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This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 569/3/789    most recent jphysiol.2005.098160v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Huang, C.-C. Articles by Hsu, K.-S. Search for Related Content PubMed PubMed Citation Articles by Huang, C.-C. Articles by Hsu, K.-S.

¹ Department of Pharmacology
² Institute of Basic Medical Sciences, College of Medicine
³ Centre for Gene Regulation and Signal transduction Research, National Cheng Kung University, Tainan 701, Taiwan

The molecular mechanisms underlying long-term potentiation (LTP) in the CA1 region of the hippocampus are known to vary with developmental age. The physiological factors regulating this developmental change, however, have not yet been elucidated. Here we show that mild neonatal isolation accelerates the developmental switch in the signalling cascades for hippocampal CA1 LTP induction from a cyclic AMP-dependent protein kinase (PKA)- to a Ca²⁺/calmodulin-dependent protein kinase II (CaMKII)-dependent pattern via the activation of the corticotrophin-releasing factor (CRF) system. Furthermore, this action appears to be mediated through an increased transcription of the isoform of the CaMKII (CaMKII) gene. We also demonstrate that application of CRF to cultured hippocampal neurones significantly increases the expression of CaMKII, which is blocked by the non-specific CRF receptor antagonist astressin, the specific CRF receptor 1 antagonist NBI 27911, and the PKA inhibitor KT5720, but not by the CRF receptor 2 antagonist K 41498, or the protein kinase C inhibitor, bisindolylmaleimide I. CRF signalling also mediates the normal maturation of LTP. These results suggest a novel role for CRF in regulating early developmental events in the hippocampus, and indicate that, although maternal deprivation is stressful for the neonate, appropriate neonatal isolation can serve to promote an endocrine state that fosters the rate of maturation of the signalling cascades underlying the induction of LTP in the developing hippocampus.

(Received 5 September 2005; accepted after revision 7 October 2005; first published online 13 October 2005)
Corresponding author K.-S. Hsu: Department of Pharmacology, College of Medicine, National Cheng Kung University, No. 1, University Road, Tainan 701, Taiwan. Email: richard{at}mail.ncku.edu.tw