Neonatal isolation accelerates the developmental switch in the signalling cascades for long-term potentiation induction.
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 alpha isoform of the CaMKII (CaMKIIalpha) gene. We also demonstrate that application of CRF to cultured hippocampal neurones significantly increases the expression of CaMKIIalpha, 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.
Huang
Chiung-Chun
CC
Department of Pharmacology, College of Medicine, National Cheng Kung University, No. 1, University Road, Tainan 701, Taiwan.
Chou
Pei-Hsuan
PH
Yang
Chih-Hao
CH
Hsu
Kuei-Sen
KS
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002227:Carbazoles / Q000494:pharmacology; D002478:Cells, Cultured; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology* / Q000254:growth & development; D007211:Indoles / Q000494:pharmacology; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D008426:Maternal Deprivation; D009474:Neurons / Q000187:drug effects / Q000201:enzymology; D010446:Peptide Fragments / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018019:Receptors, Corticotropin-Releasing Hormone / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects; D000099052:CRF Receptor, Type 1
D002227:Carbazoles; D004791:Enzyme Inhibitors; D007211:Indoles; D010446:Peptide Fragments; D011758:Pyrroles; D012333:RNA, Messenger; D018019:Receptors, Corticotropin-Releasing Hormone; C104416:astressin; C057416:KT 5720; D000099052:CRF Receptor, Type 1; D003346:Corticotropin-Releasing Hormone; D017868:Cyclic AMP-Dependent Protein Kinases; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases