Reversible modulations of neuronal plasticity by VEGF

Tamar Licht, Inbal Goshen, Avi Avital, Tirzah Kreisel, Salman Zubedat, Ronen Eavri, Menahem Segal, Raz Yirmiya, Eli Keshet*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

207 Scopus citations

Abstract

Neurons, astrocytes, and blood vessels are organized in functional "neurovascular units" in which the vasculature can impact neuronal activity and, in turn, dynamically adjust to its change. Here we explored different mechanisms by which VEGF, a pleiotropic factor known to possess multiple activities vis-à-vis blood vessels and neurons, may affect adult neurogenesis and cognition. Conditional transgenic systems were used to reversibly overexpress VEGF or block endogenous VEGF in the hippocampus of adult mice. Importantly, this was done in settings that allowed the uncoupling of VEGF-promoted angiogenesis, neurogenesis, and memory. VEGF overexpression was found to augment all three processes, whereas VEGF blockade impaired memory without reducing hippocampal perfusion or neurogenesis. Pertinent to the general debate regarding the relative contribution of adult neurogenesis to memory, we found that memory gain by VEGF overexpression and memory impairment by VEGF blockade were already evident at early time points at which newly added neurons could not yet have become functional. Surprisingly, VEGF induction markedly increased in vivo long-term potentiation (LTP) responses in the dentate gyrus, and VEGF blockade completely abrogated LTP. Switching off ectopic VEGF production resulted in a return to a normal memory and LTP, indicating that ongoing VEGF is required to maintain increased plasticity. In summary, the study not only uncovered a surprising role for VEGF in neuronal plasticity, but also suggests that improved memory by VEGF is primarily a result of increasing plasticity of mature neurons rather than the contribution of newly added hippocampal neurons.

Original languageAmerican English
Pages (from-to)5081-5086
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number12
DOIs
StatePublished - 22 Mar 2011

Keywords

  • Learning
  • Neural stem cells
  • Vascular biology

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