Tonic facilitation of glutamate release by presynaptic NR2B-containing NMDA receptors is increased in the entorhinal cortex of chronically epileptic rats

Abstract

We have shown previously that when postsynaptic NMDA receptors are blocked, the frequency, but not amplitude, of spontaneous EPSCs (sEPSCs) at synapses in the entorhinal cortex is reduced by NMDA receptor antagonists, demonstrating that glutamate release is tonically facilitated by presynaptic NMDA autoreceptors. In the present study, we recorded sEPSCs using whole-cell voltage clamp in neurons in layer V in slices of the rat entorhinal cortex. Using specific antagonists for NR2A [(R)-[(S)-1-(4-bromo-phenyl)-ethylamino]-(2,3- dioxo-1,2,3,4-tetrahydroquinoxalin-5-yl)-methyl]-phosphonic acid] and NR2B [(αR,βS)-α-(4-hydroxyphenyl)-β-methyl-4-(phenylmethyl) -1-piperidinepropanol hydrochloride (Ro 25-6981)] subunit-containing receptors, we confirmed that in slices from juvenile rats (4-6 weeks of age), the autoreceptor is predominantly of the NR1-NR2B subtype. In older (4-6 months of age) control animals, the effect of the NR2B antagonist was less marked, suggesting a decline in autoreceptor function with development. In slices from rats (aged 4-6 months) exhibiting spontaneous recurrent seizures induced with a lithium-pilocarpine protocol, Ro 25-6981 again robustly reduced sEPSC frequency. The effect was equal to or greater than that seen in the juvenile slices and much more pronounced than that seen in the age-matched control animals. In all three groups, the NR2A antagonist was without effect on sEPSCs. These results suggest that there is a developmental decrease in NMDA autoreceptor function, which is reversed in a chronic epileptic condition. The enhanced autoreceptor function may contribute to seizure susceptibility and epileptogenesis in temporal lobe structures.

Publication DOI: https://doi.org/10.1523/JNEUROSCI.4413-05.2006
Divisions: College of Health & Life Sciences > Aston Pharmacy School
College of Health & Life Sciences
College of Health & Life Sciences > Clinical and Systems Neuroscience
College of Health & Life Sciences > Aston Brain Centre
Additional Information: Copyright © 2006 Society for Neuroscience
Uncontrolled Keywords: Chronic epilepsy,Entorhinal,Glutamate,NMDA,NR2B receptors,Presynaptic,Neuroscience(all)
Full Text Link:
Related URLs: http://www.scop ... tnerID=8YFLogxK (Scopus URL)
https://www.jne ... ontent/26/2/406 (Publisher URL)
PURE Output Type: Article
Published Date: 2006-01-11
Authors: Yang, Jian
Woodhall, Gavin L. (ORCID Profile 0000-0003-1281-9008)
Jones, Roland S G

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