Three main questions leading to avenues of innovation are:
- What are the mechanisms of memory storage and retrieval?
- What causes the large differences in memory capacity during our lifetime both in health and disease?
- What causes the large differences in memory capacity between individuals?
We feel that a real understanding of memory lies in answering these three questions and combining them into a single framework. TN2 will study the ins and outs of memory processing from the level of protein-protein interactions up to behavioral traits in population cohorts. More specifically, we will connect basic and clinical research in two directions: from synapse-to-patient and back from patient-to-synapse.
From synapse-to-patient
In the first direction, we will use molecular tools to understand memory processes from synaptic plasticity to network and systems operations, requiring identification and targeting of key components and understanding their role. Mouse transgenes will be used to identify gene function in the different forms and stages of memory processing.
With the introduction of optogenetics in the field of neuroscience, we can now at will excite or inhibit specific cell types in the brain, allowing us for the first time to study causal relations in memory operations.
These studies in animal models will generate predictions and hypotheses that will be bridged to the human brain by genetics, functional imaging, electrophysiological recording and stimulation in vivo and in vitro, pharmaceutical intervention, and modeling.
From patient-to-synapse
In the second direction, going from patient to synapse, we will perform genetic, molecular, cellular, biomarker and neuro-imaging screens in unique cohorts of patients and healthy subjects to identify risk factors for learning and memory. We will investigate the impact of these risk factors using patient-derived stem cells and direct pharmaceutical intervention.
Correction of aberrant function in cognitive disorders will be a dedicated ambition, and will require development of new leads for intervention in the human brain. Only this integrated approach combining innovations that span time scales and levels of investigation will allow us to crack the memory enigma.
