Interneuron‐mediated inhibition synchronizes neuronal activity during slow oscillation

• Published in: The Journal of physiology Vol. 590; no. 16; pp. 3987 - 4010
• Main Authors: Chen, Jen‐Yung, Chauvette, Sylvain, Skorheim, Steven, Timofeev, Igor, Bazhenov, Maxim
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.08.2012; Wiley Subscription Services, Inc; Blackwell Science Inc
• Subjects: Action Potentials; Animals; Biological Clocks - physiology; Cats - physiology; Cerebral Cortex - physiology; Cortical Synchronization - physiology; Interneurons - physiology; Nerve Net - physiology; Neurons - physiology; Neuroscience: Behavioural/Systems/Cognitive; Sleep; Sleep - physiology
• ISSN: 0022-3751; 1469-7793; 1469-7793
• DOI: 10.1113/jphysiol.2012.227462

Key points •  A signature of deep sleep in the EEG is large‐amplitude fluctuation of field potential, which reflects alternating periods of activity and silence in the thalamocortical network. •  Transitions between active and silent states of sleep slow oscillation are well synchronous between remote populations of neurons with the onsets of silent states synchronized better than the onsets of activity. •  We found that synaptic inhibition plays a major role in terminating active cortical states; strong synaptic inhibition is necessary to synchronize onsets of silent states during normal sleep slow oscillation. •  We further show that when synaptic inhibition is significantly reduced, active state termination is mediated by intrinsic hyperpolarizing conductances. •  Our study suggests that inhibitory interaction in the cortical network actively mediates the patterns of neural activity during slow‐wave sleep and may, therefore, contribute to various brain functions developed during deep sleep.   The signature of slow‐wave sleep in the electroencephalogram (EEG) is large‐amplitude fluctuation of the field potential, which reflects synchronous alternation of activity and silence across cortical neurons. While initiation of the active cortical states during sleep slow oscillation has been intensively studied, the biological mechanisms which drive the network transition from an active state to silence remain poorly understood. In the current study, using a combination of in vivo electrophysiology and thalamocortical network simulation, we explored the impact of intrinsic and synaptic inhibition on state transition during sleep slow oscillation. We found that in normal physiological conditions, synaptic inhibition controls the duration and the synchrony of active state termination. The decline of interneuron‐mediated inhibition led to asynchronous downward transition across the cortical network and broke the regular slow oscillation pattern. Furthermore, in both in vivo experiment and computational modelling, we revealed that when the level of synaptic inhibition was reduced significantly, it led to a recovery of synchronized oscillations in the form of seizure‐like bursting activity. In this condition, the fast active state termination was mediated by intrinsic hyperpolarizing conductances. Our study highlights the significance of both intrinsic and synaptic inhibition in manipulating sleep slow rhythms.