scholarly journals Inactivation of Prefrontal Cortex Delays Emergence From Sevoflurane Anesthesia

2021 ◽  
Vol 15 ◽  
Author(s):  
Emma R. Huels ◽  
Trent Groenhout ◽  
Christopher W. Fields ◽  
Tiecheng Liu ◽  
George A. Mashour ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Brain Regions ◽  
Association Cortex ◽  
Sprague Dawley ◽  
Subcortical Structures ◽  
Behavioral Arousal ◽  
Barrel Field ◽  
Loss Of Righting Reflex ◽  
Parietal Association Cortex ◽  
Righting Reflex

Studies aimed at investigating brain regions involved in arousal state control have been traditionally limited to subcortical structures. In the current study, we tested the hypothesis that inactivation of prefrontal cortex, but not two subregions within parietal cortex—somatosensory barrel field and medial/lateral parietal association cortex—would suppress arousal, as measured by an increase in anesthetic sensitivity. Male and female Sprague Dawley rats were surgically prepared for recording electroencephalogram and bilateral infusion into prefrontal cortex (N = 13), somatosensory barrel field (N = 10), or medial/lateral parietal association cortex (N = 9). After at least 10 days of post-surgical recovery, 156 μM tetrodotoxin or saline was microinjected into one of the cortical sites. Ninety minutes after injection, rats were anesthetized with 2.5% sevoflurane and the time to loss of righting reflex, a surrogate for loss of consciousness, was measured. Sevoflurane was stopped after 45 min and the time to return of righting reflex, a surrogate for return of consciousness, was measured. Tetrodotoxin-mediated inactivation of all three cortical sites decreased (p < 0.05) the time to loss of righting reflex. By contrast, only inactivation of prefrontal cortex, but not somatosensory barrel field or medial/lateral parietal association cortex, increased (p < 0.001) the time to return of righting reflex. Burst suppression ratio was not altered following inactivation of any of the cortical sites, suggesting that there was no global effect due to pharmacologic lesion. These findings demonstrate that prefrontal cortex plays a causal role in emergence from anesthesia and behavioral arousal.

Human Prefrontal Cortex

2021 ◽  
pp. 372-419
Author(s):  
Richard E. Passingham
Keyword(s):  
Prefrontal Cortex ◽  
Medial Prefrontal Cortex ◽  
Visual Imagery ◽  
Great Apes ◽  
Integrated System ◽  
The Self ◽  
Demand System ◽  
Association Cortex ◽  
Parietal Association Cortex ◽  
Global Workspace

This chapter and the next one consider how to account for the astonishing difference in intelligence between humans and our nearest living ancestors, the great apes. An integrated system that includes the dorsal prefrontal cortex and the parietal association cortex is activated when subjects attempt tests of non-verbal intelligence. It has been suggested that this system might act as a ‘multiple-demand system’ or ‘global workspace’ that can deal with any problem. However, closer examination suggests that the tasks used to support this claim have in common that they involve abstract sequences. These problems can be solved by visual imagery alone. But humans also have the advantage that they also have access to a propositional code. This means that they can solve problems that involve verbal reasoning, as well as being able to form detailed plans for the future. They can also form explicit judgements about themselves, including their perceptions, actions, and memories, and this means that they can represent themselves as individuals. The representation of the self depends in part on tissue in the medial prefrontal cortex (PF).

scholarly journals Luxotonic signals in human prefrontal cortex: A possible substrate for effects of light on mood and cognition

2020 ◽  
Author(s):  
Shai Sabbah ◽  
Michael S. Worden ◽  
Daniel Laniado ◽  
Rebeca Waugh ◽  
David M. Berson ◽  
...  
Keyword(s):  
Motor Control ◽  
Prefrontal Cortex ◽  
Visual Processing ◽  
Bright Light ◽  
Luminance Level ◽  
Brain Regions ◽  
Reward Processing ◽  
Subcortical Structures ◽  
Environmental Light ◽  
Mood And Cognition

AbstractLight impacts mood and cognition of humans and other animals in ways we are only beginning to recognize. These effects are thought to depend upon a specialized retinal output signal arising from intrinsically photosensitive retinal ganglion cells (ipRGCs) that is being dedicated to a stable representation of the intensity of environmental light. Insights from animal studies now implicate a previously unknown pathway in the effects of environmental light on mood. A subset of ipRGCs transmits light-intensity information to the dorsothalamic perihabenular nucleus, which in turn, innervates the medial prefrontal cortex that plays a key role in mood regulation. While the prefrontal cortex has been implicated in depression and other mood disorders, its ability to encode the level of environmental light (luminance) has never been reported. Here, as a first step to probing for a similar retino-thalamo-frontocortical circuit in humans, we used functional magnetic resonance imaging (fMRI) to identify brain regions in which activity depended on luminance level where activity was modulated either transiently or persistently by light. Twelve brain regions altered their steady-state activity according to luminance level. Most were in the prefrontal cortex or in the classic thalamocortical visual pathway; others were found in the cerebellum, caudate, and pineal. Prefrontal cortex and pineal exhibited reduced BOLD signal in bright light, while the other centers exhibited increased BOLD signals. The light-evoked prefrontal response was affected by light history and closely resembled those of ipRGCs. Although we did not find clear correspondence between the luxotonic regions in humans and those in mice, the persistence and luxotonic nature of light-evoked responses in the human prefrontal cortex may suggest that it receives input from ipRGCs, just like in the mouse. We also found seventeen regions in which activity varied only transiently with luminance level. These regions, which are involved in visual processing, motor control, and cognition, were in the cerebral cortex, diverse subcortical structures, and cerebellum. Therefore, our results demonstrate the effects of light on diverse brain centers that contribute to motor control, cognition, emotion, and reward processing.

scholarly journals Intraperitoneal injection of sodium pentobarbital is associated with pain in rats

2019 ◽  
Author(s):  
JN Reimer ◽  
C Schuster ◽  
CG Knight ◽  
DSJ Pang ◽  
VSY Leung
Keyword(s):  
Relative Frequency ◽  
Behavioral Assessment ◽  
Indirect Evidence ◽  
Vehicle Control ◽  
Control Group ◽  
Sodium Pentobarbital ◽  
Sprague Dawley ◽  
Control Groups ◽  
Loss Of Righting Reflex ◽  
Righting Reflex

AbstractAn effective and pain-free killing method is required to achieve the goal of euthanasia, a “good death”. Overdose of sodium pentobarbital (PB) by intraperitoneal (IP) injection is a widely accepted technique, but questions remain regarding pain associated with administration. As PB rapidly causes sedation and loss of consciousness, most studies have relied on indirect evidence of pain. The objective of this study was to assess pain associated with IP PB using an appropriate vehicle control.Adult male and female Sprague Dawley (SD) and female Wistar rats (N = 112) were block randomised by sex and strain to receive one of four treatments: 1) 800 mg/kg PB (pH 11); 2) 800 mg/kg PB with 4 mg/kg lidocaine (PB+lido); 3) saline or 4) vehicle controls (pH 11 or 12.5). Behavior (Rat Grimace Scale [RGS], writhing, back arching) was evaluated at baseline, before loss of righting reflex (PB and PB+lido groups), 80s, 151s and 10 min post-injection (PI; saline and vehicle control groups).In the vehicle control groups, the RGS scores were increased at 151s PI (SD: p = 0.0008, 95%CI −0.731 to −0.202) from baseline, as was relative frequency of writhing (SD: p < 0.00001; Wistar; p = 0.0004). RGS scores remained elevated 10 mins PI (SD: p = 0.0070, 95%CI −0.768 to −0.118; Wistar: p = 0.0236, 95%CI −0.907 to −0.0742) but the relative frequency of writhing did not (p > 0.05). The RGS scores and the relative frequency of writhing remained low in the PB, PB+lido and saline groups (p > 0.05). Back arching increased from baseline in the PB+lido group before loss of righting reflex and in the vehicle control group (SD rats) at 151s PI (p < 0.05).These results show that IP PB results in signs associated with pain. The sedative effects of PB limit behavioral assessment.

Limbic Pathways to Stress Control

2016 ◽  
Author(s):  
James P. Herman
Keyword(s):  
Neural Networks ◽  
Prefrontal Cortex ◽  
Stress Response ◽  
Hpa Axis ◽  
Stress Responses ◽  
Physiological Stress ◽  
Brain Regions ◽  
Subcortical Structures ◽  
Stress Control ◽  
Stress Activation

Appropriate control of the HPA (hypothalamo-pituitary-adrenocortical axis) is required for adaptation to physiological and environmental challenges. Inadequate control is linked to numerous stress-related pathologies, including PTSD, highlighting its importance in linking physiological stress responses with behavioral coping strategies. This chapter highlights neurocircuit mechanisms underlying HPA axis adaptation and pathology. Control of the HPA stress response is mediated by the coordinated activity of numerous limbic brain regions, including the prefrontal cortex, hippocampus, and amygdala. In general, hippocampal output inhibits anticipatory HPA axis responses, whereas amygdala subnuclei participate in stress activation. The prefrontal cortex plays an important role in inhibition of context-dependent stress responses. These regions converge on subcortical structures that relay information to paraventricular nucleus corticotropin-releasing hormone neurons, controlling the magnitude and duration of HPA axis stress responses. The output of these neural networks determines the net effect on glucocorticoid secretion, both within the normal adaptive range and in pathological circumstances.

scholarly journals Assessment of carbon dioxide, carbon dioxide/oxygen, isoflurane and pentobarbital killing methods in rats

2016 ◽  
Author(s):  
Jessica M Chisholm ◽  
Daniel SJ Pang
Keyword(s):  
Carbon Dioxide ◽  
Heart Rate ◽  
Loss Of Consciousness ◽  
Sprague Dawley ◽  
Loss Of Righting Reflex ◽  
Sprague Dawley Rats ◽  
General Order ◽  
Righting Reflex ◽  
High Concentrations ◽  
The Relationship

AbstractBackground:Exposure to carbon dioxide (CO2) gas as a killing method is aversive and exposure to high concentrations likely to be painful. Bradycardia during exposure to CO2 is associated with nociception and pain. However, it is unclear if bradycardia occurs before loss of consciousness as this is variably defined in the literature. The objectives of this study were to explore the relationship between recumbency, loss of righting reflex (LORR) and a quiescent electromyograph as measures of loss of consciousness, and identify the onset of bradycardia in relation to these measures.Methods:Thirty-two adult, female Sprague-Dawley rats were instrumented with a telemetry device and randomly assigned to one of four killing methods (100% CO2, CO2 (70%)/O2 (30%), isoflurane (5%) and intraperitoneal pentobarbital (200 mg/kg). Time to achieve recumbency, LORR, quiescent electromyograph, isoelectric electrocorticograph, heart rate and apnea were recorded.Results:The general order of progression was recumbency, LORR, quiescent electromyograph, isoelectric electrocorticograph and apnea. Recumbency preceded LORR in the majority of animals (CO2; 7/8, CO2/O2; 8/8, isoflurane; 5/8, pentobarbital; 4/8). Bradycardia occurred before recumbency in the CO2 (p = 0.0002) and CO2/O2 (p = 0.005) groups, with a 50% reduction in heart rate compared to baseline. The slowest (time to apnea) and least consistent killing methods were CO2/O2 (1180 ± 658.1s) and pentobarbital (875 [239 to 4680]s).Conclusion:Bradycardia, and consequently nociception and pain, occurs before loss of consciousness during CO2 exposure. Pentobarbital displayed an unexpected lack of consistency, questioning its classification as an acceptable euthanasia method in rats.

scholarly journals Postnatal BDNF Expression Profiles in Prefrontal Cortex and Hippocampus of a Rat Schizophrenia Model Induced by MK-801 Administration

2010 ◽  
Vol 2010 ◽  
pp. 1-5 ◽  
Author(s):  
Chunmei Guo ◽  
Yang Yang ◽  
Yun'ai Su ◽  
Tianmei Si
Keyword(s):  
Prefrontal Cortex ◽  
Nmda Receptors ◽  
Expression Profiles ◽  
Current Model ◽  
Brain Regions ◽  
Nmda Receptor Antagonist ◽  
Sprague Dawley ◽  
Bdnf Expression ◽  
Mk 801 ◽  
Protein Levels

Neonatal blockade of N-methyl-D-aspartic acid (NMDA) receptors represents one of experimental animal models for schizophrenia. This study is to investigate the long-term brain-derived neurotrophic factor (BDNF) expression profiles in different regions and correlation with “schizophrenia-like” behaviors in the adolescence and adult of this rat model. The NMDA receptor antagonist MK801 was administered to female Sprague-Dawley rats on postnatal days (PND) 5 through 14. Open-field test was performed on PND 42, and PND 77 to examine the validity of the current model. BDNF protein levels in hippocampus and prefrontal cortex (PFC) were analyzed on PND 15, PND 42, and PND 77. Results showed that neonatal challenge with MK-801 persistently elevated locomotor activity as well as BDNF expression; the alterations in BDNF expression varied at different developing stages and among brain regions. However, these findings provide neurochemical evidence that the blockade of NMDA receptors during brain development results in long-lasting alterations in BDNF expression and might contribute to neurobehavioral pathology of the present animal model for schizophrenia. Further study in the mechanisms and roles of the BDNF may lead to better understanding of the pathophysiology of schizophrenia.

Cerebral Representation of the Relief of Itch by Scratching

2009 ◽  
Vol 102 (6) ◽  
pp. 3216-3224 ◽  
Author(s):  
Verena Vierow ◽  
Miyuki Fukuoka ◽  
Akihiko Ikoma ◽  
Arnd Dörfler ◽  
Hermann Otto Handwerker ◽  
...  
Keyword(s):  
Time Course ◽  
Premotor Cortex ◽  
Brain Regions ◽  
Blood Oxygenation ◽  
Association Cortex ◽  
Parietal Association Cortex ◽  
Oxygenation Level ◽  
Contrast Analysis ◽  
And Control ◽  
Cerebral Processing

Cerebral processing of itch-scratching cycles was studied with functional magnetic resonance imaging (fMRI) in healthy volunteers. The back of the hand was repetitively scratched in the absence and presence of itch induced by histamine applied close to the scratched site. Blood-oxygenation-level-dependent (BOLD) effects were assessed in predefined cortical and subcortical brain regions of interest. Scratch-related activation clusters were found in cortical and subcortical areas which had been associated before with pain processing, namely S1, S2, parietal association cortex, motor and premotor cortex, anterior and posterior insula, anterior and medial cingulum, lateral and medial frontal areas, ipsilateral cerebellum and contralateral putamen. Cortical activations were generally stronger in the contralateral hemisphere. General linear model (GLM) analysis and GLM contrast analysis revealed stronger activations during itch-related trials in the motor and premotor cortex, in lateral frontal fields of both sides, and in a left medial frontal cluster. Subcortically, stronger activation during itch-related scratching trials was found in the contralateral putamen and in the ipsilateral cerebellum. Time course analysis showed significantly higher BOLD levels during the last 3–6 s before the start of scratching when the itch intensity was strongest. This effect was found in frontal areas, in the putamen, and in the somatosensory projection areas. During the scratching, no significant differences were found between itch and control conditions with the exception of the putamen, which showed stronger activations during itch-related scratch bouts. We interpret these itch-related activations anticipating the scratching as possible cerebral correlates of the itch processing and the craving for scratch.

scholarly journals Refinement of intraperitoneal injection of sodium pentobarbital for euthanasia in laboratory rats (Rattus norvegicus)

2016 ◽  
Author(s):  
K Zatroch ◽  
CG Knight ◽  
JN Reimer ◽  
DSJ Pang
Keyword(s):  
Coefficient Of Variation ◽  
Low Dose ◽  
High Volume ◽  
High Dose ◽  
Sodium Pentobarbital ◽  
Sprague Dawley ◽  
Loss Of Righting Reflex ◽  
Canadian Council ◽  
Righting Reflex ◽  
Low Volume

AbstractBackgroundThe Canadian Council on Animal Care and American Veterinary Medical Association classify intraperitoneal (IP) pentobarbital as an acceptable euthanasia method in rats. However, federal guidelines do not exist for a recommended dose or volume and IP euthanasia has been described as unreliable, with misinjections leading to variable success in ensuring a timely death. The aims of this study were to assess and improve efficacy and consistency of IP euthanasia.MethodsIn a randomized, blinded study, 51 adult female Sprague-Dawley rats (170-495 g) received one of four treatments: low-dose low-volume (LL) IP pentobarbital (n = 13, 200 mg/kg pentobarbital), low-dose high-volume (LH) IP pentobarbital (n = 14, 200 mg/kg diluted 1:3 with phosphate buffered saline), high-dose high-volume (HH, n = 14, 800 mg/kg pentobarbital), or saline. Times to loss of righting reflex (LORR) and cessation of heartbeat (CHB) were recorded. To identify misinjections, necropsy examinations were performed on all rats. Video recordings of LL and HH groups were analyzed for pain-associated behaviors. Between-group comparisons were performed with 1-way ANOVA and Games-Howell post hoc tests. Variability for CHB was assessed by coefficient of variation (CV) calculation.ResultsThe fastest euthanasia method (CHB) was HH (283.7 ± 38 s), compared with LL (485.8 ± 140.7 s, p = 0.002) and LH (347.7 ± 72.0 s, p = 0.039). Values for CV were: HH, 13.4%; LH, 20.7%; LL, 29.0%. LORR time was longest in LL (139.5 ± 29.6 s), compared with HH (111.6 ± 19.7 s, p = 0.046) and LH (104.2 ± 19.3 s, p = 0.01). Misinjections occurred in 15.7% (8/51) of euthanasia attempts. Pain-associated behavior incidence ranged from 36% (LL) to 46% (HH).ConclusionThese data illustrate refinement of this euthanasia technique. Both dose and volume contribute to speed of death with IP pentobarbital and an increase in volume alone does not significantly reduce variability. The proportion of misinjections was similar to that of previous studies.AbbreviationsLLlow-dose low-volumeLHlow-dose high-volumeHHhigh-dose high-volumeLORRloss of righting reflexCHBcessation of heartbeatGITgastrointestinal tractCVcoefficient of variation

scholarly journals Hippocampal regenerative medicine: neurogenic implications for addiction and mental disorders

2021 ◽  
Author(s):  
Lee Peyton ◽  
Alfredo Oliveros ◽  
Doo-Sup Choi ◽  
Mi-Hyeon Jang
Keyword(s):  
Decision Making ◽  
Prefrontal Cortex ◽  
Executive Function ◽  
General Population ◽  
Mental Disorders ◽  
Psychiatric Illness ◽  
Neural Circuitry ◽  
Brain Regions ◽  
Neuropsychiatric Disease ◽  
Motivated Behavior

AbstractPsychiatric illness is a prevalent and highly debilitating disorder, and more than 50% of the general population in both middle- and high-income countries experience at least one psychiatric disorder at some point in their lives. As we continue to learn how pervasive psychiatric episodes are in society, we must acknowledge that psychiatric disorders are not solely relegated to a small group of predisposed individuals but rather occur in significant portions of all societal groups. Several distinct brain regions have been implicated in neuropsychiatric disease. These brain regions include corticolimbic structures, which regulate executive function and decision making (e.g., the prefrontal cortex), as well as striatal subregions known to control motivated behavior under normal and stressful conditions. Importantly, the corticolimbic neural circuitry includes the hippocampus, a critical brain structure that sends projections to both the cortex and striatum to coordinate learning, memory, and mood. In this review, we will discuss past and recent discoveries of how neurobiological processes in the hippocampus and corticolimbic structures work in concert to control executive function, memory, and mood in the context of mental disorders.

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