Dorsal raphe serotonergic neurons suppress feeding through redundant forebrain circuits

Aklan, İltan; Atasoy, Nilüfer Sayar; Deng, Feiqi; Kim, Hyojin; Yavuz, Yavuz; Rysted, Jacob E.; Laule, Connor; Davis, D.; Li, Yulong; Atasoy, Deniz

doi:10.1016/j.molmet.2023.101676

Cited by 11 publications

(6 citation statements)

References 51 publications

(65 reference statements)

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“…The DR has previously been proven to be involved in the regulation of sleep–wake behavior (Cai et al., 2022), aggression, addiction (Smagin et al., 2022), depressive‐like behavior (Lin et al., 2022), thermal hypersensitivity (Liu et al., 2023), pain processing (Akbar et al., 2023), feeding inhibition (Aklan et al., 2023), mood control, and resilience to stress (Lopez‐Terrones et al., 2023). Previous studies have revealed that DR has more extensive connectivity with the cerebral cortex and basal ganglia.…”

Section: Resultsmentioning

confidence: 99%

Whole‐brain mapping of monosynaptic afferent inputs to the CRH neurons in the medial prefrontal cortex of mice

Li,

Zhu

et al. 2023

Journal of Anatomy

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Corticotropin‐releasing hormone (CRH) neurons are densely distributed in the medial prefrontal cortex (mPFC), which plays a crucial role in integrating and processing emotional and cognitive inputs from other brain regions. Therefore, it is important to know the neural afferent patterns of mPFCCRH neurons, which are still unclear. Here, we utilized a rabies virus‐based monosynaptic retrograde tracing system to map the presynaptic afferents of the mPFCCRH neurons throughout the entire brain. The results show that the mPFCCRH neurons receive inputs from three main groups of brain regions: (1) the cortex, primarily the orbital cortex, somatomotor areas, and anterior cingulate cortex; (2) the thalamus, primarily the anteromedial nucleus, mediodorsal thalamic nucleus, and central medial thalamic nucleus; and (3) other brain regions, primarily the basolateral amygdala, hippocampus, and dorsal raphe nucleus. Taken together, our results are valuable for further investigations into the roles of the mPFCCRH neurons in normal and neurological disease states. These investigations can shed light on various aspects such as cognitive processing, emotional modulation, motivation, sociability, and pain.

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Section: Resultsmentioning

confidence: 99%

Whole‐brain mapping of monosynaptic afferent inputs to the CRH neurons in the medial prefrontal cortex of mice

Li,

Zhu

et al. 2023

Journal of Anatomy

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“…It has been demonstrated that the 5-HT DRN ARH circuit regulates feeding 10,[16][17][18][19][20][21] , but it remains unclear whether this circuit regulates meal initiation or termination. Therefore, we used a closedloop optogenetic approach to determine if the 5-HT DRN ARH circuit regulates meal initiation.…”

Section: Arh Circuit Regulates Meal Initiationmentioning

confidence: 99%

5-HT Neurons Integrate GABA and Dopamine Inputs to Regulate Meal Initiation

Conde,

Wong,

Fang

et al. 2024

Preprint

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Obesity is a growing global health epidemic with limited effective therapeutics. Serotonin (5-HT) is one major neurotransmitter which remains an excellent target for new weight-loss therapies, but there remains a gap in knowledge on the mechanisms involved in 5-HT produced in the dorsal Raphe nucleus (DRN) and its involvement in meal initiation. Using a closed-loop optogenetic feeding paradigm, we showed that the 5-HTDRN→arcuate nucleus (ARH) circuit plays an important role in regulating meal initiation. Incorporating electrophysiology and ChannelRhodopsin-2-Assisted Circuit Mapping, we demonstrated that 5-HTDRNneurons receive inhibitory input partially from GABAergic neurons in the DRN, and the 5-HT response to GABAergic inputs can be enhanced by hunger. Additionally, deletion of the GABAAreceptor subunit in 5-HT neurons inhibits meal initiation with no effect on the satiation process. Finally, we identified the instrumental role of dopaminergic inputs via dopamine receptor D2 in 5-HTDRNneurons in enhancing the response to GABA-induced feeding. Thus, our results indicate that 5-HTDRNneurons are inhibited by synergistic inhibitory actions of GABA and dopamine, which allows for the initiation of a meal.

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“…33 However, a recent study demonstrated that DRN serotonergic neurons decrease feeding via redundant innervation of the lateral hypothalamic area (LHA) and the BNST. 34 Another study identified a role of an inhibitory circuit between the rostral zona incerta GABAergic neurons and the paraventricular thalamus that is innervated by the DRN serotonergic neurons to suppress feeding. 35 Therefore, it now appears that DRN serotonergic neurons innervate both hypothalamic and extra-hypothalamic areas of brain to suppress appetite.…”

Section: Serotonergic Neurons and Appetitementioning

confidence: 99%

“…It is well known that DRN serotonergic neurons innervate the mediobasal hypothalamus to suppress food intake 33 . However, a recent study demonstrated that DRN serotonergic neurons decrease feeding via redundant innervation of the lateral hypothalamic area (LHA) and the BNST 34 . Another study identified a role of an inhibitory circuit between the rostral zona incerta GABAergic neurons and the paraventricular thalamus that is innervated by the DRN serotonergic neurons to suppress feeding 35 .…”

Section: Regulation Of Appetitementioning

confidence: 99%

Serotonergic regulation of appetite and sodium appetite

Shin

Kim

Sohn

2023

J Neuroendocrinology

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Serotonin is a neurotransmitter that is synthesized and released from the brainstem raphe nuclei to affect many brain functions. It is well known that the activity of raphe serotonergic neurons is changed in response to the changes in feeding status to regulate appetite via the serotonin receptors. Likewise, changes in volume status are known to alter the activity of raphe serotonergic neurons and drugs targeting serotonin receptors were shown to affect sodium appetite. Therefore, the central serotonin system appears to regulate ingestion of both food and salt, although neural mechanisms that induce appetite in response to hunger and sodium appetite in response to volume depletion are largely distinct from each other. In this review, we discuss our current knowledge regarding the regulation of ingestion – appetite and sodium appetite – by the central serotonin system.

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Dorsal raphe serotonergic neurons suppress feeding through redundant forebrain circuits

Cited by 11 publications

References 51 publications

Whole‐brain mapping of monosynaptic afferent inputs to the CRH neurons in the medial prefrontal cortex of mice

Whole‐brain mapping of monosynaptic afferent inputs to the CRH neurons in the medial prefrontal cortex of mice

5-HT Neurons Integrate GABA and Dopamine Inputs to Regulate Meal Initiation

Serotonergic regulation of appetite and sodium appetite

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