Elucidating the role of astrocytes in structural plasticity of dendritic spines in vivo

• Applicant: Dr. Steffen Burgold, since 2/2017
• Subject Area: Molecular Biology and Physiology of Neurons and Glial Cells
• Term: from 2015 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 285728806

Synapses play an important role in learning and memory as they constitute sites of cell contacts facilitating transmission and modulation of electrical signals within the brain and periphery. According to the hebbian rules of learning information can be stored by modulating the strength of individual synapses within the neuronal network. The modulation itself depends on specific activity patterns. This ability of the brain is referred to as synaptic plasticity. However, within the past decade compelling evidence accumulated that the brain is able to stabilize, form and eliminate synapses even in adulthood. These processes became known as structural plasticity and are thought to contribute to learning and memory in concert with synaptic plasticity. Within the last two decades this bidirectional concept of synapses was extended by another partner - astrocytic endfeet processes enwrapping the majority of synapses and their corresponding synaptic cleft. These functional units of the brain became known as tripartite synapses and the view changed with time from a passive to a more active role of astrocytes within these structures. Although, knowledge about astrocyte functions increased constantly in the past, investigations on the role of astrocytes in structural plasticity of synapses - especially in vivo - are still lacking due to technical reasons. However, studying these processes is now feasible with new microscopy techniques to get new insights how the brain works and how information is processed and stored. In addition, this knowledge might help to unravel the underlying mechanisms of synapse loss in devastating diseases like dementia and other neurological diseases. In our study we aim at elucidating the role of astrocytes in structural plasticity of dendritic spines by applying a correlative workflow combining in vivo two-photon microscopy and electron microscopy. In vivo two-photon microscopy will be used to assess the dendritic spine lifetime and dynamics over several weeks in living mice. The ultrastructure of the same dendritic spines observed in vivo with their corresponding partners of the tripartite synapse will be determined by 3D electron microscopy imaging. This enormous effort is necessary, because the resolution of light microscopy is not sufficient to resolve all partners of the tripartite synapse and to assess their geometric arrangement in detail. With this approach we can determine the time course - similar to a stop-motion movie - when astrocytic endfeet processes enwrap the synaptic cleft after a new spine was formed. Moreover, we can test if stable long-lived spines are more likely to constitute a tripartite synapse compared to mobile short-lived spines. In order to get more insights into astrocytic functions in structural plasticity we will measure changes with the same experimental setup after applying a paradigm of enhanced sensory experience as well as modulating astrocytic calcium signaling.

• DFG Programme: Research Grants
• Ehemaliger Antragsteller: Dr. Mario M. Dorostkar, Ph.D., from 2/2017 until 2/2017