Absent sleep EEG spindle activity in GluA1 (Gria1) knockout mice: relevance to neuropsychiatric disorders.

Abstract

Sleep EEG spindles have been implicated in attention, sensory processing, synaptic plasticity and memory consolidation. In humans, deficits in sleep spindles have been reported in a wide range of neurological and psychiatric disorders, including schizophrenia. Genome-wide association studies have suggested a link between schizophrenia and genes associated with synaptic plasticity, including the Gria1 gene which codes for the GluA1 subunit of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor. Gria1-/- mice exhibit a phenotype relevant for neuropsychiatric disorders, including reduced synaptic plasticity and, at the behavioural level, attentional deficits leading to aberrant salience. In this study we report a striking reduction of EEG power density including the spindle-frequency range (10-15 Hz) during sleep in Gria1-/- mice. The reduction of spindle-activity in Gria1-/- mice was accompanied by longer REM sleep episodes, increased EEG slow-wave activity in the occipital derivation during baseline sleep, and a reduced rate of decline of EEG slow wave activity (0.5-4 Hz) during NREM sleep after sleep deprivation. These data provide a novel link between glutamatergic dysfunction and sleep abnormalities in a schizophrenia-relevant mouse model.

• Authors: Gauri Ang, Laura E McKillop, Ross Purple, Cristina Blanco-Duque, Stuart N Peirson, Russell G Foster, Paul J Harrison, Rolf Sprengel, Kay E Davies, Peter L Oliver, David M Bannerman, Vladyslav V Vyazovskiy
• Journal: Translational psychiatry (Transl Psychiatry) Vol. 8 Issue 1 Pg. 154 (08 14 2018) ISSN: 2158-3188 [Electronic] United States
• PMID: 30108203 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Receptors, AMPA
• glutamate receptor ionotropic, AMPA 1

Topics

• Animals
• Disease Models, Animal
• Electroencephalography
• Genome-Wide Association Study
• Humans
• Male
• Memory Consolidation
• Mice
• Mice, Knockout
• Neuronal Plasticity (physiology)
• Phenotype
• Psychomotor Agitation
• Receptors, AMPA (genetics)
• Schizophrenia (genetics, physiopathology)
• Sleep (physiology)
• Sleep Deprivation (physiopathology)
• Sleep Stages (physiology)