CV Science

Ivan Cohen Researcher in Neuroscience

Course and current status

Diplomas

Accreditation to direct research (HDR). 2019, Sorbonne Université, Paris.

PhD, Neuroscience. 1997-2002, Université Pierre et Marie Curie, Paris.

Engineering, Mathematics and Computer Science. 1992-1996, Ecole Nationale des Ponts et Chaussées, Paris.

Experience

Scientific summary

In order to address how complexity could emerge from large numbers of elementary building blocks I decided to start my education with mathematics and physics, to learn tools that could be applied to biological systems. I obtained my engineering degree in Paris with a major in mathematics and computer science. My research career began with a training period in the lab of Albert Libchaber at Rockefeller University in New York, studying actin/myosin interaction from a biophysical perspective. Immersion in a stimulating scientific environment was an occasion to interact with people from many fields. I discovered questions from modeling growth of bacterial colonies, to biophysics of protein interaction and optical studies of neuronal development.

Neuroscience appeared to me as the most exciting field. Back in Paris I joined the team of Richard Miles at Institut Pasteur to study neuronal dynamics in slice of rodent hippocampus. While most studies focused either on microscopic properties, at the single cell level, or macroscopic emerging properties, at the level of the EEG, I wanted to address how the two scales were coupled. Experimentally this translated into using simultaneously intracellular single cell and extracellular multiunit recordings. Using my background in computer science I managed to quantify the activity of hundreds of neurons in the hippocampal slice preparation. Using pharmacological tools, I could dissect the contribution of intrinsic neuronal properties and synaptic interactions mediated by glutamate and GABA. This work revealed the presence of spontaneous activity in a pharmacologically deafferented tissue and the major contribution of a di-synaptic inhibitory feedback loop. Wondering how this loop could contribute to runaway epileptic activity I adapted my experiment to human epileptic tissue resected from patients undergoing brain surgery at Hôpital Pitié Salpêtrière. These samples revealed that in the epileptic focus of the temporal lobe a population of neurons in the subiculum react unusually to GABA transmission: the focal area resembled tissue in early developmental stages.

One of my main motivation during my post-doctoral training was to study functional physiology in a intact living animal, rather than in an in vitro slice. In the lab of Fabrizio Gabbiani, in Houston, I studied an escape circuit that responds to visual looming stimuli, in the locust, from the eye down to the spinal cord, eliciting a jump. One large neuron controls this response. Combining intra- and extracellular recording I could separate how excitatory and inhibitory inputs shaped the selectivity for looming stimuli. My second post-doc intended to use new tools to address questions that were out of reach at the time of my thesis. The design of transgenic mice expressing a fluorescent marker in GABAergic cells allowed to specifically target this tiny population of inhibitory cells that exert a strong control on tissue activity. I realized that one difficulty was that fluorescence microscopes require submersed tissue. Contrary to interface chambers, immersed tissue did not show reliable spontaneous activity. I started to design new recording chambers until I obtained a permanent position, and came back to Paris, in the lab of Richard Miles, to continue this project.

Until equipment was available to pursue my own experiments I helped researchers and students in the lab with my expertise in electrophysiology and computer analysis. I helped a company (DIPSI) develop a high quality, commercial, extracellular amplifier (Xcell). For my own use I developed real time and off-line analysis software for extracellular recording. I trained PhD student Mickael Bazelot to study the extracellular field potentials generated by synaptic transmission in CA3, that I had observed at the end of my PhD. I designed surgery on P5 epileptic mice and trained PhD student Elodie Chabrol to study the emergence of seizures. As equipment became available, I completed the design of an immersed recording chamber that preserved spontaneous activity. I supervised a Master student, Lim-Anna Sieu, to observe the transformation of hippocampal tissue after epileptogenic lesion. We found changes in spontaneous activity and interneuron properties and we could observe how single interneurons contribute to extracellular potential.

Simultaneously, I met physicists who were developing ultrafast ultrasound scanners. While the technique had originally been developed to measure tissue elasticity, we joined our skills to adapt the technique to brain imaging. I designed surgery and trained a PhD student, Emilie Macé, from the group of Mickael Tanter and Mathias Fink. After we successfully measured brain mechanical properties that could help locate tumors, I suggested Doppler imaging could open new doors to study brain activity, especially in the area of epilepsy where it could be used to localize focal areas. Gabriel Montaldo, from the physics lab came, with the idea of using the new technique of « compound imaging » for this purpose. Indeed, we observed a breakthrough in sensitivity and versatility compared to other imaging modalities. We could correlate changes in blood flow with EEG during epileptic and functional activities. This laid the principles of functional ultrasound imaging (fUS). The main advantages are depth imaging throughout rodent brain, no need for contrast agent, ease of implementation and moderate cost of the scanner compared to techniques such as fMRI.

The most exciting feature of fUS is the small size of an ultrasound probe, that weighs few grams and can easily fit the head of a rat. With Lim-Anna Sieu as PhD student, we tried many different ways to image the brain of a mobile rat, designing and testing various surgical protocols, including many skull prosthetics for their permeability to ultrasound. We eventually found a procedure that provided stable, quality images, and we could further implant stereotaxic EEG electrodes. We demonstrated this fUS-EEG approach on spontaneous absence epilepsy seizures in mobile rats. Simultaneously, with Antoine Bergel as PhD student, we applied the technique to study the perfusion correlate of hippocampal theta rhythm, in sleep or in a simple spatial navigation task. fUS-EEG appeared as a convenient and powerful technique to study neuronal activity and hemodynamics in mobile rats.