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.
Highlights
EEG spindles are oscillatory events[1] that occur predominantly during non-rapid eye movement (NREM) sleep[2], and have been described in several mammalian species[3]
EEG spectral analysis during NREM sleep revealed that Gria1−/− mice had a substantially lower frontal EEG
The regional difference in SWA during NREM sleep was substantially reduced in Gria1−/− mice: while SWA was approximately 50% higher in the frontal derivation as compared to the occipital cortex in wildtype mice (WT) animals, individual Gria1−/− mice were highly variable in this respect, resulting in, on average, similar values of SWA between the frontal and the occipital derivation (WT: frontal 395.1 ± 47.5 μV2/0.25 Hz, occipital 271.1 ± 35.2; Gria1−/−: frontal 345.2 ± 41.5, occipital: 406.6 ± 97.4 μV2/0.25 Hz; frontal as % of occipital: WT 155 ± 17.0%, Gria1−/−: 99.5 ± 15.9%, p < 0.05, Wilcoxon rank sum test)
Summary
EEG spindles are oscillatory events[1] that occur predominantly during non-rapid eye movement (NREM) sleep[2], and have been described in several mammalian species[3]. Spindles are generated within the reticular thaarousal[11,12], processing of external stimuli[13,14,15,16], attention[17,18,19], cognitive performance[20] and the consolidation of freshly encoded information[21,22,23,24,25], including hippocampal-to-neocortical information transfer during sleep[26,27,28,29]. The rhyth- spindle activity and brain function is supported by the mic hyperpolarisation of thalamocortical neurons leads to rebound spike bursts, which are transferred to the neocortex as spindles[8]. Spindle-activity has been extensively consistent observation that sleep spindles are reduced or have altered dynamics in neuropsychiatric disorders[2,30,31].
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