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Memory research: Ground-breaking, Applied, and Technological Exchanges

Periodic Reporting for period 1 - M-GATE (Memory research: Ground-breaking, Applied, and Technological Exchanges)

Reporting period: 2017-10-01 to 2019-09-30

In relation to its limited volume, the hippocampus is probably the most sophisticated piece of technology human beings carry along. The hippocampus is the small neuronal network tucked deep inside the temporal lobes of our brain, which is critical to our ability to form memories for the events of our lives. Understanding the hippocampus is socially and economically important because when damaged, the hippocampus contributes to making life miserable in several pathologies. After migraine, epilepsies and Alzheimer disease are the most common neurological disorders. Temporal Lobe Epilepsy is the most common form of epilepsy in adults, is drug-resistant in 30% of the cases and is associated with co-morbidities, including cognitive deficits. Both disorders represent a huge cost to society estimated at 1.2% of world GDP. Hence, there is a clear need for further knowledge and treatment options for disorders affecting the functioning of the hippocampus. In line with this assessment, there is a great need for future experts in the field that have been trained and have developed unique multidisciplinary skills combining physiology, molecular biology, computational skills and micro-engineering in an intersectorial setting.
The M-GATE project has hired 15 ESRs, who are all enrolled in PhD programs at their host institutions. The hiring process started with extensive advertising of the openings, and followed EU sanctioned hiring principles. The ESRs (except for one whose project has been put on hold because of illness) have all started 12-18 months ago. Four of them have purely computational projects, while the remaining 11 have experimental projects. The main focus of the experimental work is the exploration of the neural circuits of memory, in the hippocampus and connected brain structures, and their relationship with cognition and behaviour. Most of the work requires high-resolution, advanced invasive techniques that can only be applied to animal models (rats and mice), except for one student (at UCL London) who works on a cognitive neuroscience project on humans using fMRI and computational methods, with approaches that strongly parallel those of the animal work in M-GATE. All experimental students received training in their respective technique, involving electrophysiology (in Nijmegen, London, Trondheim, Marseille, Beerse) as well as optical imaging (in Marseille, Nijmegen, Trondheim), and were able to start their project and acquire their first data sets. In many cases preliminary results are already available and will be completed during the upcoming period. Three of the ESR are working at translational projects, looking at neural dynamics, with the same advanced techniques used for the fundamental research, in mouse models of Alzheimer’s disease, epilepsy, and genetically inherited mental retardation. Additionally, the ESRs are contributing several technical advances, including novel combinations of imaging and electrophysiological methods, tailored to their specific research questions.
The theoretical work from ESRs in Trieste, London, and Rehovot has produced already scientific results, including a scaling law for the behaviour of human memory capacity, derived from first principles and that fits experimental data, as well as quantitative estimates of the information that may be stored in neural networks exhibiting grid cell responses as observed in the medial entorhinal cortex and in the whole hippocampal neural network, when the peculiar connectivity patterns of different hippocampal subfields is taken into account.

In addition to the research and to the training that all ESRs receive at their host institutions, we have organized Network-wide training events featuring world class speakers and instructors from within and from outside the network. Events took place in Trieste (Italy), Nijmegen (Netherlands), and Tromso (Norway). The Trieste and Tromso events – the latter in collaboration with the Norwegian Neuroscience Society – also had a public component, and were open to students from outside the network. The organization of additional events is already ongoing.
All M-GATE ESR-projects are at the forefront of the research on neuroscience of memory. At the end of the project, we will have a host of data and new findings, on the dynamics of neural networks, from the scale of a single hippocampal subfield, or cortical layer, to the global activity of the medial temporal lobe and the cortex as a whole.
The results will represent a major advance in our understanding of the circuits of memory in the brain. The interactions between experimentalists and theoreticians (which will be at its best once considerable datasets are collected) will help providing a theoretical framework for the new data. Importantly, we are applying the same cutting-edge experimental techniques that are in use in fundamental research for animal models of disease, providing new possibilities for translational research.
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