A common neuronal ensemble in nucleus accumbens regulates pain-like behaviour and sleep

Sun, Haiyan; Li, Zhilin; Qiu, Zhentong; Shen, Yu; Guo, Qingchen; Hu, Su-Wan; Ding, Hai-Lei; An, Shuming; Cao, Jun-Li

doi:10.1038/s41467-023-40450-3

Cited by 16 publications

(3 citation statements)

References 82 publications

(186 reference statements)

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“…These modes involve different modules of noradrenergic neurons operating independently in terms of circuit function within their respective efferent domains, with distinct populations of cells assuming specific responsibilities [ 52 ]. Furthermore, there is evidence suggesting that the same group of cells can assume different roles [ 53 ]. Therefore, noradrenergic neurons in different parts of the LC may have different functions in pain, and even noradrenergic neurons in the same region may have different effects.…”

Section: Discussionmentioning

confidence: 99%

The crucial role of locus coeruleus noradrenergic neurons in the interaction between acute sleep disturbance and headache

Li,

Cao,

Yuan

et al. 2024

J Headache Pain

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Background Both epidemiological and clinical studies have indicated that headache and sleep disturbances share a complex relationship. Although headache and sleep share common neurophysiological and anatomical foundations, the mechanism underlying their interaction remains poorly understood. The structures of the diencephalon and brainstem, particularly the locus coeruleus (LC), are the primary sites where the sleep and headache pathways intersect. To better understand the intricate nature of the relationship between headache and sleep, our study focused on investigating the role and function of noradrenergic neurons in the LC during acute headache and acute sleep disturbance. Method To explore the relationship between acute headache and acute sleep disturbance, we primarily employed nitroglycerin (NTG)-induced migraine-like headache and acute sleep deprivation (ASD) models. Initially, we conducted experiments to confirm that ASD enhances headache and that acute headache can lead to acute sleep disturbance. Subsequently, we examined the separate roles of the LC in sleep and headache. We observed the effects of drug-induced activation and inhibition and chemogenetic manipulation of LC noradrenergic neurons on ASD-induced headache facilitation and acute headache-related sleep disturbance. This approach enabled us to demonstrate the bidirectional function of LC noradrenergic neurons. Results Our findings indicate that ASD facilitated the development of NTG-induced migraine-like headache, while acute headache affected sleep quality. Furthermore, activating the LC reduced the headache threshold and increased sleep latency, whereas inhibiting the LC had the opposite effect. Additional investigations demonstrated that activating LC noradrenergic neurons further intensified pain facilitation from ASD, while inhibiting these neurons reduced this pain facilitation. Moreover, activating LC noradrenergic neurons exacerbated the impact of acute headache on sleep quality, while inhibiting them alleviated this influence. Conclusion The LC serves as a significant anatomical and functional region in the interaction between acute sleep disturbance and acute headache. The involvement of LC noradrenergic neurons is pivotal in facilitating headache triggered by ASD and influencing the effects of headache on sleep quality.

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Section: Discussionmentioning

confidence: 99%

The crucial role of locus coeruleus noradrenergic neurons in the interaction between acute sleep disturbance and headache

Li,

Cao,

Yuan

et al. 2024

J Headache Pain

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“…Our ndings build upon this concept, demonstrating how speci c astrocytes within ensembles, but not the entire population, integrate inputs to shape goal-related representations within the NAc. Such encoding of discrete stimuli and their corresponding behavioral responses has been demonstrated in NAc neuronal ensembles [50][51][52][53][54][55][56][57][58] . While further research is necessary to unravel the mechanistic interplay between these neuronal and astrocytic ensembles, the versatility of the AstroLight tool has the potential to advance the eld in addressing these questions.…”

Section: Discussionmentioning

confidence: 99%

Catching Astrocyte Ensembles: Astrocytic Ensembles Control Cue-motivated Behavior

Navarrete,

Serra,

Quintanilla

et al. 2023

Preprint

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Astrocytes, dynamic cells that play a crucial role in brain function, have traditionally been overshadowed by the emphasis on neuronal activity in regulating behavior. This is in part due to the lack of tools to experimentally map and manipulate specific subsets of astrocytes based on their functional activity, which hampers our understanding of how astrocyte networks contribute to the organization of behavior. Here, using a tool that can translate astrocytic activity–mediated calcium signals into gene expression in a light-dependent manner, we have identified an active astrocytic ensemble -which refers to active astrocytes working together- associated with cue-motivated behavior in the Nucleus Accumbens (NAc), a central hub in the reward system. We mapped behavior-related astrocytic ensemble activity to the ventral and posterior regions of the NAc. Furthermore, we demonstrated that direct activation of this specific astrocytic ensemble through optogenetics was sufficient to retrieve the direction of labeled reward behavior. Overall, these findings uncover the fine-tuning role of astrocytic ensembles in shaping salient behavior.

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“…Downregulation of ventral tegmental area activity causes neuropathic pain hypersensitivity, and the projection to the preoptic area leads to sleep disturbance. 488 The dual functions of the NAc may provide a target for therapies against pain and sleep disturbance comorbidity. Despite the lack of mechanistic research on frequent arousals, an observational study indicated that the arousal infraslow can appear at the interval of 50 s during non-rapid eye movement sleep.…”

Section: Mechanisms Of Pain Comorbiditiesmentioning

confidence: 99%

Pathology of pain and its implications for therapeutic interventions

Cao,

Xu,

Shi

et al. 2024

Sig Transduct Target Ther

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Pain is estimated to affect more than 20% of the global population, imposing incalculable health and economic burdens. Effective pain management is crucial for individuals suffering from pain. However, the current methods for pain assessment and treatment fall short of clinical needs. Benefiting from advances in neuroscience and biotechnology, the neuronal circuits and molecular mechanisms critically involved in pain modulation have been elucidated. These research achievements have incited progress in identifying new diagnostic and therapeutic targets. In this review, we first introduce fundamental knowledge about pain, setting the stage for the subsequent contents. The review next delves into the molecular mechanisms underlying pain disorders, including gene mutation, epigenetic modification, posttranslational modification, inflammasome, signaling pathways and microbiota. To better present a comprehensive view of pain research, two prominent issues, sexual dimorphism and pain comorbidities, are discussed in detail based on current findings. The status quo of pain evaluation and manipulation is summarized. A series of improved and innovative pain management strategies, such as gene therapy, monoclonal antibody, brain-computer interface and microbial intervention, are making strides towards clinical application. We highlight existing limitations and future directions for enhancing the quality of preclinical and clinical research. Efforts to decipher the complexities of pain pathology will be instrumental in translating scientific discoveries into clinical practice, thereby improving pain management from bench to bedside.

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A common neuronal ensemble in nucleus accumbens regulates pain-like behaviour and sleep

Cited by 16 publications

References 82 publications

The crucial role of locus coeruleus noradrenergic neurons in the interaction between acute sleep disturbance and headache

The crucial role of locus coeruleus noradrenergic neurons in the interaction between acute sleep disturbance and headache

Catching Astrocyte Ensembles: Astrocytic Ensembles Control Cue-motivated Behavior

Pathology of pain and its implications for therapeutic interventions

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