Synaptische Metallionen-Dynamiken und Signalwirkung
Synaptic Metal Ion Dynamics and Signaling
Transition metal ions such as copper, iron, and zinc play key roles in various cell biological processes in living systems. Our broad research interest is to understand the role of metal ions in neuronal information processing. We study how neuronal electrical activity such as action- and subthreshold potentials affect synaptic metal homeostasis, which is dysregulated in various brain disorders. We investigate how synaptic metal ion dynamics affect local cell biological mechanisms and thereby regulate synaptic activity and plasticity. To address the above questions, we use a combination of state-of-the-art imaging systems, electrophysiology, biochemical approaches in the mammalian brain system.
Our recent work revealed generation of miRNA and inhibition of local protein synthesis in single spines following synaptic activation suggesting complete outsourcing of complex cell biological mechanisms to distant synapses away from the neuronal cell body. We are particularly interested in how these local processes are affected by metal transients generated at the post-synaptic compartment.
At the presynaptic compartment, we investigate the role of zinc in neurotransmission. Zinc ions are known to be co-released along with glutamate at excitatory synapses and regulate postsynaptic NMDA and certain types of AMPA receptor function. However, the mechanism by which zinc could affect glutamate uptake into synaptic vesicles and alter quantal size and plasticity is not clear. We try to understand activity-dependent regulation of presynaptic processes by zinc using live-cell imaging and novel in vitro assays.
Our work aims to address the fundamental function of metal ions at the synapse, as metal ion dishomeostasis is a hallmark exhibited in both neurodegenerative and psychiatric diseases in humans.
1. Sivakumar Sambandan, Gueney Akbalik, Lisa Kochen, Josefine Kahlstatt, Caspar Glock, Jennifer Rinne, Georgi Tushev, Beatriz Alvarez-Castelao, Alexander Heckel and Erin M. Schuman. Activity-dependent spatially-localized miRNA maturation in neuronal dendrites, Science, 2017, Vol. 355, Issue 6325, p634-637
2. Sivakumar Sambandan, J.F. Sauer, I. Vida, M. Bartos. Associative plasticity at excitatory synapses facilitates recruitment of fast-spiking interneurons, Journal of Neuroscience, 2010. Vol. 30, Issue 35, p11826-11837
3. Christoph Schanzenbächer, Sivakumar Sambandan, Julian Langer, Erin M. Schuman. Nascent proteome remodeling following homeostatic scaling at hippocampal synapses, Neuron, 2016, Vol. 92, Issue 2, p358-37
4. Hanus C, Geptin H, Tushev G, Garg S, Alvarez-Castelao B, Sambandan S, Kochen L, Hafner AS, Langer JD, Schuman EM. Unconventional secretory processing diversifies neuronal ion channel properties, eLife 2016; 5:e20609 DOI: 10.7554/eLife.20609
5. Xintian You, Irena Vlatkovic, Ana Babic, Tristan Will, Irina Epstein, Georgi Tushev, Guney Akbalik, Mantian Wang, Caspar Glock, Xi Wang, Jingyi Hou, Hongyu Liu, Wei Sun, Sivakumar Sambandan, Tao Chen, Erin M. Schuman, Wei Chen. Neural circular RNAs are derived from synaptic genes and regulated by neural development and plasticity, Nature Neuroscience, 2015,
6. Gueney Akbalik, Kasper Langeback Jensen, Sivakumar Sambandan, Casper Glock, Georgi Tushev, Erin M. Schuman. Visualization of dendritic newly synthesized RNAs in rat hippocampus, RNA Biology, 2016, Vol. 14, Issue 1, p20–28
7. Irena Vlatkovic, Sivakumar Sambandan, Georgi Tushev, Mantian Wang, Irina Epstein, Caspar Glock, Nicole Fuerst, Iván Cajigas, Erin M. Schuman. Poly(A) Binding Protein Nuclear 1 regulates the polyadenylation of key synaptic plasticity genes and plays a role in homeostatic plasticity, bioRxiv, 2017, DOI: https://doi.org/10.1101/121194