Abnormal Locus Coeruleus Sleep Activity Alters Sleep Signatures of Memory Consolidation and Impairs Place Cell Stability and Spatial Memory

Swift, Kevin; Gross, Brooks A.; Frazer, Michelle; Bauer, David S.; Clark, Kyle J.D.; Vazey, Elena M.; Aston‐Jones, Gary; Li, Yong; Pickering, Anthony E.; Sara, Susan J.; Poe, Gina R.

doi:10.1016/j.cub.2018.09.054

Cited by 111 publications

(114 citation statements)

References 61 publications

(90 reference statements)

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“…Since sleep spindles are associated with higher arousal threshold during NREM sleep 45, 46 , we analyzed their occurrence during liminal LC excitation associated with increased SEA probability. Indeed, LC optogenetic activation (at 10Hz) before sounds presented during NREM sleep decreased spindle occurrence (0.052 spindles/sec vs. 0.036 spindles/sec for ‘laser off’ and ‘laser on’ trials, respectively, n=8 rats, p=0.017 via one-tail paired t-test), in agreement with previous studies 12, 38…”

Section: Resultssupporting

confidence: 91%

Locus-coeruleus norepinephrine activity gates sensory-evoked awakenings from sleep

Hayat

Regev

Matosevich

et al. 2019

Preprint

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AbstractA defining feature of sleep is reduced responsiveness to external stimuli, but the mechanisms gating sensory-evoked arousal remain unclear. We hypothesized that reduced locus-coeruleus norepinephrine (LC-NE) activity during sleep mediates unresponsiveness, and its action promotes sensory-evoked awakenings. We tested this using electrophysiological, behavioral, pharmacological, and optogenetic techniques alongside auditory stimulation in freely behaving rats. We found that systemic reduction of NE signaling lowered probability of sound-evoked awakenings (SEAs). The level of tonic LC activity during sleep anticipated SEAs. Optogenetic LC activation promoted arousal as evident in sleep-wake transitions, EEG desynchronization, and pupil dilation. Importantly, liminal LC excitation before sound presentation increased SEA probability. Optogenetic LC silencing using a soma-targeted anion-conducting channelrhodopsin (stGtACR2) suppressed LC spiking and constricted pupils. Brief periods of LC opto-silencing reduced the probability of SEAs. Thus, LC-NE activity determines the likelihood of sensory-evoked awakenings and its reduction during sleep constitutes a key factor mediating behavioral unresponsiveness.

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Section: Resultssupporting

confidence: 91%

Locus-coeruleus norepinephrine activity gates sensory-evoked awakenings from sleep

Hayat

Regev

Matosevich

et al. 2019

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…Because sleep spindles are associated with higher arousal threshold during NREM sleep (27,28), we analyzed their occurrence during minimal LC excitation associated with increased SEA probability. LC optogenetic activation (at 10 Hz) before sounds presented during NREM sleep decreased spindle occurrence (0.052 spindles/s versus 0.036 spindles/s for "laser off" and "laser on" trials, respectively; n = 8 rats, P = 0.017 via one-tail paired t test), in agreement with previous studies (13,24).…”

Section: And Fig S2; Materials and Methods)supporting

confidence: 91%

Locus coeruleus norepinephrine activity mediates sensory-evoked awakenings from sleep

et al. 2020

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A defining feature of sleep is reduced responsiveness to external stimuli, but the mechanisms mediating sensory-evoked arousal remain unclear. We hypothesized that reduced locus coeruleus (LC) norepinephrine (NE) activity during sleep mediates unresponsiveness, and its action promotes sensory-evoked awakenings. We tested this using electrophysiological, behavioral, pharmacological, and optogenetic techniques alongside auditory stimulation in freely behaving rats. We found that systemic reduction in NE signaling lowered probability of sound-evoked awakenings (SEAs). The level of tonic LC activity during sleep anticipated SEAs. Optogenetic LC activation promoted arousal as evident in sleep-wake transitions, EEG desynchronization, and pupil dilation. Minimal LC excitation before sound presentation increased SEA probability. Optogenetic LC silencing using a soma-targeted anion-conducting channelrhodopsin (stGtACR2) suppressed LC spiking and constricted pupils. Brief periods of LC opto-silencing reduced the probability of SEAs. Thus, LC-NE activity determines the likelihood of sensory-evoked awakenings, and its reduction during sleep constitutes a key factor mediating behavioral unresponsiveness.

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“…2016 ). Further, the selective optogenetic addition of a low level of noradrenergic activity during sleep alters hippocampal memory consolidation ( Swift et al. 2018 ).…”

Section: Discussionmentioning

confidence: 99%

Noradrenaline Release from Locus Coeruleus Terminals in the Hippocampus Enhances Excitation-Spike Coupling in CA1 Pyramidal Neurons Via β-Adrenoceptors

2020

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Abstract Release of the neuromodulator noradrenaline signals salience during wakefulness, flagging novel or important experiences to reconfigure information processing and memory representations in the hippocampus. Noradrenaline is therefore expected to enhance hippocampal responses to synaptic input; however, noradrenergic agonists have been found to have mixed and sometimes contradictory effects on Schaffer collateral synapses and the resulting CA1 output. Here, we examine the effects of endogenous, optogenetically driven noradrenaline release on synaptic transmission and spike output in mouse hippocampal CA1 pyramidal neurons. We show that endogenous noradrenaline release enhances the probability of CA1 pyramidal neuron spiking without altering feedforward excitatory or inhibitory synaptic inputs in the Schaffer collateral pathway. β-adrenoceptors mediate this enhancement of excitation-spike coupling by reducing the charge required to initiate action potentials, consistent with noradrenergic modulation of voltage-gated potassium channels. Furthermore, we find the likely effective concentration of endogenously released noradrenaline is sub-micromolar. Surprisingly, although comparable concentrations of exogenous noradrenaline cause robust depression of slow afterhyperpolarization currents, endogenous release of noradrenaline does not, indicating that endogenous noradrenaline release is targeted to specific cellular locations. These findings provide a mechanism by which targeted endogenous release of noradrenaline can enhance information transfer in the hippocampus in response to salient events.

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Abnormal Locus Coeruleus Sleep Activity Alters Sleep Signatures of Memory Consolidation and Impairs Place Cell Stability and Spatial Memory

Cited by 111 publications

References 61 publications

Locus-coeruleus norepinephrine activity gates sensory-evoked awakenings from sleep

Locus-coeruleus norepinephrine activity gates sensory-evoked awakenings from sleep

Locus coeruleus norepinephrine activity mediates sensory-evoked awakenings from sleep

Noradrenaline Release from Locus Coeruleus Terminals in the Hippocampus Enhances Excitation-Spike Coupling in CA1 Pyramidal Neurons Via β-Adrenoceptors

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