Acute exposure to the mitochondrial complex i toxin rotenone impairs synaptic long-term potentiation in rat hippocampal slices

Ryoichi Kimura, Lu Yao Ma, Chen Wu, Dharshaun Turner, Jian Xin Shen, Kevin Ellsworth, Makoto Wakui, Marwan Maalouf, Jie Wu

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

Aims: To evaluate the acute effects of the mitochondrial complex I inhibitor rotenone on rat hippocampal synaptic plasticity. Methods: Electrophysiological field potential recordings were used to measure basal synaptic transmission and synaptic plasticity in rat coronal hippocampal slices. Synaptic long-term potentiation (LTP) was induced by high-frequency stimulation (100 Hz, 1 second × 3 at an interval of 20 seconds). In addition, mitochondrial complex I function was measured using MitoSOX imaging in mitochondrial preparations. Results: Acute exposure of hippocampal slices to 50 nM rotenone for 1 h did not alter basal CA3-CA1 synaptic transmission though 500 nM rotenone significantly reduced basal synaptic transmission. However, 50 nM rotenone significantly impaired LTP and this rotenone's effect was prevented by co-application of rotenone plus the ketones acetoacetate and β-hydroxybutyrate (1 mM each). Finally, we measured mitochondrial function using MitoSOX imaging in mitochondrial preparations and found that 50 nM rotenone partially reduced mitochondrial function whereas 500 nM rotenone completely eliminated mitochondrial function. Conclusions: Our findings suggest that mitochondrial activity driven by complex I is a sensitive modulator of synaptic plasticity in the hippocampus. Acute exposure of the hippocampus to rotenone eliminates complex I function and in turn impairs LTP.

Original languageEnglish (US)
Pages (from-to)641-646
Number of pages6
JournalCNS Neuroscience and Therapeutics
Volume18
Issue number8
DOIs
StatePublished - Aug 2012
Externally publishedYes

Keywords

  • Hippocampal slice
  • Ketone
  • Long-term potentiation
  • Mitochondrial dysfunction
  • Rotenone

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health
  • Physiology (medical)
  • Pharmacology (medical)

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