Decoupling of Sleep-Dependent Cortical and Hippocampal Interactions in a Neurodevelopmental Model of Schizophrenia

• Published in: Neuron (Cambridge, Mass.) Vol. 76; no. 3; pp. 526 - 533
• Main Authors: Phillips, Keith G., Bartsch, Ullrich, McCarthy, Andrew P., Edgar, Dale M., Tricklebank, Mark D., Wafford, Keith A., Jones, Matt W.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 08.11.2012; Elsevier Limited; Cell Press
• Subjects: Activity patterns; Animal models; Animals; Brain; Circuits; Cortex; Data processing; Disease Models, Animal; EEG; Electrodes; Electroencephalography - methods; Electrophysiological recording; Female; Firing pattern; Hippocampus; Hippocampus - growth & development; Memory; Mental disorders; Monitoring systems; Neural networks; Neural Pathways - growth & development; Oscillations; Parvalbumin; Prefrontal Cortex - growth & development; Pregnancy; Rats; Rats, Sprague-Dawley; Rhythms; Rodents; Schizophrenia; Schizophrenia - physiopathology; Sleep; Sleep (NREM); Sleep - physiology; Spindles
• ISSN: 0896-6273; 1097-4199; 1097-4199
• DOI: 10.1016/j.neuron.2012.09.016

Rhythmic neural network activity patterns are defining features of sleep, but interdependencies between limbic and cortical oscillations at different frequencies and their functional roles have not been fully resolved. This is particularly important given evidence linking abnormal sleep architecture and memory consolidation in psychiatric diseases. Using EEG, local field potential (LFP), and unit recordings in rats, we show that anteroposterior propagation of neocortical slow-waves coordinates timing of hippocampal ripples and prefrontal cortical spindles during NREM sleep. This coordination is selectively disrupted in a rat neurodevelopmental model of schizophrenia: fragmented NREM sleep and impaired slow-wave propagation in the model culminate in deficient ripple-spindle coordination and disrupted spike timing, potentially as a consequence of interneuronal abnormalities reflected by reduced parvalbumin expression. These data further define the interrelationships among slow-wave, spindle, and ripple events, indicating that sleep disturbances may be associated with state-dependent decoupling of hippocampal and cortical circuits in psychiatric diseases. ► Abnormal neurodevelopment leads to fragmented NREM sleep in the MAM-E17 model ► Delta wave and spindle abnormalities match patterns of altered parvalbumin expression ► Spindle phase-locked units in frontal cortex fire during CA1 ripples in normal NREM ► Mistimed limbic-cortical oscillations during fragmented NREM may impair cognition A restless pillow makes a ruffled mind? Investigating sleep architecture and associated neural network activity in an animal model of schizophrenia, Phillips et al. propose a new sleep-dependent mechanism for cognitive deficits in neuropsychiatric disease.