Sleep and the hypothalamus Adamantidis, Antoine R.; de Lecea, Luis
Science (American Association for the Advancement of Science),
10/2023, Letnik:
382, Številka:
6669
Journal Article
Recenzirano
Neural substrates of wakefulness, rapid eye movement sleep (REMS), and non-REMS (NREMS) in the mammalian hypothalamus overlap both anatomically and functionally with cellular networks that support ...physiological and behavioral homeostasis. Here, we review the roles of sleep neurons of the hypothalamus in the homeostatic control of thermoregulation or goal-oriented behaviors during wakefulness. We address how hypothalamic circuits involved in opposing behaviors such as core body temperature and sleep compute conflicting information and provide a coherent vigilance state. Finally, we highlight some of the key unresolved questions and challenges, and the promise of a more granular view of the cellular and molecular diversity underlying the integrative role of the hypothalamus in physiological and behavioral homeostasis.
Thalamic dual control of sleep and wakefulness Gent, Thomas C; Bandarabadi, Mojtaba; Herrera, Carolina Gutierrez ...
Nature neuroscience,
07/2018, Letnik:
21, Številka:
7
Journal Article
Recenzirano
Odprti dostop
Slow waves (0.5-4 Hz) predominate in the cortical electroencephalogram during non-rapid eye movement (NREM) sleep in mammals. They reflect the synchronization of large neuronal ensembles alternating ...between active (UP) and quiescent (Down) states and propagating along the neocortex. The thalamic contribution to cortical UP states and sleep modulation remains unclear. Here we show that spontaneous firing of centromedial thalamus (CMT) neurons in mice is phase-advanced to global cortical UP states and NREM-wake transitions. Tonic optogenetic activation of CMT neurons induces NREM-wake transitions, whereas burst activation mimics UP states in the cingulate cortex and enhances brain-wide synchrony of cortical slow waves during sleep, through a relay in the anterodorsal thalamus. Finally, we demonstrate that CMT and anterodorsal thalamus relay neurons promote sleep recovery. These findings suggest that the tonic and/or burst firing pattern of CMT neurons can modulate brain-wide cortical activity during sleep and provides dual control of sleep-wake states.
Elucidation of the neural substrates underlying complex animal behaviors depends on precise activity control tools, as well as compatible readout methods. Recent developments in optogenetics have ...addressed this need, opening up new possibilities for systems neuroscience. Interrogation of even deep neural circuits can be conducted by directly probing the necessity and sufficiency of defined circuit elements with millisecond-scale, cell type-specific optical perturbations, coupled with suitable readouts such as electrophysiology, optical circuit dynamics measures and freely moving behavior in mammals. Here we collect in detail our strategies for delivering microbial opsin genes to deep mammalian brain structures in vivo, along with protocols for integrating the resulting optical control with compatible readouts (electrophysiological, optical and behavioral). The procedures described here, from initial virus preparation to systems-level functional readout, can be completed within 4-5 weeks. Together, these methods may help in providing circuit-level insight into the dynamics underlying complex mammalian behaviors in health and disease.
Rapid-eye movement (REM) sleep correlates with neuronal activity in the brainstem, basal forebrain and lateral hypothalamus. Lateral hypothalamus melanin-concentrating hormone (MCH)-expressing ...neurons are active during sleep, but their effects on REM sleep remain unclear. Using optogenetic tools in newly generated Tg(Pmch-cre) mice, we found that acute activation of MCH neurons (ChETA, SSFO) at the onset of REM sleep extended the duration of REM, but not non-REM, sleep episodes. In contrast, their acute silencing (eNpHR3.0, archaerhodopsin) reduced the frequency and amplitude of hippocampal theta rhythm without affecting REM sleep duration. In vitro activation of MCH neuron terminals induced GABAA-mediated inhibitory postsynaptic currents in wake-promoting histaminergic neurons of the tuberomammillary nucleus (TMN), and in vivo activation of MCH neuron terminals in TMN or medial septum also prolonged REM sleep episodes. Collectively, these results suggest that activation of MCH neurons maintains REM sleep, possibly through inhibition of arousal circuits in the mammalian brain.
The electrical activity of diverse brain cells is modulated across states of vigilance, namely wakefulness, non-rapid eye movement (NREM) sleep, and rapid eye movement (REM) sleep. Enhanced activity ...of neuronal circuits during NREM sleep impacts on subsequent awake behaviors, yet the significance of their activation, or lack thereof, during REM sleep remains unclear. This review focuses on feeding-promoting cells in the lateral hypothalamus (LH) that express the vesicular GABA and glycine transporter (vgat) as a model to further understand the impact of REM sleep on neural encoding of goal-directed behavior. It emphasizes both spatial and temporal aspects of hypothalamic cell dynamics across awake behaviors and REM sleep, and discusses a role for REM sleep in brain plasticity underlying energy homeostasis and behavioral optimization.
Hypothalamic neurons have an input–output connectivity map that encompasses much of the brain in vertebrates. These neurons are central in the modulation of homeostatic behaviors including feeding and sleep, suggesting that specific hypothalamic circuits share diverse physiological functions.Patterns of activity of lateral hypothalamus (LH) inhibitory neurons during awake feeding behavior show a high diversity of discharge profiles. These patterns of low and high cellular activities are conserved during rapid eye movement (REM) sleep. Emerging evidence reveals a role for sleep in the stabilization of the behavior encoded by these circuits.Sleep-dependent tuning of hypothalamic feeding circuits may be essential for the stability of the internal representation of behavior, optimization of strategies for behavioral adaptation to the environment, and species perpetuation.Understanding the spatiotemporal encoding of hypothalamic-controlled behaviors (e.g., reproduction, social interactions, aversion, and fight/flight responses) may lead to a more comprehensive view of the role of sleep in hypothalamic physiology and pathologies.
Oscillating circuitries in the sleeping brain Adamantidis, Antoine R; Gutierrez Herrera, Carolina; Gent, Thomas C
Nature reviews. Neuroscience,
12/2019, Letnik:
20, Številka:
12
Journal Article
Recenzirano
Brain activity during sleep is characterized by circuit-specific oscillations, including slow waves, spindles and theta waves, which are nested in thalamocortical or hippocampal networks. A major ...challenge is to determine the relationships between these oscillatory activities and the identified networks of sleep-promoting and wake-promoting neurons distributed throughout the brain. Improved understanding of the neurobiological mechanisms that orchestrate sleep-related oscillatory activities, both in time and space, is expected to generate further insight into the delineation of sleep states and their functions.
Abstract
Sleep spindle generation classically relies on an interplay between the thalamic reticular nucleus (TRN), thalamo-cortical (TC) relay cells and cortico-thalamic (CT) feedback during ...non-rapid eye movement (NREM) sleep. Spindles are hypothesized to stabilize sleep, gate sensory processing and consolidate memory. However, the contribution of non-sensory thalamic nuclei in spindle generation and the role of spindles in sleep-state regulation remain unclear. Using multisite thalamic and cortical LFP/unit recordings in freely behaving mice, we show that spike-field coupling within centromedial and anterodorsal (AD) thalamic nuclei is as strong as for TRN during detected spindles. We found that spindle rate significantly increases before the onset of rapid eye movement (REM) sleep, but not wakefulness. The latter observation is consistent with our finding that enhancing spontaneous activity of TRN cells or TRN-AD projections using optogenetics increase spindle rate and transitions to REM sleep. Together, our results extend the classical TRN-TC-CT spindle pathway to include non-sensory thalamic nuclei and implicate spindles in the onset of REM sleep.
Sleep-wake driven changes in non-rapid-eye-movement sleep (NREM) sleep (NREMS) EEG delta (δ-)power are widely used as proxy for a sleep homeostatic process. Here, we noted frequency increases in ...δ-waves in sleep-deprived mice, prompting us to re-evaluate how slow-wave characteristics relate to prior sleep-wake history. We identified two classes of δ-waves; one responding to sleep deprivation with high initial power and fast, discontinuous decay during recovery sleep (δ2) and another unrelated to time-spent-awake with slow, linear decay (δ1). Reanalysis of previously published datasets demonstrates that δ-band heterogeneity after sleep deprivation is also present in human subjects. Similar to sleep deprivation, silencing of centromedial thalamus neurons boosted subsequent δ2-waves, specifically. δ2-dynamics paralleled that of temperature, muscle tone, heart rate, and neuronal ON-/OFF-state lengths, all reverting to characteristic NREMS levels within the first recovery hour. Thus, prolonged waking seems to necessitate a physiological recalibration before typical NREMS can be reinstated.
Sleep-wake control and the thalamus Gent, Thomas C; Bassetti, Claudio LA; Adamantidis, Antoine R
Current opinion in neurobiology,
October 2018, 2018-10-00, 20181001, Letnik:
52
Journal Article
Recenzirano
•The midline and sensory thalami exhibit a dichotomy in sleep-wake control.•The thalamus, including RTN acts as integrator of sub-cortical sleep wake inputs.•Frontally originating sleep slow waves ...propagate via a relay in dorsal thalamus.•Midline thalamus projection to frontal cortex is require for sleep recovery.
Sleep is an essential component of animal behavior, controlled by both circadian and homeostatic processes. Typical brain oscillations for sleep and wake states are distinctive and reflect recurrent activity amongst neural circuits spanning localized to global brain regions. Since the original discovery of hypothalamic centers controlling both sleep and wakefulness, current views now implicate networks of neuronal and non-neuronal cells distributed brain-wide. Yet the mechanisms of sleep-wake control remain unclear. In light of recent studies, here we review experimental evidence from lesional, correlational, pharmacological and genetics studies, which support a role for the thalamus in several aspects of sleep-wake states. How these thalamo-cortical network mechanisms contribute to other executive functions such as memory consolidation and cognition, remains an open question with direct implications for neuro-psychiatric diseases and stands as a future challenge for basic science and healthcare research.
Phasic activation of dopaminergic neurons is associated with reward-predicting cues and supports learning during behavioral adaptation. While noncontingent activation of dopaminergic neurons in the ...ventral tegmental are (VTA) is sufficient for passive behavioral conditioning, it remains unknown whether the phasic dopaminergic signal is truly reinforcing. In this study, we first targeted the expression of channelrhodopsin-2 to dopaminergic neurons of the VTA and optimized optogenetically evoked dopamine transients. Second, we showed that phasic activation of dopaminergic neurons in freely moving mice causally enhances positive reinforcing actions in a food-seeking operant task. Interestingly, such effect was not found in the absence of food reward. We further found that phasic activation of dopaminergic neurons is sufficient to reactivate previously extinguished food-seeking behavior in the absence of external cues. This was also confirmed using a single-session reversal paradigm. Collectively, these data suggest that activation of dopaminergic neurons facilitates the development of positive reinforcement during reward-seeking and behavioral flexibility.
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