Dissecting a disynaptic central amygdala-parasubthalamic nucleus neural circuit that mediates cholecystokinin-induced eating suppression

Sanchez, Marina Rodriguez; Wang, Yong; Cho, Tiffany S.; Schnapp, Wesley Ilana; Schmit, Matthew B.; Fang, Caohui; Cai, Haijiang

doi:10.1016/j.molmet.2022.101443

Cited by 15 publications

(11 citation statements)

References 71 publications

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“…Interestingly, chemogenetic inhibition of PSTN Tac1 neurons attenuated but did not completely rescue the reduction in food intake caused by these hormones ( Figure 5A–J ), indicating that PSTN Tac1 neuron activity is partially necessary for the appetite-suppressing effects of these hormones. In support of these results, a recent study reported that chemogenetic inhibition of glutamatergic PSTN neurons decreases the appetite-suppressing effects of CCK ( Sanchez et al, 2022 ). These results are similar to the effects of inhibiting PBN CGRP neurons, which also attenuates but does not completely rescue decreases in food consumption following administration of anorexigenic compounds ( Campos et al, 2016 ; Carter et al, 2013 ).…”

Section: Discussionmentioning

confidence: 64%

“…Optogenetic stimulation of glutamatergic projections from the PSTN to the PVT reduces food intake ( Zhang and van den Pol, 2017 ). Finally, chemogenetic inhibition of PSTN neurons attenuates the appetite suppressing effects of the hormone cholecystokinin ( Sanchez et al, 2022 ), and chemogenetic inhibition of PSTN neurons that express tachykinin-1 (Tac1) decreases taste neophobia ( Barbier et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

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A discrete parasubthalamic nucleus subpopulation plays a critical role in appetite suppression

Kim

Kromm

Barnhill

et al. 2022

eLife

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Food intake behavior is regulated by a network of appetite-inducing and appetite-suppressing neuronal populations throughout the brain. The parasubthalamic nucleus (PSTN), a relatively unexplored population of neurons in the posterior hypothalamus, has been hypothesized to regulate appetite due to its connectivity with other anorexigenic neuronal populations and because these neurons express Fos, a marker of neuronal activation, following a meal. However, the individual cell types that make up the PSTN are not well characterized, nor are their functional roles in food intake behavior. Here we identify and distinguish between two discrete PSTN subpopulations, those that express tachykinin-1 (PSTNTac1 neurons) and those that express corticotropin-releasing hormone (PSTNCRH neurons), and use a panel of genetically encoded tools in mice to show that PSTNTac1 neurons play an important role in appetite suppression. Both subpopulations increase activity following a meal and in response to administration of the anorexigenic hormones amylin, cholecystokinin (CCK), and peptide YY (PYY). Interestingly, chemogenetic inhibition of PSTNTac1, but not PSTNCRH neurons, reduces the appetite-suppressing effects of these hormones. Consistently, optogenetic and chemogenetic stimulation of PSTNTac1 neurons, but not PSTNCRH neurons, reduces food intake in hungry mice. PSTNTac1 and PSTNCRH neurons project to distinct downstream brain regions, and stimulation of PSTNTac1 projections to individual anorexigenic populations reduces food consumption. Taken together, these results reveal the functional properties and projection patterns of distinct PSTN cell types and demonstrate an anorexigenic role for PSTNTac1 neurons in the hormonal and central regulation of appetite.

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Section: Discussionmentioning

confidence: 64%

Section: Introductionmentioning

confidence: 99%

A discrete parasubthalamic nucleus subpopulation plays a critical role in appetite suppression

Kim

Kromm

Barnhill

et al. 2022

eLife

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“…Recent papers demonstrated that the PSTN neurons are involved in appetite suppression 33,40 . Therefore, we next examined the necessity of the lPB-PSTN pathway in feeding suppression.…”

Section: Inhibition Of Pstn Neurons Attenuates Fear-induced Suppressi...mentioning

confidence: 99%

Parabrachial-to-parasubthalamic nucleus pathway mediates fear-induced suppression of feeding in male mice

et al. 2022

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Feeding behavior is adaptively regulated by external and internal environment, such that feeding is suppressed when animals experience pain, sickness, or fear. While the lateral parabrachial nucleus (lPB) plays key roles in nociception and stress, neuronal pathways involved in feeding suppression induced by fear are not fully explored. Here, we investigate the parasubthalamic nucleus (PSTN), located in the lateral hypothalamus and critically involved in feeding behaviors, as a target of lPB projection neurons. Optogenetic activation of lPB-PSTN terminals in male mice promote avoidance behaviors, aversive learning, and suppressed feeding. Inactivation of the PSTN and lPB-PSTN pathway reduces fear-induced feeding suppression. Activation of PSTN neurons expressing pituitary adenylate cyclase-activating polypeptide (PACAP), a neuropeptide enriched in the PSTN, is sufficient for inducing avoidance behaviors and feeding suppression. Blockade of PACAP receptors impaires aversive learning induced by lPB-PSTN photomanipulation. These findings indicate that lPB-PSTN pathway plays a pivotal role in fear-induced feeding suppression.

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“…Compared to the physiological condition, CORT-mice subjected to chronic PEA inhalation showed significant modifications of neural activity among a set of brain regions, namely aIC, CeA, PSTN and Hip. These particular structures are part of a complex network that has been shown to be involved in feeding behavior [88][89][90], with a key role of PSTN acting as a refraining signal through descending GABAergic projections originating from the CeA [90,91]. Furthermore, it has been described that the PSTN also receives olfactory inputs, mainly from the anterior part of both basomedial and cortical amygdalar nuclei which are densely innervated by the piriform cortex [92][93][94].…”

Section: Roi Cfos Expression (Mean Cfos+ Cells/mmmentioning

confidence: 99%

Beneficial effects of prolonged 2-phenylethyl alcohol inhalation on chronic distress-induced anxio-depressive-like phenotype in female mice

Ramadan¹,

Cabeza²,

Cramoisy³

et al. 2022

Preprint

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Chronic distress-induced hypothalamic-pituitary-adrenal axis deregulations have been associated with the development of neuropsychiatric disorders such as anxiety and depression. Currently available drugs treating such pathological conditions have limited efficacy and diverse side effects, revealing the need of new safer strategies. Aromatic plant-based compounds are largely used in herbal medicine due to their therapeutic properties on mood, physiology, and general well-being. The purpose of this study was to investigate the effects of 2-phenylethyl alcohol (PEA), one of the pharmacologically active constituents of rose essential oil, on chronic corticosterone (CORT)-induced behavioral and neurobiological changes in female mice. Animals followed a prolonged PEA inhalation exposure (30 min per day) for 15 consecutive days prior to behavioral evaluation with open-field, forced swim and novelty-suppressed feeding tests. CORT treatment induced an anxio-depressive-like phenotype, evidenced by a reduced locomotor activity in the open-field, and an increased latency to feed in the novelty-suppressed feeding paradigms. To elucidate the neural correlates of our behavioral results, cerebral cFos expression analysis was further performed to provide a global map of neuronal activity. The altered feeding behavior was accompanied by a significant decrease in the number of cFos-positive cells in the olfactory bulb, and altered brain connectivity as shown by cross-correlation-based network analysis. CORT-induced behavioral and neurobiological alterations were reversed by prolonged PEA inhalation, suggesting a therapeutic action that allows regulating the activity of neural circuits involved in sensory, emotional and feeding behaviors. These findings might contribute to better understand the therapeutic potential of PEA on anxio-depressive symptoms.

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Dissecting a disynaptic central amygdala-parasubthalamic nucleus neural circuit that mediates cholecystokinin-induced eating suppression

Cited by 15 publications

References 71 publications

A discrete parasubthalamic nucleus subpopulation plays a critical role in appetite suppression

A discrete parasubthalamic nucleus subpopulation plays a critical role in appetite suppression

Parabrachial-to-parasubthalamic nucleus pathway mediates fear-induced suppression of feeding in male mice

Beneficial effects of prolonged 2-phenylethyl alcohol inhalation on chronic distress-induced anxio-depressive-like phenotype in female mice

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