Memory storage in distributed cell assemblies
Life-long memories are formed at an instant, but considerably outlast the neuronal activity that instigated them or even the synaptic modifications that initially retained them. In addition to early processes at the cellular level, the long-term retention of memories therefore requires that entire populations of neurons in widely distributed neural systems are reorganized. Such reorganization at the systems level is not only needed to ensure that each distinct memory is retained for long time periods, but also to provide a framework that allows for the integration of individual learning events into an accumulating knowledge base. The main objective of research in our laboratory is to describe neuronal mechanisms of long-term memory storage at the systems level and to investigate how coordinated neuronal activity and synaptic plasticity in distributed cell assemblies can result in the formation of new cell assemblies. In addition, we are interested in the translational implications of this basic research and in understanding whether the neurodegenerative processes underlying dementia can result from a failure to appropriately organize neuronal activity and synaptic plasticity during our adult lives. This is addressed by recording from many single neurons (up to 100) in the brain simultaneously and by testing how their activity is coordinated before, during, and long after learning. The recording methods are complemented by computational and analytical approaches, and also by molecular techniques that allow us to manipulate the activity of neuronal networks and to test whether the identified mechanisms are necessary for memory formation. Using these methods, we previously discovered neuronal network mechanisms that combine spatial and nonspatial information in the mammalian hippocampus, and showed that orthogonal encoding of the two types of information is used to generate very different neuronal firing patterns for very similar sensory input. Such pattern separation is thought to be a prerequisite for storing a large number of separate memories. To test this hypothesis, we currently investigate how multiple memories are encoded in the hippocampus as well as in a more widely distributed cortical network. In a complementary research program, we aim to investigate how memory processing is altered in the aged brain and when the brain is affected by neurodegenerative disorders. Since memory processing first appears relatively intact in degenerating neuronal networks, but then catastrophically fails, we aim to determine in which way and to what extent a cell assembly can be degraded before failing to support memory retrieval.
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