Long-Term Potentiation Requires a Rapid Burst of Dendritic Mitochondrial Fission during Induction

Sai Sachin Divakaruni; Adam M Van Dyke; Ramesh Chandra; Tara A LeGates; Minerva Contreras; Poorna A Dharmasri; Henry N Higgs; Mary Kay Lobo; Scott M Thompson; Thomas A Blanpied

doi:10.1016/j.neuron.2018.09.025

Long-Term Potentiation Requires a Rapid Burst of Dendritic Mitochondrial Fission during Induction

Neuron. 2018 Nov 21;100(4):860-875.e7. doi: 10.1016/j.neuron.2018.09.025. Epub 2018 Oct 11.

Authors

Affiliations

¹ Medical Scientist Training Program, University of Maryland School of Medicine, Baltimore, MD 21201, USA; Program in Neuroscience, University of Maryland School of Medicine, Baltimore, MD 21201, USA; Department of Physiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
² Department of Physiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
³ Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
⁴ Program in Neuroscience, University of Maryland School of Medicine, Baltimore, MD 21201, USA; Department of Physiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
⁵ Department of Biochemistry, Geisel School of Medicine at Dartmouth College, Hanover, NH 03755, USA.
⁶ Program in Neuroscience, University of Maryland School of Medicine, Baltimore, MD 21201, USA; Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
⁷ Program in Neuroscience, University of Maryland School of Medicine, Baltimore, MD 21201, USA; Department of Physiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA. Electronic address: tblanpied@som.umaryland.edu.

Abstract

Synaptic transmission is bioenergetically demanding, and the diverse processes underlying synaptic plasticity elevate these demands. Therefore, mitochondrial functions, including ATP synthesis and Ca²⁺ handling, are likely essential for plasticity. Although axonal mitochondria have been extensively analyzed, LTP is predominantly induced postsynaptically, where mitochondria are understudied. Additionally, though mitochondrial fission is essential for their function, signaling pathways that regulate fission in neurons remain poorly understood. We found that NMDAR-dependent LTP induction prompted a rapid burst of dendritic mitochondrial fission and elevations of mitochondrial matrix Ca²⁺. The fission burst was triggered by cytosolic Ca²⁺ elevation and required CaMKII, actin, and Drp1, as well as dynamin 2. Preventing fission impaired mitochondrial matrix Ca²⁺ elevations, structural LTP in cultured neurons, and electrophysiological LTP in hippocampal slices. These data illustrate a novel pathway whereby synaptic activity controls mitochondrial fission and show that dynamic control of fission regulates plasticity induction, perhaps by modulating mitochondrial Ca²⁺ handling.

Keywords: CaMKII; Drp1; LTP; calcium; dendrite; fission; mitochondria; plasticity; spine; synapse.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Dendrites / physiology*
Female
Hippocampus / cytology
Hippocampus / physiology
Long-Term Potentiation / physiology*
Male
Mice
Mice, Inbred C57BL
Mitochondrial Dynamics / physiology*
Organ Culture Techniques
Rats
Rats, Sprague-Dawley
Time Factors

Abstract

Publication types

MeSH terms

Grants and funding