Structural and functional analysis of Cav1.2 mediated PM-ER contacts in the postsynaptic membrane

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Transient calcium nanodomain mediated signaling inside neurons and particular synapses is central to understanding neuronal communication and plasticity. Beside NMDARs, being often the initial calcium source for plasticity induction, voltage gated calcium channels (VGCCs) show a large diversity of functions in synaptic plasticity. In general, VGCC are essential for excitation-transcription coupling and involved in the local amplification of calcium signaling. One long time known but only rudimentary explored structural component contributing to the diversity of VGCC action is their communication with the endoplasmatic reticulum (ER). To unravel the structural and functional dynamics of this communication, we will focus in this project on the formation of PM-ER contacts formed by the activity driven association between CaV1.2 channels and Stromal interaction molecule (STIM) proteins within postsynaptic spines. Previous work has been shown that ER containing synapses have particular properties, which are important for the information transfer within neuronal networks and long-term memory formation. By using localization and electron microscopy methods (electron cryo-tomography, sptPALM and UPAINT) in combination with functional imaging (calcium) and electrophysiology, we will investigate how PM-ER contacts are initialized, what stabilizes these contacts and how these contacts contribute to the initiation and expression of synaptic plasticity.