Mitochondrial support of persistent presynaptic vesicle mobilization with age-dependent synaptic growth after LTP

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Abstract

Mitochondria support synaptic transmission through production of ATP, sequestration of calcium, synthesis of glutamate, and other vital functions. Surprisingly, less than 50% of hippocampal CA1 presynaptic boutons contain mitochondria, raising the question of whether synapses without mitochondria can sustain changes in efficacy. To address this question, we analyzed synapses from postnatal day 15 (P15) and adult rat hippocampus that had undergone theta-burst stimulation to produce long-term potentiation (TBS-LTP) and compared them to control or no stimulation. At 30 and 120 min after TBS-LTP, vesicles were decreased only in presynaptic boutons that contained mitochondria at P15, and vesicle decrement was greatest in adult boutons containing mitochondria. Presynaptic mitochondrial cristae were widened, suggesting a sustained energy demand. Thus, mitochondrial proximity reflected enhanced vesicle mobilization well after potentiation reached asymptote, in parallel with the apparently silent addition of new dendritic spines at P15 or the silent enlargement of synapses in adults.

DOI: http://dx.doi.org/10.7554/eLife.15275.001

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Mitochondrial morphology is dynamically controlled by a balance between fusion and fission. The physiological importance of mitochondrial fission in vertebrates is less clearly defined than that of mitochondrial fusion. Here we show that mice lacking the mitochondrial fission GTPase Drp1 have developmental abnormalities, particularly in the forebrain, and die after embryonic day 12.5. Neural cell-specific (NS) Drp1(-/-) mice die shortly after birth as a result of brain hypoplasia with apoptosis. Primary culture of NS-Drp1(-/-) mouse forebrain showed a decreased number of neurites and defective synapse formation, thought to be due to aggregated mitochondria that failed to distribute properly within the cell processes. These defects were reflected by abnormal forebrain development and highlight the importance of Drp1-dependent mitochondrial fission within highly polarized cells such as neurons. Moreover, Drp1(-/-) murine embryonic fibroblasts and embryonic stem cells revealed that Drp1 is required for a normal rate of cytochrome c release and caspase activation during apoptosis, although mitochondrial outer membrane permeabilization, as examined by the release of Smac/Diablo and Tim8a, may occur independently of Drp1 activity.

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Author and article information

Contributors

Michael Häusser

Journal

Journal ID (nlm-ta): eLife

Journal ID (iso-abbrev): Elife

Journal ID (hwp): eLife

Journal ID (publisher-id): eLife

Title: eLife

Publisher: eLife Sciences Publications, Ltd

ISSN (Electronic): 2050-084X

Publication date (Electronic, pub): 19 December 2016

Publication date Collection: 2016

Volume: 5

Electronic Location Identifier: e15275

Affiliations

[1 ]deptDepartment of Neuroscience , Center for Learning and Memory, Institute for Neuroscience, University of Texas at Austin , Austin, United States

[2 ]deptDepartment of Cell and Developmental Biology , University of Colorado Denver - Anschutz Medical Campus , Aurora, United States

[3 ]deptCenter for Neural Science , New York University , Washington, New York

[4]University College London , United Kingdom

[5]University College London , United Kingdom

Author notes

kmh2249@ 123456gmail.com

[†]

QPS, LLC, Newark, United States.

Author information

Guan Cao http://orcid.org/0000-0001-6211-5872

Kristen M Harris http://orcid.org/0000-0002-1943-4744

Article

Publisher ID: 15275

DOI: 10.7554/eLife.15275

PMC ID: 5235352

PubMed ID: 27991850

SO-VID: 79bae89c-1950-4b35-987b-866e8280d7a7

License:

This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.

History

Date received : 22 February 2016

Date accepted : 16 December 2016