Hindbrain Double-Negative Feedback Mediates Palatability-Guided Food and Water Consumption

Gong, Rong; Xu, Shi-Qiong; Hermundstad, Ann M; Yu, Yongmei; Sternson, Scott M.

doi:10.1016/j.cell.2020.07.031

Cited by 56 publications

(41 citation statements)

References 52 publications

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“…"PRISM" lens) to better avoid a contact with aqueduct. Moreover, as recently demonstrated (Gong et al, 2020), attaching tungsten wires around the cylindrical GRIN lens can provide additional mechanical support to achieve stable and high-quality imaging of hard-to-reach brain regions like the DRN during diverse behavior tasks. The absence of neural responses to aversive cues during head-fixation, both at single-cell and population levels ( Fig.…”

Section: Discussionmentioning

confidence: 98%

Dorsal Raphe Dopamine Neurons Signal Motivational Salience Dependent on Internal State, Expectation, and Behavioral Context

et al. 2021

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The ability to recognize motivationally salient events and adaptively respond to them is critical for survival. Here we tested whether dopamine (DA) neurons in the dorsal raphe nucleus (DRN) contribute to this process in both male and female mice. Population recordings of DRN DA neurons during associative learning tasks showed that their activity dynamically tracks the motivational salience, developing excitation to both reward-and shock-paired cues. The DRN DA response to reward-predicting cues was diminished after satiety, suggesting modulation by internal states. DRN DA activity was also greater for unexpected outcomes than for expected outcomes. Two-photon imaging of DRN DA neurons demonstrated that the majority of individual neurons developed activation to reward-predicting cues and reward but not to shock-predicting cues, which was surprising and qualitatively distinct from the population results. Performing the same fear learning procedures in freely-moving and head-fixed groups revealed that headfixation itself abolished the neural response to aversive cues, indicating its modulation by behavioral context. Overall, these results suggest that DRN DA neurons encode motivational salience, dependent on internal and external factors. Significance statement Dopamine (DA) contributes to motivational control, composed of at least two functional cell typesone signaling for motivational value and another for motivational salience. Here we demonstrate that DA neurons in the dorsal raphe nucleus (DRN) encode the motivational salience in associative learning tasks. Neural responses were dynamic and modulated by the animal's internal state. The majority of single-cells developed responses to reward or paired cues, but not to shock-predicting cues. Further experiments with freely-moving and head-fixed mice showed that head-fixation abolished the development of cue responses during fear learning. This work provides further characterization on the functional roles of overlooked DRN DA populations and an example that neural responses can be altered by head-fixation, which is commonly used in neuroscience.

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Section: Discussionmentioning

confidence: 98%

Dorsal Raphe Dopamine Neurons Signal Motivational Salience Dependent on Internal State, Expectation, and Behavioral Context

et al. 2021

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“…Notably, the LC has been shown to play an important role in modulating energy expenditure (Teske et al., 2013) and the LC‐norepinephrine system has been linked with reward‐behavior (Bouret & Richmond, 2015). Recent findings demonstrate LC modulation of palatability‐driven hedonic eating (Gong et al., 2020; Sciolino et al., 2019) suggesting a role for the LC in mediating the body‐weight lowering effects of amylin. In this study, the number of c‐Fos+cells were diminished in RAMP1/3 mice, indicating the importance of RAMP1/3 in mediating amylin‐induced activation of the LC.…”

Section: Discussionmentioning

confidence: 99%

Whole‐brain mapping of amylin‐induced neuronal activity in receptor activity–modifying protein 1/3 knockout mice

Skovbjerg

Roostalu

Hansen

et al. 2021

Eur J of Neuroscience

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The pancreatic hormone amylin plays a central role in regulating energy homeostasis and glycaemic control by stimulating satiation and reducing food reward, making amylin receptor agonists attractive for the treatment of metabolic diseases. Amylin receptors consist of heterodimerized complexes of the calcitonin receptor and receptor-activity modifying proteins subtype 1-3 (RAMP1-3). Neuronal activation in response to amylin dosing has been well characterized, but only in selected regions expressing high levels of RAMPs. The current study identifies global brain-wide changes in response to amylin and by comparing wild type and RAMP1/3 knockout mice reveals the importance of RAMP1/3 in mediating this response. Amylin dosing resulted in neuronal activation as measured by an increase in c-Fos labelled cells in 20 brain regions, altogether making up the circuitry of neuronal appetite regulation (e.g., area postrema (AP), nucleus of the solitary tract (NTS), parabrachial nucleus (PB), and central amygdala (CEA)). c-Fos response was also detected in distinct nuclei across the brain that typically have not been linked with amylin signalling. In RAMP1/3 knockout amylin induced low-level neuronal activation in seven regions, including the AP, NTS and PB, indicating the existence of RAMP1/3-independent mechanisms of amylin response. Under basal conditions RAMP1/3 knockout mice show reduced neuronal activity in the hippocampal formation as well as reduced hippocampal volume, suggesting a role for RAMP1/3

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“…For example, thirst can override hunger drive (dehydration-anorexia), and feeding induces thirst (prandial thirst) ( Watts and Boyle, 2010 ). Manipulation of either cortical or hindbrain neurons in mice can simultaneously impact both hunger and thirst driven ingestive behavior ( Eiselt et al, 2021 ; Gong et al, 2020 ). Moreover, thirst-driven water anticipation and subsequent intake changes the activity of a remarkably broad set of neurons throughout the mouse brain, in a manner that is time-locked to specific behavioral steps ( Allen et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

Thirst interneurons that promote water seeking and limit feeding behavior in Drosophila

Landayan

Wang

Zhou

et al. 2021

eLife

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Thirst is a motivational state that drives behaviors to obtain water for fluid homeostasis. We identified two types of central brain interneurons that regulate thirsty water seeking in Drosophila, that we term the Janu neurons. Janu-GABA, a local interneuron in the subesophageal zone, is activated by water deprivation and is specific to thirsty seeking. Janu-AstA projects from the subesophageal zone to the superior medial protocerebrum, a higher order processing area. Janu-AstA signals with the neuropeptide Allatostatin A to promote water seeking and to inhibit feeding behavior. NPF (Drosophila NPY) neurons are postsynaptic to Janu-AstA for water seeking and feeding through the AstA-R2 galanin-like receptor. NPF neurons use NPF to regulate thirst and hunger behaviors. Flies choose Janu neuron activation, suggesting that thirsty seeking up a humidity gradient is rewarding. These findings identify novel central brain circuit elements that coordinate internal state drives to selectively control motivated seeking behavior.

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Hindbrain Double-Negative Feedback Mediates Palatability-Guided Food and Water Consumption

Cited by 56 publications

References 52 publications

Dorsal Raphe Dopamine Neurons Signal Motivational Salience Dependent on Internal State, Expectation, and Behavioral Context

Dorsal Raphe Dopamine Neurons Signal Motivational Salience Dependent on Internal State, Expectation, and Behavioral Context

Whole‐brain mapping of amylin‐induced neuronal activity in receptor activity–modifying protein 1/3 knockout mice

Thirst interneurons that promote water seeking and limit feeding behavior in Drosophila

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