Browse
Submit Data
Databases
API
Help

Dataset Information

19 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

A lateral hypothalamus to basal forebrain neurocircuit promotes feeding by suppressing responses to anxiogenic environmental cues.

ABSTRACT: Animals must consider competing information before deciding to eat: internal signals indicating the desirability of food and external signals indicating the risk involved in eating within a particular environment. The behaviors driven by the former are manifestations of hunger, and the latter, anxiety. The connection between pathologic anxiety and reduced eating in conditions like typical depression and anorexia is well known. Conversely, anti-anxiety drugs such as benzodiazepines increase appetite. Here, we show that GABAergic neurons in the diagonal band of Broca (DBB^GABA) are responsive to indications of risk and receive monosynaptic inhibitory input from lateral hypothalamus GABAergic neurons (LH^GABA). Activation of this circuit reduces anxiety and causes indiscriminate feeding. We also found that diazepam rapidly reduces DBB^GABA activity while inducing indiscriminate feeding. Our study reveals that the LH^GABA→DBB^GABA neurocircuit overrides anxiogenic environmental cues to allow feeding and that this pathway may underlie the link between eating and anxiety-related disorders.

SUBMITTER: Cassidy RM

PROVIDER: S-EPMC6402846 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Activation of basal forebrain-to-lateral habenula circuitry drives reflexive aversion and suppresses feeding behavior.

Project description:Environmental cues and internal states such as mood, reward, or aversion directly influence feeding behaviors beyond homeostatic necessity. The hypothalamus has been extensively investigated for its role in homeostatic feeding. However, many of the neural circuits that drive more complex, non-homeostatic feeding that integrate valence and sensory cues (such as taste and smell) remain unknown. Here, we describe a basal forebrain (BF)-to-lateral habenula (LHb) circuit that directly modulates non-homeostatic feeding behavior. Using viral-mediated circuit mapping, we identified a population of glutamatergic neurons within the BF that project to the LHb, which responds to diverse sensory cues, including aversive and food-related odors. Optogenetic activation of BF-to-LHb circuitry drives robust, reflexive-like aversion. Furthermore, activation of this circuitry suppresses the drive to eat in a fasted state. Together, these data reveal a role of basal forebrain glutamatergic neurons in modulating LHb-associated aversion and feeding behaviors by sensing environmental cues.

| S-EPMC9772215 | biostudies-literature

A cholinergic basal forebrain feeding circuit modulates appetite suppression.

Project description:Atypical food intake is a primary cause of obesity and other eating and metabolic disorders. Insight into the neural control of feeding has previously focused mainly on signalling mechanisms associated with the hypothalamus, the major centre in the brain that regulates body weight homeostasis. However, roles of non-canonical central nervous system signalling mechanisms in regulating feeding behaviour have been largely uncharacterized. Acetylcholine has long been proposed to influence feeding owing in part to the functional similarity between acetylcholine and nicotine, a known appetite suppressant. Nicotine is an exogenous agonist for acetylcholine receptors, suggesting that endogenous cholinergic signalling may play a part in normal physiological regulation of feeding. However, it remains unclear how cholinergic neurons in the brain regulate food intake. Here we report that cholinergic neurons of the mouse basal forebrain potently influence food intake and body weight. Impairment of cholinergic signalling increases food intake and results in severe obesity, whereas enhanced cholinergic signalling decreases food consumption. We found that cholinergic circuits modulate appetite suppression on downstream targets in the hypothalamus. Together our data reveal the cholinergic basal forebrain as a major modulatory centre underlying feeding behaviour.

| S-EPMC5507212 | biostudies-other

The inhibitory circuit architecture of the lateral hypothalamus orchestrates feeding.

Project description:The growing prevalence of overeating disorders is a key contributor to the worldwide obesity epidemic. Dysfunction of particular neural circuits may trigger deviations from adaptive feeding behaviors. The lateral hypothalamus (LH) is a crucial neural substrate for motivated behavior, including feeding, but the precise functional neurocircuitry that controls LH neuronal activity to engage feeding has not been defined. We observed that inhibitory synaptic inputs from the extended amygdala preferentially innervate and suppress the activity of LH glutamatergic neurons to control food intake. These findings help explain how dysregulated activity at a number of unique nodes can result in a cascading failure within a defined brain network to produce maladaptive feeding.

| S-EPMC4131546 | biostudies-literature

GABAergic function in the lateral hypothalamus regulates feeding behavior: Possible mediation via orexin.

Project description:Aim: The lateral hypothalamus (LH) is known as the hunger center, but the mechanisms through which the LH regulates food intake are unclear. Since GABA neurons are reported to project to the LH, the present study investigated the role of GABAergic function in the LH in the regulation of feeding behavior.Methods: GABA levels in the LH were measured by in vivo microdialysis. Food intake after drug injection into the LH was measured every 1 hour for 4 hours. The mRNA levels were measured using RT-PCR.Results: Food intake significantly increased GABA levels in the LH, suggesting that food intake stimulates GABAergic function in the LH. Injection of the GABAA receptor agonist muscimol into the LH significantly inhibited food intake, whereas injection of the GABAA receptor antagonist bicuculline into the LH did not significantly affect food intake. The inhibitory effect of muscimol injected into the LH was blocked by co-administration of bicuculline. These results indicate that the stimulation of GABAA receptors in the LH inhibits food intake. We next examined whether the stimulation of GABAA receptors affects hypothalamic neuropeptides that are known to regulate feeding behavior. The injection of muscimol significantly decreased preproorexin mRNA in the hypothalamus.Conclusion: These results indicate that food intake activates GABAergic function in the LH, which terminates feeding behavior by stimulating GABAA receptors. Moreover, it is suggested that the stimulation of GABAA receptors in the LH reduces food intake through inhibition of orexin neurons.

| S-EPMC7292314 | biostudies-literature

A functional topography within the cholinergic basal forebrain for encoding sensory cues and behavioral reinforcement outcomes.

Project description:Basal forebrain cholinergic neurons (BFCNs) project throughout the cortex to regulate arousal, stimulus salience, plasticity, and learning. Although often treated as a monolithic structure, the basal forebrain features distinct connectivity along its rostrocaudal axis that could impart regional differences in BFCN processing. Here, we performed simultaneous bulk calcium imaging from rostral and caudal BFCNs over a 1-month period of variable reinforcement learning in mice. BFCNs in both regions showed equivalently weak responses to unconditioned visual stimuli and anticipated rewards. Rostral BFCNs in the horizontal limb of the diagonal band were more responsive to reward omission, more accurately classified behavioral outcomes, and more closely tracked fluctuations in pupil-indexed global brain state. Caudal tail BFCNs in globus pallidus and substantia innominata were more responsive to unconditioned auditory stimuli, orofacial movements, aversive reinforcement, and showed robust associative plasticity for punishment-predicting cues. These results identify a functional topography that diversifies cholinergic modulatory signals broadcast to downstream brain regions.

| S-EPMC8654357 | biostudies-literature

A distinct parabrachial-to-lateral hypothalamus circuit for motivational suppression of feeding by nociception.

Project description:The motivation to eat is not only shaped by nutrition but also competed by external stimuli including pain. How the mouse hypothalamus, the feeding regulation center, integrates nociceptive inputs to modulate feeding is unclear. Within the key nociception relay center parabrachial nucleus (PBN), we demonstrated that neurons projecting to the lateral hypothalamus (LHPBN) are nociceptive yet distinct from danger-encoding central amygdala-projecting (CeAPBN) neurons. Activation of LHPBN strongly suppressed feeding by limiting eating frequency and also reduced motivation to work for food reward. Refined approach-avoidance paradigm revealed that suppression of LHPBN, but not CeAPBN, sustained motivation to obtain food. The effect of LHPBN neurons on feeding was reversed by suppressing downstream LHVGluT2 neurons. Thus, distinct from a circuit for fear and escape responses, LHPBN neurons channel nociceptive signals to LHVGluT2 neurons to suppress motivational drive for feeding. Our study provides a new perspective in understanding feeding regulation by external competing stimuli.

| S-EPMC8104871 | biostudies-literature

Optogenetic mapping of feeding and self-stimulation within the lateral hypothalamus of the rat.

Project description:The lateral hypothalamus (LH) includes several anatomical subregions involved in eating and reward motivation. This study explored localization of function across different LH subregions in controlling food intake stimulated by optogenetic channelrhodopsin excitation, and in supporting laser self-stimulation. We particularly compared the tuberal LH subregion, the posterior LH subregion, and the lateral preoptic area. Local diameters of tissue optogenetically stimulated within the LH were assessed by measuring laser-induced Fos plumes and Jun plumes via immunofluorescence surrounding optic fiber tips. Those plume diameters were used to map localization of function for behavioral effects elicited by LH optogenetic stimulation. Optogenetic stimulation of the tuberal subsection of the LH produced the most robust eating behavior and food intake initially, but produced only mild laser self-stimulation in the same rats. However, after repeated exposures to optogenetic stimulation, tuberal LH behavioral profiles shifted toward more self-stimulation and less food intake. By contrast, stimulation of the lateral preoptic area produced relatively little food intake or self-stimulation, either initially or after extended stimulation experience. Stimulation in the posterior LH subregion supported moderate self-stimulation, but not food intake, and at higher laser intensity shifted valence to evoke escape behaviors. We conclude that the tuberal LH subregion may best mediate stimulation-bound increases in food intake stimulated by optogenetic excitation. However, incentive motivational effects of tuberal LH stimulation may shift toward self-stimulation behavior after repeated stimulation. By contrast, the lateral preoptic area and posterior LH do not as readily elicit either eating behavior or laser self-stimulation, and may be more prone to higher-intensity aversive effects.

| S-EPMC6984703 | biostudies-literature

A dorsal hippocampus-prodynorphinergic dorsolateral septum-to-lateral hypothalamus circuit mediates contextual gating of feeding.

Project description:Adaptive regulation of feeding depends on linkage of internal states and food outcomes with contextual cues. Human brain imaging has identified dysregulation of a hippocampal-lateral hypothalamic area (LHA) network in binge eating, but mechanistic instantiation of underlying cell-types and circuitry is lacking. Here, we identify an evolutionary conserved and discrete Prodynorphin (Pdyn)-expressing subpopulation of Somatostatin (Sst)-expressing inhibitory neurons in the dorsolateral septum (DLS) that receives primarily dorsal, but not ventral, hippocampal inputs. DLS(Pdyn) neurons inhibit LHA GABAergic neurons and confer context- and internal state-dependent calibration of feeding. Viral deletion of Pdyn in the DLS mimicked effects seen with optogenetic silencing of DLS Pdyn INs, suggesting a potential role for DYNORPHIN-KAPPA OPIOID RECEPTOR signaling in contextual regulation of food-seeking. Together, our findings illustrate how the dorsal hippocampus has evolved to recruit an ancient LHA feeding circuit module through Pdyn DLS inhibitory neurons to link contextual information with regulation of food consumption.

| S-EPMC11326193 | biostudies-literature

A sex-specific thermogenic neurocircuit induced by predator smell recruiting cholecystokinin neurons in the dorsomedial hypothalamus.

Project description:Olfactory cues are vital for prey animals like rodents to perceive and evade predators. Stress-induced hyperthermia, via brown adipose tissue (BAT) thermogenesis, boosts physical performance and facilitates escape. However, many aspects of this response, including thermogenic control and sex-specific effects, remain enigmatic. Our study unveils that the predator odor trimethylthiazoline (TMT) elicits BAT thermogenesis, suppresses feeding, and drives glucocorticoid release in female mice. Chemogenetic stimulation of olfactory bulb (OB) mitral cells recapitulates the thermogenic output of this response and associated stress hormone corticosterone release in female mice. Neuronal projections from OB to medial amygdala (MeA) and dorsomedial hypothalamus (DMH) exhibit female-specific cFos activity toward odors. Cell sorting and single-cell RNA-sequencing of DMH identify cholecystokinin (CCK)-expressing neurons as recipients of predator odor cues. Chemogenetic manipulation and neuronal silencing of DMHCCK neurons further implicate these neurons in the propagation of predator odor-associated thermogenesis and food intake suppression, highlighting their role in female stress-induced hyperthermia.

| S-EPMC10427624 | biostudies-literature

A novel anxiogenic role for the delta opioid receptor expressed in GABAergic forebrain neurons.

Project description:BackgroundThe delta opioid receptor (DOR) is broadly expressed throughout the nervous system; it regulates chronic pain, emotional responses, motivation, and memory. Neural circuits underlying DOR activities have been poorly explored by genetic approaches. We used conditional mouse mutagenesis to elucidate receptor function in GABAergic neurons of the forebrain.MethodsWe characterized DOR distribution in the brain of Dlx5/6-CreXOprd1(fl/fl) (Dlx-DOR) mice and tested main central DOR functions through behavioral testing.ResultsThe DOR proteins were strongly deleted in olfactory bulb and striatum and remained intact in cortex and basolateral amygdala. Olfactory perception, circadian activity, and despair-like behaviors were unchanged. In contrast, locomotor stimulant effects of SNC80 (DOR agonist) and SKF81297 (D1 agonist) were abolished and increased, respectively. The Dlx-DOR mice showed lower levels of anxiety in the elevated plus maze, opposing the known high anxiety in constitutive DOR knockout animals. Also, Dlx-DOR mice reached the food more rapidly in a novelty suppressed feeding task, despite their lower motivation for food reward observed in an operant paradigm. Finally, c-fos protein staining after novelty suppressed feeding was strongly reduced in amygdala, concordant with the low anxiety phenotype of Dlx-DOR mice.ConclusionsWe demonstrate that DORs expressed in the forebrain mediate the described locomotor effect of SNC80 and inhibit D1-stimulated hyperactivity. Our data also reveal an unanticipated anxiogenic role for this particular DOR subpopulation, with a potential novel adaptive role. In emotional responses, DORs exert dual anxiolytic and anxiogenic roles, both of which may have implications in the area of anxiety disorders.

| S-EPMC4297504 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data