scholarly journals Dynamic encoding of social threat and spatial context in the hypothalamus

2019 ◽  
Author(s):  
Piotr Krzywkowski ◽  
Beatrice Penna ◽  
Cornelius T. Gross
Keyword(s):  
Internal State ◽  
Social Defeat ◽  
Ventromedial Hypothalamus ◽  
Spatial Context ◽  
Social Threat ◽  
Sensory Cues ◽  
Dominance Status ◽  
Functional Reorganization ◽  
Instinctive Behavior

AbstractTerritorial animals must be able to express social aggression or avoidance in a manner appropriate to spatial context and dominance status. Recent studies indicate that the ventromedial hypothalamus controls both innate aggression and avoidance, suggesting that it may encode an internal state of threat common to both behaviors. Here we used single unit in vivo calcium microendoscopy to identify neurons in the mouse ventromedial hypothalamus encoding social threat. Threat neurons were activated during social defeat as well as when the animal performed risk assessment. Unexpectedly, threat neurons were also activate in the chamber where the animal had been previously defeated and a distinct set of neurons emerged that were active in its home chamber, demonstrating the dynamic encoding of spatial context in the hypothalamus. Ensemble analysis of neural activity showed that social defeat induced a change in the encoding of social information and optogenetic activation of ventromedial hypothalamus neurons was able to elicit avoidance after, but not before social defeat, demonstrating a functional reorganization of the pathway by social experience. These findings reveal how instinctive behavior circuits in the hypothalamus dynamically encode spatial and sensory cues to drive adaptive social behaviors.

scholarly journals Dynamic encoding of social threat and spatial context in the hypothalamus

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Piotr Krzywkowski ◽  
Beatrice Penna ◽  
Cornelius T Gross
Keyword(s):  
Internal State ◽  
Social Defeat ◽  
Ventromedial Hypothalamus ◽  
Social Aggression ◽  
Spatial Context ◽  
Social Threat ◽  
Firing Activity ◽  
Functional Reorganization ◽  
General Internal ◽  
Defensive Behaviors

Social aggression and avoidance are defensive behaviors expressed by territorial animals in a manner appropriate to spatial context and experience. The ventromedial hypothalamus controls both social aggression and avoidance, suggesting that it may encode a general internal state of threat modulated by space and experience. Here, we show that neurons in the mouse ventromedial hypothalamus are activated both by the presence of a social threat as well as by a chamber where social defeat previously occurred. Moreover, under conditions where the animal could move freely between a home and defeat chamber, firing activity emerged that predicted the animal’s position, demonstrating the dynamic encoding of spatial context in the hypothalamus. Finally, we found that social defeat induced a functional reorganization of neural activity as optogenetic activation could elicit avoidance after, but not before social defeat. These findings reveal how the hypothalamus dynamically encodes spatial and sensory cues to drive social behaviors.

scholarly journals Calcium functional imaging with high-resolution CT in the inner ear

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hisaya Tanioka ◽  
Sayaka Tanioka
Keyword(s):  
Internal State ◽  
Texture Synthesis ◽  
Biological Information ◽  
Endolymphatic Sac ◽  
Otolith Organs ◽  
Synthesis Algorithm ◽  
Utricular Macula ◽  
Positional Vertigo ◽  
Paroxysmal Positional Vertigo

AbstractAlthough the otolith and otolith organs correlate with vertigo and instability, there is no method to investigate them without harmful procedures. We will create the technique for 3D microanatomical images of them, and investigate the in vivo internal state and metabolisms. The otolith and otolith organs images were reconstructed from a texture synthesis algorithm under the skull volume rendering algorithm using a cutting-plane method. The utricular macula was elongated pea-shaped. The saccular macula was almost bud-shaped. The changes in the amount of CaCO3 in the maculae and the endolymphatic sac showed various morphologies, reflecting the balance status of each subject. Both shapes and volumes were not always constant depending on time. In Meniere’s disease (MD), the saccular macula was larger and the utricular macula was smaller. In benign paroxysmal positional vertigo (BPPV), the otolith increased in the utricular macula but did not change much in the saccular macula. The saccule, utricle, and endolymphatic sac were not constantly shaped according to their conditions. These created 3D microanatomical images can allow detailed observations of changes in physiological and biological information. This imaging technique will contribute to our understanding of pathology and calcium metabolism in the in vivo vestibulum.

scholarly journals Low-Molecular Weight BDNF Mimetic, Dimeric Dipeptide GSB-106, Reverses Depressive Symptoms in Mouse Chronic Social Defeat Stress

Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 252
Author(s):  
Tatiana A. Gudasheva ◽  
Anna V. Tallerova ◽  
Armen G. Mezhlumyan ◽  
Tatyana A. Antipova ◽  
Ilya O. Logvinov ◽  
...  
Keyword(s):  
Dose Range ◽  
Social Defeat ◽  
Social Defeat Stress ◽  
In Vivo Experiments ◽  
Trk Receptor ◽  
Chronic Social Defeat Stress ◽  
Swimming Test ◽  
Scientific Group

A mimetic of the BDNF loop 4, bis (N-monosuccinyl-L-seryl-L-lysine) hexamethylenediamide, named GSB-106, was designed and synthesized in our scientific group. The compound activated TrkB, MAPK/ERK, PI3K/AKT, and PLCγ in in vitro experiments. In vivo experiments with rodents revealed its antidepressant-like activity in the forced swim and the tail suspension tests at the dose range of 0.1–5.0 mg/kg (i.p., p.o.). However, GSB-106 was not studied in depression models modulating major depression in humans. In the present study, the GSB-106 antidepressant-like activity was revealed in mice at the depression model induced by 28-day social defeat stress with 21-days oral administration (0.1 mg/kg) after stress. At the same time, GSB-106 restored reduced locomotor activity and completely eliminated the anhedonia manifestations. The compound also restored reduced levels of synaptophysin and CREB in the hippocampus. In addition, the Trk receptor antagonist K252A, and the PLC inhibitor U73122, were found to completely block the antidepressant-like activity of GSB-106 in the forced swimming test in mice. Thus, the present results demonstrate the dipeptide BDNF mimetic GSB-106 reversed depressive-like behavior and restored hippocampal neuroplasticity in a rodent depression model. These effects of GSB-106 are probably regulated by TrkB signaling.

scholarly journals Design of a biochemical circuit motif for learning linear functions

2014 ◽  
Vol 11 (101) ◽  
pp. 20140902 ◽  
Author(s):  
Matthew R. Lakin ◽  
Amanda Minnich ◽  
Terran Lane ◽  
Darko Stefanovic
Keyword(s):  
Internal State ◽  
Linear Functions ◽  
Learning Performance ◽  
Adaptive Behaviour ◽  
Biological Processes ◽  
Biochemical System ◽  
Biochemical Systems ◽  
Robustness To Noise ◽  
Novel Design

Learning and adaptive behaviour are fundamental biological processes. A key goal in the field of bioengineering is to develop biochemical circuit architectures with the ability to adapt to dynamic chemical environments. Here, we present a novel design for a biomolecular circuit capable of supervised learning of linear functions, using a model based on chemical reactions catalysed by DNAzymes. To achieve this, we propose a novel mechanism of maintaining and modifying internal state in biochemical systems, thereby advancing the state of the art in biomolecular circuit architecture. We use simulations to demonstrate that the circuit is capable of learning behaviour and assess its asymptotic learning performance, scalability and robustness to noise. Such circuits show great potential for building autonomous in vivo nanomedical devices. While such a biochemical system can tell us a great deal about the fundamentals of learning in living systems and may have broad applications in biomedicine (e.g. autonomous and adaptive drugs), it also offers some intriguing challenges and surprising behaviours from a machine learning perspective.

scholarly journals Repeated social defeat induces transient glial activation and brain hypometabolism: A positron emission tomography imaging study

2017 ◽  
Vol 39 (3) ◽  
pp. 439-453 ◽  
Author(s):  
Paula Kopschina Feltes ◽  
Erik FJ de Vries ◽  
Luis E Juarez-Orozco ◽  
Ewelina Kurtys ◽  
Rudi AJO Dierckx ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Positron Emission Tomography Imaging ◽  
Imaging Study ◽  
Social Defeat ◽  
Glial Activation ◽  
Emission Tomography ◽  
Biochemical Alterations ◽  
Positron Emission

Psychosocial stress is a risk factor for the development of depression. Recent evidence suggests that glial activation could contribute to the development of depressive-like behaviour. This study aimed to evaluate in vivo whether repeated social defeat (RSD) induces short- and long-term inflammatory and metabolic alterations in the brain through positron emission tomography (PET). Male Wistar rats ( n = 40) were exposed to RSD by dominant Long-Evans rats on five consecutive days. Behavioural and biochemical alterations were assessed at baseline, day 5/6 and day 24/25 after the RSD protocol. Glial activation (11C-PK11195 PET) and changes in brain metabolism (18F-FDG PET) were evaluated on day 6, 11 and 25 (short-term), and at 3 and 6 months (long-term). Defeated rats showed transient depressive- and anxiety-like behaviour, increased corticosterone and brain IL-1β levels, as well as glial activation and brain hypometabolism in the first month after RSD. During the third- and six-month follow-up, no between-group differences in any investigated parameter were found. Therefore, non-invasive PET imaging demonstrated that RSD induces transient glial activation and reduces brain glucose metabolism in rats. These imaging findings were associated with stress-induced behavioural changes and support the hypothesis that neuroinflammation could be a contributing factor in the development of depression.

scholarly journals Multinodal regulation of the arcuate/paraventricular nucleus circuit by leptin

2010 ◽  
Vol 108 (1) ◽  
pp. 355-360 ◽  
Author(s):  
Masoud Ghamari-Langroudi ◽  
Dollada Srisai ◽  
Roger D. Cone
Keyword(s):  
Paraventricular Nucleus ◽  
Energy Homeostasis ◽  
Arcuate Nucleus ◽  
Ventromedial Hypothalamus ◽  
Postsynaptic Membrane ◽  
Firing Frequency ◽  
Dependent Manner ◽  
Primary Control ◽  
Regulation Of Activity

Melanocortin-4 receptor (MC4R) is critical for energy homeostasis, and the paraventricular nucleus of the hypothalamus (PVN) is a key site of MC4R action. Most studies suggest that leptin regulates PVN neurons indirectly, by binding to receptors in the arcuate nucleus or ventromedial hypothalamus and regulating release of products like α-melanocyte-stimulating hormone (α-MSH), neuropeptide Y (NPY), glutamate, and GABA from first-order neurons onto the MC4R PVN cells. Here, we investigate mechanisms underlying regulation of activity of these neurons under various metabolic states by using hypothalamic slices from a transgenic MC4R-GFP mouse to record directly from MC4R neurons. First, we show that in vivo leptin levels regulate the tonic firing rate of second-order MC4R PVN neurons, with fasting increasing firing frequency in a leptin-dependent manner. We also show that, although leptin inhibits these neurons directly at the postsynaptic membrane, α-MSH and NPY potently stimulate and inhibit the cells, respectively. Thus, in contrast with the conventional model of leptin action, the primary control of MC4R PVN neurons is unlikely to be mediated by leptin action on arcuate NPY/agouti-related protein and proopiomelanocortin neurons. We also show that the activity of MC4R PVN neurons is controlled by the constitutive activity of the MC4R and that expression of the receptor mRNA and α-MSH sensitivity are both stimulated by leptin. Thus, leptin acts multinodally on arcuate nucleus/PVN circuits to regulate energy homeostasis, with prominent mechanisms involving direct control of both membrane conductances and gene expression in the MC4R PVN neuron.

scholarly journals Stimulus-specific neural encoding of a persistent, internal defensive state in the hypothalamus

2019 ◽  
Author(s):  
Ann Kennedy ◽  
Prabhat S. Kunwar ◽  
Lingyun Li ◽  
Daniel Wagenaar ◽  
David J. Anderson
Keyword(s):  
Neural Activity ◽  
Internal State ◽  
Stress Hormones ◽  
Ventromedial Hypothalamus ◽  
Persistent Activity ◽  
Neural Encoding ◽  
Population Activity ◽  
Defensive Responses ◽  
Neuroendocrine Mechanisms ◽  
Threatening Stimuli

SummaryPersistent neural activity has been described in cortical, hippocampal, and motor networks as mediating short-term working memory of transiently encountered stimuli1–4. Internal emotion states such as fear also exhibit persistence following exposure to an inciting stimulus5,6, but such persistence is typically attributed to circulating stress hormones7–9; whether persistent neural activity also plays a role has not been established. SF1+/Nr5a1+ neurons in the dorsomedial and central subdivision of the ventromedial hypothalamus (VMHdm/c) are necessary for innate and learned defensive responses to predators10–13. Optogenetic activation of VMHdmSF1 neurons elicits defensive behaviors that can outlast stimulation11,14, suggesting it induces a persistent internal state of fear or anxiety. Here we show that VMHdmSF1 neurons exhibit persistent activity lasting tens of seconds, in response to naturalistic threatening stimuli. This persistent activity was correlated with, and required for, persistent thigmotaxic (anxiety-like) behavior in an open-field assay. Microendoscopic imaging of VMHdmSF1 neurons revealed that persistence reflects dynamic temporal changes in population activity, rather than simply synchronous, slow decay of simultaneously activated neurons. Unexpectedly, distinct but overlapping VMHdmSF1 subpopulations were persistently activated by different classes of threatening stimuli. Computational modeling suggested that recurrent neural networks (RNNs) incorporating slow excitation and a modest degree of neurochemical or spatial bias can account for persistent activity that maintains stimulus identity, without invoking genetically determined “labeled lines”15. Our results provide causal evidence that persistent neural activity, in addition to well-established neuroendocrine mechanisms, can contribute to the ability of emotion states to outlast their inciting stimuli, and suggest a mechanism that could prevent over-generalization of defensive responses without the need to evolve hardwired circuits specific for each type of threat.

scholarly journals Upregulation of miR-195a inhibits brain-derived neurotrophic factor in mouse hippocampus and may contribute to depression-like behaviors induced by chronic social stress

2021 ◽  
Vol 19 (12) ◽  
pp. 2537-2543
Author(s):  
Xuping Wen ◽  
Mingshuan Lin
Keyword(s):  
Protein Expression ◽  
Neurotrophic Factor ◽  
Social Defeat ◽  
Brain Derived Neurotrophic Factor ◽  
Luciferase Reporter ◽  
Control Group ◽  
Social Defeat Stress ◽  
Chronic Social Defeat Stress ◽  
Mouse Hippocampus

Purpose: To explore the effect of miR-195a on nerve cells in the hippocampal region of depressionmodel mice.Methods: A chronic social defeat stress (CSDS) model was used as a depressed mouse model. In vivo, C57BL/6J mice received CSDS treatment or miR-195a antagomir. Depression-like behaviors were evaluated. In vitro, the target relationship between miR-195a and brain-derived neurotrophic factor (BDNF) was validated by luciferase reporter assays in HEK-293 cells. In primary cortical neurons, expression levels of miR-195a and BDNF mRNA were evaluated using quantitative polymerase chain reaction (qPCR). BDNF protein expression was determined by western blotting.Results: The sucrose preference ratio and social contact of the CSDS group were significantly decreased, whereas the immobility time was significantly increased, compared with the control group (p< 0.05). Interestingly, the expression of miR-195a was upregulated in the CSDS group compared with control group (p < 0.05). Bioinformatics prediction and luciferase reporter assay data indicate that miR195a bound the BDNF 3’ untranslated region. BDNF protein expression levels were significantly reduced by miR-195a mimic but increased by miR-195a inhibitor, compared with the negative control mimic group (p < 0.05). In vivo, miR-195a antagomir alleviated depression-like behaviors compared with CSDS group. In addition, miR-195a antagomir restored the expression of BDNF in mouse hippocampus in the CSDS group (p < 0.05).Conclusion: MiR-195a inhibitor ameliorates depression-like behaviors of depressed mice by downregulation of BDNF, whereas  upregulation of miR-195a inhibits BDNF expression in mouse hippocampus and may contribute to depression. Keywords: Chronic social defeat stress, Depression, MiR-195, brain-derived neurotrophic factor, BDNF 

scholarly journals Author response: Dynamic encoding of social threat and spatial context in the hypothalamus

2020 ◽  
Author(s):  
Piotr Krzywkowski ◽  
Beatrice Penna ◽  
Cornelius T Gross
Keyword(s):  
Spatial Context ◽  
Author Response ◽  
Social Threat ◽  
Response Dynamic

scholarly journals Carnitine Palmitoyltransferase-1 (CPT-1) Activity Stimulation by Cerulenin via Sympathetic Nervous System Activation Overrides Cerulenin’s Peripheral Effect

Endocrinology ◽  
2004 ◽  
Vol 145 (7) ◽  
pp. 3197-3204 ◽  
Author(s):  
Yong-Jun Jin ◽  
Song-Zhe Li ◽  
Zheng-Shan Zhao ◽  
Juan Ji An ◽  
Ryang Yeo Kim ◽  
...  
Keyword(s):  
Nervous System ◽  
Sympathetic Nervous System ◽  
Core Temperature ◽  
Arcuate Nucleus ◽  
Late Phase ◽  
Ventromedial Hypothalamus ◽  
Sympathetic Nervous ◽  
Carnitine Palmitoyltransferase 1

Abstract To clarify the paradoxic effects of cerulenin, namely its in vitro inhibitory effects on fat catabolism and its in vivo reduction of fat mass, we studied the in vivo and in vitro effects of cerulenin on carnitine palmitoyltransferase-1 (CPT-1) activity, the rate-limiting enzyme of fatty acid oxidation. A single ip injection of cerulenin significantly reduced body weight and increased core temperature without significantly reducing food intake. In situ hybridization study revealed that a single injection of cerulenin did not affect the expression of orexigenic neuropeptide mRNA. Cerulenin’s effect on CPT-1 activity was biphasic in the liver and muscle: early suppression during the first 1 h and late stimulation in the 3–5 h after ip treatment. In vitro cerulenin treatment reduced CPT-1 activity, which was overcome by cotreating with catecholamine. Intracerebroventricular injection of cerulenin increased CPT-1 activity significantly in soleus muscle, and this effect was sustained for up to 3 h. Pretreatment with α-methyl-p-tyrosine inhibited the cerulenin-induced increase in core temperature and the late-phase stimulating effect of cerulenin on CPT-1 activity. In adrenalectomized mice, cerulenin also increased the activity. In vivo cerulenin treatment enhanced muscle CPT-1 activity in monosodium glutamate-treated arcuate nucleus lesioned mice but not in gold thioglucose-treated ventromedial hypothalamus lesioned mice. These findings suggest that cerulenin-induced late-phase stimulating effects on CPT-1 activity and energy expenditure is mediated by the activation of innervated sympathetic nervous system neurons through the firing of undefined neurons of the ventromedial hypothalamus, rather than the arcuate nucleus.

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