TY  - JOUR
AU  - Graebenitz, S.
AU  - Kedo, O.
AU  - Speckmann, E.J.
AU  - Gorji, A.
AU  - Panneck, H.
AU  - Hans, V.
AU  - Palomero-Gallagher, N.
AU  - Schleicher, A.
AU  - Zilles, K.
AU  - Pape, H.C.
TI  - Interictal-like network activity and receptor expression in the epileptic human lateral amygdala
JO  - Brain
VL  - 134
SN  - 0006-8950
CY  - Oxford
PB  - Oxford Univ. Press
M1  - PreJuSER-16335
SP  - 2929 - 2947
PY  - 2011
N1  - Deutsche 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.).
AB  - While 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.
KW  - Adolescent
KW  - Adult
KW  - Aged
KW  - Amygdala: metabolism
KW  - Amygdala: physiopathology
KW  - Child
KW  - Epilepsy: metabolism
KW  - Epilepsy: physiopathology
KW  - Female
KW  - Humans
KW  - Male
KW  - Middle Aged
KW  - Nerve Net: metabolism
KW  - Nerve Net: physiopathology
KW  - Neurons: metabolism
KW  - Receptor, Muscarinic M2: metabolism
KW  - Receptor, Serotonin, 5-HT1A: metabolism
KW  - Receptors, AMPA: metabolism
KW  - Receptors, Adrenergic, alpha-1: metabolism
KW  - Receptors, Metabotropic Glutamate: metabolism
KW  - Synapses: metabolism
KW  - Synapses: physiology
KW  - Receptor, Muscarinic M2 (NLM Chemicals)
KW  - Receptors, AMPA (NLM Chemicals)
KW  - Receptors, Adrenergic, alpha-1 (NLM Chemicals)
KW  - Receptors, Metabotropic Glutamate (NLM Chemicals)
KW  - Receptor, Serotonin, 5-HT1A (NLM Chemicals)
KW  - J (WoSType)
LB  - PUB:(DE-HGF)16
C6  - pmid:21893592
UR  - <Go to ISI:>//WOS:000295681400013
DO  - DOI:10.1093/brain/awr202
UR  - https://juser.fz-juelich.de/record/16335
ER  -