Abstract
Identifying the neuronal circuits and dynamics of sleep-to-wake transition is essential to understanding brain regulation of behavioral states, including sleep–wake cycles, arousal, and hyperarousal. Recent work by different laboratories has used optogenetics to determine the role of individual neuromodulators in state transitions. The optogenetically driven data do not yet provide a multi-dimensional schematic of the mechanisms underlying changes in vigilance states. This work presents a modeling framework to interpret, assist, and drive research on the sleep-regulatory network. We identify feedback, redundancy, and gating hierarchy as three fundamental aspects of this model. The presented model is expected to expand as additional data on the contribution of each transmitter to a vigilance state becomes available. Incorporation of conductance-based models of neuronal ensembles into this model and existing models of cortical excitability will provide more comprehensive insight into sleep dynamics as well as sleep and arousal-related disorders.
Highlights
A primary objective of this paper is to spawn motivation for analytical modeling in the study of sleep-to-wake transitions
ACh has recently been shown to be a powerful initiator of sleepto-wake transitions [79], optogenetic stimulation of the basal forebrain (BF) seems to be less effective than NE/locus coeruleus (LC) at promoting wakefulness
The authors [29, 67, 82, 85] have provided results to instantiate the coalescence of optogenetics and judicious analytical modeling
Summary
A primary objective of this paper is to spawn motivation for analytical modeling in the study of sleep-to-wake transitions. We will not address the role of individual Hcrt receptors (Hcrtr and Hcrtr2) in sleep/wake cycles, this component may be added to the model in the future. It has been recognized that new technology is needed to determine relationships between sleep and wake-promoting neural circuits and the manner in which the lateral hypothalamus, LC, dorsal raphe nucleus, laterodorsal tegmentum, VTA, tuberomammillary nucleus, and BF circuits interact to govern the sleep–wake transition. GOALS AND METHODOLOGY To explain the interaction of neural circuits that promote sleep and wakefulness, it is necessary to balance experimental and theoretical approaches. The first involves presenting insightful quantitative analysis which fits available data and explains the interactions between components of the sleep–wake circuitry This direction pertains mostly to the “interpret ” theme. The seminal work of Saper and colleagues [33,34,35] presented the flip–flop model of sleep state transition by considering two populations of mutually
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
