Regulation of dark period sleep by the Amygdala: A microinjection and optogenetics study

Wellman, Laurie L.; Lónárt, György; Adkins, Austin M.; Sanford, Larry D.

doi:10.1016/j.brainres.2022.147816

Cited by 7 publications

(4 citation statements)

References 51 publications

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“…When the dopamine level in the amygdala was instantaneously increased through photogenetic activation, NREM sleep in mice was terminated immediately, and REM sleep began simultaneously. The study confirmed that dopamine induces a transition from NREM sleep to REM sleep by binding to dopamine type II receptors on amygdala neurons ( 81 ), while inhibiting amygdala activity results in a decrease in REM sleep duration ( 82 ).…”

Section: Neural Mechanisms Of Rem Sleep Abnormalitiesmentioning

confidence: 53%

Genetic and neural mechanisms of sleep disorders in children with autism spectrum disorder: a review

Zhao

et al. 2023

Front. Psychiatry

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BackgroundThe incidence of sleep disorders in children with autism spectrum disorder (ASD) is very high. Sleep disorders can exacerbate the development of ASD and impose a heavy burden on families and society. The pathological mechanism of sleep disorders in autism is complex, but gene mutations and neural abnormalities may be involved.MethodsIn this review, we examined literature addressing the genetic and neural mechanisms of sleep disorders in children with ASD. The databases PubMed and Scopus were searched for eligible studies published between 2013 and 2023.ResultsProlonged awakenings of children with ASD may be caused by the following processes. Mutations in the MECP2, VGAT and SLC6A1 genes can decrease GABA inhibition on neurons in the locus coeruleus, leading to hyperactivity of noradrenergic neurons and prolonged awakenings in children with ASD. Mutations in the HRH1, HRH2, and HRH3 genes heighten the expression of histamine receptors in the posterior hypothalamus, potentially intensifying histamine’s ability to promote arousal. Mutations in the KCNQ3 and PCDH10 genes cause atypical modulation of amygdala impact on orexinergic neurons, potentially causing hyperexcitability of the hypothalamic orexin system. Mutations in the AHI1, ARHGEF10, UBE3A, and SLC6A3 genes affect dopamine synthesis, catabolism, and reuptake processes, which can elevate dopamine concentrations in the midbrain. Secondly, non-rapid eye movement sleep disorder is closely related to the lack of butyric acid, iron deficiency and dysfunction of the thalamic reticular nucleus induced by PTCHD1 gene alterations. Thirdly, mutations in the HTR2A, SLC6A4, MAOA, MAOB, TPH2, VMATs, SHANK3, and CADPS2 genes induce structural and functional abnormalities of the dorsal raphe nucleus (DRN) and amygdala, which may disturb REM sleep. In addition, the decrease in melatonin levels caused by ASMT, MTNR1A, and MTNR1B gene mutations, along with functional abnormalities of basal forebrain cholinergic neurons, may lead to abnormal sleep–wake rhythm transitions.ConclusionOur review revealed that the functional and structural abnormalities of sleep–wake related neural circuits induced by gene mutations are strongly correlated with sleep disorders in children with ASD. Exploring the neural mechanisms of sleep disorders and the underlying genetic pathology in children with ASD is significant for further studies of therapy.

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Section: Neural Mechanisms Of Rem Sleep Abnormalitiesmentioning

confidence: 53%

Genetic and neural mechanisms of sleep disorders in children with autism spectrum disorder: a review

Zhao

et al. 2023

Front. Psychiatry

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“…For example, noradrenergic and serotonergic neurons in the stress-responsive LC and DRN, respectively, are virtually silent during REM, and their activation has long been thought to inhibit its generation (Reviewed in ( Steriade and McCarley, 1990 )). The amygdala projects to these regions ( Krettek and Price, 1978 ; Price et al, 1987 ; Bernard et al, 1993 ; Petrov et al, 1994 ; Peyron et al, 1998 ), and we recently demonstrated that optogenetic activation of central nucleus of the amygdala (CNA) projections to RPO, but not SubC and PPT, could enhance dark period REM ( Wellman et al, 2022 ). Optogenetic activation of CNA projections into LC of rats inhibits neuronal firing which could assist in promoting REM ( Wellman et al, 2017a , Wellman et al, 2017b ), and its projections into other regions could play a role in modulating other REM related phenomena (Reviewed in ( Wellman et al, 2022 ).…”

Section: Neural Circuits and Regulation Of Integrated Stress And Fear...mentioning

confidence: 99%

“…The amygdala projects to these regions ( Krettek and Price, 1978 ; Price et al, 1987 ; Bernard et al, 1993 ; Petrov et al, 1994 ; Peyron et al, 1998 ), and we recently demonstrated that optogenetic activation of central nucleus of the amygdala (CNA) projections to RPO, but not SubC and PPT, could enhance dark period REM ( Wellman et al, 2022 ). Optogenetic activation of CNA projections into LC of rats inhibits neuronal firing which could assist in promoting REM ( Wellman et al, 2017a , Wellman et al, 2017b ), and its projections into other regions could play a role in modulating other REM related phenomena (Reviewed in ( Wellman et al, 2022 ). A variety of studies implicate these brainstem regions in mediating various aspects of the stress response.…”

Section: Neural Circuits and Regulation Of Integrated Stress And Fear...mentioning

confidence: 99%

Modeling integrated stress, sleep, fear and neuroimmune responses: Relevance for understanding trauma and stress-related disorders

Sanford

Wellman

Adkins

et al. 2023

Neurobiology of Stress

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“…Recent evidence indicates that the amygdala is part of a network together with the hippocampus and prefrontal cortex involved in fear memory consolidation during sleep (Miyawaki and Mizuseki, 2022). Furthermore, the central nucleus of the amygdala (CEA) projects to brainstem REM regulatory regions (Inagaki et al, 1983;Wellman et al, 2022) and recent evidence demonstrates that the amygdala actively participates in the regulation of sleep architecture (Hasegawa et al, 2022). Specifically, dopamine signaling in the basolateral amygdala (BL) is involved in promoting the transition from NREM to REM sleep (Hasegawa et al, 2022).…”

Section: Introductionmentioning

confidence: 99%

Regulation of dendritic spines in the amygdala following sleep deprivation

et al. 2023

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The amygdala is a hub of emotional circuits involved in the regulation of cognitive and emotional behaviors and its critically involved in emotional reactivity, stress regulation, and fear memory. Growing evidence suggests that the amygdala plays a key role in the consolidation of emotional memories during sleep. Neuroimaging studies demonstrated that the amygdala is selectively and highly activated during rapid eye movement sleep (REM) and sleep deprivation induces emotional instability and dysregulation of the emotional learning process. Regulation of dendritic spines during sleep represents a morphological correlate of memory consolidation. Several studies indicate that dendritic spines are remodeled during sleep, with evidence for broad synaptic downscaling and selective synaptic upscaling in several cortical areas and the hippocampus. Currently, there is a lack of information regarding the regulation of dendritic spines in the amygdala during sleep. In the present work, we investigated the effect of 5 h of sleep deprivation on dendritic spines in the mouse amygdala. Our data demonstrate that sleep deprivation results in differential dendritic spine changes depending on both the amygdala subregions and the morphological subtypes of dendritic spines. We observed decreased density of mushroom spines in the basolateral amygdala of sleep deprived mice, together with increased neck length and decreased surface area and volume. In contrast, we observed greater densities of stubby spines in sleep deprived mice in the central amygdala, indicating that downscaling selectively occurs in this spine type. Greater neck diameters for thin spines in the lateral and basolateral nuclei of sleep deprived mice, and decreases in surface area and volume for mushroom spines in the basolateral amygdala compared to increases in the cental amygdala provide further support for spine type-selective synaptic downscaling in these areas during sleep. Our findings suggest that sleep promotes synaptic upscaling of mushroom spines in the basolateral amygdala, and downscaling of selective spine types in the lateral and central amygdala. In addition, we observed decreased density of phosphorylated cofilin immunoreactive and growth hormone immunoreactive cells in the amygdala of sleep deprived mice, providing further support for upscaling of dendritic spines during sleep. Overall, our findings point to region- and spine type-specific changes in dendritic spines during sleep in the amygdala, which may contribute to consolidation of emotional memories during sleep.

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Regulation of dark period sleep by the Amygdala: A microinjection and optogenetics study

Cited by 7 publications

References 51 publications

Genetic and neural mechanisms of sleep disorders in children with autism spectrum disorder: a review

Genetic and neural mechanisms of sleep disorders in children with autism spectrum disorder: a review

Modeling integrated stress, sleep, fear and neuroimmune responses: Relevance for understanding trauma and stress-related disorders

Regulation of dendritic spines in the amygdala following sleep deprivation

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