A neural circuit mechanism for mechanosensory feedback control of ingestion

Kim, Dong Yoon; Heo, Gyuryang; Kim, Minyoo; Kim, Hyunseo; Jin, Ju Ae; Kim, Hyun Kyung; Jung, Sieun; An, Myungmo; Ahn, Benjamin Hyunju; Park, Jong Hwi; Park, Han Eol; Lee, Myungsun; Lee, Sang Eun; Schwartz, Gary J.; Kim, Sung-Yon

doi:10.1038/s41586-020-2167-2

Cited by 94 publications

(70 citation statements)

References 47 publications

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“…It reduced food intake in fed state, but not in fasted state (fig. S3, J and K), which is consistent with its function in tension-induced feedback inhibition of food intake ( 29 ). Similarly, DREADD activation of LPB CCK soma reduced T core , EE, and physical activity (fig.…”

Section: Resultssupporting

confidence: 75%

Parabrachial neuron types categorically encode thermoregulation variables during heat defense

Yang

Zhang

et al. 2020

Sci. Adv.

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Heat defense is crucial for survival and fitness. Transmission of thermosensory signals into hypothalamic thermoregulation centers represents a key layer of regulation in heat defense. Yet, how these signals are transmitted into the hypothalamus remains poorly understood. Here, we reveal that lateral parabrachial nucleus (LPB) glutamatergic prodynorphin and cholecystokinin neuron populations are progressively recruited to defend elevated body temperature. These two nonoverlapping neuron types form circuits with downstream preoptic hypothalamic neurons to inhibit the thermogenesis of brown adipose tissues (BATs) and activate tail vasodilation, respectively. Both circuits are activated by warmth and can limit fever development. The prodynorphin circuit is further required for regulating energy expenditure and body weight homeostasis. Thus, these findings establish that the genetic and functional specificity of heat defense neurons occurs as early as in the LPB and uncover categorical neuron types for encoding two heat defense variables, inhibition of BAT thermogenesis and activation of vasodilation.

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Section: Resultssupporting

confidence: 75%

Parabrachial neuron types categorically encode thermoregulation variables during heat defense

Yang

Zhang

et al. 2020

Sci. Adv.

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“…Prior evidence has suggested critical roles for inputs from the PBN to the POA in regulating temperature (Geerling et al, 2016;Miyaoka et al, 1998;Morrison, 2016). The PBN is, however, a highly heterogenous structure with multiple subpopulations known to relay various sensory information from the periphery (thirst, salt-appetite, taste, pain, itch, temperature, etc) (Chiang et al, 2020;Kim et al, 2020;Palmiter, 2018). The studies here examine roles for parabrachial glutamatergic neurons expressing the opioid peptides dynorphin and enkephalin.…”

Section: Introductionmentioning

confidence: 98%

Parabrachial Opioidergic Projections to Preoptic Hypothalamus Mediate Behavioral and Physiological Thermal Defenses

Norris

Shaker

Cone

et al. 2020

Preprint

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Maintaining stable body temperature through environmental thermal stressors requires detection of temperature changes, relay of information, and coordination of physiological and behavioral responses. Studies have implicated areas in the preoptic hypothalamic area (POA) and the parabrachial nucleus (PBN) as nodes in the thermosensory neural circuitry and indicate the opioid system within the POA is vital in regulating body temperate. In the present study we identify neurons projecting to the POA from PBN expressing the opioid peptides Dynorphin (Dyn) and Enkephalin (Enk). We determine that warm-activated PBN neuronal populations overlap with both Dyn and Enk expressing PBN populations. We demonstrate that Dyn and Enk expressing neurons are partially overlapping subsets of a glutamatergic population in the PBN. Using optogenetic approaches we selectively activate projections in the POA from PBN Dyn, Enk, and VGLUT2 expressing neurons. Our findings demonstrate that Dyn, Enk, and VGLUT2 expressing PBN neurons are critical for physiological and behavioral heat defense. potential roles of opioid receptor mediated behaviors in both Dyn+ and Enk+ PBN-POA projections. Here we report that glutamatergic, Dyn+, and Enk+ neuronal populations projecting from PBN to POA initiate physiological and behavioral heat defensive behaviors. Chemogenetic inhibition of glutamatergic PBN neurons blocks vasomotor responses to thermal heat challenge.The studies reported here provide new insights into the thermoregulatory properties of parabrachial neuropeptide-containing projections to the hypothalamus in homeostatic and metabolic behavior. Results Ambient warmth activates Dyn+ and Enk+ neurons in PBNEffects of mu and kappa receptor signaling on body temperature have been described and mRNA for preprodynorphin and preproenkephalin has been reported to be expressed in the PBN (Baker and Meert, 2002;Chen et al., 2005;Clark, 1979;Engstrom et al., 2001;Hermanson and Blomqvist, 1997;Hermanson et al., 1998). To examine if PBN neurons expressing dynophin or enkephalin opioid neuropeptides are activated by ambient warmth, we exposed mice to ambient warmth (38°C) or room temperature (21-23°C) for four hours prior to preparation of brain for fos staining. We performed immunohistochemistry (IHC) on collected brains sections containing the PBN with antibody directed against c-Fos (anti-c-Fos) to examine induction of c-Fos expression as a marker of neuronal activation (Sheng and Greenberg, 1990). Consistent with recent reports, we observed induction of c-Fos expression in the lateral PBN (LPBN) (Figure 1B-C) (Geerling et al., 2016). In brain sections from warm exposed mice (n=8) compared to room temperature controls (n=4), c-Fos staining revealed a robust and significant (p=0.003) increase in mean ±SEM number of neurons positive for c-Fos expression in the LPBN per brain: 265.8 ±41.9 in warm exposed mice compared to 23.2 ±4.0 in room temperature controls (Figure 1C).Cells in LPBN, lateral to superior cerebellar peduncle, in sections corresponding -5.0 ...

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“…Although the vagus nerve relays the physiological information from the gut, it is well established that noxious information, including pain and injury, is conveyed through the spinal cord. For example, vagotomy, but not spinal transection, inhibits the delivery of information about nutrition sensing in the gut or mechanical stretch of the stomach [88,89]. However, visceral pain occurs when the sensory neurons in the gut are sensitized, and the ascending spinal neurons are subsequently over-activated [90,91].…”

Section: Spinal Cordmentioning

confidence: 99%

Mental Disorders Linked to Crosstalk between The Gut Microbiome and The Brain

Choi

Koo

2020

Exp Neurobiol

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Often called the second brain, the gut communicates extensively with the brain and vice versa. The conversation between these two organs affects a variety of physiological mechanisms that are associated with our mental health. Over the past decade, a growing body of evidence has suggested that the gut microbiome builds a unique ecosystem inside the gastrointestinal tract to maintain the homeostasis and that compositional changes in the gut microbiome are highly correlated with several mental disorders. There are ongoing efforts to treat or prevent mental disorders by regulating the gut microbiome using probiotics. These attempts are based on the seminal findings that probiotics can control the gut microbiome and affect mental conditions. However, some issues have yet to be conclusively addressed, especially the causality between the gut microbiome and mental disorders. In this review, we focus on the mechanisms by which the gut microbiome affects mental health and diseases. Furthermore, we discuss the potential use of probiotics as therapeutic agents for psychiatric disorders.

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A neural circuit mechanism for mechanosensory feedback control of ingestion

Cited by 94 publications

References 47 publications

Parabrachial neuron types categorically encode thermoregulation variables during heat defense

Parabrachial neuron types categorically encode thermoregulation variables during heat defense

Parabrachial Opioidergic Projections to Preoptic Hypothalamus Mediate Behavioral and Physiological Thermal Defenses

Mental Disorders Linked to Crosstalk between The Gut Microbiome and The Brain

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