Journal article
Presynaptic Mitochondria Volume and Abundance Increase during Development of a High-Fidelity Synapse
The Journal of neuroscience, Vol.39(41), pp.7994-8012
10/09/2019
DOI: 10.1523/JNEUROSCI.0363-19.2019
PMCID: PMC6786813
PMID: 31455662
Abstract
The calyx of Held, a large glutamatergic presynaptic terminal in the auditory brainstem undergoes developmental changes to support the high action-potential firing rates required for auditory information encoding. In addition, calyx terminals are morphologically diverse, which impacts vesicle release properties and synaptic plasticity. Mitochondria influence synaptic plasticity through calcium buffering and are crucial for providing the energy required for synaptic transmission. Therefore, it has been postulated that mitochondrial levels increase during development and contribute to the morphological-functional diversity in the mature calyx. However, the developmental profile of mitochondrial volumes and subsynaptic distribution at the calyx of Held remains unclear. To provide insight on this, we developed a helper-dependent adenoviral vector that expresses the genetically encoded peroxidase marker for mitochondria, mito-APEX2, at the mouse calyx of Held. We developed protocols to detect labeled mitochondria for use with serial block face scanning electron microscopy to carry out semiautomated segmentation of mitochondria, high-throughput whole-terminal reconstruction, and presynaptic ultrastructure in mice of either sex. Subsequently, we measured mitochondrial volumes and subsynaptic distributions at the immature postnatal day (P)7 and the mature (P21) calyx. We found an increase of mitochondria volumes in terminals and axons from P7 to P21 but did not observe differences between stalk and swelling subcompartments in the mature calyx. Based on these findings, we propose that mitochondrial volumes and synaptic localization developmentally increase to support high firing rates required in the initial stages of auditory information processing.
Elucidating the developmental processes of auditory brainstem presynaptic terminals is critical to understanding auditory information encoding. Additionally, morphological-functional diversity at these terminals is proposed to enhance coding capacity. Mitochondria provide energy for synaptic transmission and can buffer calcium, impacting synaptic plasticity; however, their developmental profile to ultimately support the energetic demands of synapses following the onset of hearing remains unknown. Therefore, we created a helper-dependent adenoviral vector with the mitochondria-targeting peroxidase mito-APEX2 and expressed it at the mouse calyx of Held. Volumetric reconstructions of serial block face electron microscopy data of immature and mature labeled calyces reveal that mitochondrial volumes are increased to support high firing rates upon maturity.
Details
- Title: Subtitle
- Presynaptic Mitochondria Volume and Abundance Increase during Development of a High-Fidelity Synapse
- Creators
- Connon I Thomas - Electron Microscopy Core FacilityChristian Keine - Department of Anatomy and Cell Biology, Iowa Neuroscience Institute, University of Iowa, Iowa City, Iowa 52242, andSatoko Okayama - Molecular Mechanisms of Synaptic Function, Max Planck Florida Institute, Jupiter, Florida 33458Rachel Satterfield - Molecular Mechanisms of Synaptic Function, Max Planck Florida Institute, Jupiter, Florida 33458Morgan Musgrove - Electron Microscopy Core FacilityDebbie Guerrero-Given - Electron Microscopy Core FacilityNaomi Kamasawa - Electron Microscopy Core Facility, naomi.kamasawa@mpfi.org samuel-m-young@uiowa.eduSamuel M Young Jr - Department of Otolaryngology, University of Iowa, Iowa City, Iowa 52242
- Resource Type
- Journal article
- Publication Details
- The Journal of neuroscience, Vol.39(41), pp.7994-8012
- DOI
- 10.1523/JNEUROSCI.0363-19.2019
- PMID
- 31455662
- PMCID
- PMC6786813
- NLM abbreviation
- J Neurosci
- ISSN
- 0270-6474
- eISSN
- 1529-2401
- Publisher
- United States
- Grant note
- R01 DC014093 / NIDCD NIH HHS
- Language
- English
- Date published
- 10/09/2019
- Academic Unit
- Anatomy and Cell Biology; Iowa Neuroscience Institute; Otolaryngology
- Record Identifier
- 9984070321602771
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