Neurochemical Research

, Volume 35, Issue 2, pp 239–246 | Cite as

Phosphorylation Changes of CaMKII, ERK1/2, PKB/Akt Kinases and CREB Activation During Early Long-Term Potentiation at Schaffer Collateral-CA1 Mouse Hippocampal Synapses

  • Mauro Racaniello
  • Alessio Cardinale
  • Cristiana Mollinari
  • Margherita D’Antuono
  • Giovanna De Chiara
  • Virginia Tancredi
  • Daniela Merlo


Protein phosphorylation is the main signaling system known to trigger synaptic changes underlying long-term potentiation (LTP). The timing of these phosphorylations plays an essential role to maintain the potentiated state of synapses. However, in mice a simultaneous analysis of phosphorylated proteins during early-LTP (E-LTP) has not been thoroughly carried out. Here we described phosphorylation changes of αCaMKII, ERK1/2, PKB/Akt and CREB at different times after E-LTP induced at Schaffer collateral/commissural fiber-CA1 synapses by 1 s 100 Hz tetanic stimulation in mouse hippocampal slices. We found that phosphorylation levels of all the molecules examined rapidly increased after tetanisation and remained above the basal level up to 30 min. Notably, we observed a sustained increment in the phosphorylation level of Akt at Ser473, whereas the phosphorylation level of Akt at Thr308 was unchanged. Unexpectedly, we also detected a marked increase of CREB target genes expression levels, c-fos, Egr-1 and exon-III containing BDNF transcripts. Our findings, besides providing a detailed timing of phosphorylation of the major kinases involved in E-LTP in mice, revealed that a modest LTP induction paradigm specifically triggers CREB-mediated gene expression.


Early-long term potentiation Mouse hippocampal slices Protein phosphorylation Gene expression 



This study was supported in part by the Italian Ministry of Health—Research Project Neurodegenerative Diseases, ex art. 56: “Role of Herpes Simplex-I infection in the pathogenesis of Alzheimer’s Disease and transmissible spongiform encephalopathies”.


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Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Mauro Racaniello
    • 1
    • 2
  • Alessio Cardinale
    • 1
  • Cristiana Mollinari
    • 3
  • Margherita D’Antuono
    • 2
  • Giovanna De Chiara
    • 3
  • Virginia Tancredi
    • 2
  • Daniela Merlo
    • 1
    • 3
  1. 1.IRCCS San Raffaele PisanaRomeItaly
  2. 2.Department of NeuroscienceUniversity of Rome Tor VergataRomeItaly
  3. 3.Department of Cell Biology and NeuroscienceIstituto Superiore di SanitàRomeItaly

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