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OBJECTIVE: The contribution of seizures to cognitive changes remains controversial. We tested the hypothesis that a single episode of neonatal seizures (sNS) on rat postnatal day (P) 7 permanently impairs hippocampal-dependent function in mature (P60) rats because of long-lasting changes at the synaptic level. METHODS: sNS was induced with subcutaneously injected kainate on P7. Learning, memory, mossy fiber sprouting, spine density, hippocampal synaptic plasticity, and glutamate receptor expression and subcellular distribution were measured at P60. RESULTS: sNS selectively impaired working memory in a hippocampal-dependent radial arm water-maze task without inducing mossy fiber sprouting or altering spine density. sNS impaired CA1 hippocampal long-term potentiation and enhanced long-term depression. Subcellular fractionation and cross-linking, used to determine whether glutamate receptor trafficking underlies the alterations of memory and synaptic plasticity, demonstrated that sNS induced a selective reduction in the membrane pool of glutamate receptor 1 subunits. sNS induced a decrease in the total amount of N-methyl-D-aspartate receptor 2A and an increase in the primary subsynaptic scaffold, PSD-95. INTERPRETATION: These molecular consequences are consistent with the alterations in plasticity and memory caused by sNS at the synaptic level. Our data demonstrate the cognitive impact of sNS and associate memory deficits with specific alterations in glutamatergic synaptic function.

Original publication

DOI

10.1002/ana.21071

Type

Journal article

Journal

Ann Neurol

Publication Date

05/2007

Volume

61

Pages

411 - 426

Keywords

Animals, Animals, Newborn, Blotting, Western, Cross-Linking Reagents, Dendrites, Disks Large Homolog 4 Protein, Electrophysiology, Excitatory Amino Acid Agonists, Female, Glutamic Acid, Hippocampus, Immunohistochemistry, Intracellular Signaling Peptides and Proteins, Kainic Acid, Maze Learning, Membrane Proteins, Memory, Mental Recall, Mossy Fibers, Hippocampal, Neuronal Plasticity, Pregnancy, Rats, Rats, Sprague-Dawley, Receptors, N-Methyl-D-Aspartate, Seizures, Subcellular Fractions, Synapses