Neonatal isolation delays the developmental decline of long-term depression in the CA1 region of rat hippocampus.
Activity-dependent alterations of synaptic efficacy or connectivity are essential for the development, signal processing, and learning and memory functions of the nervous system. It was observed that, in particular in the CA1 region of the hippocampus, low-frequency stimulation (LFS) became progressively less effective at inducing long-term depression (LTD) with advancing developmental age. The physiological factors regulating this developmental plasticity change, however, have not yet been elucidated. Here we examined the hypothesis that neonatal isolation (once per day for 1 h from postnatal days 1-7) is able to alter processes underlying the developmental decline of LTD. We confirm that the magnitude of LTD induced by LFS (900 stimuli at 1 Hz) protocol correlates negatively with developmental age and illustrates that neonatal isolation delays this developmental decline via the activation of corticotrophin-releasing factor (CRF) system. Furthermore, this modulation appears to be mediated by an increased transcription of N-methyl-D-aspartate receptor NR2B subunits. We also demonstrate that intracerebroventricular injection of CRF postnatally mimicked the effect of neonatal isolation to increase the expression of NR2B subunits and delayed the developmental decline of LTD, which was specifically blocked by CRF receptor 1 antagonist NBI27914 pretreatment. These results suggest a novel role for CRF in regulating developmental events in the hippocampus and indicate that although maternal deprivation is stressful for neonate, appropriate neonatal isolation can serve to promote an endocrine state that may regulate the gradual developmental change in the induction rules for synaptic plasticity in the hippocampal CA1 region.
Ku
Hsiao-Yun
HY
Department of Pharmacology, National Cheng Kung University, Tainan, Taiwan.
Huang
Yu-Fei
YF
Chao
Pei-Hsuan
PH
Huang
Chiung-Chun
CC
Hsu
Kuei-Sen
KS
D000375:Aging / Q000502:physiology*; D000814:Aniline Compounds / Q000494:pharmacology; D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism / Q000494:pharmacology; D004558:Electric Stimulation; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000033:anatomy & histology / Q000254:growth & development*; D036881:Long-Term Synaptic Depression / Q000502:physiology*; D008426:Maternal Deprivation; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009490:Neurosecretory Systems / Q000502:physiology; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D011743:Pyrimidines / Q000494:pharmacology; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics; D012934:Social Isolation / Q000523:psychology*; D013315:Stress, Psychological / Q000378:metabolism / Q000503:physiopathology; D009435:Synaptic Transmission / Q000502:physiology*; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology; D000099052:CRF Receptor, Type 1
C471210:2-methyl-4-(N-propyl-N-cycloproanemethylamino)-5-chloro-6-(2,4,6-trichloranilino)pyrimidine; D000814:Aniline Compounds; C121001:NR2B NMDA receptor; D011743:Pyrimidines; D012333:RNA, Messenger; D018019:Receptors, Corticotropin-Releasing Hormone; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D000099052:CRF Receptor, Type 1; D003346:Corticotropin-Releasing Hormone