Cellular pathology of amygdala neurons in human temporal lobe epilepsy.
The amygdala complex substantially contributes to the generation and propagation of focal seizures in patients suffering from temporal lobe epilepsy (TLE). A cellular substrate for increased excitability in the human amygdala, however, remains to be identified. Here, we analyzed the three-dimensional morphology of 264 neurons from different subregions of the amygdaloid complex obtained from 17 "en bloc" resected surgical specimens using intracellular Lucifer Yellow (LY) injection and confocal laser scanning microscopy. Autopsy samples from unaffected individuals ( n=3, 20 neurons) served as controls. We have identified spine-laden, spine-sparse and aspinous cells in the lateral, basal, accessory basal and granular nuclei. Semiquantitative analysis points to significant changes in neuronal soma size, number of dendrites and spine densities in specimens from epilepsy patients compared to controls. Neuronal somata in the epilepsy group were smaller compared to controls ( P<0.01), neurons had fewer first-order dendrites ( P<0.01), whereas the maximum density of spines per dendritic segment in these cells was increased in TLE patients ( P<0.01). There were also dendritic alterations such as focal constrictions or spine bifurcations. These changes were consistent between amygdaloid subregions. The dendritic morphology of amygdaloid neurons in TLE patients points to substantial changes in synaptic connectivity and would be compatible with altered neuronal circuitries operating in the epileptic human amygdala. Although the morphological alterations differ from those described in hippocampal subregions of a similar cohort of TLE patients, they appear to reflect a characteristic pathological substrate associated with seizure activity/propagation within the amygdaloid complex.
Aliashkevich
Ales F
AF
Department of Neurosurgery, University of Bonn Medical Center, Sigmund-Freud-Str. 25, 53105 Bonn, Germany. ales_al@web.de
Yilmazer-Hanke
Deniz
D
Van Roost
Dirk
D
Mundhenk
Björn
B
Schramm
Johannes
J
Blümcke
Ingmar
I
D000328:Adult; D000679:Amygdala / Q000473:pathology*; D016022:Case-Control Studies; D003712:Dendrites / Q000648:ultrastructure; D004833:Epilepsy, Temporal Lobe / Q000473:pathology*; D006801:Humans; D008875:Middle Aged; D009474:Neurons / Q000473:pathology*