Optobiology
Prof. Dr. Marina Mikhaylova
Neuronal synapses form the basis for neuronal communication and the storage of information in brain. Excitatory synapses of pyramidal neurons are frequently located on dendritic spines, which are considered basic units of synaptic integration. However, dendritic spines are not fully autonomous units: their strength and persistence are tightly regulated and the plastic properties of neighbored dendritic synapses are also determined by molecular and electrical signaling in dendritic compartments. Thus, potentiation of a dendritic spine favors the potentiation of its neighbor. In this regard, the dendritic branch forms a perfect compartment for confined signaling. Conversely, synapses located in different neuronal compartments, for instance apical and basal dendrites differ in their stability and functional properties and may contain distinct molecular make-up. Such a complex organization of the dendritic tree allows for various degrees of autonomy. For instance, in response to synaptic activity, membrane receptors can be trapped, inserted, or removed from specific dendritic compartments or local translation of dendritic mRNA can rapidly increase the availability of plasticity-related proteins. At the same time, it also provides means for very efficient signal integration, which can result in global change of neuronal activity and affect gene transcription.
The overall aim of our group is to understand what defines a dendritic compartment as a "plasticity unit". Our research questions are dealing with different levels of dendritic compartmentalization, namely, plasticity and stability at the single synapse level, biochemical communication between nearby spines and the molecular mechanisms leading to the dendritic asymmetry of pyramidal neurons.
We are applying biochemical, biophysical, molecular biological methods and advanced fluorescence imaging techniques such as a single molecule imaging, super-resolution nanoscopy (STED), TIRF, 2-photon and a spinning disc confocal microscopy to tackle questions dealing with i) synaptic plasticity and stability; ii)molecular, structural and functional diversity of dendritic spines; iii) biochemical communication between nearby spines as well as iv) mRNA targeting and local protein translation, processing, recycling and degradation in tuning of synaptic inputs. The role of microtubule and actin cytoskeleton as well as trafficking rules and signaling controlling active organelle transport and positioning are in particular interests in this respect.
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