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000016335 0247_ $$2pmid$$apmid:21893592
000016335 0247_ $$2DOI$$a10.1093/brain/awr202
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000016335 041__ $$aeng
000016335 082__ $$a610
000016335 084__ $$2WoS$$aClinical Neurology
000016335 084__ $$2WoS$$aNeurosciences
000016335 1001_ $$0P:(DE-HGF)0$$aGraebenitz, S.$$b0
000016335 245__ $$aInterictal-like network activity and receptor expression in the epileptic human lateral amygdala
000016335 260__ $$aOxford$$bOxford Univ. Press$$c2011
000016335 300__ $$a2929 - 2947
000016335 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article
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000016335 3367_ $$2BibTeX$$aARTICLE
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000016335 3367_ $$2DRIVER$$aarticle
000016335 440_0 $$0935$$aBrain$$v134$$x0006-8950$$y10
000016335 500__ $$aDeutsche Forschungsgemeinschaft (DFG; SFB-TR3, TP C3; to H. C. P. and E.J.S.); a research award (Max-Planck-Research Award 2007; to H. C. P.); the Helmholtz Alliances HelMA (Health in an Aging Society, to K.Z.); Systems Biology (to K.Z.).
000016335 520__ $$aWhile the amygdala is considered to play a critical role in temporal lobe epilepsy, conclusions on underlying pathophysiological mechanisms have been derived largely from experimental animal studies. Therefore, the present study aimed to characterize synaptic network interactions, focusing on spontaneous interictal-like activity, and the expression profile of transmitter receptors in the human lateral amygdala in relation to temporal lobe epilepsy. Electrophysiological recordings, obtained intra-operatively in vivo in patients with medically intractable temporal lobe epilepsy, revealed the existence of interictal activity in amygdala and hippocampus. For in vitro analyses, slices were prepared from surgically resected specimens, and sections from individual specimens were used for electrophysiological recordings, receptor autoradiographic analyses and histological visualization of major amygdaloid nuclei for verification of recording sites. In the lateral amygdala, interictal-like activity appeared as spontaneous slow rhythmic field potentials at an average frequency of 0.39 Hz, which occurred at different sites with various degrees of synchronization in 33.3% of the tested slices. Pharmacological blockade of glutamate α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors, but not N-methyl-D-aspartate receptors, abolished interictal-like activity, while the γ-aminobutyric acid A-type receptor antagonist bicuculline resulted in a dampening of activity, followed by highly synchronous patterns of slow rhythmic activity during washout. Receptor autoradiographic analysis revealed significantly higher α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, kainate, metabotropic glutamate type 2/3, muscarinic type 2 and adrenoceptor α(1) densities, whereas muscarinergic type 3 and serotonergic type 1A receptor densities were lower in the lateral amygdala from epileptic patients in comparison to autopsy controls. Concerning γ-aminobutyric acid A-type receptors, agonist binding was unaltered whereas antagonist binding sites were downregulated in the epileptic lateral amygdala, suggesting an altered high/low-affinity state ratio and concomitant reduced pool of total γ-aminobutyric acid A-type receptors. Together these data indicate an abnormal pattern of receptor densities and synaptic function in the lateral nucleus of the amygdala in epileptic patients, involving critical alterations in glutamate and γ-aminobutyric acid receptors, which may give rise to domains of spontaneous interictal discharges contributing to seizure activity in the amygdala.
000016335 536__ $$0G:(DE-Juel1)FUEK409$$2G:(DE-HGF)$$aFunktion und Dysfunktion des Nervensystems (FUEK409)$$cFUEK409$$x0
000016335 536__ $$0G:(DE-HGF)POF2-89571$$a89571 - Connectivity and Activity (POF2-89571)$$cPOF2-89571$$fPOF II T$$x1
000016335 588__ $$aDataset connected to Web of Science, Pubmed
000016335 65320 $$2Author$$alateral amygdala
000016335 65320 $$2Author$$ahuman temporal lobe epilepsy
000016335 65320 $$2Author$$afield potentials
000016335 65320 $$2Author$$atransmitter receptors
000016335 65320 $$2Author$$aintra-operative recording
000016335 650_2 $$2MeSH$$aAdolescent
000016335 650_2 $$2MeSH$$aAdult
000016335 650_2 $$2MeSH$$aAged
000016335 650_2 $$2MeSH$$aAmygdala: metabolism
000016335 650_2 $$2MeSH$$aAmygdala: physiopathology
000016335 650_2 $$2MeSH$$aChild
000016335 650_2 $$2MeSH$$aEpilepsy: metabolism
000016335 650_2 $$2MeSH$$aEpilepsy: physiopathology
000016335 650_2 $$2MeSH$$aFemale
000016335 650_2 $$2MeSH$$aHumans
000016335 650_2 $$2MeSH$$aMale
000016335 650_2 $$2MeSH$$aMiddle Aged
000016335 650_2 $$2MeSH$$aNerve Net: metabolism
000016335 650_2 $$2MeSH$$aNerve Net: physiopathology
000016335 650_2 $$2MeSH$$aNeurons: metabolism
000016335 650_2 $$2MeSH$$aReceptor, Muscarinic M2: metabolism
000016335 650_2 $$2MeSH$$aReceptor, Serotonin, 5-HT1A: metabolism
000016335 650_2 $$2MeSH$$aReceptors, AMPA: metabolism
000016335 650_2 $$2MeSH$$aReceptors, Adrenergic, alpha-1: metabolism
000016335 650_2 $$2MeSH$$aReceptors, Metabotropic Glutamate: metabolism
000016335 650_2 $$2MeSH$$aSynapses: metabolism
000016335 650_2 $$2MeSH$$aSynapses: physiology
000016335 650_7 $$00$$2NLM Chemicals$$aReceptor, Muscarinic M2
000016335 650_7 $$00$$2NLM Chemicals$$aReceptors, AMPA
000016335 650_7 $$00$$2NLM Chemicals$$aReceptors, Adrenergic, alpha-1
000016335 650_7 $$00$$2NLM Chemicals$$aReceptors, Metabotropic Glutamate
000016335 650_7 $$0112692-38-3$$2NLM Chemicals$$aReceptor, Serotonin, 5-HT1A
000016335 650_7 $$2WoSType$$aJ
000016335 7001_ $$0P:(DE-Juel1)VDB20460$$aKedo, O.$$b1$$uFZJ
000016335 7001_ $$0P:(DE-HGF)0$$aSpeckmann, E.J.$$b2
000016335 7001_ $$0P:(DE-HGF)0$$aGorji, A.$$b3
000016335 7001_ $$0P:(DE-HGF)0$$aPanneck, H.$$b4
000016335 7001_ $$0P:(DE-HGF)0$$aHans, V.$$b5
000016335 7001_ $$0P:(DE-Juel1)VDB1208$$aPalomero-Gallagher, N.$$b6$$uFZJ
000016335 7001_ $$0P:(DE-HGF)0$$aSchleicher, A.$$b7
000016335 7001_ $$0P:(DE-Juel1)131714$$aZilles, K.$$b8$$uFZJ
000016335 7001_ $$0P:(DE-HGF)0$$aPape, H.C.$$b9
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000016335 8567_ $$uhttp://dx.doi.org/10.1093/brain/awr202
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000016335 915__ $$0StatID:(DE-HGF)0010$$aJCR/ISI refereed
000016335 9141_ $$y2011
000016335 9132_ $$0G:(DE-HGF)POF3-571$$1G:(DE-HGF)POF3-570$$2G:(DE-HGF)POF3-500$$aDE-HGF$$bKey Technologies$$lDecoding the Human Brain$$vConnectivity and Activity$$x0
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000016335 9201_ $$0I:(DE-Juel1)INM-2-20090406$$gINM$$kINM-2$$lMolekulare Organisation des Gehirns$$x0
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