AG Michaelsen

Research interests:

• Actin dynamics at developing synapses and during processes of plasticity

The remarkable diversity of tasks our brain is able to perform depends on the precise communication between 100 billion neurons that are connected by synapses to form functional neuronal networks. During development, synapses form at high rates and the actin cytoskeleton is a key mediator that allows for rapid changes in the morphology of these nascent synapses. However, the fine-tuning of neuronal networks persists throughout adulthood and is crucial also for the mature brain as it provides the basis for processes of learning and memory storage. Hence, functional and structural plasticity in our brain depend on tightly regulated actin dynamics, both during development as well in the mature nervous system. So far, the underlying mechanisms and molecules are only poorly understood. It is especially unclear if the same actin binding molecules are involved in the initial growth of a synapse as well as in morphological alterations that occur upon changes in activity at a mature dendritic spine.

To investigate actin dynamics at developing and mature synapses we use time-lapse confocal and 2-Photon microscopy in primary cultures and organotypic slice cultures of the murine hippocampus. Changes in the amount of F-actin in single dendritic spines can be visualized by expression of GFP-actin or by using a small peptide termed Lifeact that binds specifically to F-actin without interfering with actin dynamics. At the same time calcium imaging techniques can be used to monitor synaptic activity and therefore to correlate between changes in synaptic function and structure.