Henry MarkramHenry Markram started a dual scientific and medical career at the University of Cape Town, in South Africa. His scientific work in the 80s revealed the polymodal receptive fields of pontomedullary reticular formation neurons in vivo and how acetylcholine re-organized these sensory maps.
He moved to Israel in 1988 and obtained his PhD at the Weizmann Institute where he discovered a link between acetylcholine and memory mechanisms by being the first to show that acetylcholine modulates the NMDA receptor in vitro studies, and thereby gates which synapses can undergo synaptic plasticity. He was also the first to characterize the electrical and anatomical properties of the cholinergic neurons in the medial septum diagonal band.
He carried out a first postdoctoral study as a Fulbright Scholar at the NIH, on the biophysics of ion channels on synaptic vesicles using sub-fractionation methods to isolate synaptic vesicles and patch-clamp recordings to characterize the ion channels. He carried out a second postdoctoral study at the Max Planck Institute, as a Minerva Fellow, where he discovered that individual action potentials propagating back into dendrites also cause pulsed influx of Ca2 into the dendrites and found that sub-threshold activity could also activated a low threshold Ca2 channel. He developed a model to show how different types of electrical activities can divert Ca2 to activate different intracellular targets depending on the speed of Ca2 influx an insight that helps explain how Ca2 acts as a universal second messenger. His most well known discovery is that of the millisecond watershed to judge the relevance of communication between neurons marked by the back-propagating action potential. This phenomenon is now called Spike Timing Dependent Plasticity (STDP), which many laboratories around the world have subsequently found in multiple brain regions and many theoreticians have incorporated as a learning rule. At the Max-Planck he also started exploring the micro-anatomical and physiological principles of the different neurons of the neocortex and of the mono-synaptic connections that they form - the first step towards a systematic reverse engineering of the neocortical microcircuitry to derive the blue prints of the cortical column in a manner that would allow computer model reconstruction.
He received a tenure track position at the Weizmann Institute where he continued the reverse engineering studies and also discovered a number of core principles of the structural and functional organization such as differential signaling onto different neurons, models of dynamic synapses with Misha Tsodyks, the computational functions of dynamic synapses, and how GABAergic neurons map onto interneurons and pyramidal neurons. A major contribution during this period was his discovery of Redistribution of Synaptic Efficacy (RSE), where he showed that co-activation of neurons does not only alter synaptic strength, but also the dynamics of transmission. At the Weizmann, he also found the tabula rasa principle which governs the random structural connectivity between pyramidal neurons and a non-random functional connectivity due to target selection. Markram also developed a novel computation framework with Wolfgang Maass to account for the impact of multiple time constants in neurons and synapses on information processing called liquid computing or high entropy computing.
In 2002, he was appointed Full professor at the EPFL where he founded and directed the Brain Mind Institute. During this time Markram continued his reverse engineering approaches and developed a series of new technologies to allow large-scale multi-neuron patch-clamp studies. Markrams lab discovered a novel microcircuit plasticity phenomenon where connections are formed and eliminated in a Darwinian manner as apposed to where synapses are strengthening or weakened as found for LTP. This was the first demonstration that neural circuits are constantly being re-wired and excitation can boost the rate of re-wiring.
At the EPFL he also completed the much of the reverse engineering studies on the neocortical microcircuitry, revealing deeper insight into the circuit design and built databases of the blue-print of the cortical column. In 2005 he used these databases to launched the Blue Brain Project. The BBP used IBMs most advanced supercomputers to reconstruct a detailed computer model of the neocortical column composed of 10000 neurons, more than 340 different types of neurons distributed according to a layer-based recipe of composition and interconnected with 30 million synapses (6 different types) according to synaptic mapping recipes. The Blue Brain team built dozens of applications that now allow automated reconstruction, simulation, visualization, analysis and calibration of detailed microcircuits. This Proof of Concept completed, Markrams lab has now set the agenda towards whole brain and molecular modeling.
With an in depth understanding of the neocortical microcircuit, Markram set a path to determine how the neocortex changes in Autism. He found hyper-reactivity due to hyper-connectivity in the circuitry and hyper-plasticity due to hyper-NMDA expression. Similar findings in the Amygdala together with behavioral evidence that the animal model of autism expressed hyper-fear led to the novel theory of Autism called the Intense World Syndrome proposed by Henry and Kamila Markram. The Intense World Syndrome claims that the brain of an Autist is hyper-sensitive and hyper-plastic which renders the world painfully intense and the brain overly autonomous. The theory is acquiring rapid recognition and many new studies have extended the findings to other brain regions and to other models of autism.
Markram aims to eventually build detailed computer models of brains of mammals to pioneer simulation-based research in the neuroscience which could serve to aggregate, integrate, unify and validate our knowledge of the brain and to use such a facility as a new tool to explore the emergence of intelligence and higher cognitive functions in the brain, and explore hypotheses of diseases as well as treatments.
Lenka ZdeborováLenka Zdeborová is a Professor of Physics and of Computer Science in École Polytechnique Fédérale de Lausanne where she leads the Statistical Physics of Computation Laboratory. She received a PhD in physics from University Paris-Sud and from Charles University in Prague in 2008. She spent two years in the Los Alamos National Laboratory as the Director's Postdoctoral Fellow. Between 2010 and 2020 she was a researcher at CNRS working in the Institute of Theoretical Physics in CEA Saclay, France. In 2014, she was awarded the CNRS bronze medal, in 2016 Philippe Meyer prize in theoretical physics and an ERC Starting Grant, in 2018 the Irène Joliot-Curie prize, in 2021 the Gibbs lectureship of AMS. She is an editorial board member for Journal of Physics A, Physical Review E, Physical Review X, SIMODS, Machine Learning: Science and Technology, and Information and Inference. Lenka's expertise is in applications of concepts from statistical physics, such as advanced mean field methods, replica method and related message-passing algorithms, to problems in machine learning, signal processing, inference and optimization. She enjoys erasing the boundaries between theoretical physics, mathematics and computer science.
Alexander MathisAlexander studied pure mathematics with a minor in logic and theory of science at the Ludwig Maximilians University in Munich. For his PhD also at LMU, he worked on optimal coding approaches to elucidate the properties of grid cells. As a postdoctoral fellow with Prof. Venkatesh N. Murthy at Harvard University and Prof. Matthias Bethge at Tuebingen AI, he decided to study olfactory behaviors such as odor-guided navigation, social behaviors and the cocktail party problem in mice. During this time, he increasingly got interested sensorimotor behaviors beyond olfaction and started working on proprioception, motor adaption, as well as computer vision tools for measuring animal behavior.
In his group, he is interested in elucidating how the brain gives rise to adaptive behavior. One of the major goals is to synthesize large datasets into computationally useful information. For those purposes, he develops algorithms and systems to analyze animal behavior (e.g. DeepLabCut), neural data, as well as creates experimentally testable computational models.
Rachid GuerraouiRachid Guerraoui has been affiliated with Ecole des Mines of Paris, the Commissariat à l'Energie Atomique of Saclay, Hewlett Packard Laboratories and the Massachusetts Institute of Technology. He has worked in a variety of aspects of distributed computing, including distributed algorithms and distributed programming languages. He is most well known for his work on (e-)Transactions, epidemic information dissemination and indulgent algorithms.
He co-authored a book on Transactional Systems (Hermes) and a book on reliable distributed programming (Springer). He was appointed program chair of ECOOP 1999, ACM Middleware 2001, IEEE SRDS 2002, DISC 2004 and ACM PODC 2010.
His publications are available at http://lpdwww.epfl.ch/rachid/papers/generalPublis.html Mackenzie MathisCenter for NeuroprostheticsEPFL ELLIS Unit Faculty MemberCenter for Intelligent Systems
