Perisomatic Inhibition and Its Relation to Epilepsy and to Synchrony Generation in the Human Neocortex

躯体周围抑制及其与癫痫和人类新皮质同步生成的关系

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作者:Estilla Zsófia Tóth, Felicia Gyöngyvér Szabó, Ágnes Kandrács, Noémi Orsolya Molnár, Gábor Nagy, Attila G Bagó, Loránd Erőss, Dániel Fabó, Boglárka Hajnal, Bence Rácz, Lucia Wittner, István Ulbert, Kinga Tóth

Abstract

Inhibitory neurons innervating the perisomatic region of cortical excitatory principal cells are known to control the emergence of several physiological and pathological synchronous events, including epileptic interictal spikes. In humans, little is known about their role in synchrony generation, although their changes in epilepsy have been thoroughly investigated. This paper demonstraits how parvalbumin (PV)- and type 1 cannabinoid receptor (CB1R)-positive perisomatic interneurons innervate pyramidal cell bodies, and their role in synchronous population events spontaneously emerging in the human epileptic and non-epileptic neocortex, in vitro. Quantitative electron microscopy showed that the overall, PV+ and CB1R+ somatic inhibitory inputs remained unchanged in focal cortical epilepsy. On the contrary, the size of PV-stained synapses increased, and their number decreased in epileptic samples, in synchrony generating regions. Pharmacology demonstrated-in conjunction with the electron microscopy-that although both perisomatic cell types participate, PV+ cells have stronger influence on the generation of population activity in epileptic samples. The somatic inhibitory input of neocortical pyramidal cells remained almost intact in epilepsy, but the larger and consequently more efficient somatic synapses might account for a higher synchrony in this neuron population. This, together with epileptic hyperexcitability, might make a cortical region predisposed to generate or participate in hypersynchronous events.

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