Activity-dependent constraints on catecholamine signaling

Li, Li; Rana, Akshay N.; Li, Esther M.; Feng, Jiesi; Li, Yulong; Bruchas, Michael R.

doi:10.1016/j.celrep.2023.113566

Cell Reports

2023

DOI: 10.1016/j.celrep.2023.113566

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Activity-dependent constraints on catecholamine signaling

Li Li,

Akshay N. Rana,

Esther M. Li

et al.

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2024

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Cited by 9 publications

References 52 publications

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The Effects of Locus Coeruleus Optogenetic Stimulation on Global Spatiotemporal Patterns in Rats

Anumba,

Kelberman,

Pan

et al. 2024

Preprint

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Whole-brain intrinsic activity as detected by resting-state fMRI can be summarized by three primary spatiotemporal patterns. These patterns have been shown to change with different brain states, especially arousal. The noradrenergic locus coeruleus (LC) is a key node in arousal circuits and has extensive projections throughout the brain, giving it neuromodulatory influence over the coordinated activity of structurally separated regions. In this study, we used optogenetic-fMRI in rats to investigate the impact of LC stimulation on the global signal and three primary spatiotemporal patterns. We report small, spatially specific changes in global signal distribution as a result of tonic LC stimulation, as well as regional changes in spatiotemporal patterns of activity at 5 Hz tonic and 15 Hz phasic stimulation. We also found that LC stimulation had little to no effect on the spatiotemporal patterns detected by complex principal component analysis. These results show that the effects of LC activity on the BOLD signal in rats may be small and regionally concentrated, as opposed to widespread and globally acting.

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The Effects of Locus Coeruleus Optogenetic Stimulation on Global Spatiotemporal Patterns in Rats

Anumba,

Kelberman,

Pan

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

Noradrenergic tuning of arousal is coupled to coordinated movements

Li,

Rana,

et al. 2024

Preprint

Self Cite

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Matching arousal level to the motor activity of an animal is important for efficiently allocating cognitive resources and metabolic supply in response to behavioral demands, but how the brain coordinates changes in arousal and wakefulness in response to motor activity remains an unclear phenomenon. We hypothesized that the locus coeruleus (LC), as the primary source of cortical norepinephrine (NE) and promoter of cortical and sympathetic arousal, is well-positioned to mediate movement-arousal coupling. Here, using a combination of physiological recordings, fiber photometry, optogenetics, and behavioral tracking, we show that the LCNEactivation is tightly coupled to the return of organized movements during waking from an anesthetized state. Moreover, in an awake animal, movement initiations are coupled to LCNEactivation, while movement arrests, to LCNEdeactivation. We also report that LCNEactivity covaries with the depth of anesthesia and that LCNEphotoactivation leads to sympathetic activation, consistent with its role in mediating increased arousal. Together, these studies reveal a more nuanced, modulatory role that LCNEplays in coordinating movement and arousal.

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Restoration of locus coeruleus noradrenergic transmission during sleep

Sima,

Zhang,

Farriday

et al. 2024

Preprint

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Sleep is indispensable for health and wellbeing, but its basic function remains elusive. The locus coeruleus (LC) powerfully promotes arousal by releasing noradrenaline. We found that noradrenaline transmission is reduced by prolonged wakefulness and restored during sleep. Fiber-photometry imaging of noradrenaline using its biosensor showed that its release evoked by optogenetic LC neuron activation was strongly attenuated by three hours of sleep deprivation and restored during subsequent sleep. This is accompanied by the reduction and recovery of the wake-promoting effect of the LC neurons. The reduction of both LC evoked noradrenaline release and wake-inducing potency is activity dependent, and the rate of noradrenaline transmission recovery depends on mammalian target of rapamycin (mTOR) signaling. The decline and recovery of noradrenaline transmission also occur in spontaneous sleep-wake cycles on a timescale of minutes. Together, these results reveal an essential role of sleep in restoring transmission of a key arousal-promoting neuromodulator.

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Activity-dependent constraints on catecholamine signaling

Cited by 9 publications

References 52 publications

The Effects of Locus Coeruleus Optogenetic Stimulation on Global Spatiotemporal Patterns in Rats

The Effects of Locus Coeruleus Optogenetic Stimulation on Global Spatiotemporal Patterns in Rats

Noradrenergic tuning of arousal is coupled to coordinated movements

Restoration of locus coeruleus noradrenergic transmission during sleep

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