Axo-somatic inhibition of projection neurons in the lateral nucleus of amygdala in human temporal lobe epilepsy: an ultrastructural study

Here, we report ultrastructural alterations in the synaptic circuitry of the human amygdala related to neuronal cell densities in surgical specimens of patients suffering from temporal lobe epilepsy (TLE). The neuronal cell densities quantified in the basolateral complex of amygdala were significantly reduced only in the lateral nucleus (LA) of TLE patients as compared to autopsy or non-Ammon’s horn sclerosis (AHS) controls (Nissl staining, immunostaining against the neuronal marker NeuN). For this reason, we focussed on the LA to perform a more detailed quantitative ultrastructural analysis, which revealed an inverse correlation between the number of axo-somatic inhibitory synaptic profiles at the somata of glutamic acid decarboxylase (GAD)-negative projection neurons and the extent of perisomatic fibrillary gliosis. In contrast, the density of GAD-immunoreactive interneurons positively correlated with the number of axo-somatic inhibitory synaptic profiles. The fibrillary material in perisomatic glial cell processes was preferentially labeled by the astroglial marker S100B. In addition, a qualitative study of the dendrites of GAD- and parvalbumin (PARV)-containing interneurons showed that they were often contacted by asymmetrical excitatory synapses. Our results are in line with anatomical data from rodents and cats, which show that amygdalar interneurons form axo-somatic inhibitory synapses on GAD-negative projection neurons, whereas the interneurons themselves receive excitatory input from recurrent collaterals of projection neurons and from cortico- and thalamo-amygdalar afferents. The structural reorganization patterns observed in the GABAergic circuitry are compatible with a reduced feedback or feed forward inhibition of amygdalar projection neurons in human TLE.