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Identifier

000443434

Title

Investigation of neurophysiological mechanisms in the neonatal, juvenile and adolescent prefrontal cortex of a schizophrenia mouse model

Alternative Title

Μελέτη των νευροφυσιολογικών μηχανισμών του προμετοπιαίου φλοιού κατά τη νεογνική, νεανική και εφηβική ηλικία σε ένα μοντέλο σχιζοφρένειας μυών

Author

Δίσκος, Κωνσταντίνος Α.

Thesis advisor

Σιδηροπούλου, Κυριακή

Reviewer

Καραγωγέους, Δόμνα
Βιδάκη, Μαρίνα

Abstract

Schizophrenia is a common, severe and multifactorial neuropsychiatric disorder, for which current medication mainly focuses on treating the positive symptoms of the disease. In our study we aim to identify early-life neurophysiological changes using the methylazoxymethanol acetate (MAM) mouse model of schizophrenia compared to control mice (saline-treated). Our experiments included neonatal (P8-P11), juvenile (P15-P21) and adolescent (P40-P45), female and male C57BL/6J mice. Neonatal and juvenile mice were euthanatized and prefrontal cortical (PFC) brain slices were acquired for extracellular local field potential (LFP) recordings, followed by analysis for neuronal oscillations and up states frequency present in the recordings. Adolescent mice performed the temporal object recognition (TOR) task, and afterwards PFC brain slices were acquired, either for LFP or voltage clamp recordings to determine GABAA receptor reversal potential. Our results revealed a significant reduction regarding the resting-state neuronal oscillations of delta, theta, alpha and beta rhythms in neonatal MAM mice, but not in juvenile or adolescent MAM mice, compared to controls. Additionally, juvenile MAM PFC slices exhibited a significant increase in up states frequency. In control adolescent mice, ketamine application in PFC brain slices tended to increase the beta and gamma frequencies; however, in MAM adolescent mice ketamine tended to reduce the contribution of these frequencies, while simultaneously GABA-A reversal potential was more positive in MAM PFC slices compared to controls. Finally, adolescent MAM mice exhibited a significantly reduced discrimination index compared to control mice in TOR task. In conclusion, early-life alterations of neuronal oscillations could affect prefrontal cortical development and lead to cognitive deficits (recency memory deficits) observed in adolescence in MAM mice.

Language

English

Subject

Diazepam

Ketamine

MAM

Neuronal oscillations

Temporal order object recognition

UP states

Voltage clamp

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