Impaired cognitive discrimination and discoordination of coupled theta-gamma oscillations in Fmr1 knockout mice

Neurobiology of Disease
Basma RadwanAndré Fenton

Abstract

Fragile X syndrome (FXS) patients do not make the fragile X mental retardation protein (FMRP). The absence of FMRP causes dysregulated translation, abnormal synaptic plasticity and the most common form of inherited intellectual disability. But FMRP loss has minimal effects on memory itself, making it difficult to understand why the absence of FMRP impairs memory discrimination and increases risk of autistic symptoms in patients, such as exaggerated responses to environmental changes. While Fmr1 knockout (KO) and wild-type (WT) mice perform cognitive discrimination tasks, we find abnormal patterns of coupling between theta and gamma oscillations in perisomatic and dendritic hippocampal CA1 local field potentials of the KO. Perisomatic CA1 theta-gamma phase-amplitude coupling (PAC) decreases with familiarity in both the WT and KO, but activating an invisible shock zone, subsequently changing its location, or turning it off, changes the pattern of oscillatory events in the LFPs recorded along the somato-dendritic axis of CA1. The cognition-dependent changes of this pattern of neural activity are relatively constrained in WT mice compared to KO mice, which exhibit abnormally weak changes during the cognitive challenge caused by cha...Continue Reading

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Citations

Dec 9, 2017·Nature Reviews. Drug Discovery·Elizabeth M Berry-KravisSébastien Jacquemont
Nov 17, 2017·Learning & Memory·Ain ChungAndré A Fenton
Dec 9, 2016·Journal of Neurophysiology·Stephen KeeleyJohn Rinzel
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Mar 21, 2017·Journal of Neurodevelopmental Disorders·Jun WangJohn A Sweeney
Mar 31, 2018·Frontiers in Molecular Neuroscience·Regina Dahlhaus
Aug 5, 2017·Frontiers in Human Neuroscience·Haleh AghajaniAhmet Omurtag
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Nov 9, 2018·Frontiers in Psychology·Elliot Murphy, Antonio Benítez-Burraco
Nov 7, 2017·Frontiers in Molecular Neuroscience·Laura CeolinEmma Puighermanal
Jun 26, 2020·Frontiers in Psychiatry·Nicholas MurphyRaymond Y Cho
Feb 20, 2021·Experimental Neurology·Rebeca Hernández-SotoFernando Peña-Ortega
Apr 30, 2021·Molecular Autism·Michael G MariscalUNKNOWN Developmental Synaptopathies Consortium
Oct 15, 2021·Journal of Neurodevelopmental Disorders·Patricia S PirbhoyDevin K Binder

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