Robert Renden, Ph.D.
Mitochondrial profiles have been observed at neuronal presynaptic terminals since the first electron micrographs were produced. More recently, mitochondria have been recognized as dynamic organelles that rapidly relocate throughout neurons to help control synaptic function, and are a major causative factor in neurodegenerative disease. However, their role at the presynaptic terminal is still poorly understood, with most experimental information coming from invertebrate preparations. Currently, mitochondria are envisaged as having three roles at the presynaptic terminal: a local source of ATP to power synaptic vesicle recycling, buffering activity-dependent intracellular Calcium concentration, and providing cell-signaling cues for morphological changes, e.g. apoptosis.
We exploit the calyx of Held, a giant glutamatergic synapse in the auditory brainstem of rodents, as a model for the study of presynaptic physiology and synaptic vesicle recycling, and the role of mitochondria in these processes. Previously, we have described dramatic molecular, structural, and morphological changes during the first three weeks following birth, which allow the calyx synapse to encode and transmit information at high frequency, with high temporal fidelity. During maturation at this synapse, mitochondria organize synaptic vesicle clusters at release sites, providing a potential additional structural role for mitochondria at the presynaptic terminal.
We use detailed electrophysiology recordings of synaptic activity at this synapse, combined with in vivo perturbation via viral transgenics, and pharmacological manipulation to determine the real-time role of mitochondria on synaptic recycling. We also use volumetric confocal reconstruction of this synapse to confirm the role of mitochondria on synaptic vesicle localization adjacent to presynaptic release sites. Results from these studies will inform treatment of synaptic neuropathies where mitochondrial dynamics are dysfunctional, such as Parkinson's disease.
Project 5 Team
Robert Renden, Ph.D.
Project 5 Leader
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Christopher von Bartheld, M.D.
Project 5 Mentor / CORE A Leader
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James Kenyon, Ph.D.
Project 5 Mentor
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