REM sleep stabilizes hypothalamic representation of feeding behavior

Oesch, Lukas; Gazea, Mary; Gent, Thomas C.; Bandarabadi, Mojtaba; Herrera, Carolina Gutierrez; Adamantidis, Antoine

doi:10.1073/pnas.1921909117

Cited by 21 publications

(7 citation statements)

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“…Importantly, rather than extracting calcium spikes, we decided to base our analyses on the original fluorescence signal, thus allowing the inclusion of subthreshold calcium activity in neurons which are likely implicated in sleep-dependent downregulation processes ( Bartram et al, 2017 ). This approach is commonly used for studying brain state-dependent changes of calcium activity that develop at a slow pace over several minutes in distinct cortical cell populations ( Cox et al, 2016 ; Oesch et al, 2020 ). Extracting calcium spikes would not be an optimal approach in these conditions, as the relatively low temporal resolution of the signal leads to distorted spike detection, especially in the presence of burst-like spike activity which typically accompanies spindles ( Peyrache et al, 2011 ; Fernandez and Lüthi, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Cell-Type-Specific Dynamics of Calcium Activity in Cortical Circuits over the Course of Slow-Wave Sleep and Rapid Eye Movement Sleep

2021

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Sleep shapes cortical network activity, fostering global homeostatic down-regulation of excitability while maintaining or even up-regulating excitability in selected networks in a manner that supports memory consolidation. Here we used two-photon calcium imaging of cortical layer 2/3 neurons in sleeping male mice to examine how these seemingly opposing dynamics are balanced in cortical networks. During slow-wave sleep (SWS) episodes, mean calcium activity of excitatory pyramidal (Pyr) cells decreased. Simultaneously, however, variance in Pyr population calcium activity increased, contradicting the notion of a homogenous down-regulation of network activity. Indeed, we identified a subpopulation of Pyr cells distinctly up-regulating calcium activity during SWS, which were highly active during sleep spindles known to support mnemonic processing. REM episodes following SWS were associated with a general down-regulation of Pyr cells -including the subpopulation of Pyr cells active during spindles -which persisted into following stages of sleep and wakefulness. Parvalbumin-positive inhibitory interneurons (PV-In) showed an increase in calcium activity during SWS episodes, while activity remained unchanged during REM sleep episodes. This supports the view that down-regulation of Pyr calcium activity during SWS results from increased somatic inhibition via PV-In, whereas down-regulation during REM sleep is achieved independently of such inhibitory activity. Overall, our findings show that SWS enables up-regulation of select cortical circuits (likely those which were involved in mnemonic processing) through a spindle-related process, whereas REM sleep mediates general down-regulation, possibly through synaptic renormalization. Significance Sleep is thought to globally down-regulate cortical excitability and, concurrently, to upregulate synaptic connections in neuron ensembles with newly encoded memory, with upregulation representing a function of sleep spindles. Using in-vivo two-photon calcium imaging in combination with surface EEG recordings, we classified cells based on their calcium activity during sleep spindles. Spindle-active pyramidal cells persistently increased calcium activity during slow wave sleep (SWS) episodes while spindle-inactive cells decreased calcium activity. Subsequent rapid-eye movement (REM) sleep episodes profoundly reduced calcium activity in both cell clusters. Results indicate that SWS allows for a spindle-related differential upregulation of ensembles whereas REM sleep functions to globally down-regulate networks.

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Section: Discussionmentioning

confidence: 99%

Cell-Type-Specific Dynamics of Calcium Activity in Cortical Circuits over the Course of Slow-Wave Sleep and Rapid Eye Movement Sleep

2021

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“…DR GABA neuronal stimulation also promoted wakefulness, possibly by suppressing or activating local sleep-or wake-promoting neurons in the LH, respectively. One may speculate that GABA release from DR GABA synapses could suppress the activity of sleep-promoting neurons, including REM sleep-promoting MCH neurons (Jego et al, 2013;Konadhode et al, 2013;Tsunematsu et al, 2014), REM active LH VGAT neurons (Hassani et al, 2010;Oesch et al, 2020), and REM-active Lh6x GABA neurons from the ventral zona incerta (K. Liu et al, 2017). In contrast, it could inhibit local inhibitory circuits that would result in the activation of the wake-promoting hypocretins/orexins neurons (Adamantidis et al, 2007), or wake-active LH VGAT neurons (Hassani et al, 2010;Herrera et al, 2016;Oesch et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

Reciprocal Lateral Hypothalamic and Raphe GABAergic Projections Promote Wakefulness

et al. 2021

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The lateral hypothalamus (LH), together with multiple neuromodulatory systems of the brain, such as the dorsal raphe nucleus (DR), is implicated in arousal, yet interactions between these systems are just beginning to be explored. Using a combination of viral tracing, circuit mapping, electrophysiological recordings from identified neurons, and combinatorial optogenetics in mice, we show that GABAergic neurons in the LH selectively inhibit GABAergic neurons in the DR, resulting in increased firing of a substantial fraction of its neurons that ultimately promotes arousal. These DR GABA neurons are wake active and project to multiple brain areas involved in the control of arousal, including the LH, where their specific activation potently influences local network activity leading to arousal from sleep. Our results show how mutual inhibitory projections between the LH and the DR promote wakefulness and suggest a complex arousal control by intimate interactions between long-range connections and local circuit dynamics.

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“…DR GABA neuronal stimulation also promoted wakefulness, possibly by suppressing or activating local sleep- or wake-promoting neurons in the LH, respectively. One may speculate that GABA release from DR GABA synapses could suppress the activity of sleep-promoting neurons including REM-sleep promoting MCH neurons (Jego et al, 2013; Konadhode et al, 2013; Tsunematsu et al, 2014), REM active LH VGAT neurons (Hassani et al, 2010; Oesch et al, 2020), REM-active Lh6x GABA neurons from the ventral zona incerta (Liu et al, 2017). In contrast, it could inhibit local inhibitory circuits that would result in the activation of the wake-promoting hypocretins/orexins neurons (Adamantidis et al, 2007), or wake-active LH VGAT neurons (Hassani et al, 2010; Herrera et al, 2016; Oesch et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

Reciprocal lateral hypothalamic and raphé GABAergic projections promote wakefulness

Gazea

Furdan

Sere

et al. 2020

Preprint

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The lateral hypothalamus (LH), together with multiple neuromodulatory systems of the brain, such as the dorsal raphe nucleus (DR), is implicated in arousal, yet interactions between these systems are just beginning to be explored. Using a combination of viral tracing, circuit mapping, electrophysiological recordings from identified neurons and combinatorial optogenetics, we show that GABAergic neurons in the LH selectively inhibit GABAergic neurons in the DR resulting in disinhibition of a substantial fraction of its neurons that ultimately promotes arousal. These DR GABAergic neurons are wake active and project to multiple brain areas involved in the control of arousal including the LH, where their specific activation potently influences local network activity leading to arousal from sleep. Our results show how mutual inhibitory projections between the LH and the DR promote wakefulness through disinhibitory mechanisms and suggest a complex arousal control by intimate interactions between long-range connections and local circuit dynamics.

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REM sleep stabilizes hypothalamic representation of feeding behavior

Cited by 21 publications

References 50 publications

Cell-Type-Specific Dynamics of Calcium Activity in Cortical Circuits over the Course of Slow-Wave Sleep and Rapid Eye Movement Sleep

Cell-Type-Specific Dynamics of Calcium Activity in Cortical Circuits over the Course of Slow-Wave Sleep and Rapid Eye Movement Sleep

Reciprocal Lateral Hypothalamic and Raphe GABAergic Projections Promote Wakefulness

Reciprocal lateral hypothalamic and raphé GABAergic projections promote wakefulness

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