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.

Citations

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, 'Absent sleep EEG spindle activity in GluA1 (Gria1) knockout mice: relevance to neuropsychiatric disorders', Translational Psychiatry (2018) 8:154

Sponsorship: Supported by: Wellcome Trust Strategic Award (098461/Z/12/Z), MRC NIRG (MR/L003635/1), BBSRC Industrial CASE grant (BB/K011847/1), FP7-PEOPLE-CIG (PCIG11-GA-2012-322050), John Fell OUP Research Fund Grant (131/032). RS receives support from the Ingeborg-Ständer Foundation, and from the German Research foundation (SFB1134/B01).

URI: https://www.oxfordhealth.nhs.uk/orka/title/absent-sleep-eeg-spindle-activity-in-glua1-gria1-knockout-mice-relevance-to-neuropsychiatric-disorders/