Rescue of sharp wave-ripples and prevention of network hyperexcitability in the ventral but not the dorsal hippocampus of a rat model of fragile X syndrome.

Autor: Leontiadis LJ; Laboratory of Neurophysiology, Department of Medicine, University of Patras, Rion, Greece., Trompoukis G; Laboratory of Neurophysiology, Department of Medicine, University of Patras, Rion, Greece., Tsotsokou G; Laboratory of Neurophysiology, Department of Medicine, University of Patras, Rion, Greece., Miliou A; Laboratory of Neurophysiology, Department of Medicine, University of Patras, Rion, Greece., Felemegkas P; Laboratory of Neurophysiology, Department of Medicine, University of Patras, Rion, Greece., Papatheodoropoulos C; Laboratory of Neurophysiology, Department of Medicine, University of Patras, Rion, Greece.
Jazyk: angličtina
Zdroj: Frontiers in cellular neuroscience [Front Cell Neurosci] 2023 Dec 01; Vol. 17, pp. 1296235. Date of Electronic Publication: 2023 Dec 01 (Print Publication: 2023).
DOI: 10.3389/fncel.2023.1296235
Abstrakt: Fragile X syndrome (FXS) is a genetic neurodevelopmental disorder characterized by intellectual disability and is related to autism. FXS is caused by mutations of the fragile X messenger ribonucleoprotein 1 gene ( Fmr1 ) and is associated with alterations in neuronal network excitability in several brain areas including hippocampus. The loss of fragile X protein affects brain oscillations, however, the effects of FXS on hippocampal sharp wave-ripples (SWRs), an endogenous hippocampal pattern contributing to memory consolidation have not been sufficiently clarified. In addition, it is still not known whether dorsal and ventral hippocampus are similarly affected by FXS. We used a Fmr1 knock-out (KO) rat model of FXS and electrophysiological recordings from the CA1 area of adult rat hippocampal slices to assess spontaneous and evoked neural activity. We find that SWRs and associated multiunit activity are affected in the dorsal but not the ventral KO hippocampus, while complex spike bursts remain normal in both segments of the KO hippocampus. Local network excitability increases in the dorsal KO hippocampus. Furthermore, specifically in the ventral hippocampus of KO rats we found an increased effectiveness of inhibition in suppressing excitation and an upregulation of α1GABA A receptor subtype. These changes in the ventral KO hippocampus are accompanied by a striking reduction in its susceptibility to induced epileptiform activity. We propose that the neuronal network specifically in the ventral segment of the hippocampus is reorganized in adult Fmr1 -KO rats by means of balanced changes between excitability and inhibition to ensure normal generation of SWRs and preventing at the same time derailment of the neural activity toward hyperexcitability.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.
(Copyright © 2023 Leontiadis, Trompoukis, Tsotsokou, Miliou, Felemegkas and Papatheodoropoulos.)
Databáze: MEDLINE
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