A D2 to D1 shift in dopaminergic inputs to midbrain 5-HT neurons causes anorexia in mice

Cai, Xing; Liu, Hailan; Feng, Bing; Yu, Meng; He, Yang; Liu, Hesong; Liang, Changhong; Yang, Yongjie; Tu, Longlong; Zhang, Nan; Wang, Lina; Yin, Na; Han, Junying; Yan, Zili; Wang, Chunmei; Xu, Pingwen; Wu, Qi; Tong, Qingchun; He, Yanlin; Xu, Yong

doi:10.1038/s41593-022-01062-0

Cited by 22 publications

(24 citation statements)

References 72 publications

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“…Similarly, administration of D2/3 antagonists ameliorates the ABA phenotypes in mice 35 . These results are consistent with a recent study demonstrating that a D2 to D1 shift in dopaminergic pathway regulates ABA, and that interruption or inhibition of the dopamine signaling pathways attenuates ABA 36 . However, these manipulations of the dopamine pathways tend to have only a mild attenuation effect on ABA development, with majority of the animals still developing ABA, but in a delayed manner.…”

Section: Discussionsupporting

confidence: 93%

Central extended amygdala neurons in the development of activity-based anorexia

Schnapp

Kim

Wang

et al. 2022

Preprint

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Anorexia nervosa (AN) is a serious psychiatric disease characterized by restricted eating, fear of gaining weight, as well as excessive exercise, and also is often comorbid with emotional disorders such as anxiety and depression. However, the etiology of AN is unknown and the neural mechanism that leads to AN remains to be determined. Here, we show that a specific subpopulation of neurons, marked by the expression of protein kinase C-delta (PKC-δ), in two nuclei of the central extended amygdala (EAc)— central nucleus (CeA) and oval region of bed nucleus of stria terminalis (ovBNST)—regulates development of activity-based anorexia (ABA), the current best animal model of AN. Specifically, simultaneous dual ablation of CeAPKC-δand ovBNSTPKC-δneurons prevents the key phenotypes of ABA: increases in wheel activity, decreases in food intake, and life-threatening body weight loss. However, ablating PKC-δ neurons in CeA or ovBNST alone is not sufficient to prevent ABA. Correspondingly, activation of PKC-δ neurons in one type of nuclei continues to suppress food intake even when PKC-δ neurons in the other nuclei are silenced. Consistent with their role in suppressing food intake when activated, these PKC-δ neurons show increased activity with ABA development. Together, our study illuminates how neurons in the amygdala regulate ABA development and supports the complex and heterogenous etiology of AN.

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Section: Discussionsupporting

confidence: 93%

Central extended amygdala neurons in the development of activity-based anorexia

Schnapp

Kim

Wang

et al. 2022

Preprint

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“…In summary, we identified novel downstream forebrain circuits through which DRN SERT neurons suppress feeding. Given that hyperactivation of serotonergic neurons has been linked to anorexia [ 1 , 2 ], and obesity suppresses serotonin levels in hypothalamus [ 5 , 6 ], future research is warranted to determine how the activity in these circuits maladapt to altered 5HT levels in order to refine potential therapeutic targets.…”

Section: Discussionmentioning

confidence: 99%

“…Serotonergic dysregulation has been implicated in both obesity and anorexia nervosa (AN). Overactive serotonergic neurons have been linked to AN and consistently, multiple human GWAS studies have identified polymorphisms in 5HT receptor (5HTR) subunits from AN patients [ [1] , [2] , [3] , [4] ]. Conversely, obesity decreases serotonin levels in hypothalamus [ 5 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

Dorsal raphe serotonergic neurons suppress feeding through redundant forebrain circuits

Aklan

Atasoy

Deng

et al. 2023

Molecular Metabolism

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“…These brainstem neurotransmitters nuclei have widespread projections to several subcortical and cortical areas, including vmPFC, amygdala, insula and dACC (Conio et al, 2020). A very recent study using a mouse model of AN discovered that the dopamine–serotonin circuit is super activated in AN, when compared to controls, and responsible for the lack of appetite and excessive exercising seen in the animals (Cai et al, 2022). Although very speculative, it is possible that the higher complexity of the FC time series observed in AN patients may be a consequence of a dysregulation in the serotonin and dopamine activities, which does not allow to keep the system stable.…”

Section: Discussionmentioning

confidence: 99%

Dynamic changes in the central autonomic network of patients with anorexia nervosa

Cruz

Schumann

Suttkus

et al. 2023

Eur J of Neuroscience

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Autonomic cardiac dysfunction is a common complication in patients with anorexia nervosa (AN). Despite its high prevalence, physicians often overlook this clinical condition, and little research has been dedicated so far. To probe the functional role of the neurocircuitry underpinning the poorly understood autonomic cardiac dysfunction, we examined dynamic functional differences in the central autonomic network (CAN) between 21 acute AN individuals and 24 age, sex and heart rate‐matched healthy controls (HC). We assessed functional connectivity (FC) changes in CAN using seeds in the ventromedial prefrontal cortex, left and right anterior insular cortex, left and right amygdala and dorsal anterior cingulate cortex. The overall FC between the six investigated seeds is reduced in AN individuals compared to HC, although no changes were observed for single connections. Moreover, AN exhibited higher complexity in the FC time series of such CAN regions. Contrary to HC, we found that the degree of complexity between FC and heart rate (HR) series did not correlate in AN, suggesting a shift from central to peripheral control of the heart in AN individuals. Using dynamic FC analysis, we showed that the CAN transits across five functional states with no preference for any. Strikingly, at the state of weakest connectivity, the entropy significantly diverges between healthy and AN individuals, reaching its minimum and maximum values, respectively. Overall, our findings provide evidence that core regions of the CAN engaged in cardiac regulation are functionally affected in acute AN.

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A D2 to D1 shift in dopaminergic inputs to midbrain 5-HT neurons causes anorexia in mice

Cited by 22 publications

References 72 publications

Central extended amygdala neurons in the development of activity-based anorexia

Central extended amygdala neurons in the development of activity-based anorexia

Dorsal raphe serotonergic neurons suppress feeding through redundant forebrain circuits

Dynamic changes in the central autonomic network of patients with anorexia nervosa

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