Thalamic reticular nucleus induces fast and local modulation of arousal state

Lewis, Laurie; Voigts, Jakob; Flores, Francisco; Schmitt, L. Ian; Wilson, Matthew A.; Halassa, Michael M.; Brown, Emery N.

doi:10.7554/elife.08760

Cited by 168 publications

(210 citation statements)

References 76 publications

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“…S6), δ oscillations are coherent between cortex and thalamus. This suggests that slow oscillations might be generated locally in different regions of cortex or thalamus (22,24,52,53), whereas δ oscillations involve interactions between cortex and thalamus (54,55). Overall, our results suggest that propofol can induce a variety of dynamics that mediate functional impairment of both cortical and thalamocortical circuits.…”

Section: Discussionmentioning

confidence: 81%

“…Recordings in deafferented cortex show that slow oscillations can occur in the absence of thalamic connections (22). Yet basic functional anatomic and neurophysiological reasoning suggests that the thalamus is likely a significant participant in slow and δ oscillations (23,24). To address these questions in the context of induction and emergence from propofol anesthesia, we analyzed the coherence between the superficial layer (2/3, referred to as SL) and deep layers (5 and 6, referred to as DLs), layers of prelimbic cortex, and the different high-order thalamic nuclei (M, C, and S).…”

Section: Layers Of Prefrontal Cortex Are Differentially Affected By Pmentioning

confidence: 99%

“…Electroencephalogram (EEG) recordings in humans during gradual induction of unconsciousness with propofol show the appearance of frontal β oscillations (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30) at the onset of sedation, followed by the appearance of coherent frontal α (8-12 Hz) oscillations (7)(8)(9)(10) and widespread slow (0.1-1 Hz) and δ (1-4 Hz) oscillations (7,11,12) when subjects no longer respond to sensory stimuli. Biophysical models of neuronal dynamics have shown that whereas α and β oscillations can be generated by propofol's actions in cortex alone (13), coherent α oscillations require the participation of both thalamus and cortex (14).…”

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confidence: 99%

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Thalamocortical synchronization during induction and emergence from propofol-induced unconsciousness

Flores

Hartnack

Fath

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

151

130

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General anesthesia (GA) is a reversible drug-induced state of altered arousal required for more than 60,000 surgical procedures each day in the United States alone. Sedation and unconsciousness under GA are associated with stereotyped electrophysiological oscillations that are thought to reflect profound disruptions of activity in neuronal circuits that mediate awareness and cognition. Computational models make specific predictions about the role of the cortex and thalamus in these oscillations. In this paper, we provide in vivo evidence in rats that alpha oscillations (10-15 Hz) induced by the commonly used anesthetic drug propofol are synchronized between the thalamus and the medial prefrontal cortex. We also show that at deep levels of unconsciousness where movement ceases, coherent thalamocortical delta oscillations (1-5 Hz) develop, distinct from concurrent slow oscillations (0.1-1 Hz). The structure of these oscillations in both cortex and thalamus closely parallel those observed in the human electroencephalogram during propofol-induced unconsciousness. During emergence from GA, this synchronized activity dissipates in a sequence different from that observed during loss of consciousness. A possible explanation is that recovery from anesthesiainduced unconsciousness follows a "boot-up" sequence actively driven by ascending arousal centers. The involvement of medial prefrontal cortex suggests that when these oscillations (alpha, delta, slow) are observed in humans, self-awareness and internal consciousness would be impaired if not abolished. These studies advance our understanding of anesthesia-induced unconsciousness and altered arousal and further establish principled neurophysiological markers of these states.anesthesia | prefrontal cortex | thalamus | coherence | propofol G eneral anesthesia (GA) is a reversible drug-induced state consisting of unconsciousness, analgesia, amnesia, akinesia, and physiological stability (1). In the United States nearly 60,000 surgical procedures are conducted under GA every day, making GA one of the most common manipulations of the brain and central nervous system in medicine (1). The molecular mechanisms by which anesthetic drugs alter brain function have been well characterized (2, 3). Detailed analyses of neural circuitand systems-level mechanisms of GA are more recent (1, 4, 5). Understanding the system-wide effects of anesthetic drugs is necessary in order to understand how these drugs produce states of altered arousal and unconsciousness.One of the most commonly used anesthetic drugs is 2,6-diisopropylphenol (propofol), a GABA-A receptor agonist (6). Electroencephalogram (EEG) recordings in humans during gradual induction of unconsciousness with propofol show the appearance of frontal β oscillations (15-30 Hz) at the onset of sedation, followed by the appearance of coherent frontal α (8-12 Hz) oscillations (7-10) and widespread slow (0.1-1 Hz) and δ (1-4 Hz) oscillations (7, 11, 12) when subjects no longer respond to sensory stimuli. Biophysical models of neuronal dy...

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Section: Discussionmentioning

confidence: 81%

Section: Layers Of Prefrontal Cortex Are Differentially Affected By Pmentioning

confidence: 99%

mentioning

confidence: 99%

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Thalamocortical synchronization during induction and emergence from propofol-induced unconsciousness

Flores

Hartnack

Fath

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

151

130

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“…SWs emerge spontaneously in the neocortex, even after cortical de-afferentation 51 , but can also be elicited by optogenetic manipulation of TRN and thalamocortical neurons 52,53 suggesting that thalamic input shapes SW expression 22 . In contrast, spindle frequency rhythms are seen in the isolated TRN 54,55 , but not in the isolated cortex or other thalamic nuclei 55,56 .…”

Section: Discussionmentioning

confidence: 99%

Coordination of Slow Waves With Sleep Spindles Predicts Sleep-Dependent Memory Consolidation in Schizophrenia

Demanuele

Bartsch

Baran

et al. 2016

Sleep

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General rightsThis document is made available in accordance with publisher policies. Please cite only the published version using the reference above. Full terms of use are available: http://www.bristol.ac.uk/pure/about/ebr-terms Demanuele et al., 2016 1 This study is not a clinical trial. Demanuele et al., 2016 3 Coordination of Slow Waves with Sleep Spindles Predicts Sleep-Dependent Memory Consolidation in Schizophrenia AbstractStudy Objectives: Schizophrenia patients have correlated deficits in sleep spindle density and sleep-dependent memory consolidation. In addition to spindle density, memory consolidation is thought to rely on the precise temporal coordination of spindles with slow waves (SWs). We investigated whether this coordination is intact in schizophrenia and its relation to motor procedural memory consolidation.Methods: Twenty-one chronic medicated schizophrenia patients and 17 demographicallymatched healthy controls underwent two nights of polysomnography with training on the finger tapping motor sequence task (MST) on the second night and testing the following morning. We detected SWs (0.5-4Hz) and spindles during non-rapid eye-movement (NREM) sleep. We measured SW-spindle phase-amplitude coupling and its relation with overnight improvement of MST performance.Results: Patients did not differ from controls in the timing of SW-spindle coupling. In both groups spindles peaked during the SW upstate. For patients only, the later in the SW upstate that spindles peaked and the more reliable this phase relationship, the greater the overnight MST improvement.Regression models that included both spindle density and SW-spindle coordination predicted overnight improvement significantly better than either parameter alone suggesting that both contribute to memory consolidation.Conclusions: Schizophrenia patients show intact spindle-SW temporal coordination and these timing relationships, together with spindle density, predict sleep-dependent memory consolidation.These relations were seen only in patients suggesting that their memory is more dependent on optimal spindle-SW timing, possibly due to reduced spindle density. Interventions to improve memory may need to both increase spindle density and optimize the coordination of NREM oscillations.

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“…The slow oscillations modulate the alpha oscillations (7) and phaselimited spiking activity (8). Propofol's simultaneous actions in the cortex, thalamus, and in several brainstem nuclei contribute to these dynamics (2,6,8,9). Less research has been done on the neurophysiology of emergence from general anesthesia.…”

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confidence: 99%

Optogenetic activation of dopamine neurons in the ventral tegmental area induces reanimation from general anesthesia

Taylor

Dort

Kenny

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

211

179

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Dopamine (DA) promotes wakefulness, and DA transporter inhibitors such as dextroamphetamine and methylphenidate are effective for increasing arousal and inducing reanimation, or active emergence from general anesthesia. DA neurons in the ventral tegmental area (VTA) are involved in reward processing, motivation, emotion, reinforcement, and cognition, but their role in regulating wakefulness is less clear. The current study was performed to test the hypothesis that selective optogenetic activation of VTA DA neurons is sufficient to induce arousal from an unconscious, anesthetized state. Floxed-inverse (FLEX)-Channelrhodopsin2 (ChR2) expression was targeted to VTA DA neurons in DA transporter (DAT)-cre mice (ChR2+ group; n = 6). Optical VTA stimulation in ChR2+ mice during continuous, steady-state general anesthesia (CSSGA) with isoflurane produced behavioral and EEG evidence of arousal and restored the righting reflex in 6/6 mice. Pretreatment with the D1 receptor antagonist SCH-23390 before optical VTA stimulation inhibited the arousal responses and restoration of righting in 6/6 ChR2+ mice. In control DAT-cre mice, the VTA was targeted with a viral vector lacking the ChR2 gene (ChR2− group; n = 5). VTA optical stimulation in ChR2− mice did not restore righting or produce EEG changes during isoflurane CSSGA in 5/5 mice. These results provide compelling evidence that selective stimulation of VTA DA neurons is sufficient to induce the transition from an anesthetized, unconscious state to an awake state, suggesting critical involvement in behavioral arousal.anesthesia | ventral tegmental area | dopamine | optogenetics | arousal

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Thalamic reticular nucleus induces fast and local modulation of arousal state

Cited by 168 publications

References 76 publications

Thalamocortical synchronization during induction and emergence from propofol-induced unconsciousness

Thalamocortical synchronization during induction and emergence from propofol-induced unconsciousness

Coordination of Slow Waves With Sleep Spindles Predicts Sleep-Dependent Memory Consolidation in Schizophrenia

Optogenetic activation of dopamine neurons in the ventral tegmental area induces reanimation from general anesthesia

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