Alterations in perisomatic inhibition contributes to the higher synchrony in human epileptic neocortical tissues
Estilla Zsófia Tóth1, 2, Loránd Erőss3, László Entz3, Attila Bagó3, Dániel Fabó3, István Ulbert1, 3, 4, Lucia Wittner1, 3, 4, Kinga Tóth1
Postoperative neocortical tissue of epileptic and non-epileptic (tumor) patients generates spontaneous synchronous population activity (SPA), in vitro. We described differences in the electrophysiological characteristics of SPAs generated by epileptic or non-epileptic samples: Higher excitability and synchrony characterized the neuronal circuits of epileptic neocortex which might contribute to the initiation of epileptiform synchronies. To reveal the possible structural basis of this hyperexcitability, the perisomatic innervation of pyramidal cells was examined (n=3 tumor-, n=3 epileptic specimens) and related to the generation of synchronies. The parvalbumin (PV)-positive perisomatic inhibitory innervation of pyramidal cells were studied at the electron microscopic level in regions where SPA emerged, in vitro (layer III). The synaptic coverage was determined as the sum of synaptic active zones (µm) per 100 µm soma perimeter.The number of PV-positive cells decreased in the epileptic neocortex, whereas no difference was seen in the axonal cloud. The total synaptic coverage of the perisomatic region of pyramidal cells was increased in the epileptic tissue compared to tumor, whereas the synaptic coverage provided by PV-immunolabelled terminals was significantly decreased. The increased perisomatic inhibitory innervation of principal cells suggest the sprouting of basket- and axo-axonic cell axons which may contribute to the elevated synchronization of the excitatory cells. The decreased number of PV-labelled interneurons and their reduced contribution to the synaptic coverage, may be the result of either the loss of PV-positive neurons or the lack of staining. Our results may shed light on how structural differences may impact in the development of pathological synchronies.