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.
Key Words
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Article info
Publication history
Published online: April 23, 2012
Accepted:
March 18,
2012
Received in revised form:
March 15,
2012
Received:
November 29,
2011
Identification
Copyright
© 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
