Neonatal Isolation Delays the Developmental Decline of Long-Term Depression in the CA1 Region of Rat Hippocampus

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.

Short-term environmental enrichment enhances synaptic plasticity in hippocampal slices from aged rats

“…We also could not find compelling evidence for the effect of post-weaning social isolation on LTD. However, neonatal social isolation delayed the age-related decline in the magnitude of LTD (Ku et al, 2008). If social isolation has the same effect in adult rodents, we would expect it to positively influence induction of LTD.…”

Unconjugated Bilirubin Exposure Impairs Hippocampal Long-Term Synaptic Plasticity

“…The PCR mixtures were incubated at 95°C for 10 min, and then 35 PCR cycles were conducted (95°C for 10 sec, 55°C for 15 sec and 68°C for 20 sec). The primer combinations were designed by referring to the rat studies by Pickering et al [61] and Ku et al [62]: NR1 5′-CTGCAACCCTCACTTTTGAG-3′ (forward) and 5′-TGCAAA AGCCAGCTGCATCT-5′ (reverse); NR2A, 5′-GACGGTCTTGGGATCTTA AC-3′ (forward) and 5′-TGACCATGAAATTGGTGCAGG-3′ (reverse); NR2B 5′-TGC ACAATTACTCCTCGACG-3′ (forward) and 5′-TCCGATTCTTCTTCTGAGCC-3′ (reverse); β-actin, 5′-TTCTACAATGAGCTGCGTGTGGC-3′ (forward) and 5′-CTCATAGCTCTTCTCCAGGGAGGA-3′ (reverse). Real-time RT-PCR reactions on mRNA obtained from control or neonatal isolated rat hippocampal CA1 total RNA samples were performed at the same time.…”

Activation of NMDA receptors reduces metabotropic glutamate receptor-induced long-term depression in the nucleus accumbens via a CaMKII-dependent mechanism

“…The concentration of DMSO in the perfusion medium was 0.1%, which alone had no effect on the excitatory glutamatergic transmission (Huang and Hsu, 2006). Drug doses were selected on the basis of published studies (Schnabel et al, 1999;Bartlett et al, 2007;Huang and Hsu, 2008;Ku et al, 2008;Huang et al, 2011) and pilot experiments in our laboratory. DHPG, MK-801, APV, R-(R,S)-a-(4-hydroxyphenyl)-b-methyl-4-(phenylmethyl)-1-piperidine propranol maleate (Ro25-6981), ifenprodil, LY367385, MPEP, gabazine, okadaic acid and KN-62 were purchased from Tocris Cookson (Bristol, UK).…”