SFB-F44 - Cell signaling in chronic CNS disorders
Project 15:
Importance of Cav1.3 intra-and extracellular modulators for synapse stability in normal and diseased striatal MSNs
Gerald Obermair and Bernhard Flucher
In brain dendritic spines are small postsynaptic membrane protrusions on neuronal dendrites involved in excitatory synaptic transmission and synaptic plasticity. Neuronal L-type calcium channels are located in dendritic spines and contribute to the local concentration of the ubiquitous second messenger calcium. Thereby calcium channels integrate synaptic signals, effect changes in spine morphology and the synaptic structure and contribute to basic neuronal functions including learning and memory formation. Neurological diseases are often accompanied by synaptic adaptations including altered form and function of dendritic spines. For example, a specific loss of dendritic spines of striatal neurons has previously been shown to be involved in the pathology of Parkinson’s disease (PD). Interestingly a loss of dendritic spines in the striatum may also underlie the development of L-DOPA-induced dyskinesia, the major debilitating side effect of the common treatment for Parkinson’s disease. In our project of the first SFB funding period we have identified a specific role of a specific L-type calcium channel and it’s interaction with postsynaptic proteins in regulating the stability of dendritic spines. Building on this important result, we now test in the ongoing project whether and how this proposed mechanism contributes to the etiology of Parkinson’s and other neuronal diseases. To this end we are employing high- and super-resolution fluorescence microscopy and state-of-the-art electrophysiology. Our results will contribute to the understanding of synaptic adaptations during neurological disorders and probe the therapeutic potential of targeting the identified synaptic mechanisms.
