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Molecular Mechanisms of Synaptic Plasticity and Stability

Human brains consist of billions of nerve cells organized in defined neuronal networks. They control biological processes such as learning and memory and enable individuals to interact with other individuals in a changing environment. Research projects of the ZMNH department of Molecular Neurogenetics focus on the question how plastic changes become persistent and which synaptic molecules and mechanisms change synaptic strength and cognition. We study individual genes and proteins inside neurons and ask which molecular mechanisms stabilize the structure and function of neuronal synapses.

Cytoskeleton Dynamics and Cellular Trafficking

Plasticity-related proteins dynamically enter and leave neuronal synapses in an activity-dependent manner. These trafficking processes require a dynamic actin- and microtubule cytoskeleton and apply molecular motors to power the delivery and removal of synaptic components, such as postsynaptic neurotransmitter receptors. Although synapses unlikely contain a molecular address, the delivery of new material during plasticity is highly controlled. For instance, the combinatorial use of different cargo adapters or the posttranslational modifications of microtubules, the tracks along which motors move, contribute to transport specificity. Our goal is to understand, how cytoskeletal dynamics and trafficking regulation participate in shifting the dynamic equilibrium of synaptic components in plasticity.

Behavioral analysis / Learning and Memory

We investigate learning and memory in genetic mouse models to get insight whether and how the loss or dysfunction of individual genes contributes to mammalian behavior. Using reverse genetics, we study genes that control exploration, anxiety, motor function and cognitive performance. A major aim is to interpret molecular findings at neuronal synapses in the functional context of a complex brain.

Dementia and Neurodegeneration

Dysfunction of several genes encoding synaptic proteins and trafficking components underlies intellectual disability, cognitive decline and neurodegeneration. Accordingly, autism spectrum disorders and schizophrenia are known as “synaptopathies”. Synaptic dysfunction also occurs in Alzheimer´s disease and dementia and is thought to contribute to the loss of nerve cells. To identify pathogenic mechanisms that may help to develop drugs and neuroprotective strategies in fighting brain disease and cognitive decline we study the dynamics of key proteins in synaptic disease, such as APP, tau and prions.