Synaptic dysfunction, memory deficits and hippocampal atrophy due to ablation of mitochondrial fission in adult forebrain neurons

B. Oettinghaus, J. M. Schulz, L. M. Restelli, M. Licci, C. Savoia, A. Schmidt, K. Schmitt, A. Grimm, L. Morè, J. Hench, M. Tolnay, A. Eckert, P. D'adamo, P. Franken, N. Ishihara, K. Mihara, J. Bischofberger, L. Scorrano, S. Frank

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Abstract

Well-balanced mitochondrial fission and fusion processes are essential for nervous system development. Loss of function of the main mitochondrial fission mediator, dynamin-related protein 1 (Drp1), is lethal early during embryonic development or around birth, but the role of mitochondrial fission in adult neurons remains unclear. Here we show that inducible Drp1 ablation in neurons of the adult mouse forebrain results in progressive, neuronal subtype-specific alterations of mitochondrial morphology in the hippocampus that are marginally responsive to antioxidant treatment. Furthermore, DRP1 loss affects synaptic transmission and memory function. Although these changes culminate in hippocampal atrophy, they are not sufficient to cause neuronal cell death within 10 weeks of genetic Drp1 ablation. Collectively, our in vivo observations clarify the role of mitochondrial fission in neurons, demonstrating that Drp1 ablation in adult forebrain neurons compromises critical neuronal functions without causing overt neurodegeneration.

Original languageEnglish
Pages (from-to)18-28
Number of pages11
JournalCell Death and Differentiation
Volume23
Issue number1
DOIs
Publication statusPublished - Jan 1 2016

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ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Oettinghaus, B., Schulz, J. M., Restelli, L. M., Licci, M., Savoia, C., Schmidt, A., Schmitt, K., Grimm, A., Morè, L., Hench, J., Tolnay, M., Eckert, A., D'adamo, P., Franken, P., Ishihara, N., Mihara, K., Bischofberger, J., Scorrano, L., & Frank, S. (2016). Synaptic dysfunction, memory deficits and hippocampal atrophy due to ablation of mitochondrial fission in adult forebrain neurons. Cell Death and Differentiation, 23(1), 18-28. https://doi.org/10.1038/cdd.2015.39