A medullary hub for controlling REM sleep and pontine waves

Schott, Amanda L.; Baik, Justin; Chung, Shinjae; Weber, Franz

doi:10.1038/s41467-023-39496-0

Cited by 14 publications

(18 citation statements)

References 69 publications

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“…1F ). We used a linear regression model to predict the current POA GAD2 →TMN neural activity based on the preceding and following spectral EEG features (Weber et al, 2010; Schott et al, 2023). We found that the activity of POA GAD2 →TMN neurons is preceded by an increase in the θ and σ power and reduction in the δ (0.5-4.5 Hz) power ( Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Wake was defined by low δ power, high EMG power and high γ power (if not otherwise classified as REMs). Our automatic algorithm that has been previously used in (Weber et al, 2015, 2018; Chung et al, 2017; Antila et al, 2022; Smith et al, 2022; Stucynski et al, 2022; Schott et al, 2023) has 90.256 % accuracy compared with the manual scoring by expert annotators. We manually verified the automatic classification using a graphical user interface visualizing the raw EEG and EMG signals, EEG spectrograms, EMG amplitudes, and the hypnogram to correct for errors, by visiting each single 2.5 s epoch in the hypnograms.…”

Section: Methodsmentioning

confidence: 99%

“…We employed an automatic REMs detection algorithm (Weber et al, 2015, 2018; Stucynski et al, 2022; Schott et al, 2023) and used a small vibrating motor to terminate/restrict REMs (Cardis et al, 2021; Osorio-Forero et al, 2023) (https://github.com/luthilab/IntanLuthiLab). A small vibrating motor (DC 3V Mini Vibration Motor, diameter: 10mm, thickness: 3mm, BOJACK) with a soldered lobster claw clasp was attached to a small wire hook secured in the dental cement of each mouse head.…”

Section: Methodsmentioning

confidence: 99%

“…Wake was defined by low δ power, high EMG power and high γ power (if not otherwise classified as REMs). Our automatic algorithm that has been previously used in (Weber et al, 2015(Weber et al, , 2018Chung et al, 2017;Antila et al, 2022;Smith et al, 2022;Stucynski et al, 2022;Schott et al, 2023) Fiber photometry recordings were excluded if the signals suddenly shifted, likely due to a loose connection between the optic fiber and patch cable.…”

Section: Polysomnographic Recordingsmentioning

confidence: 99%

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Homeostatic regulation of REM sleep by the preoptic area of the hypothalamus

Maurer,

Lin,

Jin

et al. 2023

Preprint

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Rapid-eye-movement sleep (REMs) is characterized by activated electroencephalogram (EEG) and muscle atonia, accompanied by vivid dreams. REMs is homeostatically regulated, ensuring that any loss of REMs is compensated by a subsequent increase in its amount. However, the neural mechanisms underlying the homeostatic control of REMs are largely unknown. Here, we show that GABAergic neurons in the preoptic area of the hypothalamus projecting to the tuberomammillary nucleus (POAGAD2→TMN neurons) are crucial for the homeostatic regulation of REMs. POAGAD2→TMN neurons are most active during REMs, and inhibiting them specifically decreases REMs. REMs restriction leads to an increased number and amplitude of calcium transients in POAGAD2→TMN neurons, reflecting the accumulation of REMs pressure. Inhibiting POAGAD2→TMN neurons during REMs restriction blocked the subsequent rebound of REMs. Our findings reveal a hypothalamic circuit whose activity mirrors the buildup of homeostatic REMs pressure during restriction and that is required for the ensuing rebound in REMs.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Polysomnographic Recordingsmentioning

confidence: 99%

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Homeostatic regulation of REM sleep by the preoptic area of the hypothalamus

Maurer,

Lin,

Jin

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…3A ). To detect the onset of REMs, we adapted a previously applied automatic REMs detection algorithm (Weber et al, 2015Schott et al, 2023 ). Briefly, the animal's brain state was classified based on real-time analysis of the EEG/EMG signals.…”

Section: Poa Gad2 →Tmn Neurons Exhibit An Increased Number Of Calcium...mentioning

confidence: 99%

Homeostatic regulation of rapid eye movement sleep by the preoptic area of the hypothalamus

Maurer,

Lin,

Jin

et al. 2024

eLife

Self Cite

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Rapid-eye-movement sleep (REMs) is characterized by activated electroencephalogram (EEG) and muscle atonia, accompanied by vivid dreams. REMs is homeostatically regulated, ensuring that any loss of REMs is compensated by a subsequent increase in its amount. However, the neural mechanisms underlying the homeostatic control of REMs are largely unknown. Here, we show that GABAergic neurons in the preoptic area of the hypothalamus projecting to the tuberomammillary nucleus (POA GAD2 →TMN neurons) are crucial for the homeostatic regulation of REMs. POA GAD2 →TMN neurons are most active during REMs, and inhibiting them specifically decreases REMs. REMs restriction leads to an increased number and amplitude of calcium transients in POA GAD2 →TMN neurons, reflecting the accumulation of REMs pressure. Inhibiting POA GAD2 →TMN neurons during REMs restriction blocked the subsequent rebound of REMs. Our findings reveal a hypothalamic circuit whose activity mirrors the buildup of homeostatic REMs pressure during restriction and that is required for the ensuing rebound in REMs.

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Neuropathological spectrum of anti-IgLON5 disease and stages of brainstem tau pathology: updated neuropathological research criteria of the disease-related tauopathy

Gelpi,

Reinecke,

Gaig

et al. 2024

Acta Neuropathol

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Anti-IgLON5 disease is a unique condition that bridges autoimmunity and neurodegeneration. Since its initial description 10 years ago, an increasing number of autopsies has led to the observation of a broader spectrum of neuropathologies underlying a particular constellation of clinical symptoms. In this study, we describe the neuropathological findings in 22 patients with anti-IgLON5 disease from 9 different European centers. In 15 patients (68%), we observed a hypothalamic and brainstem-predominant tauopathy of varying severity in which the original research neuropathological criteria were readily applicable. This pathology was observed in younger patients (median age at onset 61 years) with a long disease duration (median 9 years). In contrast, in 7 (32%) patients, the originally described brainstem tauopathy was nearly absent or only minimal in the form of delicate threads, despite mild-to-moderate neurodegenerative features, consistent clinical symptoms and the presence of anti-IgLON5 antibodies in CSF and serum. These patients were older at onset (median 79 years) and had shorter disease duration (median < 1 year). Overall, about one-third of the patients showed concomitant TDP-43 pathology within the regions affected by tau pathology and/or neurodegeneration. Based on these observations and in view of the spectrum of the tau burden in the core regions involved in the disease, we propose a simple staging system: stage 1 mild neurodegeneration without overt or only minimal tau pathology, stage 2 moderate neurodegeneration and mild/ moderate tauopathy and stage 3 prominent neurodegeneration and tau pathology. This staging intends to reflect a potential (age- and time-dependent) progression of tau pathology, supporting the current notion that tau accumulation is a secondary phenomenon related to the presence of anti-IgLON5 antibodies in the CNS. Finally, we adapt the original research criteria of the anti-IgLON5 disease-related tauopathy to include the spectrum of pathologies observed in this larger postmortem series.

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A medullary hub for controlling REM sleep and pontine waves

Cited by 14 publications

References 69 publications

Homeostatic regulation of REM sleep by the preoptic area of the hypothalamus

Homeostatic regulation of REM sleep by the preoptic area of the hypothalamus

Homeostatic regulation of rapid eye movement sleep by the preoptic area of the hypothalamus

Neuropathological spectrum of anti-IgLON5 disease and stages of brainstem tau pathology: updated neuropathological research criteria of the disease-related tauopathy

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