An Inhibitory Lateral Hypothalamic-Preoptic Circuit Mediates Rapid Arousals from Sleep

Venner, Anne; Luca, Roberto De; Sohn, Lauren T.; Bandaru, Sathyajit S.; Verstegen, Anne M.J.; Arrigoni, Elda; Fuller, Patrick M.

doi:10.1016/j.cub.2019.10.026

Cited by 53 publications

(52 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We speculate that activation of VP GABAergic neurons may inhibit LH inhibitory interneurons and disinhibit wakepromoting neurons (i.e., orexinergic neurons) [36], which would explain why we found increased c-Fos expression in LH orexinergic neurons following activation of VP GABAergic neurons. Indeed, a subset of LH GABAergic neurons send inputs to the sleep-promoting ventrolateral preoptic area and regulate wakefulness [37], whereas another subset sends inputs to other wake-promoting regions, including the tuberomammillary nucleus, ventral periaqueductal gray, and locus coeruleus, all of which may promote sleep. Nevertheless, certain subtypes of inhibitory interneurons may also receive VP GABAergic projections and regulate arousal.…”

Section: Discussionmentioning

confidence: 99%

Ventral pallidal GABAergic neurons control wakefulness associated with motivation through the ventral tegmental pathway

Luo

et al. 2020

Mol Psychiatry

View full text Add to dashboard Cite

The ventral pallidum (VP) regulates motivation, drug addiction, and several behaviors that rely on heightened arousal. However, the role and underlying neural circuits of the VP in the control of wakefulness remain poorly understood. In the present study, we sought to elucidate the specific role of VP GABAergic neurons in controlling sleep–wake behaviors in mice. Fiber photometry revealed that the population activity of VP GABAergic neurons was increased during physiological transitions from non-rapid eye movement (non-REM, NREM) sleep to either wakefulness or REM sleep. Moreover, chemogenetic and optogenetic manipulations were leveraged to investigate a potential causal role of VP GABAergic neurons in initiating and/or maintaining arousal. In vivo optogenetic stimulation of VP GABAergic neurons innervating the ventral tegmental area (VTA) strongly promoted arousal via disinhibition of VTA dopaminergic neurons. Functional in vitro mapping revealed that VP GABAergic neurons, in principle, inhibited VTA GABAergic neurons but also inhibited VTA dopaminergic neurons. In addition, optogenetic stimulation of terminals of VP GABAergic neurons revealed that they promoted arousal by innervating the lateral hypothalamus, but not the mediodorsal thalamus or lateral habenula. The increased wakefulness chemogenetically evoked by VP GABAergic neuronal activation was completely abolished by pretreatment with dopaminergic D1 and D2/D3 receptor antagonists. Furthermore, activation of VP GABAergic neurons increased exploration time in both the open-field and light–dark box tests but did not modulate depression-like behaviors or food intake. Finally, chemogenetic inhibition of VP GABAergic neurons decreased arousal. Taken together, our findings indicate that VP GABAergic neurons are essential for arousal related to motivation.

show abstract

Section: Discussionmentioning

confidence: 99%

Ventral pallidal GABAergic neurons control wakefulness associated with motivation through the ventral tegmental pathway

Luo

et al. 2020

Mol Psychiatry

View full text Add to dashboard Cite

show abstract

“…Following sleep deprivation, the PFC to LH projection could induce NREM sleep by inhibiting arousal-promoting GABA and orexin neurons in the LH 66,67 ; this would be a similar mechanism to how VTA GABA neurons induce NREM sleep by sending their GABAergic projections to the LH 23,68,69 . Sustained local stimulation of this projection could disinhibit REM sleep-promoting MCH/GABA cells 70 .…”

Section: Discussionmentioning

confidence: 99%

Sleep deprivation triggers somatostatin neurons in prefrontal cortex to initiate nesting and sleep via the preoptic and lateral hypothalamus

Tossell

Soto

et al. 2020

Preprint

View full text Add to dashboard Cite

AbstractAnimals undertake specific behaviors before sleep. Little is known about whether these innate behaviors, such as nest building, are actually an intrinsic part of the sleep-inducing circuitry. We found, using activity-tagging genetics, that mouse prefrontal cortex (PFC) somatostatin/GABAergic (SOM/GABA) neurons, which become activated during sleep deprivation, induce nest building when opto-activated. These tagged neurons induce sustained global NREM sleep if their activation is prolonged metabotropically. Sleep-deprivation-tagged PFC SOM/GABA neurons have long-range projections to the lateral preoptic (LPO) and lateral hypothalamus (LH). Local activation of tagged PFC SOM/GABA terminals in LPO and the LH induced nesting and NREM sleep respectively. Our findings provide a circuit link for how the PFC responds to sleep deprivation by coordinating sleep preparatory behavior and subsequent sleep.

show abstract

“…For photometry experiments, AAV10-EF1α-DIO-GCaMP6s (40 nl; acquired from PMF 65 was injected into the left SCN in male VIP-IRES-Cre mice.…”

Section: Methodsmentioning

confidence: 99%

Suprachiasmatic VIP neurons are required for normal circadian rhythmicity and comprised of molecularly distinct subpopulations

et al. 2020

Self Cite

View full text Add to dashboard Cite

The hypothalamic suprachiasmatic (SCN) clock contains several neurochemically defined cell groups that contribute to the genesis of circadian rhythms. Using cell-specific and genetically targeted approaches we have confirmed an indispensable role for vasoactive intestinal polypeptide-expressing SCN (SCN VIP) neurons, including their molecular clock, in generating the mammalian locomotor activity (LMA) circadian rhythm. Optogenetic-assisted circuit mapping revealed functional, di-synaptic connectivity between SCN VIP neurons and dorsomedial hypothalamic neurons, providing a circuit substrate by which SCN VIP neurons may regulate LMA rhythms. In vivo photometry revealed that while SCN VIP neurons are acutely responsive to light, their activity is otherwise behavioral state invariant. Single-nuclei RNAsequencing revealed that SCN VIP neurons comprise two transcriptionally distinct subtypes, including putative pacemaker and non-pacemaker populations. Altogether, our work establishes necessity of SCN VIP neurons for the LMA circadian rhythm, elucidates organization of circadian outflow from and modulatory input to SCN VIP cells, and demonstrates a subpopulation-level molecular heterogeneity that suggests distinct functions for specific SCN VIP subtypes.

show abstract

An Inhibitory Lateral Hypothalamic-Preoptic Circuit Mediates Rapid Arousals from Sleep

Cited by 53 publications

References 55 publications

Ventral pallidal GABAergic neurons control wakefulness associated with motivation through the ventral tegmental pathway

Ventral pallidal GABAergic neurons control wakefulness associated with motivation through the ventral tegmental pathway

Sleep deprivation triggers somatostatin neurons in prefrontal cortex to initiate nesting and sleep via the preoptic and lateral hypothalamus

Suprachiasmatic VIP neurons are required for normal circadian rhythmicity and comprised of molecularly distinct subpopulations

Contact Info

Product

Resources

About