Abstract
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.
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This work was supported by a research grant (NSC96-2752-B-006-002-PAE) from the National Science Council of Taiwan.
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We declare that there are no actual or potential conflicts of interest. We affirm that there are no financial, personal, or other relationships with other people or organizations that have inappropriately influenced or biased our work.
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Ku, HY., Huang, YF., Chao, PH. et al. Neonatal Isolation Delays the Developmental Decline of Long-Term Depression in the CA1 Region of Rat Hippocampus. Neuropsychopharmacol 33, 2847–2859 (2008). https://doi.org/10.1038/npp.2008.36
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DOI: https://doi.org/10.1038/npp.2008.36
