title: Interictal-like network activity and receptor expression in the epileptic human lateral amygdala.
abstract: 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.
authors: Institute of Physiology I, Westfaelische Wilhelms-Universität Münster, D-48149 Münster, Germany.
authors: Stéphanie
authors: S
authors: Graebenitz
authors: Olga
authors: O
authors: Kedo
authors: Erwin-Josef
authors: EJ
authors: Speckmann
authors: Ali
authors: A
authors: Gorji
authors: Heinz
authors: H
authors: Panneck
authors: Volkmar
authors: V
authors: Hans
authors: Nicola
authors: N
authors: Palomero-Gallagher
authors: Axel
authors: A
authors: Schleicher
authors: Karl
authors: K
authors: Zilles
authors: Hans-Christian
authors: HC
authors: Pape
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000679:Amygdala / Q000378:metabolism / Q000503:physiopathology*; D002648:Child; D004827:Epilepsy / Q000378:metabolism / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009415:Nerve Net / Q000378:metabolism / Q000503:physiopathology*; D009474:Neurons / Q000378:metabolism; D043585:Receptor, Muscarinic M2 / Q000378:metabolism; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism; D018091:Receptors, AMPA / Q000378:metabolism; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism; D013569:Synapses / Q000378:metabolism / Q000502:physiology*
chemical_list: D043585:Receptor, Muscarinic M2; D018091:Receptors, AMPA; D018340:Receptors, Adrenergic, alpha-1; D018094:Receptors, Metabotropic Glutamate; D044282:Receptor, Serotonin, 5-HT1A