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One team of scientists within the consortium is working on various forms of neuroplasticity at the systems level in health and disease. Brigitte Röder and Christian Büchel have used a visual deprivation model in humans and demonstrated crossmodal compensatory plasticity in congenitally blind humans. The observation that occipital cortex activation was linked to superior tactile abilities was directly confirmed by a virtual lesion approach by Christian Gerloff. Apart from his earlier work on phantom limb associated plasticity and brain lesions Stefan Knecht was able to show that a virtual lesion over the occipital pole interfered with verbal processing in the blind. In a similar manner, Andrej Kral has used auditory deprivation to demonstrate functional deficits in the auditory cortex in an animal model as well as in humans. For the adult human brain, Arne May has recently shown that learning of a visuomotor skill leads to structural changes that can be assessed using neuroimaging. These changes can also occur after daily input of nociceptive information. These approaches are complemented in the theoretical domain by Jianwei Zhang who has developed different learning algorithms including rapid supervised learning and self-valuing reinforcement learning. These algorithms have been applied to modelling highly nonlinear dynamic systems and sensorimotor control of robots. Assembly formation as a crucial element of learning and memory has been investigated by Andreas Engel who demonstrated the importance of oscillatory activity for feature binding using microelectrode recordings in animals and using MEG in humans. The role of slow oscillations for the consolidation of declarative memory during sleep has been established by Jan Born. Developmental mechanisms of sensory abilities and underlying neural circuits have been identified by Ileana Hanganu-Opatz who provided evidence for the role of synchronized activity in the formation of cognition-relevant networks. Neuronal excitability and plasticity are closely related. The modulation of neuronal excitability and cortical activity by ion channels as well as its link to hippocampus-dependent cognitive function have been studied by Dirk Isbrandt using genetically modified mice.
Another team of scientists are focusing on learning, memory and plasticity in health and disease at the cellular and molecular level. Dietmar Kuhl has investigated the contribution of activity-induced gene transcription to the consolidation of memories. One of the genes first identified in his laboratory serves a pivotal role in this process and has been implicated in mental diseases such as fragile X and autism. Matthias Kneussel has recently identified a number of novel protein-protein interactions between postsynaptic receptors and molecular motor protein complexes that drive synaptic cargo to and from synapses and underlie the structural and functional regulation of synaptic plasticity over time. Targeting pathophysiological mechanisms of neurological disease Markus Glatzel and Eckhard Mandelkow have studied molecular modes of action of several proteins responsible for the decay of brain cells such as prion protein (Creutzfeldt-Jakob disease) and tau protein (Alzheimer disease, frontotemporal dementias). They have elucidated pathways of abnormal protein aggregation and misdirected signalling pathways. This has led to the generation of cellular and mouse models of different aspects of the disease and novel diagnostic approaches. To identify new disease genes for neurological disorders Kerstin Kutsche has used chromosomal rearrangements and identified a gene (ARHGEF6/αPIX) for a novel X-linked mental retardation.
Both lines of research have led to substantial insights into the physiology and pathophysiology of learning, memory and plasticity as documented by publications in journals like Nature, Nature Medicine, Nature Neuroscience, Nature Genetics, Science, Lancet and Neuron.
However, a pivotal question remains: how are genes and molecules linked to large scale neuronal interactions and behaviour? This question can be most successfully addressed by an interdisciplinary effort of all groups listed above in a cooperative work program that we attempt to facilitate through this initiative.
