellular neuronal stimulation 01.07.2014 Reutlingen, Germany Bakkum Douglas; Radivojevic Milos;
Society for Neuroscience Conference Poster Local differences in axonal action potential conduction velocity 09.11.2013 San Diego, United States of America Bakkum Douglas; Radivojevic Milos;
3rd International Symposium Frontiers in Neurophotonics Talk given at a conference Electrical imaging of axon function 01.10.2013 Bordeaux, France Radivojevic Milos; Bakkum Douglas;
Society for Neuroscience Conference Talk given at a conference Capability of an 11,011-electrode CMOS array to study action potential propagation plasticity 13.10.2012 New Orleans, United States of America Radivojevic Milos; Bakkum Douglas;
8th International Meeting on Substrate-Integrated Micro Electrode Arrays (SIMEA) Poster Capability of an 11,011-electrode CMOS array to study action potential propagation plasticity 10.07.2012 Reutlingen, Germany Bakkum Douglas; Radivojevic Milos;
Medical Physics and Biomedical Engineering (MPBE) World Congress Talk given at a conference Capability of an 11,011-electrode CMOS array to study action potential propagation plasticity 26.05.2012 Beijing, China Radivojevic Milos; Bakkum Douglas;
Swiss Society for Neuroscience Annual Meeting Talk given at a conference Capability of an 11,011-electrode CMOS array to study action potential propagation plasticity 03.02.2012 Zurich, Switzerland, Switzerland Bakkum Douglas; Radivojevic Milos;
8th International Brain Research Organization (IBRO) World Congress of Neuroscience Poster Capability of an 11,011-electrode CMOS array to study action potential propagation plasticity 14.07.2011 Florence, Italy Bakkum Douglas; Radivojevic Milos;


Self-organised

Title Date Place
1st Biannual Symposium of CMOS-based MEA Collaborators 10.07.2012 Reutlingen, Germany

Communication with the public

Communication Title Media Place Year
New media (web, blogs, podcasts, news feeds etc.) 11,000-electrode reprogrammable chip takes brain-computer interfaces to a new level International 2013
New media (web, blogs, podcasts, news feeds etc.) Haste and waste on neuronal pathways International 2013
New media (web, blogs, podcasts, news feeds etc.) Kein Tempolimit im Kopf International 2013
New media (web, blogs, podcasts, news feeds etc.) Neuroscience Research Collaboration between ETHZ, University of Tokyo and RIKEN International 2013
Media relations: print media, online media 日や部位で速度変化,東大が解明脳神経信号の伝わり方 Nikkei Sangyo Newspaper International 2013
New media (web, blogs, podcasts, news feeds etc.) 東大など、神経回路内の複雑な活動電位の伝播の様子を可視化することに成功 International 2013
New media (web, blogs, podcasts, news feeds etc.) 脳内の神経信号の伝播速度は時々刻々と変動していることを明らかに 2 mm角に1万個以上の電極を用いて活動電位の伝播を可視化 University of Tokyo and RIKEN press release International 2013
Media relations: radio, television Wenn lebende und tote Materie kommunizieren German-speaking Switzerland 2011

Abstract

The brain is arguably the most complex system studied in science. A human brain contains about one hundred billion brain cells (neurons), each of which communicate electrically and chemically with tens of thousands of other neurons and make up about a quadrillion (10^15) synaptic connections. The patterns and strengths of connections (the synapses) constantly change with experience and no two brains are alike. Neurons use voltage spikes called action potentials to relay sensations of the world, filtered through the connections in the brain, into commands for muscles to move the body and produce speech. Their manipulation gives rise to perceptions, interpretation, memories, consciousness, imagination, language, and adaptive behavior. Such manipulations are thought to emerge from the collective activity of ensembles of neurons, but much remains unknown about the fundamental rules governing information processing in the brain. With this in mind, individual neurons have been studied extensively at the cellular and molecular levels. However, mainly due to technological limitations, little is yet known about how the activity of individual neurons can combine to produce behavior, learning, and memory. Therefore, to investigate the population dynamics and plasticity of neural networks, a state-of-the-art 11,011-electrode complementary metal oxide semiconductor (CMOS) array was developed by the host laboratory [1]. The densely packed electrodes allow for the first time 2-way access to any neuron grown over the array. Electrodes can both detect signals from multiple neurons in parallel and electrically evoke new signals, providing a long-term (months) communication between a neural network and a computer. Recording channels can be routed within milliseconds to connect to nearly any arbitrary set of 126 of the electrodes, and any electrode can supply stimulation. By then embodying the neurons with a simulated body situated within an artificial environment, we can observe in detail the population dynamics while the networks are expressing behaviors: recorded action potentials would determine movement while behavior would determine the subsequent feedback of electrical stimuli. For the Ambizione grant, we propose embodying cortical neurons (and glia) grown over 11,011-electrode CMOS arrays in order to investigate the network dynamics responsible for learning and memory in the brain. The proposed plan will continue past work in which I have already used a closed-loop approach to demonstrate simple behavior and learning in a cortical network grown over a 60-electrode array [2](selected as one of the Journal of Neural Engineering’s highlights of 2008). The plan is divided into two parallel themes. The first theme investigates what are the capabilities of embodied cortical networks to process information and achieve complex behavior. The second theme investigates what new capabilities can the CMOS array provide to describe cellular and network dynamics; analytical techniques from this theme and the preliminary data will then be used to determine how the networks processed information and produced behavior in the first theme. We seek to address both scientific and engineering issues. What is the capacity of neural tissue to encode and store information? What network and cellular dynamics are responsible for this? Can we find basic computational rules to create new types of artificial (or even biological) control systems? Could a better understanding of the electrode-neuron interface help inform the design of future sensory and motor neuroprosthetics? These are but a few of the questions that could be addressed with the CMOS array.[1] Frey U, Egert U, Heer F, Hafizovic S, Hierlemann A. (2009). Microelectronic system for high-resolution mapping of extra-cellular electric fields applied to brain slices. Biosensors and Bioelectronics: 24.[2]Bakkum DJ, Chao ZC, Potter SM. (2008) "Spatio-temporal electrical stimuli shape behavior of an embodied cortical network in a goal-directed learning task". Journal of Neural Engineering: 5(3) 310-323.
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