Inhibition of Mitochondrial Complex II Induces a Long-Term Potentiation of NMDA-Mediated Synaptic Excitation in the Striatum Requiring Endogenous Dopamine - Archive ouverte HAL Access content directly
Journal Articles Journal of Neuroscience Year : 2001

Inhibition of Mitochondrial Complex II Induces a Long-Term Potentiation of NMDA-Mediated Synaptic Excitation in the Striatum Requiring Endogenous Dopamine

Paolo Calabresi
  • Function : Author
Paolo Gubellini
  • Function : Author
Barbara Picconi
  • Function : Author
Diego Centonze
  • Function : Author
Antonio Pisani
  • Function : Author
Paola Bonsi
  • Function : Author
Paul Greengard
  • Function : Author
Robert Hipskind
  • Function : Author
Giorgio Bernardi
  • Function : Author

Abstract

Abnormal involuntary movements and cognitive impairment represent the classical clinical symptoms of Huntington's disease (HD). This genetic disorder involves degeneration of striatal spiny neurons, but not striatal large cholinergic interneurons, and corresponds to a marked decrease in the activity of mitochondrial complex II [succinate dehydrogenase (SD)] in the brains of HD patients. Here we have examined the possibility that SD inhibitors exert their toxic action by increasing glutamatergic transmission. We report that SD inhibitors such as 3-nitroproprionic acid (3-NP), but not an inhibitor of mitochondrial complex I, produce a long-term potentiation of the NMDA-mediated synaptic excitation (3-NP-LTP) in striatal spiny neurons. In contrast, these inhibitors had no effect on excitatory synaptic transmission in striatal cholinergic interneurons and pyramidal cortical neurons. 3-NP-LTP involves increased intracellular calcium and activation of the mitogen-activated protein kinase extracellular signal-regulated kinase and is critically dependent on endogenous dopamine acting via D2 receptors, whereas it is negatively regulated by D1 receptors. Thus 3-NP-LTP might play a key role in the regional and cell type-specific neuronal death observed in HD.

Dates and versions

hal-04107435 , version 1 (26-05-2023)

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Paolo Calabresi, Paolo Gubellini, Barbara Picconi, Diego Centonze, Antonio Pisani, et al.. Inhibition of Mitochondrial Complex II Induces a Long-Term Potentiation of NMDA-Mediated Synaptic Excitation in the Striatum Requiring Endogenous Dopamine. Journal of Neuroscience, 2001, 21 (14), pp.5110-5120. ⟨10.1523/JNEUROSCI.21-14-05110.2001⟩. ⟨hal-04107435⟩
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