Activation of Preoptic GABAergic or Glutamatergic Neurons Modulates Sleep-Wake Architecture, but Not Anesthetic State Transitions

Vanini, Giancarlo; Bassana, Marina; Mast, Megumi; Mondino, Alejandra; Cerda, Ivo; Phyle, Margaret; Chen, Vivian; Colmenero, Angelo; Hambrecht-Wiedbusch, Viviane S.; Mashour, George A.

doi:10.1016/j.cub.2019.12.063

Cited by 69 publications

(116 citation statements)

References 47 publications

(81 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For Cre-recombinase dependent expression of the excitatory designer receptor hM3Dq in preoptic glutamatergic (Vglut2+) neurons we used the adeno-associated viral vector AAV-hSyn-DIO-hM3D(Gq)-mCherry (Addgene; Cat.# 50459-AAV5) (Krashes et al, 2011;Vanini et al, 2020). In a separate group of mice used for control experiments, we used the Cre-dependent vector AAV-hSyn-DIO-mCherry (Addgene; Cat.# 50459-AAV5) that lacked the coding sequence for the designer receptor and only contained the fluorescent reporter mCherry.…”

Section: Viral Vector and Drugsmentioning

confidence: 99%

“…Core body temperature was maintained at 37 -38 ºC with a water-filled pad connected to a heat pump (Gaymar Industries, Orchard Park, NY, USA). For the medial-lateral preoptic region, vector injections were performed bilaterally (36 nL on each side); stereotaxic coordinates: AP = +0.15 mm, ML = ±0.5 mm and DV = -5.0 mm from bregma (Vanini et al, 2020). Injections were performed at a rate of 5 nL/min using a Hamilton Neuros Syringe 7000 (5 mL; Hamilton Company, Reno, NV, USA) mounted on a microinjection syringe pump, driven by a digital Micro2T controller (Model UMP3T-2; World Precision Instruments, Sarasota, FL, USA).…”

Section: Viral Injection and Electrode Implantation For Sleep Studiesmentioning

confidence: 99%

“…States of wakefulness, NREM, and REM sleep were manually scored in Spike2 in 5-second epochs using standard criteria described in a previous publication (Vanini et al, 2020). Wakefulness was defined by 8 low-amplitude, high-frequency EEG activity accompanied by an active EMG characterized by high tone with phasic movements.…”

Section: Analysis Of Sleep-wake Statesmentioning

confidence: 99%

“…The mean latency to NREM sleep and REM sleep onset was compared between treatment conditions. Additionally, we reanalyzed sleep recordings from a group of Vglut2-Cre mice used in a recent study with confirmed hM3Dq receptor expression within the MnPO of the hypothalamus (Vanini et al, 2020). The viral vector, surgical procedures, experimental design and dose of CNO were identical in both studies.…”

Section: Analysis Of Sleep-wake Statesmentioning

confidence: 99%

“…GABAergic neurons in the median, ventrolateral, and lateral-medial preoptic area are sleep-active (most co-express galanin) and innervate monoaminergic arousal-promoting systems (Sherin et al, 1998;Gaus et al, 2002;Uschakov et al, 2006;Hsieh et al, 2011;Chung et al, 2017). Activation of preoptic GABAergic and galaninergic neurons promotes NREM sleep (Chung et al, 2017;Harding et al, 2018;Kroeger et al, 2018;Vanini et al, 2020), and lesion (Lu et al, 2000;Ma et al, 2019) or neuromodulation of these neurons (Harding et al, 2018;Kroeger et al, 2018) alters the electroencephalogram (EEG) during sleep-wake states. Furthermore, a recent study using activity-dependent tagging and subsequent stimulation of previously tagged neurons showed that a subgroup of glutamatergic neurons within the median and medial preoptic nucleus of the hypothalamus promotes body cooling and NREM sleep (Harding et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Glutamatergic neurons in the preoptic hypothalamus promote wakefulness, destabilize NREM sleep, suppress REM sleep, and regulate cortical dynamics

Mondino

Hambrecht-Wiedbusch

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

Clinical and experimental data from the last nine decades indicate that the preoptic area of the hypothalamus is a critical node in a brain network that controls sleep onset and homeostasis. By contrast, we recently reported that a group of glutamatergic neurons in the lateral and medial preoptic area increases wakefulness, challenging the long-standing notion in sleep neurobiology that the preoptic area is exclusively somnogenic. However, the precise role of these subcortical neurons in the control of behavioral state transitions and cortical dynamics remains unknown. Therefore, in this study we used conditional expression of excitatory hM3Dq receptors in these preoptic glutamatergic (Vglut2+) neurons and show that their activation initiates wakefulness, decreases non-rapid eye movement (NREM) sleep, and causes a persistent suppression of rapid eye movement (REM) sleep. Activation of preoptic glutamatergic neurons also causes a high degree of NREM sleep fragmentation, promotes state instability with frequent arousals from sleep, and shifts cortical dynamics (including oscillations, connectivity, and complexity) to a more wake-like state. We conclude that a subset of preoptic glutamatergic neurons may initiate (but not maintain) arousals from sleep, and their inactivation may be required for NREM stability and REM sleep generation. Further, these data provide novel empirical evidence supporting the conclusion that the preoptic area causally contributes to the regulation of both sleep and wakefulness.

show abstract

Section: Viral Vector and Drugsmentioning

confidence: 99%

Section: Viral Injection and Electrode Implantation For Sleep Studiesmentioning

confidence: 99%

Section: Analysis Of Sleep-wake Statesmentioning

confidence: 99%

Section: Analysis Of Sleep-wake Statesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Glutamatergic neurons in the preoptic hypothalamus promote wakefulness, destabilize NREM sleep, suppress REM sleep, and regulate cortical dynamics

Mondino

Hambrecht-Wiedbusch

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

Divergent Neural Activity in the VLPO During Anesthesia and Sleep

Luo

Liu

et al. 2022

Advanced Science

View full text Add to dashboard Cite

The invention of general anesthesia (GA) represents a significant advance in modern clinical practices. However, the exact mechanisms of GA are not entirely understood. Because of the multitude of similarities between GA and sleep, one intriguing hypothesis is that anesthesia may engage the sleep‐wake regulation circuits. Here, using fiber photometry and micro‐endoscopic imaging of Ca2+ signals at both population and single‐cell levels, it investigates how various anesthetics modulate the neural activity in the ventrolateral preoptic nucleus (vLPO), a brain region essential for the initiation of sleep. It is found that different anesthetics primarily induced suppression of neural activity and tended to recruit a similar group of vLPO neurons; however, each anesthetic caused comparable modulations of both wake‐active and sleep‐active neurons. These results demonstrate that anesthesia creates a different state of neural activity in the vLPO than during natural sleep, suggesting that anesthesia may not engage the same vLPO circuits for sleep generation.

show abstract

Changes in sensorimotor cortex oscillatory activity by orexin‐A in the ventrolateral preoptic area of the hypothalamus reflect increased muscle tone

Mavanji

Teske

Kotz

et al. 2023

J of Neuroscience Research

View full text Add to dashboard Cite

Orexin-A (OXA) is a hypothalamic neuropeptide implicated in the regulation of wakefulness, appetite, reward processing, muscle tone, motor activity, and other physiological processes. The broad range of systems affected stems from the widespread projections of orexin neurons toward multiple brain regions regulating numerous physiological processes. Orexin neurons integrate nutritional, energetic, and behavioral cues and modulate the functions of target structures. Orexin promotes spontaneous physical activity (SPA), and we recently showed that orexin injected into the ventrolateral preoptic area (VLPO) of the hypothalamus increases behavioral arousal and SPA in rats. However, the specific mechanisms underlying the role of orexin in physical activity are unknown. Here we tested the hypothesis that OXA injected into the VLPO alters the oscillatory activity in the electroencephalogram (EEG) to reflect an increased excitability of the sensorimotor cortex, which may explain the associated increase in SPA. The results showed that OXA increased wakefulness following injections into the VLPO. In addition, OXA altered the power spectrum of the EEG during the awake state by decreasing the power of 5-19 Hz oscillations and increasing the power of >35 Hz oscillations, which are markers of increased sensorimotor excitability. Consistently, we found that OXA induced greater muscle activity. Furthermore, we found a similar change in power spectrum during slow-wave sleep, which suggests that OXA altered the EEG activity in a fundamental way, even in the absence of physical activity. These results support the idea that OXA increases the excitability of the sensorimotor system, which may explain the corresponding increase in awake time, muscle tone, and SPA.

show abstract

Activation of Preoptic GABAergic or Glutamatergic Neurons Modulates Sleep-Wake Architecture, but Not Anesthetic State Transitions

Cited by 69 publications

References 47 publications

Glutamatergic neurons in the preoptic hypothalamus promote wakefulness, destabilize NREM sleep, suppress REM sleep, and regulate cortical dynamics

Glutamatergic neurons in the preoptic hypothalamus promote wakefulness, destabilize NREM sleep, suppress REM sleep, and regulate cortical dynamics

Divergent Neural Activity in the VLPO During Anesthesia and Sleep

Changes in sensorimotor cortex oscillatory activity by orexin‐A in the ventrolateral preoptic area of the hypothalamus reflect increased muscle tone

Contact Info

Product

Resources

About