Oscillatory Population-Level Activity of Dorsal Raphe Serotonergic Neurons Is Inscribed in Sleep Structure

Kato, Tomonobu; Mitsukura, Yasue; Yoshida, Kouji; Mimura, Masaru; Takata, Norio; Tanaka, Kenji F.

doi:10.1523/jneurosci.2288-21.2022

Cited by 24 publications

(24 citation statements)

References 44 publications

(60 reference statements)

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“…During NREM sleep, PD fluctuates with increasing amplitude along with NREM duration, 33 indicating that mouse NREM sleep was not a monotonic state but was instead composed of different sleep depths, similar to that of humans. 63 A recent report noted that the oscillatory population-level activity of dorsal raphe serotonin neurons gradually increased in amplitude during NREM sleep, 64 which implies a relation between deeper NREM sleep and larger PD fluctuations. During REM sleep, two microstates can be defined using eye movement frequencies 65,66 : phasic REM sleep accompanies bursts of eye movements, and tonic REM sleep has fewer eye movements.…”

Section: Discussionmentioning

confidence: 99%

Pupil Dynamics-derived Sleep Stage Classification of a Head-fixed Mouse Using a Recurrent Neural Network

2023

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The standard method for sleep state classification is thresholding the amplitudes of electroencephalography (EEG) and electromyography (EMG) data, followed by manual correction by an expert. Although popular, this method has some shortcomings: (1) the time-consuming manual correction by human experts is sometimes a bottleneck hindering sleep studies, (2) EEG electrodes on the skull interfere with wide-field imaging of the cortical activity of a head-fixed mouse under a microscope, (3) invasive surgery to fix the electrodes on the thin mouse skull risks brain tissue injury, and (4) metal electrodes for EEG and EMG recording are difficult to apply to some experimental apparatus such as that for functional magnetic resonance imaging. To overcome these shortcomings, we propose a pupil dynamicsbased vigilance state classification method for a head-fixed mouse using a long short-term memory (LSTM) model, a variant of a recurrent neural network, for multi-class labeling of NREM, REM, and WAKE states. For supervisory hypnography, EEG and EMG recording were performed on head-fixed mice. This setup was combined with left eye pupillometry using a USB camera and a markerless tracking toolbox, DeepLabCut. Our open-source LSTM model with feature inputs of pupil diameter, pupil location, pupil velocity, and eyelid opening for 10 s at a 10 Hz sampling rate achieved vigilance state estimation with a higher classification performance (macro F1 score, 0.77; accuracy, 86%) than a feedforward neural network. Findings from a diverse range of pupillary dynamics implied possible subdivision of the vigilance states defined by EEG and EMG. Pupil dynamics-based hypnography can expand the scope of alternatives for sleep stage scoring of head-fixed mice.

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Section: Discussionmentioning

confidence: 99%

Pupil Dynamics-derived Sleep Stage Classification of a Head-fixed Mouse Using a Recurrent Neural Network

2023

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“…In addition to the NE system, previous studies also found disturbances in the serotonergic system, causing hyperactivity, reduced sociability and difficulties in coping with acute stress in 16p11.2 deletion mice [34,35]. Serotonergic neurons in the dorsal raphe nucleus are also activated with the infraslow σ rhythm during NREMs [36]. For future studies, it would be interesting to test whether the activity of serotonergic neurons in 16p11.2 del/+ mice is also disturbed during sleep, possibly contributing to sleep disturbances and whether restoring sleep can alleviate hyperactivity and improve sociability.…”

Section: Discussionmentioning

confidence: 98%

Circuit mechanism underlying fragmented sleep and memory deficits in 16p11.2 deletion mouse model of autism

Chung,

Choi,

Smith

et al. 2024

Preprint

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Sleep disturbances are prevalent in children with autism spectrum disorder (ASD) and have a major impact on the quality of life. Strikingly, sleep problems are positively correlated with the severity of ASD symptoms, such as memory impairment. However, the neural mechanisms underlying sleep disturbances and cognitive deficits in ASD are largely unexplored. Here, we show that non-rapid eye movement sleep (NREMs) is highly fragmented in the 16p11.2 deletion mouse model of ASD. The degree of sleep fragmentation is reflected in an increased number of calcium transients in the activity of locus coeruleus noradrenergic (LC-NE) neurons during NREMs. Exposure to a novel environment further exacerbates sleep disturbances in 16p11.2 deletion mice by fragmenting NREMs and decreasing rapid eye movement sleep (REMs). In contrast, optogenetic inhibition of LC-NE neurons and pharmacological blockade of noradrenergic transmission using clonidine reverse sleep fragmentation. Furthermore, inhibiting LC-NE neurons restores memory. Rabies-mediated unbiased screening of presynaptic neurons reveals altered connectivity of LC-NE neurons with sleep- and memory regulatory brain regions in 16p11.2 deletion mice. Our findings demonstrate that heightened activity of LC-NE neurons and altered brain-wide connectivity underlies sleep fragmentation in 16p11.2 deletion mice and identify a crucial role of the LC-NE system in regulating sleep stability and memory in ASD.

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“…In addition to the NE system, previous studies also found disturbances in the serotonergic system, causing hyperactivity, reduced sociability and difficulties in coping with acute stress in 16p11.2 deletion mice (Panzini et al, 2017; Mitchell et al, 2020). Serotonergic neurons in the dorsal raphe nucleus are also activated with the infraslow σ rhythm during NREMs (Kato et al, 2022). For future studies, it would be interesting to test whether the activity of serotonergic neurons in 16p11.2 del/+ mice is also disturbed during sleep, possibly contributing to sleep disturbances and whether restoring sleep can alleviate hyperactivity and improve sociability.…”

Section: Discussionmentioning

confidence: 99%

Circuit mechanism underlying fragmented sleep and memory deficits in 16p11.2 deletion mouse model of autism

Choi,

Smith,

Wang

et al. 2023

Preprint

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SUMMARYSleep disturbances are prevalent in children with autism spectrum disorder (ASD) and have a major impact on the quality of life. Strikingly, sleep problems are positively correlated with the severity of ASD symptoms, such as memory impairment. However, the neural mechanisms underlying sleep disturbances and cognitive deficits in ASD are largely unexplored. Here, we show that non-rapid eye movement sleep (NREMs) is highly fragmented in the 16p11.2 deletion mouse model of ASD. The degree of sleep fragmentation is reflected in an increased number of calcium transients in the activity of locus coeruleus noradrenergic (LC-NE) neurons during NREMs. Exposure to a novel environment further exacerbates sleep in 16p11.2 deletion mice by fragmenting NREMs and decreasing rapid eye movement sleep (REMs). In contrast, optogenetic inhibition of LC-NE neurons and pharmacological blockade of noradrenergic transmission using clonidine reverse sleep fragmentation in 16p11.2 deletion mice. Furthermore, inhibiting LC-NE neurons restores memory. Rabies-mediated unbiased screening of presynaptic neurons reveals altered connectivity of LC-NE neurons with sleep- and memory regulatory brain regions in 16p11.2 deletion mice. Our findings reveal that heightened activity of LC-NE neurons and altered brain-wide connectivity underlies sleep fragmentation in 16p11.2 deletion mice and identify a crucial role of the LC-NE system in regulating sleep stability and memory in ASD.

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Oscillatory Population-Level Activity of Dorsal Raphe Serotonergic Neurons Is Inscribed in Sleep Structure

Cited by 24 publications

References 44 publications

Pupil Dynamics-derived Sleep Stage Classification of a Head-fixed Mouse Using a Recurrent Neural Network

Pupil Dynamics-derived Sleep Stage Classification of a Head-fixed Mouse Using a Recurrent Neural Network

Circuit mechanism underlying fragmented sleep and memory deficits in 16p11.2 deletion mouse model of autism

Circuit mechanism underlying fragmented sleep and memory deficits in 16p11.2 deletion mouse model of autism

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