Molecular Dynamics of periSynaptic Extracellular Matrix
Learning and memory formation entails changes in information flow and processing within brain circuits. These functional changes are driven by activity-dependent structural plasticity. While structural plasticity is high in the young developing brain, it is much less evident in adulthood, where stable neuronal circuits are required for persistent memory storage. Thus, the adult brain must maintain a delicate balance between structural plasticity and tenacity to allow for learning and to protect live long memory. Recent discoveries highlight the central role of the extracellular matrix (ECM) of the brain in this process. In our research we want to understand how the ECM regulates learning, memory formation and synaptic plasticity on the systemic, cellular and molecular level. Further we investigate to what degree altered ECM turnover contributes to reduced brain plasticity and memory loss during aging.
The brain comprises a specialized form of extracellular matrix (ECM), a complex meshwork of proteoglycans and glycoproteins that emerges during adolescence. This specialized ECM has been identified as a major factor suppressing structural plasticity and supporting stability of neuronal networks in the mature brain. However, how is learning and structural plasticity achieved in the mature brain in presence of the ECM? We hypothesize that specific and local degradation of the ECM is necessary for experience-driven reorganisation of brain circuitry during learning. Subsequent replenishment of the ECM by protein synthesis and secretion stabilizes newly established neuronal networks to protect acquired memories. Following this idea, we are investigating cellular and molecular mechanisms involved in activity-dependent regulation of the ECM, their impact on synaptic transmission, synaptic plasticity and structural changes leading to network rearrangements. Further, we aim to unravel ECM-derived signalling mechanisms supporting or conversely, reducing synaptic plasticity. Finally, we are testing whether manipulation of the ECM supports learning and memory functions. Together, we hope to better understand how the balance between plasticity and stability is maintained in the brain. A balance that is necessary for efficient brain function and is dysregulated in several mental disorders such as post-traumatic stress disorder, schizophrenia and dementia.
In our research we apply molecular biological, biochemical and cell biological approaches. We have expertise in super-resolution microscopy and live-cell imaging in cultured primary neurons and brain slices. In collaboration, we perform several learning paradigms and apply electrophysiological methods.
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