Navigating for reward

Nature reviews. Neuroscience, Год журнала: 2021, Номер 22(8), С. 472 - 487

Опубликована: Июль 6, 2021

Язык: Английский

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Putting Together Pieces of the Lateral Septum: Multifaceted Functions and Its Neural Pathways

eNeuro, Год журнала: 2021, Номер 8(6), С. ENEURO.0315 - 21.2021

Опубликована: Ноя. 1, 2021

Abstract The lateral septum (LS) is implicated as a hub that regulates variety of affects, such reward, feeding, anxiety, fear, sociability, and memory. However, it remains unclear how the LS, previously treated structure homogeneity, exhibits multifaceted functions. Emerging evidence suggests different functions LS are mediated largely by its diverse input output connections. It has also become clear heterogeneous region, where dorsal ventral poles play dissociable often opposing roles. This functional heterogeneity can be explained distinct hippocampal inputs along dorsoventral axis, well antagonizing connections between subregions. Similarly, outputs from subregions to respective downstream targets, hypothalamic, preoptic, tegmental areas, account for this heterogeneity. In review, we provide an updated perspective on subregion classification, connectivity, We identify key questions have yet addressed in field.

Язык: Английский

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The physiological control of eating: signals, neurons, and networks

Physiological Reviews, Год журнала: 2021, Номер 102(2), С. 689 - 813

Опубликована: Сен. 6, 2021

During the past 30 yr, investigating physiology of eating behaviors has generated a truly vast literature. This is fueled in part by dramatic increase obesity and its comorbidities that coincided with an ever increasing sophistication genetically based manipulations. These techniques have produced results remarkable degree cell specificity, particularly at signaling level, played lead role advancing field. However, putting these findings into brain-wide context connects physiological signals neurons to behavior somatic requires thorough consideration neuronal connections: field also seen extraordinary technological revolution. Our goal present comprehensive balanced assessment how associated energy homeostasis interact many brain levels control behaviors. A major theme engage sets interacting neural networks throughout are defined specific connections. We begin discussing some fundamental concepts, including ones still engender vigorous debate, provide necessary frameworks for understanding controls meal initiation termination. include key word definitions, ATP availability as pivotal regulated variable homeostasis, neuropeptide signaling, homeostatic hedonic eating, structure. Within this context, we discuss network models regions endbrain (or telencephalon), hypothalamus, hindbrain, medulla, vagus nerve, spinal cord work together gastrointestinal tract enable complex motor events permit animals eat diverse situations.

Язык: Английский

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Drugs of abuse hijack a mesolimbic pathway that processes homeostatic need

Science, Год журнала: 2024, Номер 384(6693)

Опубликована: Апрель 18, 2024

Drugs of abuse are thought to promote addiction in part by “hijacking” brain reward systems, but the underlying mechanisms remain undefined. Using whole-brain FOS mapping and vivo single-neuron calcium imaging, we found that drugs augment dopaminoceptive ensemble activity nucleus accumbens (NAc) disorganize overlapping responses natural rewards a cell type–specific manner. Combining FOS-Seq, CRISPR-perturbation, single-nucleus RNA sequencing, identified Rheb as molecular substrate regulates signal transduction NAc while enabling suppress consumption. Mapping NAc-projecting regions activated revealed input-specific effects on These findings characterize dynamic, circuit basis common pathway, wherein interfere with fulfillment innate needs.

Язык: Английский

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Separate orexigenic hippocampal ensembles shape dietary choice by enhancing contextual memory and motivation

Nature Metabolism, Год журнала: 2025, Номер unknown

Опубликована: Янв. 15, 2025

The hippocampus (HPC) has emerged as a critical player in the control of food intake, beyond its well-known role memory. While previous studies have primarily associated HPC with intake inhibition, recent research suggests appetitive processes. Here we identified spatially distinct neuronal populations within dorsal (dHPC) that respond to either fats or sugars, potent natural reinforcers contribute obesity development. Using activity-dependent genetic capture nutrient-responsive dHPC neurons, demonstrate causal both promoting nutrient-specific through different mechanisms. Sugar-responsive neurons encoded spatial memory for sugar location, whereas fat-responsive selectively enhanced preference and motivation fat intake. Importantly, stimulation increased while ablation differentially impacted obesogenic diet consumption prevented diet-induced weight gain. Collectively, these findings uncover previously unknown orexigenic circuits underlying macronutrient-specific provide foundation developing potential treatments. Yang et al. identify characterize sugar- their contribution development obesity.

Язык: Английский

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Genetic mapping of etiologic brain cell types for obesity

eLife, Год журнала: 2020, Номер 9

Опубликована: Сен. 21, 2020

The underlying cell types mediating predisposition to obesity remain largely obscure. Here, we integrated recently published single-cell RNA-sequencing (scRNA-seq) data from 727 peripheral and nervous system spanning 17 mouse organs with body mass index (BMI) genome-wide association study (GWAS) >457,000 individuals. Developing a novel strategy for integrating scRNA-seq GWAS data, identified 26, exclusively neuronal, the hypothalamus, subthalamus, midbrain, hippocampus, thalamus, cortex, pons, medulla, pallidum that were significantly enriched BMI heritability (p<1.6×10 −4 ). Using genes harboring coding mutations associated obesity, replicated midbrain anterior pretectal nucleus periaqueductal gray (p<1.2×10 Together, our results suggest brain nuclei regulating integration of sensory stimuli, learning memory are likely play key role in provide testable hypotheses mechanistic follow-up studies.

Язык: Английский

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A limbic circuit selectively links active escape to food suppression

eLife, Год журнала: 2020, Номер 9

Опубликована: Сен. 7, 2020

Stress has pleiotropic physiologic effects, but the neural circuits linking stress to these responses are not well understood. Here, we describe a novel population of lateral septum neurons expressing neurotensin (LS Nts ) in mice that selectively tuned specific types stress. LS increase their activity during active escape, responding when flight is viable option, associated with freezing or immobility. Chemogenetic activation decreases food intake and body weight, without altering locomotion anxiety. co-express several molecules including Glp1r (glucagon-like peptide one receptor) manipulations signaling recapitulates behavioral effects activation. Activation terminals hypothalamus (LH) also intake. These results show escape can reduce consumption via on hypothalamic pathways.

Язык: Английский

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Gut microbial taxa elevated by dietary sugar disrupt memory function

Translational Psychiatry, Год журнала: 2021, Номер 11(1)

Опубликована: Март 31, 2021

Abstract Emerging evidence highlights a critical relationship between gut microbiota and neurocognitive development. Excessive consumption of sugar other unhealthy dietary factors during early life developmental periods yields changes in the microbiome as well impairments. However, it is unclear whether these two outcomes are functionally connected. Here we explore excessive added sugars negatively impacts memory function via microbiome. Rats were given free access to sugar-sweetened beverage (SSB) adolescent stage Memory anxiety-like behavior assessed adulthood bacterial brain transcriptome analyses conducted. Taxa-specific microbial enrichment experiments examined functional sugar-induced outcomes. Chronic impaired adult hippocampal-dependent without affecting body weight or behavior. Adolescent SSB adolescence also altered microbiome, including elevated abundance species genus Parabacteroides ( P. distasonis johnsonii ) that correlated with hippocampal function. Transferred specific taxa rats adulthood. Hippocampus revealed gene expression intracellular kinase synaptic neurotransmitter signaling pathways, whereas pathways associated metabolic function, neurodegenerative disease, dopaminergic signaling. Collectively results identify role for “dysbiosis” mediating detrimental effects on

Язык: Английский

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Ghrelin and Orexin Interact to Increase Meal Size Through a Descending Hippocampus to Hindbrain Signaling Pathway

Biological Psychiatry, Год журнала: 2019, Номер 87(11), С. 1001 - 1011

Опубликована: Окт. 29, 2019

Язык: Английский

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Bidirectional Regulation of Cognitive and Anxiety-like Behaviors by Dentate Gyrus Mossy Cells in Male and Female Mice

Journal of Neuroscience, Год журнала: 2021, Номер 41(11), С. 2475 - 2495

Опубликована: Янв. 20, 2021

The dentate gyrus (DG) of the hippocampus is important for cognition and behavior. However, circuits underlying these functions are unclear. DG mossy cells (MCs) potentially because their excitatory synapses on primary cell type, granule (GCs). MCs also activate GABAergic neurons, which inhibit GCs. We used viral delivery designer receptors exclusively activated by drugs (DREADDs) in mice to implement a gain- loss-of-function study diverse behaviors. Using this approach, manipulations could bidirectionally regulate results suggest that inhibiting can reduce anxiety-like behavior improve cognitive performance. not all or anxiety-related behaviors were influenced, suggesting specific roles some, but all, types anxiety. Notably, several showed sex-specific effects, with females often showing more pronounced effects than males. immediate early gene c-Fos address whether DREADDs regulated MC GC activity. confirmed increased c-Fos. there was no change c-Fos, consistent activation leading inhibition In contrast, inhibitory led large increase reduction excitation reduced Together, anxiety ways. raise possibility performance may be improved reducing anxiety.SIGNIFICANCE STATEMENT has many as well being associated affective This addressed how glutamatergic type called contributes behaviors, timely it known activity (GCs), influences show, surprisingly, activating lead adverse behavioral outcomes, have an opposite effect. Importantly, appeared task-dependent testing both sexes important. Additional experiments indicated what circuitry involved. influence involve DG.

Язык: Английский

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