Identification of genes co-upregulated with Arc during BDNF-induced long-term potentiation in adult rat dentate gyrus in vivo

Eur J Neurosci. 2006 Mar;23(6):1501-11. doi: 10.1111/j.1460-9568.2006.04687.x.


Brain-derived neurotrophic factor (BDNF) is a critical regulator of transcription-dependent adaptive neuronal responses, such as long-term potentiation (LTP). Brief infusion of BDNF into the dentate gyrus of adult anesthetized rats triggers stable LTP at medial perforant path-granule synapses that is transcription-dependent and requires induction of the immediate early gene Arc. Rather than acting alone, Arc is likely to be part of a larger BDNF-induced transcriptional program. Here, we used cDNA microarray expression profiling to search for genes co-upregulated with Arc 3 h after BDNF-LTP induction. Of nine cDNAs encoding for known genes and up-regulated more than four-fold, we selected five genes, Narp, neuritin, ADP-ribosylation factor-like protein-4 (ARL4L), TGF-beta-induced immediate early gene-1 (TIEG1) and CARP, for further validation. Real-time PCR confirmed robust up-regulation of these genes in an independent set of BDNF-LTP experiments, whereas infusion of the control protein cytochrome C had no effect. In situ hybridization histochemistry further revealed up-regulation of all five genes in somata of post-synaptic granule cells following both BDNF-LTP and high-frequency stimulation-induced LTP. While Arc synthesis is critical for local actin polymerization and stable LTP formation, several of the co-upregulated genes have known functions in excitatory synaptogenesis, axon guidance and glutamate receptor clustering. These results provide novel insight into gene expression responses underlying BDNF-induced synaptic consolidation in the adult brain in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons / physiology
  • Blotting, Western
  • Brain-Derived Neurotrophic Factor / pharmacology*
  • Cytoskeletal Proteins / biosynthesis
  • Cytoskeletal Proteins / genetics*
  • DNA Fingerprinting
  • DNA, Complementary / biosynthesis
  • DNA, Complementary / genetics
  • Dentate Gyrus / cytology
  • Dentate Gyrus / drug effects*
  • Dentate Gyrus / growth & development
  • Electrophoresis, Polyacrylamide Gel
  • Electrophysiology
  • In Situ Hybridization
  • Injections
  • Long-Term Potentiation / drug effects*
  • Male
  • Nerve Tissue Proteins / biosynthesis
  • Nerve Tissue Proteins / genetics*
  • Oligonucleotide Array Sequence Analysis
  • Poly A / metabolism
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Glutamate / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / drug effects
  • Synapses / physiology
  • Up-Regulation / physiology


  • Brain-Derived Neurotrophic Factor
  • Cytoskeletal Proteins
  • DNA, Complementary
  • Nerve Tissue Proteins
  • RNA, Messenger
  • Receptors, Glutamate
  • activity regulated cytoskeletal-associated protein
  • Poly A