scholarly journals A gut-brain neural circuit for nutrient sensory transduction

Science ◽  
2018 ◽  
Vol 361 (6408) ◽  
pp. eaat5236 ◽  
Author(s):  
Melanie Maya Kaelberer ◽  
Kelly L. Buchanan ◽  
Marguerita E. Klein ◽  
Bradley B. Barth ◽  
Marcia M. Montoya ◽  
...  
Keyword(s):  
Neural Circuit ◽  
Enteroendocrine Cells ◽  
Sensory Transduction ◽  
Intestinal Lumen ◽  
Excitable Cells ◽  
Enteroendocrine Cell ◽  
Temporal Precision ◽  
Passive Release ◽  
Sensor Cell ◽  
The Brain

The brain is thought to sense gut stimuli only via the passive release of hormones. This is because no connection has been described between the vagus and the putative gut epithelial sensor cell—the enteroendocrine cell. However, these electrically excitable cells contain several features of epithelial transducers. Using a mouse model, we found that enteroendocrine cells synapse with vagal neurons to transduce gut luminal signals in milliseconds by using glutamate as a neurotransmitter. These synaptically connected enteroendocrine cells are referred to henceforth as neuropod cells. The neuroepithelial circuit they form connects the intestinal lumen to the brainstem in one synapse, opening a physical conduit for the brain to sense gut stimuli with the temporal precision and topographical resolution of a synapse.

scholarly journals Neuropod Cells: The Emerging Biology of Gut-Brain Sensory Transduction

2020 ◽  
Vol 43 (1) ◽  
pp. 337-353 ◽  
Author(s):  
Melanie Maya Kaelberer ◽  
Laura E. Rupprecht ◽  
Winston W. Liu ◽  
Peter Weng ◽  
Diego V. Bohórquez
Keyword(s):  
Epithelial Cells ◽  
Vagus Nerve ◽  
Nutritional Value ◽  
Sensory Systems ◽  
Enteroendocrine Cells ◽  
Sensory Transduction ◽  
Sensory Signals ◽  
Passive Release ◽  
The Brain

Guided by sight, scent, texture, and taste, animals ingest food. Once ingested, it is up to the gut to make sense of the food's nutritional value. Classic sensory systems rely on neuroepithelial circuits to convert stimuli into signals that guide behavior. However, sensation of the gut milieu was thought to be mediated only by the passive release of hormones until the discovery of synapses in enteroendocrine cells. These are gut sensory epithelial cells, and those that form synapses are referred to as neuropod cells. Neuropod cells provide the foundation for the gut to transduce sensory signals from the intestinal milieu to the brain through fast neurotransmission onto neurons, including those of the vagus nerve. These findings have sparked a new field of exploration in sensory neurobiology—that of gut-brain sensory transduction.

scholarly journals Synergistic Effect of Several Neurotransmitters in PFC-NAc-VTA Neural Circuit for the Anti-Depression Effect of Shuganheweitang in a Chronic Unpredictable Mild Stress Model

2021 ◽  
Vol 16 (3) ◽  
pp. 1934578X2110024
Author(s):  
Xin Chen ◽  
Yuanchun Ma ◽  
Xiongjun Mou ◽  
Hao Liu ◽  
Hao Ming ◽  
...  
Keyword(s):  
Animal Behavior ◽  
Neural Circuit ◽  
Concentration Level ◽  
Brain Regions ◽  
Mild Stress ◽  
Depression Effect ◽  
Monoamine Neurotransmitters ◽  
Reward Circuitry ◽  
High Doses ◽  
The Brain

Depression, a major worldwide mental disorder, leads to massive disability and can result in death. The PFC-NAc-VTA neuro circuit is related to emotional, neurovegetative, and cognitive functions, which emerge as a circuit-level framework for understanding reward deficits in depression. Neurotransmitters, which are widely distributed in different brain regions, are important detected targets for the evaluation of depression. Shuganheweitang (SGHWT) is a popular prescription in clinical therapy for depression. In order to investigate its possible pharmacodynamics and anti-depressive mechanism, the complex plant material was separated into different fractions. These in low and high doses, along with low and high doses of SGHWT were tested in animal behavior tests. The low and high doses of SGHWT were more effective than the various fractions, which indicate the importance of synergistic function in traditional Chinese medicine. Furthermore, amino acid (GABA, Glu) and monoamine neurotransmitters (DA, 5-HT, NA, 5-HIAA) in the PFC-NAc-VTA neuro circuit were investigated by UPLC-MS/MS. The level trend of DA and 5-HT were consistent in the PFC-NAc-VTA neuro circuit, whereas 5-HIAA was decreased in the PFC, Glu was decreased in the PFC and VTA, and NA and GABA were decreased in the NAc. The results indicate that the pathogenesis of depression is associated with dysfunction of the PFC-NAc-VTA neural circuit, mainly through the neural projection effects of neurotransmitters associated with various brain regions in the neural circuit. PCA and OPLS-DA score plots demonstrated the similarities of individuals within each group and the differences among the groups. In this study, SGHWT could regulate the concentration level of different neurotransmitters in the PFC-NAc-VTA neuro circuit to improve the depression, which benefitted from the recognition of the brain reward circuitry in mood disorders.

Duodenal-jejunal bypass protects GK rats from β-cell loss and aggravation of hyperglycemia and increases enteroendocrine cells coexpressing GIP and GLP-1

2011 ◽  
Vol 300 (5) ◽  
pp. E923-E932 ◽  
Author(s):  
Madeleine Speck ◽  
Young Min Cho ◽  
Ali Asadi ◽  
Francesco Rubino ◽  
Timothy J. Kieffer
Keyword(s):  
Glucose Tolerance ◽  
Glucose Homeostasis ◽  
Wistar Rats ◽  
Enteroendocrine Cells ◽  
Cell Populations ◽  
Cell Area ◽  
Β Cell ◽  
Enteroendocrine Cell ◽  
Gk Rats ◽  
Jejunal Bypass

Dramatic improvement of type 2 diabetes is commonly observed after bariatric surgery. However, the mechanisms behind the alterations in glucose homeostasis are still elusive. We examined the effect of duodenal-jejunal bypass (DJB), which maintains the gastric volume intact while bypassing the entire duodenum and the proximal jejunum, on glycemic control, β-cell mass, islet morphology, and changes in enteroendocrine cell populations in nonobese diabetic Goto-Kakizaki (GK) rats and nondiabetic control Wistar rats. We performed DJB or sham surgery in GK and Wistar rats. Blood glucose levels and glucose tolerance were monitored, and the plasma insulin, glucagon-like peptide-1 (GLP-1), and glucose-dependent insulinotropic polypeptide (GIP) levels were measured. β-Cell area, islet fibrosis, intestinal morphology, and the density of enteroendocrine cells expressing GLP-1 and/or GIP were quantified. Improved postprandial glycemia was observed from 3 mo after DJB in diabetic GK rats, persisting until 12 mo after surgery. Compared with the sham-GK rats, the DJB-GK rats had an increased β-cell area and a decreased islet fibrosis, increased insulin secretion with increased GLP-1 secretion in response to a mixed meal, and an increased population of cells coexpressing GIP and GLP-1 in the jejunum anastomosed to the stomach. In contrast, DJB impaired glucose tolerance in nondiabetic Wistar rats. In conclusion, although DJB worsens glucose homeostasis in normal nondiabetic Wistar rats, it can prevent long-term aggravation of glucose homeostasis in diabetic GK rats in association with changes in intestinal enteroendocrine cell populations, increased GLP-1 production, and reduced β-cell deterioration.

Striatal dopamine mediates hallucination-like perception in mice

Science ◽  
2021 ◽  
Vol 372 (6537) ◽  
pp. eabf4740
Author(s):  
K. Schmack ◽  
M. Bosc ◽  
T. Ott ◽  
J. F. Sturgill ◽  
A. Kepecs
Keyword(s):  
Psychotic Disorders ◽  
Neural Circuit ◽  
Dopamine Neurons ◽  
Striatal Dopamine ◽  
Model Organisms ◽  
High Confidence ◽  
Optogenetic Stimulation ◽  
The Brain ◽  
Central Symptom ◽  
Stimulation Of

Hallucinations, a central symptom of psychotic disorders, are attributed to excessive dopamine in the brain. However, the neural circuit mechanisms by which dopamine produces hallucinations remain elusive, largely because hallucinations have been challenging to study in model organisms. We developed a task to quantify hallucination-like perception in mice. Hallucination-like percepts, defined as high-confidence false detections, increased after hallucination-related manipulations in mice and correlated with self-reported hallucinations in humans. Hallucination-like percepts were preceded by elevated striatal dopamine levels, could be induced by optogenetic stimulation of mesostriatal dopamine neurons, and could be reversed by the antipsychotic drug haloperidol. These findings reveal a causal role for dopamine-dependent striatal circuits in hallucination-like perception and open new avenues to develop circuit-based treatments for psychotic disorders.

scholarly journals Astrocytes: Heterogeneous and Dynamic Phenotypes in Neurodegeneration and Innate Immunity

2018 ◽  
Vol 25 (5) ◽  
pp. 455-474 ◽  
Author(s):  
Colm Cunningham ◽  
Aisling Dunne ◽  
Ana Belen Lopez-Rodriguez
Keyword(s):  
Neural Circuit ◽  
Phenotypic Diversity ◽  
Significant Heterogeneity ◽  
Therapeutic Implications ◽  
Numerous Cell ◽  
Health And Disease ◽  
The Subject ◽  
The Brain ◽  
Substantial Heterogeneity ◽  
Homogenous Population

Astrocytes are the most numerous cell type in the brain and perform several essential functions in supporting neuronal metabolism and actively participating in neural circuit and behavioral function. They also have essential roles as innate immune cells in responding to local neuropathology, and the manner in which they respond to brain injury and degeneration is the subject of increasing attention in neuroscience. Although activated astrocytes have long been thought of as a relatively homogenous population, which alter their phenotype in a relatively stereotyped way upon central nervous system injury, the last decade has revealed substantial heterogeneity in the basal state and significant heterogeneity of phenotype during reactive astrocytosis. Thus, phenotypic diversity occurs at two distinct levels: that determined by regionality and development and that determined by temporally dynamic changes to the environment of astrocytes during pathology. These inflammatory and pathological states shape the phenotype of these cells, with different consequences for destruction or recovery of the local tissue, and thus elucidating these phenotypic changes has significant therapeutic implications. In this review, we will focus on the phenotypic heterogeneity of astrocytes in health and disease and their propensity to change that phenotype upon subsequent stimuli.

Perinatal Development of the Medial Nucleus of the Trapezoid Body

2018 ◽  
pp. 244-272
Author(s):  
Shobhana Sivaramakrishnan ◽  
Ashley Brandebura ◽  
Paul Holcomb ◽  
Daniel Heller ◽  
Douglas Kolson ◽  
...  
Keyword(s):  
Axon Guidance ◽  
Neural Circuit ◽  
Neural Cells ◽  
Calyx Of Held ◽  
Medial Nucleus ◽  
Target Neuron ◽  
Circuit Formation ◽  
Key Events ◽  
The Brain ◽  
Trapezoid Body

Bushy cells (BC) of the cochlear nucleus mono-innervate their target neuron, the principal cell of the medial nucleus of the trapezoid body (MNTB), via the calyx of Held (CH) terminal, which is a typically mammalian structure and perhaps the largest nerve terminal in the brain. CH:MNTB innervation has become an attractive model to study neural circuit formation because it forms quickly, passing through stages of competition in mice within 2–4 days. BCs innervate MNTB neurons by E17, but CHs do not begin to grow for another five days (P3). Progress has been made to identify molecular factors for axon guidance, CH growth, and physiological maturation of synaptic partners, but important details remain to be discovered. We summarize key events in CH formation and highlight unresolved issues in molecular and physiological signaling, roles for non-neural cells, and the nature of competition during the first postnatal week.

scholarly journals THE VISUAL SYSTEM: A "CHICKEN AND EGG" PROBLEM SOLVED

2009 ◽  
Vol 05 (01) ◽  
pp. 115-121
Author(s):  
ANDREW R. PARKER ◽  
H. JOHN CAULFIELD
Keyword(s):  
Visual System ◽  
Neural Plasticity ◽  
Neural Circuit ◽  
Process Data ◽  
System A ◽  
New Information ◽  
The Brain

"What comes first: the chicken or the egg?" Eyes and vision were a great concern for Darwin. Recently, religious fundamentalists have started to attack evolution on the grounds that this is a chicken and egg problem. How could eyes improve without the brain module to use the new information that eye provides? But how could the brain evolve a neural circuit to process data not available to it until a new eye capability emerges? We argue that neural plasticity in the brain allows it to make use of essentially any useful information the eye can produce. And it does so easily within the animal's lifetime. Richard Gregory suggested something like this 40 years ago. Our work resolves a problem with his otherwise-insightful work.

scholarly journals A neural circuit linking two sugar sensors regulates satiety-dependent fructose drive in Drosophila

2021 ◽  
Author(s):  
Pierre-Yves Musso ◽  
Pierre Junca ◽  
Michael D Gordon
Keyword(s):  
Feeding Behavior ◽  
Synaptic Input ◽  
Neural Circuit ◽  
Internal State ◽  
Calcium Activity ◽  
Shaped Body ◽  
Body Activity ◽  
The Brain

ABSTRACTIngestion of certain sugars leads to activation of fructose sensors within the brain of flies, which then sustain or terminate feeding behavior depending on internal state. Here, we describe a three-part neural circuit that links satiety with fructose sensing. We show that AB-FBl8 neurons of the Fan-shaped body display oscillatory calcium activity when hemolymph glycemia is high, and that these oscillations require synaptic input from SLP-AB neurons projecting from the protocerebrum to the asymmetric body. Suppression of activity in this circuit, either by starvation or genetic silencing, promotes specific drive for fructose ingestion. Moreover, neuropeptidergic signaling by tachykinin bridges fan-shaped body activity and Gr43a-mediated fructose sensing. Together, our results demonstrate how a three-layer neural circuit links the detection of two sugars to impart precise satiety-dependent control over feeding behavior.

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