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.
Legend of the image above: A straightened neuronal dendrite showing super resolved axon terminals containing individual synaptic vesicles labelled against zinc transporter 3, a protein responsible for zinc uptake into the vesicles.