scholarly journals Identification of a novel breathing circuit that controls pain and anxiety

2020 ◽  
Author(s):  
Shijia Liu ◽  
Mao Ye ◽  
Gerald M. Pao ◽  
Samuel Myeongsup Song ◽  
Jinho Jhang ◽  
...  
Keyword(s):  
Neural Circuit ◽  
Breathing Circuit ◽  
Critical Role ◽  
Respiratory Rhythm ◽  
Breathing Rate ◽  
Homeostatic Regulation ◽  
Motivational Aspect ◽  
Regulation Of Breathing ◽  
Μ Opioid Receptor ◽  
Controlled Breathing

AbstractAlleviating pain with controlled breathing has been practiced throughout human history. Despite its wide use and long history, a neural circuit-based understanding of the pain-breathing interaction is largely lacking. Here we report a novel breathing circuit that regulates non-homeostatic breathing rhythm, as well as pain and anxiety. We identify that a cluster of neurons expressing the Oprm1 gene, which encodes the μ-opioid receptor (MOR) in the lateral subdivision of parabrachial nucleus (PBLOprm1), directly regulates breathing rate in mice by conveying signals from the limbic areas to respiratory rhythm generating neurons in the medullary preBötzinger Complex (preBötC). In addition, we found that pain signals rapidly increase breathing rate by activating these neurons in both awake and anesthetized mice. Inactivating these neurons not only decreases the breathing rate, but it also substantially decreases anxiety-like behaviors and induces strong appetitive behaviors. Furthermore, PBLOprm1 inactivation alleviates pain by attenuating the perception of the affective-motivational aspect of pain. These results suggest that PBLOprm1 neurons play a critical role in the non-homeostatic regulation of breathing and in the regulation of pain and anxiety through breathing.

Normoxic and hypoxic breathing pattern in newborn grey seals

1989 ◽  
Vol 67 (2) ◽  
pp. 483-487 ◽  
Author(s):  
Jacopo P. Mortola ◽  
Clement Lanthier
Keyword(s):  
Tidal Volume ◽  
Breathing Pattern ◽  
Halichoerus Grypus ◽  
Breathing Rate ◽  
Allometric Relationships ◽  
Breathing Patterns ◽  
Hypoxic Conditions ◽  
Regulation Of Breathing ◽  
Expiratory Flow

We studied the breathing patterns of three newborn grey seals (Halichoerus grypus) at 2 – 3 days of age under normoxic and hypoxic conditions with the barometric technique, which does not require the animal to be restrained. Normoxic tidal volume was deeper and breathing rate slower than expected for newborns of this size on the basis of previously published allometric relationships. In addition, two characteristics were readily apparent: (i) occasional sudden long apneas, often exceeding 30 s in duration, and (ii) consistent brief interruptions of expiratory flow. Neither aspect is common in terrestrial newborns of this age, but both have been previously observed in adult seals. During hypoxia (10 min of 15% O2 and 10 min of 10% O2), ventilation increased markedly and steadily, at variance with what occurs in newborns of other species, indicating a precocial development of the regulation of breathing. This latter result also suggests that the blunted response to hypoxia previously reported in adult seals may be acquired postnatally with diving experience.

scholarly journals Differences in chloride gradients allow for three distinct types of synaptic modulation by endocannabinoids

2016 ◽  
Vol 116 (2) ◽  
pp. 619-628 ◽  
Author(s):  
Yanqing Wang ◽  
Brian D. Burrell
Keyword(s):  
Neural Circuit ◽  
Critical Role ◽  
Low Frequency ◽  
Inhibitory Synapses ◽  
Primary Role ◽  
Synaptic Modulation ◽  
Hirudo Verbana ◽  
Frequency Stimulation ◽  
Circuit Output

Endocannabinoids can elicit persistent depression of excitatory and inhibitory synapses, reducing or enhancing (disinhibiting) neural circuit output, respectively. In this study, we examined whether differences in Cl−gradients can regulate which synapses undergo endocannabinoid-mediated synaptic depression vs. disinhibition using the well-characterized central nervous system (CNS) of the medicinal leech, Hirudo verbana. Exogenous application of endocannabinoids or capsaicin elicits potentiation of pressure (P) cell synapses and depression of both polymodal (Npoly) and mechanical (Nmech) nociceptive synapses. In P synapses, blocking Cl−export prevented endocannabinoid-mediated potentiation, consistent with a disinhibition process that has been indicated by previous experiments. In Nmechneurons, which are depolarized by GABA due to an elevated Cl−equilibrium potentials (ECl), endocannabinoid-mediated depression was prevented by blocking Cl−import, indicating that this decrease in synaptic signaling was due to depression of excitatory GABAergic input (disexcitation). Npolyneurons are also depolarized by GABA, but endocannabinoids elicit depression in these synapses directly and were only weakly affected by disruption of Cl−import. Consequently, the primary role of elevated EClmay be to protect Npolysynapses from disinhibition. All forms of endocannabinoid-mediated plasticity required activation of transient potential receptor vanilloid (TRPV) channels. Endocannabinoid/TRPV-dependent synaptic plasticity could also be elicited by distinct patterns of afferent stimulation with low-frequency stimulation (LFS) eliciting endocannabinoid-mediated depression of Npolysynapses and high-frequency stimulus (HFS) eliciting endocannabinoid-mediated potentiation of P synapses and depression of Nmechsynapses. These findings demonstrate a critical role of differences in Cl−gradients between neurons in determining the sign, potentiation vs. depression, of synaptic modulation under normal physiological conditions.

Mechanoreceptor modulation of endogenous respiratory rhythms in vertebrates

1990 ◽  
Vol 259 (5) ◽  
pp. R898-R910 ◽  
Author(s):  
W. K. Milsom
Keyword(s):  
Breathing Pattern ◽  
Respiratory Rhythm ◽  
Flow Distribution ◽  
Respiratory Pattern ◽  
Respiratory Drive ◽  
Lung Inflation ◽  
Phase Switching ◽  
Separate Control ◽  
Regulation Of Breathing ◽  
Receptor Input

While pulmonary mechanoreceptors appear to play little or no role in determining the eupneic breathing pattern in some species of vertebrates, they do in others as well as in all species under conditions of elevated respiratory drive. Tonic and phasic inputs from this receptor group have independent roles in determining breathing pattern. Thus withholding lung inflation produces very different results from receptor denervation. There are at least five phases to the respiratory cycle that appear to be under separate control. Tonic receptor input is involved primarily in regulating the length of the respiratory pause, which can occur at the end of inspiration or expiration, depending on the species. Phasic receptor input has different effects during different phases of the cycle as well as different effects at different times during a single phase. This activity contributes to phase switching during the ventilation cycle and thus to the regulation of breathing frequency and tidal volume. The significance of the modulatory effects of phasic input on the duration of different phases of the ventilation cycle is not totally clear, but the evidence suggests that phasic input acts to stabilize the respiratory pattern and may be instrumental in optimizing the breathing pattern in terms of ergometric costs. This appears to be the case in all vertebrate classes, despite dramatic differences in the mechanical events associated with ventilation arising from different respiratory pumps. These receptors also appear to have significant roles other than those associated with modulation of respiratory rhythm, particularly in lower vertebrates. Many of these roles, such as maintaining the integrity of the gill curtain in fish or buoyancy control and regulation of blood flow distribution in reptiles, may be as important as their role in modulating the endogenous rhythm.

scholarly journals Suppression of Alcohol Preference by Naltrexone in the Rhesus Macaque: A Critical Role of Genetic Variation at the μ-Opioid Receptor Gene Locus

2010 ◽  
Vol 67 (1) ◽  
pp. 78-80 ◽  
Author(s):  
Christina S. Barr ◽  
Scott A. Chen ◽  
Melanie L. Schwandt ◽  
Stephen G. Lindell ◽  
Hui Sun ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Rhesus Macaque ◽  
Opioid Receptor ◽  
Gene Locus ◽  
Receptor Gene ◽  
Critical Role ◽  
Alcohol Preference ◽  
Μ Opioid Receptor

scholarly journals Processing of motion boundary orientation in macaque V2

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Heng Ma ◽  
Pengcheng Li ◽  
Jiaming Hu ◽  
Xingya Cai ◽  
Qianling Song ◽  
...  
Keyword(s):  
Neural Circuit ◽  
Neuronal Response ◽  
Critical Role ◽  
Neural Mechanisms ◽  
Orientation Discrimination ◽  
Boundary Orientation ◽  
Area V2 ◽  
Correlated Activity ◽  
Object Based ◽  
Motion Boundaries

Human and nonhuman primates are good at identifying an object based on its motion, a task that is believed to be carried out by the ventral visual pathway. However, the neural mechanisms underlying such ability remains unclear. We trained macaque monkeys to do orientation discrimination for motion boundaries (MBs) and recorded neuronal response in area V2 with microelectrode arrays. We found 10.9% of V2 neurons exhibited robust orientation selectivity to MBs, and their responses correlated with monkeys’ orientation-discrimination performances. Furthermore, the responses of V2 direction-selective neurons recorded at the same time showed correlated activity with MB neurons for particular MB stimuli, suggesting that these motion-sensitive neurons made specific functional contributions to MB discrimination tasks. Our findings support the view that V2 plays a critical role in MB analysis and may achieve this through a neural circuit within area V2.

scholarly journals Role of matrix metalloproteinase-9 in neurodevelopmental disorders and plasticity in Xenopus tadpoles

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Sayali V Gore ◽  
Eric J James ◽  
Lin-chien Huang ◽  
Jenn J Park ◽  
Andrea Berghella ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Neurodevelopmental Disorders ◽  
Neuronal Development ◽  
Neural Circuit ◽  
Critical Role ◽  
Matrix Metalloproteinase 9 ◽  
Abnormal Development ◽  
Synaptic Connectivity ◽  
And Behavior ◽  
Metalloproteinase 9

Matrix metalloproteinase-9 (MMP-9) is a secreted endopeptidase targeting extracellular matrix proteins, creating permissive environments for neuronal development and plasticity. Developmental dysregulation of MMP-9 may also lead to neurodevelopmental disorders (ND). Here we test the hypothesis that chronically elevated MMP-9 activity during early neurodevelopment is responsible for neural circuit hyperconnectivity observed in Xenopus tadpoles after early exposure to valproic acid (VPA), a known teratogen associated with ND in humans. In Xenopus tadpoles, VPA exposure results in excess local synaptic connectivity, disrupted social behavior and increased seizure susceptibility. We found that overexpressing MMP-9 in the brain copies effects of VPA on synaptic connectivity, and blocking MMP-9 activity pharmacologically or genetically reverses effects of VPA on physiology and behavior. We further show that during normal neurodevelopment MMP-9 levels are tightly regulated by neuronal activity and required for structural plasticity. These studies show a critical role for MMP-9 in both normal and abnormal development.

Contributions from rostral medullary nuclei to coordination of swallowing and breathing in awake goats

2002 ◽  
Vol 93 (2) ◽  
pp. 581-591 ◽  
Author(s):  
Thom R. Feroah ◽  
H. V. Forster ◽  
Carla G. Fuentes ◽  
Julie Wenninger ◽  
Paul Martino ◽  
...  
Keyword(s):  
Receptor Agonist ◽  
Cerebral Spinal Fluid ◽  
Neural Circuit ◽  
Excitatory Amino Acid ◽  
Volume Effect ◽  
Spinal Fluid ◽  
Excitatory Amino Acid Receptor ◽  
Respiratory Phase ◽  
Regulation Of Breathing ◽  
Medullary Nuclei

The purpose of this study was to determine whether neurons in the facial (FN), gigantocellularis reticularis (RGN), and vestibular (VN) nuclei contribute to the regulation of breathing, swallowing, and the coordination of these two functions. Microtubules were chronically implanted bilaterally in goats. Two weeks later during wakefulness, 100-nl unilateral injections were made of mock cerebral spinal fluid or an excitatory amino acid receptor agonist or antagonists. When the agonist, N-methyl-d-aspartic acid, was injected into any nuclei, breathing and swallowing increased transiently (15–30%; P < 0.05), whereas only injections of the antagonist 2,3-dihydroxy-6-nitro-7-sulfamoylbenzo-(f)quinoxaline into VN increased swallowing (20%; P < 0.05). The phase of breathing in which the swallows occurred was not altered by any injections. However, more importantly, injections of the agonist and the antagonists significantly altered ( P < 0.05) by 5–50% the respiratory phase-dependent timing and tidal volume effect of swallows on breathing relative to mock cerebral spinal fluid injections. In addition, these effects were not uniform for all three nuclei. We conclude that the FN, RGN, and VN are part of a neural circuit in the rostral medulla that regulates and/or modulates breathing, swallowing, and their coordination in the awake state.

From the periphery to the brain: Wiring the olfactory system

2011 ◽  
Vol 2 (4) ◽  
Author(s):  
Albert Blanchart ◽  
Laura López-Mascaraque
Keyword(s):  
Olfactory Bulb ◽  
Olfactory System ◽  
Neural Circuit ◽  
Critical Role ◽  
Precise Location ◽  
Reliable Transmission ◽  
Molecular Events ◽  
Perfect Model ◽  
Molecular Signals ◽  
The Brain

AbstractThe olfactory system represents a perfect model to study the interactions between the central and peripheral nervous systems in order to establish a neural circuit during early embryonic development. In addition, another important feature of this system is the capability to integrate new cells generated in two neurogenic zones: the olfactory epithelium in the periphery and the wall of the lateral ventricles in the CNS, both during development and adulthood. In all these processes the combination and sequence of specific molecular signals plays a critical role in the wiring of the olfactory axons, as well as the precise location of the incoming cell populations to the olfactory bulb. The purpose of this review is to summarize recent insights into the cellular and molecular events that dictate cell settling position and axonal trajectories from their origin in the olfactory placode to the formation of synapses in the olfactory bulb to ensure rapid and reliable transmission of olfactory information from the nose to the brain.

scholarly journals Microglia-Induced Maladaptive Plasticity Can Be Modulated by NeuropeptidesIn Vivo

2015 ◽  
Vol 2015 ◽  
pp. 1-15 ◽  
Author(s):  
Stefano Morara ◽  
Anna Maria Colangelo ◽  
Luciano Provini
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Neural Circuit ◽  
Critical Role ◽  
Adult Life ◽  
Experimental Models ◽  
Brain Diseases ◽  
Maladaptive Plasticity ◽  
The Central Nervous System

Microglia-induced maladaptive plasticity is being recognized as a major cause of deleterious self-sustaining pathological processes that occur in neurodegenerative and neuroinflammatory diseases. Microglia, the primary homeostatic guardian of the central nervous system, exert critical functions both during development, in neural circuit reshaping, and during adult life, in the brain physiological and pathological surveillance. This delicate critical role can be disrupted by neural, but also peripheral, noxious stimuli that can prime microglia to become overreactive to a second noxious stimulus or worsen underlying pathological processes. Among regulators of microglia, neuropeptides can play a major role. Their receptors are widely expressed in microglial cells and neuropeptide challenge can potently influence microglial activityin vitro. More relevantly, this regulator activity has been assessed alsoin vivo, in experimental models of brain diseases. Neuropeptide action in the central nervous system has been associated with beneficial effects in neurodegenerative and neuroinflammatory pathological experimental models. This review describes some of the mechanisms of the microglia maladaptive plasticityin vivoand how neuropeptide activity can represent a useful therapeutical target in a variety of human brain pathologies.

scholarly journals Input-specific modulation of murine nucleus accumbens differentially regulates hedonic feeding

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Daniel J. Christoffel ◽  
Jessica J. Walsh ◽  
Boris D. Heifets ◽  
Paul Hoerbelt ◽  
Sophie Neuner ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Neural Circuit ◽  
Critical Role ◽  
Synaptic Strength ◽  
Fat Intake ◽  
High Fat ◽  
Cell Type Specific ◽  
Paraventricular Thalamus ◽  
Opposing Effects ◽  
Motivated Behaviors

AbstractHedonic feeding is driven by the “pleasure” derived from consuming palatable food and occurs in the absence of metabolic need. It plays a critical role in the excessive feeding that underlies obesity. Compared to other pathological motivated behaviors, little is known about the neural circuit mechanisms mediating excessive hedonic feeding. Here, we show that modulation of prefrontal cortex (PFC) and anterior paraventricular thalamus (aPVT) excitatory inputs to the nucleus accumbens (NAc), a key node of reward circuitry, has opposing effects on high fat intake in mice. Prolonged high fat intake leads to input- and cell type-specific changes in synaptic strength. Modifying synaptic strength via plasticity protocols, either in an input-specific optogenetic or non-specific electrical manner, causes sustained changes in high fat intake. These results demonstrate that input-specific NAc circuit adaptations occur with repeated exposure to a potent natural reward and suggest that neuromodulatory interventions may be therapeutically useful for individuals with pathologic hedonic feeding.

Sign in / Sign up

Export Citation Format

Share Document