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.
Christian EnzChristian C. Enz (M84, S'12) received the M.S. and Ph.D. degrees in Electrical Engineering from the EPFL in 1984 and 1989 respectively. From 1984 to 1989 he was research assistant at the EPFL, working in the field of micro-power analog IC design. In 1989 he was one of the founders of Smart Silicon Systems S.A. (S3), where he developed several low-noise and low-power ICs, mainly for high energy physics applications. From 1992 to 1997, he was an Assistant Professor at EPFL, working in the field of low-power analog CMOS and BiCMOS IC design and device modeling. From 1997 to 1999, he was Principal Senior Engineer at Conexant (formerly Rockwell Semiconductor Systems), Newport Beach, CA, where he was responsible for the modeling and characterization of MOS transistors for the design of RF CMOS circuits. In 1999, he joined the Swiss Center for Electronics and Microtechnology (CSEM) where he launched and lead the RF and Analog IC Design group. In 2000, he was promoted Vice President, heading the Microelectronics Department, which became the Integrated and Wireless Systems Division in 2009. He joined the EPFL as full professor in 2013, where he is currently the director of the Institute of Microengineering (IMT) and head of the Integrated Circuits Laboratory (ICLAB).He is lecturing and supervising undergraduate and graduate students in the field of Analog and RF IC Design at EPFL. His technical interests and expertise are in the field of very low-power analog and RF IC design, semiconductor device modeling, and inexact and error tolerant circuits and systems.He has published more than 200 scientific papers and has contributed to numerous conference presentations and advanced engineering courses. Together with E. Vittoz and F. Krummenacher he is one of the developer of the EKV MOS transistor model and the author of the book "Charge-Based MOS Transistor Modeling - The EKV Model for Low-Power and RF IC Design" (Wiley, 2006). He has been member of several technical program committees, including the International Solid-State Circuits Conference (ISSCC) and European Solid-State Circuits Conference (ESSCIRC). He has served as a vice-chair for the 2000 International Symposium on Low Power Electronics and Design (ISLPED), exhibit chair for the 2000 International Symposium on Circuits and Systems (ISCAS) and chair of the technical program committee for the 2006 European Solid-State Circuits Conference (ESSCIRC). Since 2012 he has been elected as member of the IEEE Solid-State Circuits Society (SSCS) Administrative Commmittee (AdCom). He is also Chair of the IEEE SSCS Chapter of Switzerland.
