Long-term effects of epileptic seizures during development in hippocampal and entorhinal cortex functions (Doctoral thesis)

Λισγάρας, Χρήστος-Παναγιώτης

We have earlier demonstrated that a single episode of early-life Status Epilepticus (SE) provokeslasting neurobiological effects persisting to adulthood and detectable in vitro and in vivo. In this work, we studied possible changes in adult IED frequency and concurrent HFOs (Rs, FRs) in hippocampal CA3 and medial entorhinal cortex networks (mEC), addressing their evolution and cholinergic control post-SE. In this setting, we have also aimed at detecting any correlation patterns between the IED frequency and HFOs, if any. Field potential recordings were made from the CA3 subfield of Temporal (T) and Septal (S) hippocampal slices or simultaneously from the pyramidal CA3 and mEC deep layers of hippocampalmEC (combined) slices. The slices were obtained either from Normal (N) or from animals subjected to a single PTZ-induced (60-90mg/Kg) generalized, sustained SE-like seizure (hereafter termed as “SE”) at PND 20. Spontaneous IEDs were induced in both areas (CA3, mEC) by bathing the slices (hippocampal, combined) either in Mg2+-free ACSF or in 4-Aminopyridine (4-AP, 50 μΜ). CA3 IED frequency of hippocampal slices was similar in same origin N slices across models, but differed in SE slices, being lower in Mg2+-free ACSF than in 4-AP, suggesting a long-term post-SE increase of a 4-AP sensitive K+ conductance(s). Bath application of cholinergics increased hippocampal-CA3 IED rates universally, but had region- and conditioning-specific effects on HFOs suggesting that IEDs and HFOs are different hypersynchronous phenomena generated within similar neuronal networks. Paired recordings from the pyramidal CA3 and mEC deep layers (V-VI) of combined (N or SE) slices, revealed that IED frequency was lower in mEC compared to CA3 in both models; isolation of the 2 areas did not alter this relationship. Also, CA3 IED frequency was similar in all slices (N, SE) however, mEC IED frequency was higher in SE vs N slices in both models. CA3 HFOs had 100 times higher power than those recorded from mEC. FR/R ratio was lower in CA3 vs mEC when they were functionally connected (Intact), a difference that disappeared when they were isolated. The FR/R ratio increased in CA3 in the absence of mEC; both in N and SE slices. Interestingly, the direction of the R and FR power changes post-SE was a mirror image between CA3 and mEC and also between N, SE slices, that is power increases in mEC corresponded to power decreases in CA3 post-SE. Immature SE has a profound impact on the communication modalities of CA3-mEC circuitry in the long term and results in region-specific effects across the septotemporal hippocampal axis. The post-SE changes in mEC network may enable this area to serve as an independent epileptogenic substrate post-SE, while the enhanced cholinergic facilitation of IED frequency in septal hippocampal extremity, suggests that at least to this area, the seizure threshold could be modified in a stimulus specific way. Overall, the sequalae of the early-life seizures depend on the affected area and on the stimuli that the adult brain faces.
Alternative title / Subtitle: χολινεργικός έλεγχος κι υψίσυχνες ταλαντώσεις μεσοκρισικών εκφορτίσεων in vitro
cholinergic control and high-frequency oscillations of interictal discharges in vitro
Institution and School/Department of submitter: Πανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Βιολογικών Εφαρμογών και Τεχνολογιών
Subject classification: Επιληψία
Keywords: Επιληψία,ιππόκαμπος,υψίσυχνες ταλαντώσεις,χολινεργικό σύστημα,epilepsy,hippocampus,high-frequency,cholinergic system
URI: https://olympias.lib.uoi.gr/jspui/handle/123456789/29624
Appears in Collections:Διδακτορικές Διατριβές

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