BDNF facilitates L-LTP maintenance in the absence of protein synthesis through PKMζ

PLoS One. 2011;6(6):e21568. doi: 10.1371/journal.pone.0021568. Epub 2011 Jun 29.

Abstract

Late-phase long term potentiation (L-LTP) is thought to be the cellular basis for long-term memory (LTM). While LTM as well as L-LTP is known to depend on transcription and translation, it is unclear why brain-derived neurotrophic factor (BDNF) could sustain L-LTP when protein synthesis is inhibited. The persistently active protein kinase ζ (PKMζ) is the only molecule implicated in perpetuating L-LTP maintenance. Here, in mouse acute brain slices, we show that inhibition of PKMζ reversed BDNF-dependent form of L-LTP. While BDNF did not alter the steady-state level of PKMζ, BDNF together with the L-LTP inducing theta-burst stimulation (TBS) increased PKMζ level even without protein synthesis. Finally, in the absence of de novo protein synthesis, BDNF maintained TBS-induced PKMζ at a sufficient level. These results suggest that BDNF sustains L-LTP through PKMζ in a protein synthesis-independent manner, revealing an unexpected link between BDNF and PKMζ.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Brain-Derived Neurotrophic Factor / metabolism*
  • Gene Expression Regulation, Enzymologic
  • Long-Term Potentiation*
  • Mice
  • Mice, Inbred C57BL
  • Neurons / cytology
  • Neurons / metabolism
  • Protein Kinase C / biosynthesis
  • Protein Kinase C / metabolism*
  • Time Factors

Substances

  • Brain-Derived Neurotrophic Factor
  • protein kinase C zeta
  • Protein Kinase C