scholarly journals Remote control of glucose-sensing neurons to analyze glucose metabolism

2018 ◽  
Vol 315 (3) ◽  
pp. E327-E339 ◽  
Author(s):  
Alexandra Alvarsson ◽  
Sarah A. Stanley
Keyword(s):  
Firing Rate ◽  
Brain Regions ◽  
Glucose Sensing ◽  
Neural Stimulation ◽  
Neural Activation ◽  
Glucose Levels ◽  
Disease States ◽  
Neural Populations ◽  
Synthetic Ligand ◽  
The Central Nervous System

The central nervous system relies on a continual supply of glucose, and must be able to detect glucose levels and regulate peripheral organ functions to ensure that its energy requirements are met. Specialized glucose-sensing neurons, first described half a century ago, use glucose as a signal and modulate their firing rates as glucose levels change. Glucose-excited neurons are activated by increasing glucose concentrations, while glucose-inhibited neurons increase their firing rate as glucose concentrations fall and decrease their firing rate as glucose concentrations rise. Glucose-sensing neurons are present in multiple brain regions and are highly expressed in hypothalamic regions, where they are involved in functions related to glucose homeostasis. However, the roles of glucose-sensing neurons in healthy and disease states remain poorly understood. Technologies that can rapidly and reversibly activate or inhibit defined neural populations provide invaluable tools to investigate how specific neural populations regulate metabolism and other physiological roles. Optogenetics has high temporal and spatial resolutions, requires implants for neural stimulation, and is suitable for modulating local neural populations. Chemogenetics, which requires injection of a synthetic ligand, can target both local and widespread populations. Radio- and magnetogenetics offer rapid neural activation in localized or widespread neural populations without the need for implants or injections. These tools will allow us to better understand glucose-sensing neurons and their metabolism-regulating circuits.

scholarly journals Inhibitory neurons exhibit high controlling ability in the cortical microconnectome

2021 ◽  
Vol 17 (4) ◽  
pp. e1008846
Author(s):  
Motoki Kajiwara ◽  
Ritsuki Nomura ◽  
Felix Goetze ◽  
Masanori Kawabata ◽  
Yoshikazu Isomura ◽  
...  
Keyword(s):  
Firing Rate ◽  
Brain Regions ◽  
Inhibitory Neurons ◽  
Connectivity Pattern ◽  
Disease States ◽  
Neuronal Interactions ◽  
Excitatory Neurons ◽  
The Brain ◽  
Random Connectivity

The brain is a network system in which excitatory and inhibitory neurons keep activity balanced in the highly non-random connectivity pattern of the microconnectome. It is well known that the relative percentage of inhibitory neurons is much smaller than excitatory neurons in the cortex. So, in general, how inhibitory neurons can keep the balance with the surrounding excitatory neurons is an important question. There is much accumulated knowledge about this fundamental question. This study quantitatively evaluated the relatively higher functional contribution of inhibitory neurons in terms of not only properties of individual neurons, such as firing rate, but also in terms of topological mechanisms and controlling ability on other excitatory neurons. We combined simultaneous electrical recording (~2.5 hours) of ~1000 neurons in vitro, and quantitative evaluation of neuronal interactions including excitatory-inhibitory categorization. This study accurately defined recording brain anatomical targets, such as brain regions and cortical layers, by inter-referring MRI and immunostaining recordings. The interaction networks enabled us to quantify topological influence of individual neurons, in terms of controlling ability to other neurons. Especially, the result indicated that highly influential inhibitory neurons show higher controlling ability of other neurons than excitatory neurons, and are relatively often distributed in deeper layers of the cortex. Furthermore, the neurons having high controlling ability are more effectively limited in number than central nodes of k-cores, and these neurons also participate in more clustered motifs. In summary, this study suggested that the high controlling ability of inhibitory neurons is a key mechanism to keep balance with a large number of other excitatory neurons beyond simple higher firing rate. Application of the selection method of limited important neurons would be also applicable for the ability to effectively and selectively stimulate E/I imbalanced disease states.

scholarly journals Inflow of oxygen and glucose in brain tissue induced by intravenous norepinephrine: relationships with central metabolic and peripheral vascular responses

2018 ◽  
Vol 119 (2) ◽  
pp. 499-508 ◽  
Author(s):  
R. Aaron Bola ◽  
Eugene A. Kiyatkin
Keyword(s):  
Brain Tissue ◽  
High Speed ◽  
Cardiac Activity ◽  
Sensory Nerves ◽  
Neural Activation ◽  
Glucose Levels ◽  
The Central Nervous System ◽  
Freely Moving ◽  
A Chain ◽  
The Brain

As an essential part of sympathetic activation that prepares the organism for “fight or flight,” peripheral norepinephrine (NE) plays an important role in regulating cardiac activity and the tone of blood vessels, increasing blood flow to the heart and the brain and decreasing blood flow to the organs not as necessary for immediate survival. To assess whether this effect is applicable to the brain, we used high-speed amperometry to measure the changes in nucleus accumbens (NAc) levels of oxygen and glucose induced by intravenous injections of NE in awake freely moving rats. We found that NE at low doses (2–18 μg/kg) induces correlative increases in NAc oxygen and glucose, suggesting local vasodilation and enhanced entry of these substances in brain tissue from the arterial blood. By using temperature recordings from the NAc, temporal muscle, and skin, we show that this central effect is associated with strong skin vasoconstriction and phasic increases in intrabrain heat production, indicative of metabolic neural activation. A tight direct correlation between NE-induced changes in metabolic activity and NAc levels of oxygen and glucose levels suggests that local cerebral vasodilation is triggered via a neurovascular coupling mechanism. Our data suggest that NE, by changing vascular tone and cardiac activity, triggers a visceral sensory signal that rapidly reaches the central nervous system via sensory nerves and induces neural activation. This neural activation leads to a chain of neurovascular events that promote entry of oxygen and glucose in brain tissue, thus preventing any possible metabolic deficit during functional activation. NEW & NOTEWORTHY Using high-speed amperometry and thermorecording in freely moving rats, we demonstrate that intravenous norepinephrine at physiological doses induces rapid correlative increases in nucleus accumbens oxygen and glucose levels coupled with increased intrabrain heat production. Although norepinephrine cannot cross the blood-brain barrier, by changing cardiac activity and vascular tone, it creates a sensory signal that reaches the central nervous system via sensory nerves, induces neural activation, and triggers a chain of neurovascular events that promotes intrabrain entry of oxygen and glucose.

Brain glucose sensing and body energy homeostasis: role in obesity and diabetes

1999 ◽  
Vol 276 (5) ◽  
pp. R1223-R1231 ◽  
Author(s):  
Barry E. Levin ◽  
Ambrose A. Dunn-Meynell ◽  
Vanessa H. Routh
Keyword(s):  
Firing Rate ◽  
Energy Homeostasis ◽  
Glucose Sensing ◽  
Diabetic Rats ◽  
Brain Glucose ◽  
Physiological Regulation ◽  
Glucose Levels ◽  
Obesity And Diabetes ◽  
Sympathoadrenal Activity ◽  
Insulin Dependent Diabetic

The brain has evolved mechanisms for sensing and regulating glucose metabolism. It receives neural inputs from glucosensors in the periphery but also contains neurons that directly sense changes in glucose levels by using glucose as a signal to alter their firing rate. Glucose-responsive (GR) neurons increase and glucose-sensitive (GS) decrease their firing rate when brain glucose levels rise. GR neurons use an ATP-sensitive K+ channel to regulate their firing. The mechanism regulating GS firing is less certain. Both GR and GS neurons respond to, and participate in, the changes in food intake, sympathoadrenal activity, and energy expenditure produced by extremes of hyper- and hypoglycemia. It is less certain that they respond to the small swings in plasma glucose required for the more physiological regulation of energy homeostasis. Both obesity and diabetes are associated with several alterations in brain glucose sensing. In rats with diet-induced obesity and hyperinsulinemia, GR neurons are hyporesponsive to glucose. Insulin-dependent diabetic rats also have abnormalities of GR neurons and neurotransmitter systems potentially involved in glucose sensing. Thus the challenge for the future is to define the role of brain glucose sensing in the physiological regulation of energy balance and in the pathophysiology of obesity and diabetes.

scholarly journals β-Elemene Suppresses Obesity-Induced Imbalance in the Microbiota-Gut-Brain Axis

Biomedicines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 704
Author(s):  
Yingyu Zhou ◽  
Wanyi Qiu ◽  
Yimei Wang ◽  
Rong Wang ◽  
Tomohiro Takano ◽  
...  
Keyword(s):  
Intestinal Microbiota ◽  
High Fat Diet ◽  
Brain Regions ◽  
Cerebral Metabolites ◽  
The Central Nervous System ◽  
Cerebral Inflammation ◽  
Regulatory Effects ◽  
Induced Changes ◽  
Pearson Correlations ◽  
Glucose Cycle

As a kind of metabolically triggered inflammation, obesity influences the interplay between the central nervous system and the enteral environment. The present study showed that β-elemene, which is contained in various plant substances, had effects on recovering the changes in metabolites occurring in high-fat diet (HFD)-induced obese C57BL/6 male mice brains, especially in the prefrontal cortex (PFC) and hippocampus (HIP). β-elemene also partially reversed HFD-induced changes in the composition and contents of mouse gut bacteria. Furthermore, we evaluated the interaction between cerebral metabolites and intestinal microbiota via Pearson correlations. The prediction results suggested that Firmicutes were possibly controlled by neuron integrity, cerebral inflammation, and neurotransmitters, and Bacteroidetes in mouse intestines might be related to cerebral aerobic respiration and the glucose cycle. Such results also implied that Actinobacteria probably affected cerebral energy metabolism. These findings suggested that β-elemene has regulatory effects on the imbalanced microbiota-gut-brain axis caused by obesity and, therefore, would contribute to the future study in on the interplay between cerebral metabolites from different brain regions and the intestinal microbiota of mice.

scholarly journals Insulin blunts the response of glucose-excited neurons in the ventrolateral-ventromedial hypothalamic nucleus to decreased glucose

2009 ◽  
Vol 296 (5) ◽  
pp. E1101-E1109 ◽  
Author(s):  
Victoria E. Cotero ◽  
Vanessa H. Routh
Keyword(s):  
Energy Homeostasis ◽  
Ventromedial Hypothalamus ◽  
Glucose Sensing ◽  
Hypothalamic Nucleus ◽  
Compensatory Mechanisms ◽  
Glucose Levels ◽  
Compound C ◽  
Obesity And Diabetes ◽  
Extracellular Glucose ◽  
Pi3k Signaling Pathway

Insulin signaling is dysfunctional in obesity and diabetes. Moreover, central glucose-sensing mechanisms are impaired in these diseases. This is associated with abnormalities in hypothalamic glucose-sensing neurons. Glucose-sensing neurons reside in key areas of the brain involved in glucose and energy homeostasis, such as the ventromedial hypothalamus (VMH). Our results indicate that insulin opens the KATP channel on VMH GE neurons in 5, 2.5, and 0.1 mM glucose. Furthermore, insulin reduced the sensitivity of VMH GE neurons to a decrease in extracellular glucose level from 2.5 to 0.1 mM. This change in the glucose sensitivity in the presence of insulin was reversed by the phosphatidylinositol 3-kinase (PI3K) inhibitor wortmannin (10 nM) but not by the mitogen-activated kinase (MAPK) inhibitor PD-98059 (PD; 50 μM). Finally, neither the AMPK inhibitor compound C nor the AMPK activator AICAR altered the activity of VMH GE neurons. These data suggest that insulin attenuates the ability of VMH GE neurons to sense decreased glucose via the PI3K signaling pathway. Furthermore, these data are consistent with the role of insulin as a satiety factor. That is, in the presence of insulin, glucose levels must decline further before GE neurons respond. Thus, the set point for detection of glucose deficit and initiation of compensatory mechanisms would be lowered.

Low concentrations of hydrogen sulphide alter monoamine levels in the developing rat central nervous system

1992 ◽  
Vol 70 (11) ◽  
pp. 1515-1518 ◽  
Author(s):  
B. Skrajny ◽  
R. S. Hannah ◽  
S. H. Roth
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Frontal Cortex ◽  
Hydrogen Sulphide ◽  
Chronic Exposure ◽  
Brain Regions ◽  
Target Organs ◽  
Low Concentrations ◽  
The Central Nervous System ◽  
Developing Rat

The central nervous system is one of the primary target organs for hydrogen sulphide (H2S) toxicity; however, there are limited data on the neurotoxic effects of low-dose chronic exposure on the developing nervous system. Levels of serotonin and norepinephrine in the developing rat cerebellum and frontal cortex were determined following chronic exposure to 20 and 75 ppm H2S during perinatal development. Both monoamines were altered in rats exposed to 75 ppm H2S compared with controls; serotonin levels were significantly increased at days 14 and 21 postnatal in both brain regions, and norepinephrine levels were significantly increased at days 7, 14, and 21 postnatal in cerebellum and at day 21 in the frontal cortex. Exposure to 20 ppm H2S significantly increased the levels of serotonin in the frontal cortex at day 21, whereas levels of norepinephrine were significantly reduced in the frontal cortex at days 14 and 21, and at day 14 in the cerebellum.Key words: hydrogen sulphide, monoamines, serotonin, norepinephrine, neurotoxicity.

Refining the Effects Observed in a Developmental Neurobehavioral Study of Ammonium Perchlorate Administered Orally in Drinking Water to Rats. II. Behavioral and Neurodevelopment Effects

2005 ◽  
Vol 24 (6) ◽  
pp. 451-467 ◽  
Author(s):  
Raymond G. York ◽  
John Barnett ◽  
Michael F. Girard ◽  
David R. Mattie ◽  
Marni V. K. Bekkedal ◽  
...  
Keyword(s):  
Drinking Water ◽  
Ammonium Perchlorate ◽  
Brain Regions ◽  
Male Rats ◽  
Male Rat ◽  
Sprague Dawley ◽  
Continuous Access ◽  
Brain Morphometry ◽  
The Central Nervous System ◽  
The Right

A developmental neurotoxicity study was conducted to generate additional data on the potential functional and morphological hazard to the central nervous system caused by ammonium perchlorate in offspring from in utero and lactation exposure. Female Sprague-Dawley rats (23 to 25/group) were given continuous access to 0 (carrier), 0.1, 1.0, 3.0, and 10.0 mg/kg-day perchlorate in the drinking water beginning 2 weeks prior to mating and continuing through day 10 of lactation for the behavioral function assessment or given continuous access to 0 (carrier), 0.1, 1.0, 3.0, and 30.0 mg/kg-day beginning on gestation day 0 and continuing through day 10 of lactation for neurodevelopment assessments. Motor activity was conducted on postpartum days 14, 18, and 22 and juvenile brain weights, neurohistopathological examinations, and regional brain morphometry were conducted on postpartum days 10 and 22. This research revealed a sexually dimorphic response, with some brain regions being larger in perchlorate-treated male rats than in comparable controls. Even so, there was no evidence of any obvious exposure-related effects on male rat brain weights or neuropathology. The most consistent exposure-related effect in the male pups was on the thickness of the corpus callosum, with both the right- and left-sided measures of the thickness of this white matter tract being significantly greater for the male pups in the 0.1 and 1.0 mg/kg-day exposure groups. The behavioral testing suggests prenatal exposure to ammonium perchlorate does not affect the development of gross motor movements in the pups.

scholarly journals Two glucose sensing/signaling pathways stimulate glucose-induced inactivation of maltose permease in Saccharomyces.

1997 ◽  
Vol 8 (7) ◽  
pp. 1293-1304 ◽  
Author(s):  
H Jiang ◽  
I Medintz ◽  
C A Michels
Keyword(s):  
Signaling Pathways ◽  
Glucose Transport ◽  
Glucose Sensor ◽  
Constitutive Expression ◽  
Glucose Sensing ◽  
Regulation Of Transcription ◽  
Carbohydrate Utilization ◽  
Maltose Permease ◽  
Glucose Levels ◽  
Dependent Signal

Glucose is a global metabolic regulator in Saccharomyces. It controls the expression of many genes involved in carbohydrate utilization at the level of transcription, and it induces the inactivation of several enzymes by a posttranslational mechanism. SNF3, RGT2, GRR1 and RGT1 are known to be involved in glucose regulation of transcription. We tested the roles of these genes in glucose-induced inactivation of maltose permease. Our results suggest that at least two signaling pathways are used to monitor glucose levels. One pathway requires glucose sensor transcript and the second pathway is independent of glucose transport. Rgt2p, which along with Snf3p monitors extracellular glucose levels, appears to be the glucose sensor for the glucose-transport-independent pathway. Transmission of the Rgt2p-dependent signal requires Grr1p. RGT2 and GRR1 also play a role in regulating the expression of the HXT genes, which appear to be the upstream components of the glucose-transport-dependent pathway regulating maltose permease inactivation. RGT2-1, which was identified as a dominant mutation causing constitutive expression of several HXT genes, causes constitutive proteolysis of maltose permease, that is, in the absence of glucose. A model of these glucose sensing/signaling pathways is presented.

scholarly journals High-Sugar, but Not High-Fat, Food Activates Supraoptic Nucleus Neurons in the Male Rat

Endocrinology ◽  
2017 ◽  
Vol 158 (7) ◽  
pp. 2200-2211 ◽  
Author(s):  
Catherine Hume ◽  
Nancy Sabatier ◽  
John Menzies
Keyword(s):  
Firing Rate ◽  
Supraoptic Nucleus ◽  
Male Rat ◽  
Plasma Sodium ◽  
Neural Activation ◽  
High Fat ◽  
Gastric Distention ◽  
High Sugar ◽  
Anesthetized Rats

Abstract Oxytocin is a potent anorexigen and is believed to have a role in satiety signaling. We developed rat models to study the activity of oxytocin neurons in response to voluntary consumption or oral gavage of foods using c-Fos immunohistochemistry and in vivo electrophysiology. Using c-Fos expression as an indirect marker of neural activation, we showed that the percentage of magnocellular oxytocin neurons expressing c-Fos increased with voluntary consumption of sweetened condensed milk (SCM). To model the effect of food in the stomach, we gavaged anesthetized rats with SCM. The percentage of supraoptic nucleus and paraventricular nucleus magnocellular oxytocin-immunoreactive neurons expressing c-Fos increased with SCM gavage but not with gastric distention. To further examine the activity of the supraoptic nucleus, we made in vivo electrophysiological recordings from SON neurons, where anesthetized rats were gavaged with SCM or single cream. Pharmacologically identified oxytocin neurons responded to SCM gavage with a linear, proportional, and sustained increase in firing rate, but cream gavage resulted in a transient reduction in firing rate. Blood glucose increased after SCM gavage but not cream gavage. Plasma osmolarity and plasma sodium were unchanged throughout. We show that in response to high-sugar, but not high-fat, food in the stomach, there is an increase in the activity of oxytocin neurons. This does not appear to be a consequence of stomach distention or changes in osmotic pressure. Our data suggest that the presence of specific foods with different macronutrient profiles in the stomach differentially regulates the activity of oxytocin neurons.

Distinct Effects of D9-tetrahydrocannabinol and Cannabidiol on Neural Activation During Emotional Processing

2009 ◽  
Vol 24 (S1) ◽  
pp. 1-1 ◽  
Author(s):  
P. Fusar-Poli
Keyword(s):  
Emotional Processing ◽  
Electrodermal Activity ◽  
Brain Regions ◽  
Posterior Cingulate Cortex ◽  
Psychotic Symptoms ◽  
Neural Activation ◽  
Double Blind ◽  
Posterior Cingulate ◽  
Fearful Faces ◽  
Scanning Session

Aims:Cannabis use can both increase and reduce anxiety in humans. The neurophysiological substrates of these effects are unknown.Method:Fifteen healthy English-native right-handed men were studied on three separate occasions using an event-related fMRI paradigm while viewing faces that implicitly elicited different levels of anxiety. Each scanning session was preceded by the ingestion of either 10mg of D-9-THC, 600mg of CBD, or a placebo, in a double-blind, randomised, placebo controlled design. Electrodermal activity (Skin Conductance Response, SCR) and objective and subjective ratings of anxiety were recorded durign the scanning.Results:D-9THC increased anxiety, as well as levels of intoxication, sedation and psychotic symptoms, whereas there was a trend for a reduction in anxiety following administration of CBD. The number of SCR fluctuations during the processing of intensely fearful faces increased following administration of D-9THC but decreased following administration of CBD. CBD attenuated the BOLD signal in the amygdala and the anterior and posterior cingulate cortex while subjects were processing intensely fearful faces, and its suppression of the amygdalar and posterior cingulate responses was correlated with the concurrent reduction in SCR fluctuations. D-9-THC mainly modulated activation in frontal and parietal areas.Conclusions:D-9-THC and CBD had clearly distinct effects on the neural, eclectrodermal and symptomatic response to fearful faces. The effects of CBD on activation in limbic and paralimbic regions may contribute to its ability to reduce autonomic arousal and subjective anxiety, whereas the anxiogenic effects of D-9-THC may be related to effects in other brain regions.

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