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A single episode of neonatal seizures permanently alters glutamatergic synapses
Author(s) -
Cornejo Brandon J.,
Mesches Michael H.,
Coultrap Steven,
Browning Michael D.,
Benke Timothy A.
Publication year - 2007
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.21071
Subject(s) - neuroscience , long term potentiation , synaptic plasticity , glutamate receptor , glutamatergic , hippocampal formation , ampa receptor , hippocampus , dendritic spine , kainate receptor , metaplasticity , biology , psychology , receptor , biochemistry
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. Ann Neurol 2007