cJun N-terminal kinase (JNK) mediates cortico-striatal signaling in a model of Parkinson's disease

Giada Spigolon, Anna Cavaccini, Massimo Trusel, Raffaella Tonini, Gilberto Fisone

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


The cJun N-terminal kinase (JNK) signaling pathway has been extensively studied with regard to its involvement in neurodegenerative processes, but little is known about its functions in neurotransmission. In a mouse model of Parkinson's disease (PD), we show that the pharmacological activation of dopamine D1 receptors (D1R) produces a large increase in JNK phosphorylation. This effect is secondary to dopamine depletion, and is restricted to the striatal projection neurons that innervate directly the output structures of the basal ganglia (dSPN). Activation of JNK in dSPN relies on cAMP-induced phosphorylation of the dopamine- and cAMP-regulated phosphoprotein of 32 kDa (DARPP-32), but does not require N-methyl-D-aspartate (NMDA) receptor transmission. Electrophysiological experiments on acute brain slices from PD mice show that inhibition of JNK signaling in dSPN prevents the increase in synaptic strength caused by activation of D1Rs. Together, our findings show that dopamine depletion confers to JNK the ability to mediate dopamine transmission, informing the future development of therapies for PD.

Original languageEnglish (US)
Pages (from-to)37-46
Number of pages10
JournalNeurobiology of Disease
StatePublished - Feb 2018
Externally publishedYes


  • Dopamine
  • L-DOPA
  • Long-term depression
  • Mouse
  • Parkinson's disease
  • Striatum

ASJC Scopus subject areas

  • Neurology


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