BDNF-TrkB signaling in striatopallidal neurons controls inhibition of locomotor behavior

Dario Besusso, Mirjam Geibel, Dana Kramer, Tomasz Schneider, Valentina Pendolino, Barbara Picconi, Paolo Calabresi, David M. Bannerman, Liliana Minichiello

Research output: Contribution to journalArticle

Abstract

The physiology of brain-derived neurotrophic factor signaling in enkephalinergic striatopallidal neurons is poorly understood. Changes in cortical Bdnf expression levels, and/or impairment in brain-derived neurotrophic factor anterograde transport induced by mutant huntingtin (mHdh) are believed to cause striatopallidal neuron vulnerability in early-stage Huntington's disease. Although several studies have confirmed a link between altered cortical brain-derived neurotrophic factor signaling and striatal vulnerability, it is not known whether the effects are mediated via the brain-derived neurotrophic factor receptor TrkB, and whether they are direct or indirect. Using a novel genetic mouse model, here, we show that selective removal of brain-derived neurotrophic factor-TrkB signaling from enkephalinergic striatal targets unexpectedly leads to spontaneous and drug-induced hyperlocomotion. This is associated with dopamine D2 receptor-dependent increased striatal protein kinase C and MAP kinase activation, resulting in altered intrinsic activation of striatal enkephalinergic neurons. Therefore, brain-derived neurotrophic factor/TrkB signaling in striatopallidal neurons controls inhibition of locomotor behavior by modulating neuronal activity in response to excitatory input through the protein kinase C/MAP kinase pathway.

Original languageEnglish
Article number2031
JournalNature Communications
Volume4
DOIs
Publication statusPublished - 2013

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Chemistry(all)
  • Physics and Astronomy(all)

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    Besusso, D., Geibel, M., Kramer, D., Schneider, T., Pendolino, V., Picconi, B., Calabresi, P., Bannerman, D. M., & Minichiello, L. (2013). BDNF-TrkB signaling in striatopallidal neurons controls inhibition of locomotor behavior. Nature Communications, 4, [2031]. https://doi.org/10.1038/ncomms3031