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Maternal care influences hippocampal N-methyl-D-aspartate receptor function and dynamic regulation by corticosterone in adulthood.

Abstract：

BACKGROUND:Variations in maternal care in the rat associate with robust differences in hippocampal development and synaptic plasticity in the offspring. Maternal care also influences pituitary-adrenal stress responses and corticosterone (CORT) regulation of hippocampal plasticity. N-methyl-D-aspartate receptors (NMDAR) regulate synaptic plasticity, and NMDAR function is modulated by stress and CORT. We hypothesized that altered NMDAR function underlies the interaction of maternal and stress effects on hippocampal synaptic plasticity. METHODS:We used electrophysiology and western blot to examine NMDAR synaptic function/expression and NMDAR-dependent long-term potentiation (LTP) in adult offspring of mothers that varied in the frequency of pup licking/grooming (LG) (i.e., High or Low LG). RESULTS:Basal NMDAR synaptic function was enhanced in the hippocampal dentate gyrus (DG) of adult Low LG offspring. Synaptic expression of NMDAR but not α-amino-3-hydroxy-methyl-4-isoxazole propionic acid receptors was also increased. Stress level CORT (100 nmol/L) rapidly (< 20 min) and robustly increased NMDAR function in High LG offspring, eliminating the maternal effect. Corticosterone did not affect NMDAR function in Low LG offspring. Bovine serum albumin-conjugated CORT reproduced the CORT effect in High LG offspring, implicating a membrane-bound corticosteroid receptor. NMDAR hyperfunction might impair synaptic plasticity. Partial NMDAR antagonism by low concentration DL-2-Amino-5-phosphonopentanoic acid rescued a basal LTP deficit in Low LG offspring and inhibited LTP in High LG offspring. CONCLUSIONS:Low LG offspring exhibit basally elevated NMDAR function coupled with insensitivity to CORT modulation indicative of a chronic alteration of NMDAR function. Elevated NMDAR function in the hippocampus might underlie impaired LTP in Low LG offspring.

journal_name

Biol Psychiatry

journal_title

Biological psychiatry

authors

Bagot RC,Tse YC,Nguyen HB,Wong AS,Meaney MJ,Wong TP

doi

10.1016/j.biopsych.2012.03.016

subject

Has Abstract

pub_date

2012-09-15 00:00:00

pages

491-8

issue

eissn

0006-3223

issn

1873-2402

pii

S0006-3223(12)00264-8

journal_volume

pub_type

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Maternal care influences hippocampal N-methyl-D-aspartate receptor function and dynamic regulation by corticosterone in adulthood.