Neurotrophin-mediated dendrite-to-nucleus signaling revealed by microfluidic compartmentalization of dendrites

Michael S. Cohen, Carlos Bas Orth, Hyung Joon Kim, Noo Li Jeon, Samie R. Jaffrey

Research output: Contribution to journalArticle

63 Scopus citations

Abstract

Signaling from dendritic synapses to the nucleus regulates important aspects of neuronal function, including synaptic plasticity. The neurotrophin brain-derived neurotrophic factor (BDNF) can induce long-lasting strengthening of synapses in vivo and this effect is dependent on transcription. However, the mechanism of signaling to the nucleus is not well understood. Here we describe a microfluidic culture device to investigate dendrite-to-nucleus signaling. Using these microfluidic devices, we demonstrate that BDNF can act directly on dendrites to elicit an anterograde signal that induces transcription of the immediate early genes, Arc and c-Fos. Induction of Arc is dependent on dendrite- and cell body-derived calcium, whereas induction of c-Fos is calcium-independent. In contrast to retrograde neurotrophin-mediated axon-to-nucleus signaling, which is MEK5-dependent, BDNF-mediated anterograde dendrite-to-nucleus signaling is dependent on MEK1/2. Intriguingly, the activity of TrkB, the BDNF receptor, is required in the cell body for the induction of Arc and c-Fos mediated by dendritically applied BDNF. These results are consistent with the involvement of a signaling endosome-like pathway that conveys BDNF signals from the dendrite to the nucleus.

Original languageEnglish (US)
Pages (from-to)11246-11251
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number27
DOIs
Publication statusPublished - Jul 5 2011

    Fingerprint

Keywords

  • Gene expression
  • mRNA translation

ASJC Scopus subject areas

  • General

Cite this