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Periaqueductal gray

Xiao-Lin Chou, Xiyue Wang, Zheng-Gang Zhang, Li Shen, Brian Zingg, Junxiang Huang, Wen Zhong, Lukas Mesik, Li I Zhang, Huizhong Whit Tao
Zona incerta (ZI) is a functionally mysterious subthalamic nucleus containing mostly inhibitory neurons. Here, we discover that GABAergic neurons in the rostral sector of ZI (ZIr) directly innervate excitatory but not inhibitory neurons in the dorsolateral and ventrolateral compartments of periaqueductal gray (PAG), which can drive flight and freezing behaviors respectively. Optogenetic activation of ZIr neurons or their projections to PAG reduces both sound-induced innate flight response and conditioned freezing response, while optogenetic suppression of these neurons enhances these defensive behaviors, likely through a mechanism of gain modulation...
March 20, 2018: Nature Communications
Arvina Grahl, Selim Onat, Christian Büchel
In placebo hypoalgesia research, the strength of treatment expectations and experiences are key components. However, the reliability or precision of expectations had been mostly ignored although being a likely source for interindividual differences. In the present study, we adopted a Bayesian framework, naturally combining expectation magnitudes and precisions. This postulates that expectations (prior) are integrated with incoming nociceptive information (likelihood) and both are weighted by their relative precision to form the pain percept and placebo effect...
March 20, 2018: ELife
Lígia Renata Rodrigues Tavares, Daniela Baptista-de-Souza, Azair Canto-de-Souza
It is well-known that the exposure of rodents to threatening environments [e.g., the open arm of the elevated-plus maze (EPM)] elicits pain inhibition. Systemic and/or intracerebral [e.g., periaqueductal gray matter, amygdala) injections of antiaversive drugs [e.g., serotonin (5-HT) ligands, selective serotonin reuptake inhibitors (SSRIs)] have been used to change EPM-open arm confinement induced antinociception (OAA). Here, we investigated (i) the role of the 5-HT1A and 5-HT2C receptors located in the amygdaloid complex on OAA as well as (ii) the effects of systemic pretreatment with fluoxetine (an SSRI) on the effects of intra-amygdala injections of 8-OH-DPAT (a 5-HT1A agonist) or MK-212 (a 5-HT2C agonist) on nociception in mice confined to the open arm or enclosed arm of the EPM...
March 13, 2018: Neuropharmacology
Sophie Kobuch, Azharuddin Fazalbhoy, Rachael Brown, Vaughan G Macefield, Luke A Henderson
Introduction: Long-lasting experimental muscle pain elicits divergent muscle sympathetic responses, with some individuals exhibiting a persistent increase in muscle sympathetic nerve activity (MSNA), and others a decrease. These divergent responses are thought to result from sustained functional changes in specific brain regions that modulate the cardiovascular responses to pain. Aim: The aim of this study was to investigate brain regions that are functionally coupled to the generation of an MSNA burst at rest and to determine their behavior during tonic muscle pain...
March 2018: Brain and Behavior
M C Carvalho, A C Veloni, K Genaro, M L Brandão
A single threatening experience may change the behavior of an animal in a long-lasting way and elicit generalized behavioral responses to a novel threatening situation that is unrelated to the original aversive experience. Electrical stimulation (ES) of the dorsal periaqueductal gray (dPAG) produces a range of defensive reactions, characterized by freezing, escape, and post-stimulation freezing (PSF). The latter reflects the processing of ascending aversive information to prosencephalic structures, including the central nucleus of the amygdala (CeA), which allows the animal to evaluate the consequences of the aversive situation...
February 2018: Neurobiology of Learning and Memory
Petr Dubový, Ilona Klusáková, Ivana Hradilová-Svíženská, Marek Joukal, Pere Boadas-Vaello
Peripheral nerve injuries (PNIs) may result in cellular and molecular changes in supraspinal structures possibly involved in neuropathic pain (NPP) maintenance. Activated glial cells in specific supraspinal subregions may affect the facilitatory role of descending pathways. Sterile chronic compression injury (sCCI) and complete sciatic nerve transection (CSNT) in rats were used as NPP models to study the activation of glial cells in the subregions of periaqueductal gray (PAG) and rostral ventromedial medulla (RVM)...
2018: Frontiers in Cellular Neuroscience
Song Qi, Demis Hassabis, Jiayin Sun, Fangjian Guo, Nathaniel Daw, Dean Mobbs
Flight initiation distance (FID), the distance at which an organism flees from an approaching threat, is an ecological metric of cost-benefit functions of escape decisions. We adapted the FID paradigm to investigate how fast- or slow-attacking "virtual predators" constrain escape decisions. We show that rapid escape decisions rely on "reactive fear" circuits in the periaqueductal gray and midcingulate cortex (MCC), while protracted escape decisions, defined by larger buffer zones, were associated with "cognitive fear" circuits, which include posterior cingulate cortex, hippocampus, and the ventromedial prefrontal cortex, circuits implicated in more complex information processing, cognitive avoidance strategies, and behavioral flexibility...
March 5, 2018: Proceedings of the National Academy of Sciences of the United States of America
K Sakai
A total of 668 single units were recorded in the mouse periaqueductal gray (PAG) and adjacent deep mesencephalic nucleus (DpMe) in order to determine their role in the switching of sleep-wake states, i.e. wakefulness (W), slow-wave sleep (SWS), and paradoxical (or rapid eye movement) sleep (PS) in general, and, in particular, to determine whether PS-on and PS-off neurons involved in PS state switching are present in these structures and to identify neuronal substrates for the SWS-PS switching mediated by DpMe neurons...
March 2, 2018: European Journal of Neuroscience
Linda Solstrand Dahlberg, Clas N Linnman, Danielle Lee, Rami Burstein, Lino Becerra, David Borsook
Migraineurs show hypersensitivity to sensory stimuli at various stages throughout the migraine cycle. A number of putative processes have been implicated including a dysfunction in the descending pain modulatory system in which the periaqueductal gray (PAG) is considered to play a crucial role. Recurring migraine attacks could progressively perturb this system, lowering the threshold for future attacks, and contribute to disease chronification. Here, we investigated PAG connectivity with other brain regions during a noxious thermal stimulus to determine changes in migraineurs, and associations with migraine frequency...
2018: Frontiers in Neurology
Hillary L Woodworth, Juliette A Brown, Hannah M Batchelor, Raluca Bugescu, Gina M Leinninger
Pharmacologic treatment with the neuropeptide neurotensin (Nts) modifies motivated behaviors such as feeding, locomotor activity, and reproduction. Dopamine (DA) neurons of the ventral tegmental area (VTA) control these behaviors, and Nts directly modulates the activity of DA neurons via Nts receptor-1. While Nts sources to the VTA have been described in starlings and rats, the endogenous sources of Nts to the VTA of mice remain incompletely understood, impeding determination of which Nts circuits orchestrate specific behaviors in this model...
February 15, 2018: Neuropeptides
Douglas W Barrett, F Gonzalez-Lima
This study is a new analysis to obtain novel metabolic data on the functional connectivity of prefrontal-limbic regions in Pavlovian fear acquisition and extinction of tone-footshock conditioning. Mice were analyzed with the fluorodeoxyglucose (FDG) autoradiographic method to metabolically map regional brain activity. New FDG data were sampled from the nuclei of the habenula and other regions implicated in aversive conditioning, such as infralimbic cortex, amygdala and periaqueductal gray regions. The activity patterns among these regions were inter-correlated during acquisition, extinction or pseudorandom training to develop a functional connectivity model...
February 22, 2018: Neuroscience
Cindy F Yang, Jack L Feldman
The preBötzinger complex (preBötC), a compact medullary region essential for generating normal breathing rhythm and pattern, is the kernel of the breathing central pattern generator (CPG). Excitatory preBötC neurons in rats project to major breathing-related brainstem regions. Here, we provide a brainstem connectivity map in mice for both excitatory and inhibitory preBötC neurons. Using a genetic strategy to label preBötC neurons, we confirmed extensive projections of preBötC excitatory neurons within the brainstem breathing CPG including the contralateral preBötC, Bötzinger Complex (BötC), ventral respiratory group (VRG), nucleus of the solitary tract (NTS), parahypoglossal nucleus, parafacial region (RTN/pFRG or alternatively, pFL /pFV ), parabrachial and Kölliker-Füse nuclei, as well as major projections to the midbrain periaqueductal gray (PAG)...
February 23, 2018: Journal of Comparative Neurology
Olena Bukalo, Andrew Holmes
In this issue of Neuron, Rozeske et al. (2018) use an ingenuous behavioral paradigm to change pertinent sensory stimuli defining a given context to interrogate how the dorsomedial prefrontal cortex (dmPFC) and periaqueductal gray (PAG) interact during contextual fear discrimination.
February 21, 2018: Neuron
Ana Cristina Borges-Aguiar, Luana Zanoni Schauffer, Edo Ronald de Kloet, Luiz Carlos Schenberg
The present study examined whether early life maternal separation (MS), a model of childhood separation anxiety, predisposes to panic at adulthood. For this purpose, male pups were submitted to 3-h daily maternal separations along postnatal (PN) days of either the 'stress hyporesponsive period' (SHRP) from PN4 to PN14 (MS11) or throughout lactation from PN2 to PN21 (MS20). Pups were further reunited to conscious (CM) or anesthetized (AM) mothers to assess the effect of mother-pup interaction upon reunion. Controls were subjected to brief handling (15 s) once a day throughout lactation (BH20)...
February 18, 2018: Behavioural Brain Research
Danielle A Lopes, Thaissa M O Souza, José S de Andrade, Mariana F S Silva, Hanna K M Antunes, Luciana Le Seur Maluf, Isabel C Céspedes, Milena B Viana
Environmental enrichment (EE) is an animal management technique, which seems to improve adaptation to the experimental conditions of housing in laboratory animals. Previous studies have pointed to different beneficial effects of the procedure in the treatment of several disorders, including psychiatric conditions such as depression. The anxiolytic effects induced by EE, on the other hand, are not as clear. In fact, it has been proposed that EE acts as a mild stressor agent. To better understand the relationship of EE with anxiety-related responses, the present study exposed rats to one week of EE and subsequently tested these animals in the inhibitory avoidance and escape tasks of the elevated T-maze (ETM)...
February 12, 2018: Behavioural Brain Research
Sevasti Gaspari, Immanuel Purushothaman, Valeria Cogliani, Farhana Sakloth, Rachael L Neve, David Howland, Robert H Ring, Elliott M Ross, Li Shen, Venetia Zachariou
Regulator of G protein signaling z1 (RGSz1), a member of the RGS family of proteins, is present in several networks expressing mu opioid receptors (MOPRs). By using genetic mouse models for global or brain region-targeted manipulations of RGSz1 expression, we demonstrated that the suppression of RGSz1 function increases the analgesic efficacy of MOPR agonists in male and female mice and delays the development of morphine tolerance while decreasing the sensitivity to rewarding and locomotor activating effects...
February 12, 2018: Proceedings of the National Academy of Sciences of the United States of America
Otto Muzik, Kaice T Reilly, Vaibhav A Diwadkar
The defense of body temperature against environmental thermal challenges is a core objective of homeostatic regulation governed by the autonomic nervous system. Autonomous mechanisms of thermoregulation are only weakly affected by top-down modulation, allowing only transient tolerance for extreme cold. There is however, anecdotal evidence of a unique set of individuals known for extreme cold tolerance. Here we present a case study of a 57-year old Dutch national, Wim Hof, the so-called "Iceman", with the ability to withstand frequent prolonged periods of extreme cold exposure based on the practice of a self-developed technique involving a combination of forced breathing, cold exposure and meditation (collectively referred to as the Wim Hof Method, henceforth "WHM")...
February 10, 2018: NeuroImage
Jia Li, Tian Yu, Fu Shi, Yu Zhang, Zikun Duan, Bao Fu, Yi Zhang
It has been reported that central dopaminergic system is implicated in the mechanism underlying general anesthesia. Whether dopamine (DA) neurons in midbrain ventral periaqueductal gray (vPAG) are involved in general anesthesia and how general anesthetics affect these neurons remain sparsely documented. To determine the role of vPAG DA neurons in propofol-induced anesthesia, we performed microinjection of 6-hydroxydopamine (6-OHDA) into vPAG to damage DA neurons and investigated the alteration in somatosensory electroencephalogram (EEG), as well as the induction and recovery time of propofol anesthesia...
February 7, 2018: Neurochemical Research
Devin P Merullo, Jeremy A Spool, Changjiu Zhao, Lauren V Riters
Animals communicate in distinct social contexts to convey information specific to those contexts, such as sexual or agonistic motivation. In seasonally-breeding male songbirds, seasonal changes in day length and increases in testosterone stimulate sexually-motivated song directed at females for courtship and reproduction. Dopamine and testosterone may act in the same brain regions to stimulate sexually-motivated singing. The neuropeptide neurotensin, acting at the neurotensin receptor 1 (NTR1), can strongly influence dopamine transmission...
January 30, 2018: Journal of Chemical Neuroanatomy
Natalia I Yarushkina, Ludmila P Filaretova
The corticotropin-releasing factor (CRF) is involved in somatic pain regulation and may produce an analgesic effect in humans and animals, although the mechanisms of the CRF-induced analgesia remain unclear. CRF action is mediated by the CRF receptors of subtypes 1 and 2 (CRF-R1 and CRF-R2, respectively). Activation of the hypothalamic -pituitary -adrenocortical axis (HPA) is provided by CRF-R1; but CRF-R2 are also involved in the regulation of the HPA axis, and, respectively, glucocorticoids, the end hormones of the HPA axis, also participate in somatic pain regulation...
February 5, 2018: Inflammopharmacology
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