Abstract
Prenatal exposure to alcohol affects the expression and function of glutamatergic neurotransmitter receptors in diverse brain regions. The present study was undertaken to fill a current gap in knowledge regarding the regional specificity of ethanol-related alterations in glutamatergic receptors in the frontal cortex. We quantified subregional expression and function of glutamatergic neurotransmitter receptors (AMPARs, NMDARs, GluN2B-containing NMDARs, mGluR1s, and mGluR5s) by radioligand binding in the agranular insular cortex (AID), lateral orbital area (LO), prelimbic cortex (PrL) and primary motor cortex (M1) of adult rats exposed to moderate levels of ethanol during prenatal development. Increased expression of GluN2B-containing NMDARs was observed in AID of ethanol-exposed rats compared to modest reductions in other regions. We subsequently performed slice electrophysiology measurements in a whole-cell patch-clamp preparation to quantify the sensitivity of evoked NMDAR-mediated excitatory postsynaptic currents (EPSCs) in layer II/III pyramidal neurons of AID to the GluN2B negative allosteric modulator ifenprodil. Consistent with increased GluN2B expression, ifenprodil caused a greater reduction in NMDAR-mediated EPSCs from prenatal alcohol-exposed rats than saccharin-exposed control animals. No alterations in AMPAR-mediated EPSCs or the ratio of AMPARs/NMDARs were observed. Together, these data indicate that moderate prenatal alcohol exposure has a significant and lasting impact on GluN2B-containing receptors in AID, which could help to explain ethanol-related alterations in learning and behaviors that depend on this region.
Highlights
Exposure to alcohol during nervous system development results in deficits in behavior and cognition [1,2,3,4,5,6,7,8,9,10]
In order to better understand the impacts of prenatal alcohol exposure (PAE) on excitatory neurotransmission in the frontal cortex, initial experiments in this study focused on autoradiography analysis of radioligand binding to glutamatergic neurotransmitter receptors in layer II/III pyramidal neurons in the frontal cortex
PAE did not have a significant effect on ligand binding to total NMDA, amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), mGluR2/3, or mGluR5 receptors in the regions examined (AID, lateral orbital area (LO), prelimbic cortex (PrL), M1). [3H]-Ifenprodil binding to GluN2B-containing NMDA receptors (NMDARs) was affected by PAE with increased [3H]-ifenprodil binding in cortical layers II/III of AID compared to modest decreases in binding in PrL, LO and M1
Summary
Exposure to alcohol during nervous system development results in deficits in behavior and cognition [1,2,3,4,5,6,7,8,9,10]. Recent studies estimate that between 2% and 5% of children in the United States
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