Effect of varied gestational stress on acquisition of spatial memory, hippocampal LTP and synaptic proteins in juvenile male rats

Some but not other forms of prenatal stress have been shown to impair spatial memory in adult male offspring. It is not clear if this is because of the intensity of the stress, age of rats, or the way in which learning is assessed. We examined the effect of daily varied prenatal stress consisting of 30 min restraint, saline injections and 15 min forced swim on day 17-21 of gestation on spatial learning, synaptic plasticity and the expression of key proteins of the post synaptic density (PSD) in the hippocampus of males aged 4-5 weeks. Prenatal stress impaired spatial learning in the Morris water maze and induced a significant decrease in long-term potentiation (LTP) in hippocampal slices. There was no change in the paired pulse facilitation ratio but there was a significant reduction in the expression of the NR2B subunit of the Glutamate type NMDA receptor and the GluR I subunit of the AMPA receptor, both of which are important modulators of LTP. These changes were accompanied by a remarkable increase in the scaffolding protein PSD95, which interacts with the intracellular carboxy terminal domains of the NR2 subunits. The high levels of PSD95 may have contributed to the impairment of LTP by disrupting the clustering of NMDA receptors in CA1 synapses. The alteration by prenatal stress in the relative amounts of scaffolding proteins and those which compose glutamate receptors could explain the depression of LTP and impairment in the acquisition of spatial learning. (c) 2007 Elsevier B.V. All rights reserved.