Rapid eye movement sleep deprivation induces an increase in acetylcholinesterase activity in discrete rat brain regions

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Benedito M.A.C.

2001-01-01

Full Text Available Some upper brainstem cholinergic neurons (pedunculopontine and laterodorsal tegmental nuclei are involved in the generation of rapid eye movement (REM sleep and project rostrally to the thalamus and caudally to the medulla oblongata. A previous report showed that 96 h of REM sleep deprivation in rats induced an increase in the activity of brainstem acetylcholinesterase (Achase, the enzyme which inactivates acetylcholine (Ach in the synaptic cleft. There was no change in the enzyme's activity in the whole brain and cerebrum. The components of the cholinergic synaptic endings (for example, Achase are not uniformly distributed throughout the discrete regions of the brain. In order to detect possible regional changes we measured Achase activity in several discrete rat brain regions (medulla oblongata, pons, thalamus, striatum, hippocampus and cerebral cortex after 96 h of REM sleep deprivation. Naive adult male Wistar rats were deprived of REM sleep using the flower-pot technique, while control rats were left in their home cages. Total, membrane-bound and soluble Achase activities (nmol of thiocholine formed min-1 mg protein-1 were assayed photometrically. The results (mean ± SD obtained showed a statistically significant (Student t-test increase in total Achase activity in the pons (control: 147.8 ± 12.8, REM sleep-deprived: 169.3 ± 17.4, N = 6 for both groups, P<0.025 and thalamus (control: 167.4 ± 29.0, REM sleep-deprived: 191.9 ± 15.4, N = 6 for both groups, P<0.05. Increases in membrane-bound Achase activity in the pons (control: 171.0 ± 14.7, REM sleep-deprived: 189.5 ± 19.5, N = 6 for both groups, P<0.05 and soluble enzyme activity in the medulla oblongata (control: 147.6 ± 16.3, REM sleep-deprived: 163.8 ± 8.3, N = 6 for both groups, P<0.05 were also observed. There were no statistically significant differences in the enzyme's activity in the other brain regions assayed. The present findings show that the increase in Achase activity

Cholinergic Modulation of Restraint Stress Induced Neurobehavioral ...

African Journals Online (AJOL)

The involvement of the cholinergic system in restraint stress induced neurobehavioral alterations was investigated in rodents using the hole board, elevated plus maze, the open field and the light and dark box tests. Restraint stress (3h) reduced significantly (p<0.05) the number of entries and time spent in the open arm, ...

Higher sensitivity to cadmium induced cell death of basal forebrain cholinergic neurons: A cholinesterase dependent mechanism

International Nuclear Information System (INIS)

Del Pino, Javier; Zeballos, Garbriela; Anadon, María José; Capo, Miguel Andrés; Díaz, María Jesús; García, Jimena; Frejo, María Teresa

2014-01-01

Cadmium is an environmental pollutant, which is a cause of concern because it can be greatly concentrated in the organism causing severe damage to a variety of organs including the nervous system which is one of the most affected. Cadmium has been reported to produce learning and memory dysfunctions and Alzheimer like symptoms, though the mechanism is unknown. On the other hand, cholinergic system in central nervous system (CNS) is implicated on learning and memory regulation, and it has been reported that cadmium can affect cholinergic transmission and it can also induce selective toxicity on cholinergic system at peripheral level, producing cholinergic neurons loss, which may explain cadmium effects on learning and memory processes if produced on central level. The present study is aimed at researching the selective neurotoxicity induced by cadmium on cholinergic system in CNS. For this purpose we evaluated, in basal forebrain region, the cadmium toxic effects on neuronal viability and the cholinergic mechanisms related to it on NS56 cholinergic mourine septal cell line. This study proves that cadmium induces a more pronounced, but not selective, cell death on acetylcholinesterase (AChE) on cholinergic neurons. Moreover, MTT and LDH assays showed a dose dependent decrease of cell viability in NS56 cells. The ACh treatment of SN56 cells did not revert cell viability reduction induced by cadmium, but siRNA transfection against AChE partially reduced it. Our present results provide new understanding of the mechanisms contributing to the harmful effects of cadmium on the function and viability of neurons, and the possible relevance of cadmium in the pathogenesis of neurodegenerative diseases

Cholinergic basal forebrain structures are not essential for mediation of the arousing action of glutamate.

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Lelkes, Zoltán; Abdurakhmanova, Shamsiiat; Porkka-Heiskanen, Tarja

2017-09-18

The cholinergic basal forebrain contributes to cortical activation and receives rich innervations from the ascending activating system. It is involved in the mediation of the arousing actions of noradrenaline and histamine. Glutamatergic stimulation in the basal forebrain results in cortical acetylcholine release and suppression of sleep. However, it is not known to what extent the cholinergic versus non-cholinergic basal forebrain projection neurones contribute to the arousing action of glutamate. To clarify this question, we administered N-methyl-D-aspartate (NMDA), a glutamate agonist, into the basal forebrain in intact rats and after destruction of the cholinergic cells in the basal forebrain with 192 immunoglobulin (Ig)G-saporin. In eight Han-Wistar rats with implanted electroencephalogram/electromyogram (EEG/EMG) electrodes and guide cannulas for microdialysis probes, 0.23 μg 192 IgG-saporin was administered into the basal forebrain, while the eight control animals received artificial cerebrospinal fluid. Two weeks later, a microdialysis probe targeted into the basal forebrain was perfused with cerebrospinal fluid on the baseline day and for 3 h with 0.3 mmNMDA on the subsequent day. Sleep-wake activity was recorded for 24 h on both days. NMDA exhibited a robust arousing effect in both the intact and the lesioned rats. Wakefulness was increased and both non-REM and REM sleep were decreased significantly during the 3-h NMDA perfusion. Destruction of the basal forebrain cholinergic neurones did not abolish the wake-enhancing action of NMDA. Thus, the cholinergic basal forebrain structures are not essential for the mediation of the arousing action of glutamate. © 2017 European Sleep Research Society.

Activation of vascular cholinergic and adrenergic receptors induced by gamma rays

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Alya, G.

1999-10-01

Activation of vascular cholinergic receptors and adrenoceptors plays an important role in vasomotoricity and peripheric vascular resistance. These factors are essential in maintaining a stable blood pressure. The aim of this study is to investigate the radiosensitivity differences between vascular cholinergic receptors and adrenoceptors, and consequently to determinate the effects of ionizing radiation (whole body irradiation) on contractile response regulation of vascular smooth muscle fibers VSMF isolated from rat portal vein. Our results show that Clonidine, (non-specific adrenergic agonist), and phenylephrine which is more specific α1-adrenoceptor agonist, increase the VSMF contractions. The maximum effect is obtained at 10 -5 - 3.10 -5 M. On irradiated rats (1-3-5 Gy), there is an important shift thus, the maximal response (E m ax) can be obtained in lower concentrations of clonidine and phenylephrine. Irradiation deceases the contractile responses of VSMF mediated by cholinergic stimulation, in a dose dependant manner. With E m ax 1 Gy>E m ax 3 Gy>E m ax 5 Gy. Irradiated muscular fibers became less sensitive to acetylcholine, thus 3.10 -8 M. A. ch induced more than 50% of contraction force increase in normal conditions. This concentration induce generally a negligible effect after irradiation. The results reveal the existence of radiosensitivity differences between vascular cholinergic and adrenergic receptors. (author)

Unraveling the mechanism of neuroprotection of curcumin in arsenic induced cholinergic dysfunctions in rats

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Srivastava, Pranay [CSIR-Indian Institute of Toxicology Research, Post Box 80, MG Marg, Lucknow 226 001 (India); Yadav, Rajesh S. [CSIR-Indian Institute of Toxicology Research, Post Box 80, MG Marg, Lucknow 226 001 (India); Department of Crimnology and Forensic Science, Harisingh Gour University, Sagar 470 003 (India); Chandravanshi, Lalit P.; Shukla, Rajendra K.; Dhuriya, Yogesh K.; Chauhan, Lalit K.S. [CSIR-Indian Institute of Toxicology Research, Post Box 80, MG Marg, Lucknow 226 001 (India); Dwivedi, Hari N. [Babu Banarasi Das University, BBD City, Faizabad Road, Lucknow 227 015 (India); Pant, Aditiya B. [CSIR-Indian Institute of Toxicology Research, Post Box 80, MG Marg, Lucknow 226 001 (India); Khanna, Vinay K., E-mail: vkkhanna1@gmail.com [CSIR-Indian Institute of Toxicology Research, Post Box 80, MG Marg, Lucknow 226 001 (India)

2014-09-15

Earlier, we found that arsenic induced cholinergic deficits in rat brain could be protected by curcumin. In continuation to this, the present study is focused to unravel the molecular mechanisms associated with the protective efficacy of curcumin in arsenic induced cholinergic deficits. Exposure to arsenic (20 mg/kg body weight, p.o) for 28 days in rats resulted to decrease the expression of CHRM2 receptor gene associated with mitochondrial dysfunctions as evident by decrease in the mitochondrial membrane potential, activity of mitochondrial complexes and enhanced apoptosis both in the frontal cortex and hippocampus in comparison to controls. The ultrastructural images of arsenic exposed rats, assessed by transmission electron microscope, exhibited loss of myelin sheath and distorted cristae in the mitochondria both in the frontal cortex and hippocampus as compared to controls. Simultaneous treatment with arsenic (20 mg/kg body weight, p.o) and curcumin (100 mg/kg body weight, p.o) for 28 days in rats was found to protect arsenic induced changes in the mitochondrial membrane potential and activity of mitochondrial complexes both in frontal cortex and hippocampus. Alterations in the expression of pro- and anti-apoptotic proteins and ultrastructural damage in the frontal cortex and hippocampus following arsenic exposure were also protected in rats simultaneously treated with arsenic and curcumin. The data of the present study reveal that curcumin could protect arsenic induced cholinergic deficits by modulating the expression of pro- and anti-apoptotic proteins in the brain. More interestingly, arsenic induced functional and ultrastructural changes in the brain mitochondria were also protected by curcumin. - Highlights: • Neuroprotective mechanism of curcumin in arsenic induced cholinergic deficits studied • Curcumin protected arsenic induced enhanced expression of stress markers in rat brain • Arsenic compromised mitochondrial electron transport chain protected

Unraveling the mechanism of neuroprotection of curcumin in arsenic induced cholinergic dysfunctions in rats

International Nuclear Information System (INIS)

Srivastava, Pranay; Yadav, Rajesh S.; Chandravanshi, Lalit P.; Shukla, Rajendra K.; Dhuriya, Yogesh K.; Chauhan, Lalit K.S.; Dwivedi, Hari N.; Pant, Aditiya B.; Khanna, Vinay K.

2014-01-01

Earlier, we found that arsenic induced cholinergic deficits in rat brain could be protected by curcumin. In continuation to this, the present study is focused to unravel the molecular mechanisms associated with the protective efficacy of curcumin in arsenic induced cholinergic deficits. Exposure to arsenic (20 mg/kg body weight, p.o) for 28 days in rats resulted to decrease the expression of CHRM2 receptor gene associated with mitochondrial dysfunctions as evident by decrease in the mitochondrial membrane potential, activity of mitochondrial complexes and enhanced apoptosis both in the frontal cortex and hippocampus in comparison to controls. The ultrastructural images of arsenic exposed rats, assessed by transmission electron microscope, exhibited loss of myelin sheath and distorted cristae in the mitochondria both in the frontal cortex and hippocampus as compared to controls. Simultaneous treatment with arsenic (20 mg/kg body weight, p.o) and curcumin (100 mg/kg body weight, p.o) for 28 days in rats was found to protect arsenic induced changes in the mitochondrial membrane potential and activity of mitochondrial complexes both in frontal cortex and hippocampus. Alterations in the expression of pro- and anti-apoptotic proteins and ultrastructural damage in the frontal cortex and hippocampus following arsenic exposure were also protected in rats simultaneously treated with arsenic and curcumin. The data of the present study reveal that curcumin could protect arsenic induced cholinergic deficits by modulating the expression of pro- and anti-apoptotic proteins in the brain. More interestingly, arsenic induced functional and ultrastructural changes in the brain mitochondria were also protected by curcumin. - Highlights: • Neuroprotective mechanism of curcumin in arsenic induced cholinergic deficits studied • Curcumin protected arsenic induced enhanced expression of stress markers in rat brain • Arsenic compromised mitochondrial electron transport chain protected

Is the nonREM-REM sleep cycle reset by forced awakenings from REM sleep?

NARCIS (Netherlands)

Grozinger, M; Beersma, DGM; Fell, J; Roschke, J

In selective REM sleep deprivation (SRSD), the occurrence of stage REM is repeatedly interrupted by short awakenings. Typically, the interventions aggregate in clusters resembling the REM episodes in undisturbed sleep. This salient phenomenon can easily be explained if the nonREM-REM sleep process

Noradrenaline from Locus Coeruleus Neurons Acts on Pedunculo-Pontine Neurons to Prevent REM Sleep and Induces Its Loss-Associated Effects in Rats.

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Khanday, Mudasir Ahmad; Somarajan, Bindu I; Mehta, Rachna; Mallick, Birendra Nath

2016-01-01

Normally, rapid eye movement sleep (REMS) does not appear during waking or non-REMS. Isolated, independent studies showed that elevated noradrenaline (NA) levels inhibit REMS and induce REMS loss-associated cytomolecular, cytomorphological, psychosomatic changes and associated symptoms. However, the source of NA and its target in the brain for REMS regulation and function in health and diseases remained to be confirmed in vivo . Using tyrosine hydroxylase (TH)-siRNA and virus-coated TH-shRNA in normal freely moving rats, we downregulated NA synthesis in locus coeruleus (LC) REM-OFF neurons in vivo . These TH-downregulated rats showed increased REMS, which was prevented by infusing NA into the pedunculo-pontine tegmentum (PPT), the site of REM-ON neurons, normal REMS returned after recovery. Moreover, unlike normal or control-siRNA- or shRNA-injected rats, upon REMS deprivation (REMSD) TH-downregulated rat brains did not show elevated Na-K ATPase (molecular changes) expression and activity. To the best of our knowledge, these are the first in vivo findings in an animal model confirming that NA from the LC REM-OFF neurons (1) acts on the PPT REM-ON neurons to prevent appearance of REMS, and (2) are responsible for inducing REMSD-associated molecular changes and symptoms. These observations clearly show neuro-physio-chemical mechanism of why normally REMS does not appear during waking. Also, that LC neurons are the primary source of NA, which in turn causes some, if not many, REMSD-associated symptoms and behavioral changes. The findings are proof-of-principle for the first time and hold potential to be exploited for confirmation toward treating REMS disorder and amelioration of REMS loss-associated symptoms in patients.

Hypoglycemia induced changes in cholinergic receptor expression in the cerebellum of diabetic rats

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Anju TR

2010-02-01

Full Text Available Abstract Glucose homeostasis in humans is an important factor for the functioning of nervous system. Hypoglycemia and hyperglycemia is found to be associated with central and peripheral nerve system dysfunction. Changes in acetylcholine receptors have been implicated in the pathophysiology of many major diseases of the central nervous system (CNS. In the present study we showed the effects of insulin induced hypoglycemia and streptozotocin induced diabetes on the cerebellar cholinergic receptors, GLUT3 and muscle cholinergic activity. Results showed enhanced binding parameters and gene expression of Muscarinic M1, M3 receptor subtypes in cerebellum of diabetic (D and hypoglycemic group (D + IIH and C + IIH. α7nAchR gene expression showed a significant upregulation in diabetic group and showed further upregulated expression in both D + IIH and C + IIH group. AchE expression significantly upregulated in hypoglycemic and diabetic group. ChAT showed downregulation and GLUT3 expression showed a significant upregulation in D + IIH and C + IIH and diabetic group. AchE activity enhanced in the muscle of hypoglycemic and diabetic rats. Our studies demonstrated a functional disturbance in the neuronal glucose transporter GLUT3 in the cerebellum during insulin induced hypoglycemia in diabetic rats. Altered expression of muscarinic M1, M3 and α7nAchR and increased muscle AchE activity in hypoglycemic rats in cerebellum is suggested to cause cognitive and motor dysfunction. Hypoglycemia induced changes in ChAT and AchE gene expression is suggested to cause impaired acetycholine metabolism in the cerebellum. Cerebellar dysfunction is associated with seizure generation, motor deficits and memory impairment. The results shows that cerebellar cholinergic neurotransmission is impaired during hyperglycemia and hypoglycemia and the hypoglycemia is causing more prominent imbalance in cholinergic neurotransmission which is suggested to be a cause of cerebellar

Neurostimulation of the cholinergic anti-inflammatory pathway ameliorates disease in rat collagen-induced arthritis.

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Yaakov A Levine

Full Text Available The inflammatory reflex is a physiological mechanism through which the nervous system maintains immunologic homeostasis by modulating innate and adaptive immunity. We postulated that the reflex might be harnessed therapeutically to reduce pathological levels of inflammation in rheumatoid arthritis by activating its prototypical efferent arm, termed the cholinergic anti-inflammatory pathway. To explore this, we determined whether electrical neurostimulation of the cholinergic anti-inflammatory pathway reduced disease severity in the collagen-induced arthritis model.Rats implanted with vagus nerve cuff electrodes had collagen-induced arthritis induced and were followed for 15 days. Animals underwent active or sham electrical stimulation once daily from day 9 through the conclusion of the study. Joint swelling, histology, and levels of cytokines and bone metabolism mediators were assessed.Compared with sham treatment, active neurostimulation of the cholinergic anti-inflammatory pathway resulted in a 52% reduction in ankle diameter (p = 0.02, a 57% reduction in ankle diameter (area under curve; p = 0.02 and 46% reduction overall histological arthritis score (p = 0.01 with significant improvements in inflammation, pannus formation, cartilage destruction, and bone erosion (p = 0.02, accompanied by numerical reductions in systemic cytokine levels, not reaching statistical significance. Bone erosion improvement was associated with a decrease in serum levels of receptor activator of NF-κB ligand (RANKL from 132±13 to 6±2 pg/mL (mean±SEM, p = 0.01.The severity of collagen-induced arthritis is reduced by neurostimulation of the cholinergic anti-inflammatory pathway delivered using an implanted electrical vagus nerve stimulation cuff electrode, and supports the rationale for testing this approach in human inflammatory disorders.

Neuroprotective efficacy of curcumin in arsenic induced cholinergic dysfunctions in rats.

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Yadav, Rajesh S; Chandravanshi, Lalit P; Shukla, Rajendra K; Sankhwar, Madhu L; Ansari, Reyaz W; Shukla, Pradeep K; Pant, Aditya B; Khanna, Vinay K

2011-12-01

Our recent studies have shown that curcumin protects arsenic induced neurotoxicity by modulating oxidative stress, neurotransmitter levels and dopaminergic system in rats. As chronic exposure to arsenic has been associated with cognitive deficits in humans, the present study has been carried out to implore the neuroprotective potential of curcumin in arsenic induced cholinergic dysfunctions in rats. Rats treated with arsenic (sodium arsenite, 20mg/kg body weight, p.o., 28 days) exhibited a significant decrease in the learning activity, assessed by passive avoidance response associated with decreased binding of (3)H-QNB, known to label muscarinic-cholinergic receptors in hippocampus (54%) and frontal cortex (27%) as compared to controls. Decrease in the activity of acetylcholinesterase in hippocampus (46%) and frontal cortex (33%), staining of Nissl body, immunoreactivity of choline acetyltransferase (ChAT) and expression of ChAT protein in hippocampal region was also observed in arsenic treated rats as compared to controls. Simultaneous treatment with arsenic and curcumin (100mg/kg body weight, p.o., 28 days) increased learning and memory performance associated with increased binding of (3)H-QNB in hippocampus (54%), frontal cortex (25%) and activity of acetylcholinesterase in hippocampus (41%) and frontal cortex (29%) as compared to arsenic treated rats. Increase in the expression of ChAT protein, immunoreactivity of ChAT and staining of Nissl body in hippocampal region was also observed in rats simultaneously treated with arsenic and curcumin as compared to those treated with arsenic alone. The results of the present study suggest that curcumin significantly modulates arsenic induced cholinergic dysfunctions in brain and also exhibits neuroprotective efficacy of curcumin. Copyright © 2011 Elsevier Inc. All rights reserved.

Urtica dioica leaves modulates muscarinic cholinergic system in the hippocampus of streptozotocin-induced diabetic mice.

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Patel, Sita Sharan; Parashar, Arun; Udayabanu, Malairaman

2015-06-01

Diabetes mellitus is a chronic metabolic disorder and has been associated with cognitive dysfunction. In our earlier study, chronic Urtica dioica (UD) treatment significantly ameliorated diabetes induced associative and spatial memory deficit in mice. The present study was designed to explore the effect of UD leaves extract on muscarinic cholinergic system, which has long been known to be involved in cognition. Streptozotocin (STZ) (50 mg/kg, i.p., consecutively for 5 days) was used to induce diabetes followed by treatment with UD extract (50 mg/kg, oral) or rosiglitazone (5 mg/kg, oral) for 8 weeks. STZ-induced diabetic mice showed significant reduction in hippocampal muscarinic acetylcholine receptor-1 and choline acetyltransferase expressions. Chronic diabetes significantly up-regulated the protein expression of acetylcholinesterase associated with oxidative stress in hippocampus. Besides, STZ-induced diabetic mice showed hypolocomotion with up-regulation of muscarinic acetylcholine receptor-4 expression in striatum. Chronic UD treatment significantly attenuated the cholinergic dysfunction and oxidative stress in the hippocampus of diabetic mice. UD had no effect on locomotor activity and muscarinic acetylcholine receptor-4 expression in striatum. In conclusion, UD leaves extract has potential to reverse diabetes mediated alteration in muscarinic cholinergic system in hippocampus and thereby improve memory functions.

Sleep and dreaming: induction and mediation of REM sleep by cholinergic mechanisms.

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Hobson, J A

1992-12-01

The most important recent work on the neurobiology of sleep has focused on the precise cellular and biochemical mechanisms of rapid eye movement sleep mediation. Direct and indirect evidence implicates acetylcholine-containing neurons in the peribrachial pons as critical in the triggering and maintenance of rapid eye movement sleep. Other new studies provide support for the hypothesis that the cholinergic generator system is gated during waking by serotonergic and noradrenergic influences. A growing consensus regarding the basic neurobiology has stimulated new thinking about the brain basis of consciousness during waking and dreaming.

Nematode cholinergic pharmacology

International Nuclear Information System (INIS)

Segerberg, M.A.

1989-01-01

Nematode acetylcholine (ACh) receptors were characterized using both biochemical and electrophysiological techniques, including: (1) receptor binding studies in crude homogenates of the free-living nematode Caenorhabditis elegans and the parasitic nematode Ascaris lumbricoides with the high-affinity probe [ 3 H]N-methylscopolamine ([ 3 H]NMS) which binds to muscarinic receptors in many vertebrate and invertebrate tissues (2) measurement of depolarization and contraction induced by a variety of cholinergic agents, including N-methylscopolamine (NMS), in an innervated dorsal muscle strip preparation of Ascaris; (3) examination of the antagonistic actions of d-tubocurarine (dTC) and NMS at dorsal neuromuscular junction; (4) measurement of input resistance changes in Ascaris commissural motorneurons induced by ACh, dTC, NMS, pilocarpine and other cholinergic drugs

Satureja bachtiarica ameliorate beta-amyloid induced memory impairment, oxidative stress and cholinergic deficit in animal model of Alzheimer's disease.

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Soodi, Maliheh; Saeidnia, Soodabeh; Sharifzadeh, Mohammad; Hajimehdipoor, Homa; Dashti, Abolfazl; Sepand, Mohammad Reza; Moradi, Shahla

2016-04-01

Extracellular deposition of Beta-amyloid peptide (Aβ) is the main finding in the pathophysiology of Alzheimer's disease (AD), which damages cholinergic neurons through oxidative stress and reduces the cholinergic neurotransmission. Satureja bachtiarica is a medicinal plant from the Lamiaceae family which was widely used in Iranian traditional medicine. The aim of the present study was to investigate possible protective effects of S. bachtiarica methanolic extract on Aβ induced spatial memory impairment in Morris Water Maze (MWM), oxidative stress and cholinergic neuron degeneration. Pre- aggregated Aβ was injected into the hippocampus of each rat bilaterally (10 μg/rat) and MWM task was performed 14 days later to evaluate learning and memory function. Methanolic extract of S.bachtiarica (10, 50 and 100 mg/Kg) was injected intraperitoneally for 19 consecutive days, after Aβ injection. After the probe test the brain tissue were collected and lipid peroxidation, Acetylcholinesterase (AChE) activity and Cholin Acetyl Transferees (ChAT) immunorectivity were measured in the hippocampus. Intrahipocampal injection of Aβ impaired learning and memory in MWM in training days and probe trail. Methanolic extract of S. bachtiarica (50 and 100 mg/Kg) could attenuate Aβ-induced memory deficit. ChAT immunostaining revealed that cholinergic neurons were loss in Aβ- injected group and S. bachtiarica (100 mg/Kg) could ameliorate Aβ- induced ChAT reduction in the hippocampus. Also S. bachtiarica could ameliorate Aβ-induced lipid peroxidation and AChE activity increase in the hippocampus. In conclusion our study represent that S.bachtiarica methanolic extract can improve Aβ-induced memory impairment and cholinergic loss then we recommended this extract as a candidate for further investigation in treatment of AD.

The cholinergic-inducing effect of BMP4 on rat's cerebral neural stem cells

International Nuclear Information System (INIS)

Chang Yan; Xue Yilong; Luo Yun; Tian Lei; Pan Jingkun; Cui Xin

2004-01-01

The cholinergic-inducing effect of BMP4 on isolated and cultivated rat's cerebral neural stem cells (NSC) was examined. NSC isolated from two months old rat's brain region like hippocampus and striatum was cultivated in a DMEM/F12 medium containing EGF and bFGF, and was identified with morphological character and nestin immunocytochemistry test. After 24 hours, cultivating the NSC with the BMP4-added medium for 7-8 days, then the microscopical change were observed, ChAT and nestin double-labelling immunocytochemistry test was done. Results showed that about 34% NSC of neuron-like character was observed by microscope in the paper. That ChAT-positive cells coexist with nestin-positive cells was found by immunocytochemistry test. There were 28% ChAT-positive cells and 38% nestin-positive cells in the study. Cholinergic neurons differentiated from NSC could be induced by adding BMP4 to the medium

Effect of morphine-induced antinociception is altered by AF64A-induced lesions on cholinergic neurons in rat nucleus raphe magnus.

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Abe, Kenji; Ishida, Kota; Kato, Masatoshi; Shigenaga, Toshiro; Taguchi, Kyoji; Miyatake, Tadashi

2002-11-01

To examine the role of cholinergic neurons in the nucleus raphe magnus (NRM) in noxious heat stimulation and in the effects of morphine-induced antinociception by rats. After the cholinergic neuron selective toxin, AF64A, was microinjected into the NRM, we examined changes in the antinociceptive threshold and effects of morphine (5 mg/kg, ip) using the hot-plate (HP) and tail-flick (TF) tests. Systemic administration of morphine inhibited HP and TF responses in control rats. Microinjection of AF64A (2 nmol/site) into the NRM significantly decreased the threshold of HP response after 14 d, whereas the TF response was not affected. Morphine-induced antinociception was significantly attenuated in rats administered AF64A. Extracellular acetylcholine was attenuated after 14 d to below detectable levels in rats given AF64A. Naloxone (1 microg/site) microinjected into control rat NRM also antagonized the antinociceptive effect of systemic morphine. These findings suggest that cholinergic neuron activation in the NRM modulates the antinociceptive effect of morphine simultaneously with the opiate system.

REM sleep deprivation induces endothelial dysfunction and hypertension in middle-aged rats: Roles of the eNOS/NO/cGMP pathway and supplementation with L-arginine.

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Jiang, Jiaye; Gan, Zhongyuan; Li, Yuan; Zhao, Wenqi; Li, Hanqing; Zheng, Jian-Pu; Ke, Yan

2017-01-01

Sleep loss can induce or aggravate the development of cardiovascular and cerebrovascular diseases. However, the molecular mechanism underlying this phenomenon is poorly understood. The present study was designed to investigate the effects of REM sleep deprivation on blood pressure in rats and the underlying mechanisms of these effects. After Sprague-Dawley rats were subjected to REM sleep deprivation for 5 days, their blood pressures and endothelial function were measured. In addition, one group of rats was given continuous access to L-arginine supplementation (2% in distilled water) for the 5 days before and the 5 days of REM sleep deprivation to reverse sleep deprivation-induced pathological changes. The results showed that REM sleep deprivation decreased body weight, increased blood pressure, and impaired endothelial function of the aortas in middle-aged rats but not young rats. Moreover, nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) concentrations as well as endothelial NO synthase (eNOS) phosphorylation in the aorta were decreased by REM sleep deprivation. Supplementation with L-arginine could protect against REM sleep deprivation-induced hypertension, endothelial dysfunction, and damage to the eNOS/NO/cGMP signaling pathway. The results of the present study suggested that REM sleep deprivation caused endothelial dysfunction and hypertension in middle-aged rats via the eNOS/NO/cGMP pathway and that these pathological changes could be inhibited via L-arginine supplementation. The present study provides a new strategy to inhibit the signaling pathways involved in insomnia-induced or insomnia-enhanced cardiovascular diseases.

beta-Adrenergic and cholinergic receptors in hypertension-induced hypertrophy

International Nuclear Information System (INIS)

Vatner, D.E.; Kirby, D.A.; Homcy, C.J.; Vatner, S.F.

1985-01-01

Perinephritic hypertension was produced in dogs by wrapping one kidney with silk and removing the contralateral kidney 1 week later. Mean arterial pressure rose from 104 +/- 3 to 156 +/- 11 mm Hg, while left ventricular free wall weight, normalized for body weight, was increased by 49%. Muscarinic, cholinergic receptor density measured with [ 3 H]-quinuclidinyl benzilate, fell in hypertensive left ventricles (181 +/- 19 fmol/mg, n = 6; p less than 0.01) as compared with that found in normal left ventricles (272 +/- 16 fmol/mg, n = 8), while receptor affinity was not changed. The beta-adrenergic receptor density, measured by binding studies with [ 3 H]-dihydroalprenolol, rose in the hypertensive left ventricles (108 +/- 10 fmol/mg, n = 7; p less than 0.01) as compared with that found in normal left ventricles (68.6 +/- 5.2 fmol/mg, n = 15), while beta-adrenergic receptor affinity decreased in the hypertensive left ventricles (10.4 +/- 1.2 nM) compared with that found in the normal left ventricles (5.0 +/- 0.7 nM). Plasma norepinephrine levels were similar in the two groups, but myocardial norepinephrine levels were depressed (p less than 0.05) in dogs with hypertension. Moderate left ventricular hypertrophy induced by long-term aortic banding in dogs resulted in elevations in beta-adrenergic receptor density (115 +/- 14 fmol/mg) and decreases in affinity (10.4 +/- 2.2 nM) similar to those observed in the dogs with left ventricular hypertrophy induced by hypertension. Thus, these results suggest that perinephritic hypertension in the dog induces divergent effects on cholinergic and beta-adrenergic receptor density. The increased beta-adrenergic receptor density and decreased affinity may be a characteristic of left ventricular hypertrophy rather than hypertension

Cholinergic and VIPergic effects on thyroid hormone secretion in the mouse

International Nuclear Information System (INIS)

Ahren, B.

1985-01-01

The thyroid gland is known to harbor cholinergic and VIPergic nerves. In the present study, the influences of cholinergic stimulation by carbachol, cholinergic blockade by methylatropine and stimulation with various VIP sequences on basal, TSH-induced and VIP-induced thyroid hormone secretion were investigated in vivo in mice. The mice were pretreated with 125 I and thyroxine; the subsequent release of 125 I is an estimation of thyroid hormone secretion. It was found that basal radioiodine secretion was inhibited by both carbachol and methylatropine. Furthermore, TSH-induced radioiodine secretion was inhibited already by a low dose of carbachol. Moreover, a high dose of carbachol could inhibit VIP-induced radioiodine secretion. Methylatropine did not influence TSH- or VIP-stimulated radioiodine secretion, but counteracted the inhibitory action of carbachol on TSH- and VIP-induced radioiodine release. In addition, contrary to VIP, six various synthesized VIP fragments had no effect on basal or stimulated radioiodine release. It is concluded that basal thyroid hormone secretion is inhibited by both cholinergic activation and blockade. Furthermore, TSH-induced thyroid hormone secretion is more sensitive to inhibition with cholinergic stimulation than is VIP-induced thyroid hormone secretion. In addition, the VIP stimulation of thyroid hormone secretion seems to require the full VIP sequence

Automatic REM Sleep Detection Associated with Idiopathic REM Sleep Behavior Disorder

DEFF Research Database (Denmark)

Kempfner, Jacob; Sørensen, Gertrud Laura; Sørensen, Helge Bjarup Dissing

2011-01-01

Rapid eye movement sleep Behavior Disorder (RBD) is a strong early marker of later development of Parkinsonism. Currently there are no objective methods to identify and discriminate abnormal from normal motor activity during REM sleep. Therefore, a REM sleep detection without the use of chin...... electromyography (EMG) is useful. This is addressed by analyzing the classification performance when implementing two automatic REM sleep detectors. The first detector uses the electroencephalography (EEG), electrooculography (EOG) and EMG to detect REM sleep, while the second detector only uses the EEG and EOG......, an automatic computerized REM detection algorithm has been implemented, using wavelet packet combined with artificial neural network. Results: When using the EEG, EOG and EMG modalities, it was possible to correctly classify REM sleep with an average Area Under Curve (AUC) equal to 0:900:03 for normal subjects...

REM Sleep Phase Preference in the Crepuscular Octodon degus Assessed by Selective REM Sleep Deprivation

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Ocampo-Garcés, Adrián; Hernández, Felipe; Palacios, Adrian G.

2013-01-01

Study Objectives: To determine rapid eye movement (REM) sleep phase preference in a crepuscular mammal (Octodon degus) by challenging the specific REM sleep homeostatic response during the diurnal and nocturnal anticrepuscular rest phases. Design: We have investigated REM sleep rebound, recovery, and documented REM sleep propensity measures during and after diurnal and nocturnal selective REM sleep deprivations. Subjects: Nine male wild-captured O. degus prepared for polysomnographic recordings Interventions: Animals were recorded during four consecutive baseline and two separate diurnal or nocturnal deprivation days, under a 12:12 light-dark schedule. Three-h selective REM sleep deprivations were performed, starting at midday (zeitgeber time 6) or midnight (zeitgeber time 18). Measurements and Results: Diurnal and nocturnal REM sleep deprivations provoked equivalent amounts of REM sleep debt, but a consistent REM sleep rebound was found only after nocturnal deprivation. The nocturnal rebound was characterized by a complete recovery of REM sleep associated with an augment in REM/total sleep time ratio and enhancement in REM sleep episode consolidation. Conclusions: Our results support the notion that the circadian system actively promotes REM sleep. We propose that the sleep-wake cycle of O. degus is modulated by a chorus of circadian oscillators with a bimodal crepuscular modulation of arousal and a unimodal promotion of nocturnal REM sleep. Citation: Ocampo-Garcés A; Hernández F; Palacios AG. REM sleep phase preference in the crepuscular Octodon degus assessed by selective REM sleep deprivation. SLEEP 2013;36(8):1247-1256. PMID:23904685

Automatic REM sleep detection associated with idiopathic rem sleep Behavior Disorder

DEFF Research Database (Denmark)

Kempfner, J; Sørensen, Gertrud Laura; Sorensen, H B D

2011-01-01

Rapid eye movement sleep Behavior Disorder (RBD) is a strong early marker of later development of Parkinsonism. Currently there are no objective methods to identify and discriminate abnormal from normal motor activity during REM sleep. Therefore, a REM sleep detection without the use of chin...... electromyography (EMG) is useful. This is addressed by analyzing the classification performance when implementing two automatic REM sleep detectors. The first detector uses the electroencephalography (EEG), electrooculography (EOG) and EMG to detect REM sleep, while the second detector only uses the EEG and EOG....

Neural stem cells was induced to differentiate into cholinergic neurons in vitro

International Nuclear Information System (INIS)

Chang Yan; Xu Yilong; Pan Jingkun; Tian Lei; Gao Yuhong; Guo Shuilong

2004-01-01

The cholinergic-inducing effect of BMP4 on isolated and cultivated rat's cerebral neural stem cells (NSCs) was examined. NSCs which were isolated from two month's old rat's brain region like hippocampus and striatum were cultivated in a medium containing EGF and bFGF, and were identified with morphological character by microscope and nestin immunocytochemistry test. After 24 hours, half NSCs were cultivated with a BMP4-added medium as a experimental group instead of the primary medium, while the an other half NSCs being cultivated with the primary medium as a control group. After 8 days the expression of choline acetyltransferase (ChAT) of the cultivated cells was observated by indirect immunofluorescence test. Results showed that more positive cells were found in the experimental group, and the fluorescence intensity were stronger; while less positive cells were found in the control group, and the fluorescence intensity was weaker. The differentiational efficiency of the NSCs was examined by FITC-labelled Flow Cytometry. The results showed that about 16% cells of the experimental group appeared ChAT-positive, while that of control group only 7%. So BMP4 may have the function of inducing NSCs to differentiate into neurons with cholinergic characteristic. (authors)

The Biology of REM Sleep

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Peever, John; Fuller, Patrick M.

2018-01-01

Considerable advances in our understanding of the mechanisms and functions of rapid-eye-movement (REM) sleep have occurred over the past decade. Much of this progress can be attributed to the development of new neuroscience tools that have enabled high-precision interrogation of brain circuitry linked with REM sleep control, in turn revealing how REM sleep mechanisms themselves impact processes such as sensorimotor function. This review is intended to update the general scientific community about the recent mechanistic, functional and conceptual developments in our current understanding of REM sleep biology and pathobiology. Specifically, this review outlines the historical origins of the discovery of REM sleep, the diversity of REM sleep expression across and within species, the potential functions of REM sleep (e.g., memory consolidation), the neural circuits that control REM sleep, and how dysfunction of REM sleep mechanisms underlie debilitating sleep disorders such as REM sleep behaviour disorder and narcolepsy. PMID:26766231

Genetically-induced cholinergic hyper-innervation enhances taste learning

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Selin eNeseliler

2011-12-01

Full Text Available Acute inhibition of acetylcholine (ACh has been shown to impair many forms of simple learning, and notably conditioned taste aversion (CTA. The most adhered-to theory that has emerged as a result of this work—that ACh increases a taste’s perceived novelty, and thereby its associability—would be further strengthened by evidence showing that enhanced cholinergic function improves learning above normal levels. Experimental testing of this corollary hypothesis has been limited, however, by side-effects of pharmacological ACh agonism and by the absence of a model that achieves long-term increases in cholinergic signaling. Here, we present this further test of the ACh hypothesis, making use of mice lacking the p75 pan-neurotrophin receptor gene, which show a resultant over-abundance of cholinergic neurons in subregions of the basal forebrain (BF. We first demonstrate that the p75-/- abnormality directly affects portions of the CTA circuit, locating mouse gustatory cortex (GC using a functional assay and then using immunohistochemisty to demonstrate cholinergic hyperinnervation of GC in the mutant mice—hyperinnervation that is unaccompanied by changes in cell numbers or compensatory changes in muscarinic receptor densities. We then demonstrate that both p75-/- and wild-type mice learn robust CTAs, which extinguish more slowly in the mutants. Further testing to distinguish effects on learning from alterations in memory retention demonstrate that p75-/- mice do in fact learn stronger CTAs than wild-type mice. These data provide novel evidence for the hypothesis linking ACh and taste learning.

Post training REMs coincident auditory stimulation enhances memory in humans.

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Smith, C; Weeden, K

1990-06-01

Sleep activity was monitored in 20 freshman college students for two consecutive nights. Subjects were assigned to 4 equal groups and all were asked to learn a complex logic task before bed on the second night. Two groups of subjects learned the task with a constant clicking noise in the background (cued groups), while two groups simply learned the task (non cued). During the night, one cued and one non cued group were presented with auditory clicks during REM sleep such as to coincide with all REMs of at least 100 microvolts. The second cued group was given auditory clicks during REM sleep, but only during the REMs "quiet" times. The second non-cued control group was never given any nighttime auditory stimulations. The cued REMs coincident group showed a significant 23% improvement in task performance when tested one week later. The non cued REMs coincident group showed only an 8.8% improvement which was not significant. The cued REMs quiet and non-stimulated control groups showed no change in task performance when retested. The results were interpreted as support for the idea that the cued auditory stimulation induced a "recall" of the learned material during the REM sleep state in order for further memory processing to take place.

Perifornical orexinergic neurons modulate REM sleep by influencing locus coeruleus neurons in rats.

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Choudhary, R C; Khanday, M A; Mitra, A; Mallick, B N

2014-10-24

Activation of the orexin (OX)-ergic neurons in the perifornical (PeF) area has been reported to induce waking and reduce rapid eye movement sleep (REMS). The activities of OX-ergic neurons are maximum during active waking and they progressively reduce during non-REMS (NREMS) and REMS. Apparently, the locus coeruleus (LC) neurons also behave in a comparable manner as that of the OX-ergic neurons particularly in relation to waking and REMS. Further, as PeF OX-ergic neurons send dense projections to LC, we argued that the former could drive the LC neurons to modulate waking and REMS. Studies in freely moving normally behaving animals where simultaneously neuro-chemo-anatomo-physio-behavioral information could be deciphered would significantly strengthen our understanding on the regulation of REMS. Therefore, in this study in freely behaving chronically prepared rats we stimulated the PeF neurons without or with simultaneous blocking of specific subtypes of OX-ergic receptors in the LC while electrophysiological recording characterizing sleep-waking was continued. Single dose of glutamate stimulation as well as sustained mild electrical stimulation of PeF (both bilateral) significantly increased waking and reduced REMS as compared to baseline. Simultaneous application of OX-receptor1 (OX1R) antagonist bilaterally into the LC prevented PeF stimulation-induced REMS suppression. Also, the effect of electrical stimulation of the PeF was long lasting as compared to that of the glutamate stimulation. Further, sustained electrical stimulation significantly decreased both REMS duration as well as REMS frequency, while glutamate stimulation decreased REMS duration only. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

Is the nonREM–REM sleep cycle reset by forced awakenings from REM sleep?

NARCIS (Netherlands)

Grözinger, Michael; Beersma, Domien G.M.; Fell, Jürgen; Röschke, Joachim

2002-01-01

In selective REM sleep deprivation (SRSD), the occurrence of stage REM is repeatedly interrupted by short awakenings. Typically, the interventions aggregate in clusters resembling the REM episodes in undisturbed sleep. This salient phenomenon can easily be explained if the nonREM–REM sleep process

Cholinergic enhancement of visual attention and neural oscillations in the human brain.

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Bauer, Markus; Kluge, Christian; Bach, Dominik; Bradbury, David; Heinze, Hans Jochen; Dolan, Raymond J; Driver, Jon

2012-03-06

Cognitive processes such as visual perception and selective attention induce specific patterns of brain oscillations. The neurochemical bases of these spectral changes in neural activity are largely unknown, but neuromodulators are thought to regulate processing. The cholinergic system is linked to attentional function in vivo, whereas separate in vitro studies show that cholinergic agonists induce high-frequency oscillations in slice preparations. This has led to theoretical proposals that cholinergic enhancement of visual attention might operate via gamma oscillations in visual cortex, although low-frequency alpha/beta modulation may also play a key role. Here we used MEG to record cortical oscillations in the context of administration of a cholinergic agonist (physostigmine) during a spatial visual attention task in humans. This cholinergic agonist enhanced spatial attention effects on low-frequency alpha/beta oscillations in visual cortex, an effect correlating with a drug-induced speeding of performance. By contrast, the cholinergic agonist did not alter high-frequency gamma oscillations in visual cortex. Thus, our findings show that cholinergic neuromodulation enhances attentional selection via an impact on oscillatory synchrony in visual cortex, for low rather than high frequencies. We discuss this dissociation between high- and low-frequency oscillations in relation to proposals that lower-frequency oscillations are generated by feedback pathways within visual cortex. Copyright © 2012 Elsevier Ltd. All rights reserved.

Differential effects of non-REM and REM sleep on memory consolidation?

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Ackermann, Sandra; Rasch, Björn

2014-02-01

Sleep benefits memory consolidation. Previous theoretical accounts have proposed a differential role of slow-wave sleep (SWS), rapid-eye-movement (REM) sleep, and stage N2 sleep for different types of memories. For example the dual process hypothesis proposes that SWS is beneficial for declarative memories, whereas REM sleep is important for consolidation of non-declarative, procedural and emotional memories. In fact, numerous recent studies do provide further support for the crucial role of SWS (or non-REM sleep) in declarative memory consolidation. However, recent evidence for the benefit of REM sleep for non-declarative memories is rather scarce. In contrast, several recent studies have related consolidation of procedural memories (and some also emotional memories) to SWS (or non-REM sleep)-dependent consolidation processes. We will review this recent evidence, and propose future research questions to advance our understanding of the role of different sleep stages for memory consolidation.

REM sleep modulation by perifornical orexinergic inputs to the pedunculo-pontine tegmental neurons in rats.

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Khanday, M A; Mallick, B N

2015-11-12

Rapid eye movement sleep (REMS) is regulated by the interaction of the REM-ON and REM-OFF neurons located in the pedunculo-pontine-tegmentum (PPT) and the locus coeruleus (LC), respectively. Many other brain areas, particularly those controlling non-REMS (NREMS) and waking, modulate REMS by modulating these REMS-related neurons. Perifornical (PeF) orexin (Ox)-ergic neurons are reported to increase waking and reduce NREMS as well as REMS; dysfunction of the PeF neurons are related to REMS loss-associated disorders. Hence, we were interested in understanding the neural mechanism of PeF-induced REMS modulation. As a first step we have recently reported that PeF Ox-ergic neurons modulate REMS by influencing the LC neurons (site for REM-OFF neurons). Thereafter, in this in vivo study we have explored the role of PeF inputs on the PPT neurons (site for REM-ON neurons) for the regulation of REMS. Chronic male rats were surgically prepared with implanted bilateral cannulae in PeF and PPT and electrodes for recording sleep-waking patterns. After post-surgical recovery sleep-waking-REMS were recorded when bilateral PeF neurons were stimulated by glutamate and simultaneously bilateral PPT neurons were infused with either saline or orexin receptor1 (OX1R) antagonist. It was observed that PeF stimulation increased waking and decreased NREMS as well as REMS, which were prevented by OX1R antagonist into the PPT. We conclude that the PeF stimulation-induced reduction in REMS was likely to be due to inhibition of REM-ON neurons in the PPT. As waking and NREMS are inversely related, subject to confirmation, the reduction in NREMS could be due to increased waking or vice versa. Based on our findings from this and earlier studies we have proposed a model showing connections between PeF- and PPT-neurons for REMS regulation. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Ventromedial medulla inhibitory neuron inactivation induces REM sleep without atonia and REM sleep behavior disorder.

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Valencia Garcia, Sara; Brischoux, Frédéric; Clément, Olivier; Libourel, Paul-Antoine; Arthaud, Sébastien; Lazarus, Michael; Luppi, Pierre-Hervé; Fort, Patrice

2018-02-05

Despite decades of research, there is a persistent debate regarding the localization of GABA/glycine neurons responsible for hyperpolarizing somatic motoneurons during paradoxical (or REM) sleep (PS), resulting in the loss of muscle tone during this sleep state. Combining complementary neuroanatomical approaches in rats, we first show that these inhibitory neurons are localized within the ventromedial medulla (vmM) rather than within the spinal cord. We then demonstrate their functional role in PS expression through local injections of adeno-associated virus carrying specific short-hairpin RNA in order to chronically impair inhibitory neurotransmission from vmM. After such selective genetic inactivation, rats display PS without atonia associated with abnormal and violent motor activity, concomitant with a small reduction of daily PS quantity. These symptoms closely mimic human REM sleep behavior disorder (RBD), a prodromal parasomnia of synucleinopathies. Our findings demonstrate the crucial role of GABA/glycine inhibitory vmM neurons in muscle atonia during PS and highlight a candidate brain region that can be susceptible to α-synuclein-dependent degeneration in RBD patients.

REM sleep deprivation during 5 hours leads to an immediate REM sleep rebound and to suppression of non-REM sleep intensity

NARCIS (Netherlands)

Beersma, D.G.M.; Dijk, D.J.; Blok, Guus; Everhardus, I.

Nine healthy male subjects were deprived of REM sleep during the first 5 h after sleep onset. Afterwards recovery sleep was undisturbed. During the deprivation period the non-REM EEG power spectrum was reduced when compared to baseline for the frequencies up to 7 Hz, despite the fact that non-REM

REM sleep rescues learning from interference

Science.gov (United States)

McDevitt, Elizabeth A.; Duggan, Katherine A.; Mednick, Sara C.

2015-01-01

Classical human memory studies investigating the acquisition of temporally-linked events have found that the memories for two events will interfere with each other and cause forgetting (i.e., interference; Wixted, 2004). Importantly, sleep helps consolidate memories and protect them from subsequent interference (Ellenbogen, Hulbert, Stickgold, Dinges, & Thompson-Schill, 2006). We asked whether sleep can also repair memories that have already been damaged by interference. Using a perceptual learning paradigm, we induced interference either before or after a consolidation period. We varied brain states during consolidation by comparing active wake, quiet wake, and naps with either non-rapid eye movement sleep (NREM), or both NREM and REM sleep. When interference occurred after consolidation, sleep and wake both produced learning. However, interference prior to consolidation impaired memory, with retroactive interference showing more disruption than proactive interference. Sleep rescued learning damaged by interference. Critically, only naps that contained REM sleep were able to rescue learning that was highly disrupted by retroactive interference. Furthermore, the magnitude of rescued learning was correlated with the amount of REM sleep. We demonstrate the first evidence of a process by which the brain can rescue and consolidate memories damaged by interference, and that this process requires REM sleep. We explain these results within a theoretical model that considers how interference during encoding interacts with consolidation processes to predict which memories are retained or lost. PMID:25498222

REM and NREM sleep mentation.

Science.gov (United States)

McNamara, Patrick; Johnson, Patricia; McLaren, Deirdre; Harris, Erica; Beauharnais, Catherine; Auerbach, Sanford

2010-01-01

We review the literature on the neurobiology of rapid eye movement (REM) and non-rapid eye movement (NREM) sleep states and associated dreams. REM is associated with enhanced activation of limbic and amygdalar networks and decreased activation in dorsal prefrontal regions while stage II NREM is associated with greater cortical activation than REM. Not surprisingly, these disparate brain activation patterns tend to be associated with dramatically different dream phenomenologies and dream content. We present two recent studies which content-analyzed hundreds of dream reports from REM and NREM sleep states. These studies demonstrated that dreamer-initiated aggressive social interactions were more characteristic of REM than NREM, and dreamer-initiated friendliness was more characteristic of NREM than REM reports. Both REM and NREM dreams therefore may function to simulate opposing types of social interactions, with the REM state specializing in simulation of aggressive interactions and the NREM state specializing in simulation of friendly interactions. We close our review with a summary of evidence that dream content variables significantly predict daytime mood and social interactions. Copyright © 2010 Elsevier Inc. All rights reserved.

Intrahippocampal administration of anandamide increases REM sleep.

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Rueda-Orozco, Pavel Ernesto; Soria-Gómez, Edgar; Montes-Rodríguez, Corinne Jennifer; Pérez-Morales, Marcel; Prospéro-García, Oscar

2010-04-05

A nascent literature has postulated endocannabinoids (eCBs) as strong sleep-inducing lipids, particularly rapid-eye-movement sleep (REMs), nevertheless the exact mechanisms behind this effect remain to be determined. Anandamide and 2-arachidonyl glycerol, two of the most important eCBS, are synthesized in the hippocampus. This structure also expresses a high concentration of cannabinoid receptor 1 (CB1). Recent extensive literature supports eCBs as important regulators of hippocampal activity. It has also been shown that these molecules vary their expression on the hippocampus depending on the light-dark cycle. In this context we decided to analyze the effect of intrahippocampal administration of the eCB anandamide (ANA) on the sleep-waking cycle at two points of the light-dark cycle. Our data indicate that the administration of ANA directly into the hippocampus increases REMs in a dose dependent manner during the dark but not during the light phase of the cycle. The increase of REMs was blocked by the CB1 antagonist AM251. This effect was specific for the hippocampus since ANA administrations in the surrounding cortex did not elicit any change in REMs. These results support the idea of a direct relationship between hippocampal activity and sleep mechanisms by means of eCBs. The data presented here show, for the first time that eCBs administered into the hippocampus trigger REMs and support previous studies where chemical stimulation of limbic areas triggered sleep.

Wheel running improves REM sleep and attenuates stress-induced flattening of diurnal rhythms in F344 rats.

Science.gov (United States)

Thompson, Robert S; Roller, Rachel; Greenwood, Benjamin N; Fleshner, Monika

2016-05-01

Regular physical activity produces resistance to the negative health consequences of stressor exposure. One way that exercise may confer stress resistance is by reducing the impact of stress on diurnal rhythms and sleep; disruptions of which contribute to stress-related disease including mood disorders. Given the link between diurnal rhythm disruptions and stress-related disorders and that exercise both promotes stress resistance and is a powerful non-photic biological entrainment cue, we tested if wheel running could reduce stress-induced disruptions of sleep/wake behavior and diurnal rhythms. Adult, male F344 rats with or without access to running wheels were instrumented for biotelemetric recording of diurnal rhythms of locomotor activity, heart rate, core body temperature (CBT), and sleep (i.e. REM, NREM, and WAKE) in the presence of a 12 h light/dark cycle. Following 6 weeks of sedentary or exercise conditions, rats were exposed to an acute stressor known to disrupt diurnal rhythms and produce behaviors associated with mood disorders. Prior to stressor exposure, exercise rats had higher CBT, more locomotor activity during the dark cycle, and greater %REM during the light cycle relative to sedentary rats. NREM and REM sleep were consolidated immediately following peak running to a greater extent in exercise, compared to sedentary rats. In response to stressor exposure, exercise rats expressed higher stress-induced hyperthermia than sedentary rats. Stressor exposure disrupted diurnal rhythms in sedentary rats; and wheel running reduced these effects. Improvements in sleep and reduced diurnal rhythm disruptions following stress could contribute to the health promoting and stress protective effects of exercise.

Selective Inducible Nitric Oxide Synthase Inhibitor Reversed Zinc Chloride-Induced Spatial Memory Impairment via Increasing Cholinergic Marker Expression.

Science.gov (United States)

Tabrizian, Kaveh; Azami, Kian; Belaran, Maryam; Soodi, Maliheh; Abdi, Khosrou; Fanoudi, Sahar; Sanati, Mehdi; Mottaghi Dastjerdi, Negar; Soltany Rezaee-Rad, Mohammad; Sharifzadeh, Mohammad

2016-10-01

Zinc, an essential micronutrient and biochemical element of the human body, plays structural, catalytic, and regulatory roles in numerous physiological functions. In the current study, the effects of a pretraining oral administration of zinc chloride (10, 25, and 50 mg/kg) for 14 consecutive days and post-training bilateral intra-hippocampal infusion of 1400W as a selective inducible nitric oxide synthase (iNOS) inhibitor (10, 50, and 100 μM/side), alone and in combination, on the spatial memory retention in Morris water maze (MWM) were investigated. Animals were trained for 4 days and tested 48 h after completion of training. Also, the molecular effects of these compounds on the expression of choline acetyltransferase (ChAT), as a cholinergic marker in the CA1 region of the hippocampus and medial septal area (MSA), were evaluated. Behavioral and molecular findings of this study showed that a 2-week oral administration of zinc chloride (50 mg/kg) impaired spatial memory retention in MWM and decreased ChAT expression. Immunohistochemical analysis of post-training bilateral intra-hippocampal infusion of 1400W revealed a significant increase in ChAT immunoreactivity. Furthermore, post-training bilateral intra-hippocampal infusion of 1400W into the CA1 region of the hippocampus reversed zinc chloride-induced spatial memory impairment in MWM and significantly increased ChAT expression in comparison with zinc chloride-treated animals. Taken together, these results emphasize the role of selective iNOS inhibitors in reversing zinc chloride-induced spatial memory deficits via modulation of cholinergic marker expression.

Formation and Dynamics of Waves in a Cortical Model of Cholinergic Modulation.

Directory of Open Access Journals (Sweden)

James P Roach

2015-08-01

Full Text Available Acetylcholine (ACh is a regulator of neural excitability and one of the neurochemical substrates of sleep. Amongst the cellular effects induced by cholinergic modulation are a reduction in spike-frequency adaptation (SFA and a shift in the phase response curve (PRC. We demonstrate in a biophysical model how changes in neural excitability and network structure interact to create three distinct functional regimes: localized asynchronous, traveling asynchronous, and traveling synchronous. Our results qualitatively match those observed experimentally. Cortical activity during slow wave sleep (SWS differs from that during REM sleep or waking states. During SWS there are traveling patterns of activity in the cortex; in other states stationary patterns occur. Our model is a network composed of Hodgkin-Huxley type neurons with a M-current regulated by ACh. Regulation of ACh level can account for dynamical changes between functional regimes. Reduction of the magnitude of this current recreates the reduction in SFA the shift from a type 2 to a type 1 PRC observed in the presence of ACh. When SFA is minimal (in waking or REM sleep state, high ACh patterns of activity are localized and easily pinned by network inhomogeneities. When SFA is present (decreasing ACh, traveling waves of activity naturally arise. A further decrease in ACh leads to a high degree of synchrony within traveling waves. We also show that the level of ACh determines how sensitive network activity is to synaptic heterogeneity. These regimes may have a profound functional significance as stationary patterns may play a role in the proper encoding of external input as memory and traveling waves could lead to synaptic regularization, giving unique insights into the role and significance of ACh in determining patterns of cortical activity and functional differences arising from the patterns.

APhA 2011 REMS white paper: Summary of the REMS stakeholder meeting on improving program design and implementation.

Science.gov (United States)

American Pharmacists Association; Bough, Marcie

2011-01-01

To develop an improved risk evaluation and mitigation strategies (REMS) system for maximizing effective and safe patient medication use while minimizing burden on the health care delivery system. 34 stakeholders gathered October 6-7, 2010, in Arlington, VA, for the REMS Stakeholder Meeting, convened by the American Pharmacists Association (APhA). Participants included national health care provider associations, including representatives for physicians, physician assistants, nurses, nurse practitioners, and pharmacists, as well as representatives for patient advocates, drug distributors, community pharmacists (chain and independent), drug manufacturer associations (brand, generic, and biologic organizations), and health information technology, standards, and safety organizations. Staff from the Food and Drug Administration (FDA) Center for Drug Evaluation and Research participated as observers. The meeting built on themes from the APhA's 2009 REMS white paper. The current REMS environment presents many challenges for health care providers due to the growing number of REMS programs and the lack of standardization or similarities among various REMS programs. A standardized REMS process that focuses on maximizing patient safety and minimizing impacts on patient access and provider implementation could offset these challenges. A new process that includes effective provider interventions and standardized tools and systems for implementing REMS programs may improve patient care and overcome some of the communication issues providers and patients currently face. Metrics could be put in place to evaluate the effectiveness of REMS elements. By incorporating REMS program components into existing technologies and data infrastructures, achieving REMS implementation that is workflow neutral and minimizes administrative burden may be possible. An appropriate compensation model could ensure providers have adequate resources for patient care and REMS implementation. Overall

Melanin-concentrating hormone (MCH: role in REM sleep and depression

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Pablo eTorterolo

2015-12-01

Full Text Available The melanin-concentrating hormone (MCH is a peptidergic neuromodulator synthesized by neurons of the lateral hypothalamus and incerto-hypothalamic area. MCHergic neurons project throughout the central nervous system, including areas such as the dorsal (DR and median (MR raphe nuclei, which are involved in the control of sleep and mood.Major Depression (MD is a prevalent psychiatric disease diagnosed on the basis of symptomatic criteria such as sadness or melancholia, guilt, irritability and anhedonia. A short REM sleep latency (i.e. the interval between sleep onset and the first REM sleep period, as well as an increase in the duration of REM sleep and the density of rapid-eye movements during this state, are considered important biological markers of depression. The fact that the greatest firing rate of MCHergic neurons occurs during REM sleep and that optogenetic stimulation of these neurons induces sleep, tends to indicate that MCH plays a critical role in the generation and maintenance of sleep, especially REM sleep. In addition, the acute microinjection of MCH into the DR promotes REM sleep, while immunoneutralization of this peptide within the DR decreases the time spent in this state. Moreover, microinjections of MCH into either the DR or MR promote a depressive-like behavior. In the DR, this effect is prevented by the systemic administration of antidepressant drugs (either fluoxetine or nortriptyline and blocked by the intra-DR microinjection of a specific MCH receptor antagonist. Using electrophysiological and microdialysis techniques we demonstrated also that MCH decreases the activity of serotonergic DR neurons.Therefore, there are substantive experimental data suggesting that the MCHergic system plays a role in the control of REM sleep and, in addition, in the pathophysiology of depression. Consequently, in the present report, we summarize and evaluate the current data and hypotheses related to the role of MCH in REM sleep and MD.

Cholinergic-opioidergic interaction in the central amygdala induces antinociception in the guinea pig

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Leite-Panissi C.R.A.

2004-01-01

Full Text Available Several studies have demonstrated the involvement of the central nucleus of the amygdala (CEA in the modulation of defensive behavior and in antinociceptive regulation. In a previous study, we demonstrated the existence of a cholinergic-opioidergic interaction in the CEA, modulating the defensive response of tonic immobility in guinea pigs. In the present study, we investigated a similar interaction in the CEA, but now involved in the regulation of the nociceptive response. Microinjection of carbachol (2.7 nmol and morphine (2.2 nmol into the CEA promoted antinociception up to 45 min after microinjection in guinea pigs as determined by a decrease in the vocalization index in the vocalization test. This test consists of the application of a peripheral noxious stimulus (electric shock into the subcutaneous region of the thigh that provokes the emission of a vocalization response by the animal. Furthermore, the present results demonstrated that the antinociceptive effect of carbachol (2.7 nmol; N = 10 was blocked by previous administration of atropine (0.7 nmol; N = 7 or naloxone (1.3 nmol; N = 7 into the same site. In addition, the decrease in the vocalization index induced by the microinjection of morphine (2.2 nmol; N = 9 into the CEA was prevented by pretreatment with naloxone (1.3 nmol; N = 11. All sites of injection were confirmed by histology. These results indicate the involvement of the cholinergic and opioidergic systems of the CEA in the modulation of antinociception in guinea pigs. In addition, the present study suggests that cholinergic transmission may activate the release of endorphins/enkephalins from interneurons of the CEA, resulting in antinociception.

Hypocretinergic and cholinergic contributions to sleep-wake disturbances in a mouse model of traumatic brain injury

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Hannah E. Thomasy

2017-01-01

Full Text Available Disorders of sleep and wakefulness occur in the majority of individuals who have experienced traumatic brain injury (TBI, with increased sleep need and excessive daytime sleepiness often reported. Behavioral and pharmacological therapies have limited efficacy, in part, because the etiology of post-TBI sleep disturbances is not well understood. Severity of injuries resulting from head trauma in humans is highly variable, and as a consequence so are their sequelae. Here, we use a controlled laboratory model to investigate the effects of TBI on sleep-wake behavior and on candidate neurotransmitter systems as potential mediators. We focus on hypocretin and melanin-concentrating hormone (MCH, hypothalamic neuropeptides important for regulating sleep and wakefulness, and two potential downstream effectors of hypocretin actions, histamine and acetylcholine. Adult male C57BL/6 mice (n=6–10/group were implanted with EEG recording electrodes and baseline recordings were obtained. After baseline recordings, controlled cortical impact was used to induce mild or moderate TBI. EEG recordings were obtained from the same animals at 7 and 15 days post-surgery. Separate groups of animals (n=6–8/group were used to determine effects of TBI on the numbers of hypocretin and MCH-producing neurons in the hypothalamus, histaminergic neurons in the tuberomammillary nucleus, and cholinergic neurons in the basal forebrain. At 15 days post-TBI, wakefulness was decreased and NREM sleep was increased during the dark period in moderately injured animals. There were no differences between groups in REM sleep time, nor were there differences between groups in sleep during the light period. TBI effects on hypocretin and cholinergic neurons were such that more severe injury resulted in fewer cells. Numbers of MCH neurons and histaminergic neurons were not altered under the conditions of this study. Thus, we conclude that moderate TBI in mice reduces wakefulness and increases

Age-related changes in nicotine response of cholinergic and non-cholinergic laterodorsal tegmental neurons: implications for the heightened adolescent susceptibility to nicotine addiction

DEFF Research Database (Denmark)

Christensen, Mark Holm; Ishibashi, Masaru; Nielsen, Michael Linnemann

2014-01-01

The younger an individual starts smoking, the greater the likelihood that addiction to nicotine will develop, suggesting that neurobiological responses vary across age to the addictive component of cigarettes. Cholinergic neurons of the laterodorsal tegmental nucleus (LDT) are importantly involved...... in the development of addiction, however, the effects of nicotine on LDT neuronal excitability across ontogeny are unknown. Nicotinic effects on LDT cells across different age groups were examined using calcium imaging and whole-cell patch clamping. Within the youngest age group (P7–P15), nicotine induced larger...... intracellular calcium transients and inward currents. Nicotine induced a greater number of excitatory synaptic currents in the youngest animals, whereas larger amplitude inhibitory synaptic events were induced in cells from the oldest animals (P15–P34). Nicotine increased neuronal firing of cholinergic cells...

Dynamics of cholinergic function

International Nuclear Information System (INIS)

Hanin, I.

1986-01-01

This book presents information on the following topics; cholinergic pathways - anatomy of the central nervous system; aging, DSAT and other clinical conditions; cholinergic pre- and post-synaptic receptors; acetylcholine release; cholinesterases, anticholinesterases and reactivators; acetylcholine synthesis, metabolism and precursors; second messenger messenger mechanisms; interaction of acetylcholine with other neurotransmitter systems; cholinergic mechanisms in physiological function, including cardiovascular events; and neurotoxic agents and false transmitters

Cholinergic neuromodulation controls directed temporal communication in neocortex in vitro

Directory of Open Access Journals (Sweden)

Anita K Roopun

2010-03-01

Full Text Available Acetylcholine is the primary neuromodulator involved in cortical arousal in mammals. Cholinergic modulation is involved in conscious awareness, memory formation and attention – processes that involve intercommunication between different cortical regions. Such communication is achieved in part through temporal structuring of neuronal activity by population rhythms, particularly in the beta and gamma frequency ranges (12 – 80 Hz. Here we demonstrate, using in vitro and in silico models, that spectrally identical patterns of beta2 and gamma rhythms are generated in primary sensory areas and polymodal association areas by fundamentally different local circuit mechanisms: Glutamatergic excitation induced beta2 frequency population rhythms only in layer 5 association cortex whereas cholinergic neuromodulation induced this rhythm only in layer 5 primary sensory cortex. This region-specific sensitivity of local circuits to cholinergic modulation allowed for control of the extent of cortical temporal interactions. Furthermore, the contrasting mechanisms underlying these beta2 rhythms produced a high degree of directionality, favouring an influence of association cortex over primary auditory cortex.

Cholinergic Neuromodulation Controls Directed Temporal Communication in Neocortex in Vitro

Science.gov (United States)

Roopun, Anita K.; LeBeau, Fiona E.N.; Rammell, James; Cunningham, Mark O.; Traub, Roger D.; Whittington, Miles A.

2010-01-01

Acetylcholine is the primary neuromodulator involved in cortical arousal in mammals. Cholinergic modulation is involved in conscious awareness, memory formation and attention – processes that involve intercommunication between different cortical regions. Such communication is achieved in part through temporal structuring of neuronal activity by population rhythms, particularly in the beta and gamma frequency ranges (12–80 Hz). Here we demonstrate, using in vitro and in silico models, that spectrally identical patterns of beta2 and gamma rhythms are generated in primary sensory areas and polymodal association areas by fundamentally different local circuit mechanisms: Glutamatergic excitation induced beta2 frequency population rhythms only in layer 5 association cortex whereas cholinergic neuromodulation induced this rhythm only in layer 5 primary sensory cortex. This region-specific sensitivity of local circuits to cholinergic modulation allowed for control of the extent of cortical temporal interactions. Furthermore, the contrasting mechanisms underlying these beta2 rhythms produced a high degree of directionality, favouring an influence of association cortex over primary auditory cortex. PMID:20407636

Simulated Cholinergic Reinnervation of β (INS-1 Cells: Antidiabetic Utility of Heterotypic Pseudoislets Containing β Cell and Cholinergic Cell

Directory of Open Access Journals (Sweden)

Ao Jiao

2018-01-01

Full Text Available Cholinergic neurons can functionally support pancreatic islets in controlling blood sugar levels. However, in islet transplantation, the level of cholinergic reinnervation is significantly lower compared to orthotopic pancreatic islets. This abnormal reinnervation affects the survival and function of islet grafts. In this study, the cholinergic reinnervation of beta cells was simulated by 2D and 3D coculture of INS-1 and NG108-15 cells. In 2D culture conditions, 20 mM glucose induced a 1.24-fold increase (p<0.0001 in insulin secretion from the coculture group, while in the 3D culture condition, a 1.78-fold increase (p<0.0001 in insulin secretion from heterotypic pseudoislet group was observed. Glucose-stimulated insulin secretion (GSIS from 2D INS-1 cells showed minimal changes when compared to 3D structures. E-cadherin expressed in INS-1 and NG108-15 cells was the key adhesion molecule for the formation of heterotypic pseudoislets. NG108-15 cells hardly affected the proliferation of INS-1 cells in vitro. Heterotypic pseudoislet transplantation recipient mice reverted to normoglycemic levels faster and had a greater blood glucose clearance compared to INS-1 pseudoislet recipient mice. In conclusion, cholinergic cells can promote insulin-secreting cells to function better in vitro and in vivo and E-cadherin plays an important role in the formation of heterotypic pseudoislets.

Alpha reactivity to complex sounds differs during REM sleep and wakefulness.

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Perrine Ruby

Full Text Available We aimed at better understanding the brain mechanisms involved in the processing of alerting meaningful sounds during sleep, investigating alpha activity. During EEG acquisition, subjects were presented with a passive auditory oddball paradigm including rare complex sounds called Novels (the own first name - OWN, and an unfamiliar first name - OTHER while they were watching a silent movie in the evening or sleeping at night. During the experimental night, the subjects' quality of sleep was generally preserved. During wakefulness, the decrease in alpha power (8-12 Hz induced by Novels was significantly larger for OWN than for OTHER at parietal electrodes, between 600 and 900 ms after stimulus onset. Conversely, during REM sleep, Novels induced an increase in alpha power (from 0 to 1200 ms at all electrodes, significantly larger for OWN than for OTHER at several parietal electrodes between 700 and 1200 ms after stimulus onset. These results show that complex sounds have a different effect on the alpha power during wakefulness (decrease and during REM sleep (increase and that OWN induce a specific effect in these two states. The increased alpha power induced by Novels during REM sleep may 1 correspond to a short and transient increase in arousal; in this case, our study provides an objective measure of the greater arousing power of OWN over OTHER, 2 indicate a cortical inhibition associated with sleep protection. These results suggest that alpha modulation could participate in the selection of stimuli to be further processed during sleep.

INTRAHIPPOCAMPAL ADMINISTRATION OF IBOTENIC ACID INDUCED CHOLINERGIC DYSFUNCTION via NR2A/NR2B EXPRESSION: IMPLICATIONS OF RESVERATROL AGAINST ALZHEIMER DISEASE PATHOPHYSIOLOGY

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Chennakesavan eKarthick

2016-04-01

Full Text Available Although several drugs revealed moderate amelioration of symptoms, none of them have sufficient potency to prevent or reverse the progression towards Alzheimer’s disease (AD pathology. Resveratrol (RSV, a polyphenolic compound has shown an outstanding therapeutic effect on a broad spectrum of diseases like age-associated neurodegeneration, inflammation etc. The present study was thus conducted to assess the therapeutic efficacy of RSV in ameliorating the deleterious effects of Ibotenic acid (IBO in male Wistar rats. Stereotactic intrahippocampal administration of IBO (5µg/µl lesioned rats impairs cholinergic transmission, learning and memory performance that is rather related to AD and thus chosen as a suitable model to understand the drug efficacy in preventing AD pathophysiology. Since IBO is an agonist of glutamate, it is expected to exhibit an excitotoxic effect by altering glutamatergic receptors like NMDA receptor. The current study displayed significant alterations in the mRNA expression of NR2A and NR2B subunits of NMDA receptors, and further it is surprising to note that cholinergic receptors decreased in expression particularly α7-nAChR with increased m1AChR. RSV administration (20mg/kg body weight, i.p significantly reduced these changes in IBO induced rats. Glutamatergic and cholinergic receptor alterations were associated with significant changes in the behavioral parameters of rats induced by IBO. While RSV improved spatial learning performance, attenuated immobility and improvised open field activity in IBO induced rats. NR2B activation in the present study might mediate cell death through oxidative stress that form the basis of abnormal behavioral pattern in IBO induced rats. Interestingly, RSV that could efficiently encounter oxidative stress have significantly decreased stress markers viz., nitrite, PCO, and MDA levels by enhancing antioxidant status. Histopathological analysis displayed significant reduction in the

The muscarinic stimulation of phospholipid labeling in hippocampus is independent of its cholinergic input

International Nuclear Information System (INIS)

Fisher, S.K.; Boast, C.A.; Agranoff, B.W.

1980-01-01

The authors have examined the role of cholinergic innervation on the acetylcholine (ACh)-induced 'phospholipid labeling effect' (PLE) in synaptosomes derived from the hippocampus. The hippocampus supports a robust PLE and its sole cholinergic input from the septal nuclei can be readily disrupted by the placement of lesions in the fornix. The lesion is expected to cause degeneration of cholinergic presynaptic fibers, but should have little effect on the integrity of postsynaptic structures, and thus provide a means of further localizing the synaptosomal PLE. (Auth.)

Proposed man-rem reference values of occupational exposure

International Nuclear Information System (INIS)

Lombard, J.

1988-04-01

This report presents a proposal of referent collective dose (man-rem) values for occupational exposure related to operation of French pressurized water reactors. These values, permitting adequate choice of protection both at design and operation level, are dependent on the level of annual individual doses. The man-rem value, originating from annual individual doses less than 0.5 rem are estimated to 1 kf. The proposed value is 20 kf for annual individual exposures between 0.5 and 3 rem, and 90 kf for annual individual exposures between 3 and 5 rem. (author) [fr

REM-containing silicate concentrates

Science.gov (United States)

Pavlov, V. F.; Shabanova, O. V.; Pavlov, I. V.; Pavlov, M. V.; Shabanov, A. V.

2016-01-01

A new method of advanced complex processing of ores containing rare-earth elements (REE) is proposed to obtain porous X-ray amorphous aluminosilicate material with a stable chemical composition which concentrates oxides of rare-earth metals (REM). The ferromanganese oxide ores of Chuktukon deposit (Krasnoyarsk Region, RF) were used for the experiment. The obtained aluminosilicate material is appropriate for treatment with 5 - 15% solutions of mineral acids to leach REM.

REM-containing silicate concentrates

International Nuclear Information System (INIS)

Pavlov, V F; Shabanova, O V; Pavlov, I V; Pavlov, M V; Shabanov, A V

2016-01-01

A new method of advanced complex processing of ores containing rare-earth elements (REE) is proposed to obtain porous X-ray amorphous aluminosilicate material with a stable chemical composition which concentrates oxides of rare-earth metals (REM). The ferromanganese oxide ores of Chuktukon deposit (Krasnoyarsk Region, RF) were used for the experiment. The obtained aluminosilicate material is appropriate for treatment with 5 - 15% solutions of mineral acids to leach REM. (paper)

REM Sleep EEG Instability in REM Sleep Behavior Disorder and Clonazepam Effects.

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Ferri, Raffaele; Rundo, Francesco; Silvani, Alessandro; Zucconi, Marco; Bruni, Oliviero; Ferini-Strambi, Luigi; Plazzi, Giuseppe; Manconi, Mauro

2017-08-01

We aimed to analyze quantitatively rapid eye movement (REM) sleep electroencephalogram (EEG) in controls, drug-naïve idiopathic REM sleep behavior disorder patients (iRBD), and iRBD patients treated with clonazepam. Twenty-nine drug-naïve iRBD patients (mean age 68.2 years), 14 iRBD patients under chronic clonazepam therapy (mean age 66.3 years), and 21 controls (mean age 66.8 years) were recruited. Power spectra were obtained from sleep EEG (central derivation), using a 2-second sliding window, with 1-second steps. The power values of each REM sleep EEG spectral band (one every second) were normalized with respect to the average power value obtained during sleep stage 2 in the same individual. In drug-naïve patients, the normalized power values showed a less pronounced REM-related decrease of power in all bands with frequency sleep EEG structure changes found in this study disclose subtle but significant alterations in the cortical electrophysiology of RBD that might represent the early expression of the supposed neurodegenerative processes already taking place at this stage of the disease and might be the target of better and effective future therapeutic strategies for this condition. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

Activation of Phosphoinositide Metabolism by Cholinergic Agents.

Science.gov (United States)

1992-03-15

most notably calcium. Cholinergic agonist-induced seizures; Brain second messenger systems; Neurotransmitter/ Neuromodulator interactions; RAV; Lab...have been described: modulation by protein kinase C and modulation by neurotransmitter (or neuromodulator ) interactions. Agents which stimulate...phosphoinositide hydrolysis that has been identified consists of interactions among neurotransmitter systems or neuromodulators . Perhaps those most widely

A Neutron Rem Counter

Energy Technology Data Exchange (ETDEWEB)

Andersson, I Oe; Braun, J

1964-01-15

A neutron detector is described which measures the neutron dose rate in rem/h independently of the energy of the neutrons from thermal to 15 MeV. The detector consists of a BF{sub 3} proportional counter surrounded by a shield made of polyethylene and boron plastic that gives the appropriate amount of moderation and absorption to the impinging neutrons to obtain rem response. Two different versions have been developed. One model can utilize standard BF{sub 3} counters and is suitable for use in installed monitors around reactors and accelerators and the other model is specially designed for use in a portable survey instrument. The neutron rem counter for portable instruments has a sensitivity of 2.4 cps/mrem/h and is essentially nondirectional in response. With correct bias setting the counter is insensitive to gamma exposure up to 200 r/h from Co-60.

Posttraining Increases in REM Sleep Intensity Implicate REM Sleep in Memory Processing and Provide a Biological Marker of Learning Potential

Science.gov (United States)

Nader, Rebecca S.; Smith, Carlyle T.; Nixon, Margaret R.

2004-01-01

Posttraining rapid eye movement (REM) sleep has been reported to be important for efficient memory consolidation. The present results demonstrate increases in the intensity of REM sleep during the night of sleep following cognitive procedural/implicit task acquisition. These REM increases manifest as increases in total number of rapid eye…

The Cholinergic System Modulates Memory and Hippocampal Plasticity via Its Interactions with Non-Neuronal Cells

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Sara V. Maurer

2017-11-01

Full Text Available Degeneration of central cholinergic neurons impairs memory, and enhancement of cholinergic synapses improves cognitive processes. Cholinergic signaling is also anti-inflammatory, and neuroinflammation is increasingly linked to adverse memory, especially in Alzheimer’s disease. Much of the evidence surrounding cholinergic impacts on the neuroimmune system focuses on the α7 nicotinic acetylcholine (ACh receptor, as stimulation of this receptor prevents many of the effects of immune activation. Microglia and astrocytes both express this receptor, so it is possible that some cholinergic effects may be via these non-neuronal cells. Though the presence of microglia is required for memory, overactivated microglia due to an immune challenge overproduce inflammatory cytokines, which is adverse for memory. Blocking these exaggerated effects, specifically by decreasing the release of tumor necrosis factor α (TNF-α, interleukin 1β (IL-1β, and interleukin 6 (IL-6, has been shown to prevent inflammation-induced memory impairment. While there is considerable evidence that cholinergic signaling improves memory, fewer studies have linked the “cholinergic anti-inflammatory pathway” to memory processes. This review will summarize the current understanding of the cholinergic anti-inflammatory pathway as it relates to memory and will argue that one mechanism by which the cholinergic system modulates hippocampal memory processes is its influence on neuroimmune function via the α7 nicotinic ACh receptor.

Activation of the cholinergic anti-inflammatory pathway by nicotine ameliorates lipopolysaccharide-induced preeclampsia-like symptoms in pregnant rats.

Science.gov (United States)

Liu, Yuanyuan; Yang, Jinying; Bao, Junjie; Li, Xiaolan; Ye, Aihua; Zhang, Guozheng; Liu, Huishu

2017-01-01

Preeclampsia (PE) exerts a more intense systemic inflammatory response than normal pregnancy. Recently, the role of the cholinergic anti-inflammatory pathway (CAP) in regulating inflammation has been extensively studied. The aim of this study was to investigate the effect of nicotine, a selective cholinergic agonist, on lipopolysaccharide (LPS)-induced preeclampsia-like symptoms in pregnant rats and to determine the molecular mechanism underlying it. Rats were administered LPS (1.0 μg/kg) via tail vein injection on gestational day 14 to induce preeclampsia-like symptoms. Nicotine (1.0 mg/kg/d) and α-bungarotoxin (1.0 μg/kg/d) were injected subcutaneously into the rats from gestational day 14-19. Clinical symptoms were recorded. Serum and placentas were collected to determine cytokine levels using Luminex. The mRNA and protein expression levels of α7 nicotinic acetylcholine receptor (α7nAChR) were determined using Real time-PCR and Western blot analysis. Immunohistochemistry was performed to determine the level of activation of nuclear factor-κB (NF-κB) in placentas. Nicotine significantly ameliorated LPS-induced preeclampsia-like symptoms in pregnant rats (P preeclampsia (P preeclampsia rats. Our findings suggest that the activation of α7nAChR by nicotine attenuates preeclampsia-like symptoms, and this protective effect is likely the result of the inhibition of inflammation via the NF-κB p65 pathway. Copyright © 2016 Elsevier Ltd. All rights reserved.

Age-related changes in nicotine response of cholinergic and non-cholinergic laterodorsal tegmental neurons: implications for the heightened adolescent susceptibility to nicotine addiction

Science.gov (United States)

Christensen, Mark H.; Ishibashi, Masaru; Nielsen, Michael L.; Leonard, Christopher S.; Kohlmeier, Kristi A.

2015-01-01

The younger an individual starts smoking, the greater the likelihood that addiction to nicotine will develop, suggesting that neurobiological responses vary across age to the addictive component of cigarettes. Cholinergic neurons of the laterodorsal tegmental nucleus (LDT) are importantly involved in the development of addiction, however, the effects of nicotine on LDT neuronal excitability across ontogeny are unknown. Nicotinic effects on several parameters affecting LDT cells across different age groups were examined using calcium imaging and whole-cell patch clamping. Within the youngest age group (P7-P15), nicotine was found to induce larger intracellular calcium transients and inward currents. Nicotine induced a greater number of excitatory synaptic currents in the youngest animals, whereas larger amplitude inhibitory synaptic events were induced in cells from the oldest animals (P15-P34). Nicotine increased neuronal firing of cholinergic cells to a greater degree in younger animals, possibly linked to development associated differences found in nicotinic effects on action potential shape and afterhyperpolarization. We conclude that in addition to age-associated alterations of several properties expected to affect resting cell excitability, parameters affecting cell excitability are altered by nicotine differentially across ontogeny. Taken together, our data suggest that nicotine induces a larger excitatory response in cholinergic LDT neurons from the youngest animals, which could result in a greater excitatory output from these cells to target regions involved in development of addiction. Such output would be expected to be promotive of addiction; therefore, ontogenetic differences in nicotine-mediated increases in the excitability of the LDT could contribute to the differential susceptibility to nicotine addiction seen across age. PMID:24863041

Acetylcholine receptors and cholinergic ligands: biochemical and genetic aspects in Torpedo californica and Drosophila melanogaster

International Nuclear Information System (INIS)

Rosenthal, L.S.

1987-01-01

This study evaluates the biochemical and genetic aspects of the acetylcholine receptor proteins and cholinergic ligands in Drosophila melanogaster and Torpedo californica. Included are (1) a comparative study of nicotinic ligand-induced cation release from acetylcholine receptors isolated from Torpedo californica and from Drosophila melanogaster, (2) solution studies of the cholinergic ligands, nikethamide and ethamivan, aimed at measuring internal molecular rotational barriers in solvents of different polarity; and (3) the isolation and characterization of the gene(s) for the acetylcholine receptor in Drosophila melasogaster. Acetylcholine receptor proteins isolated from Drosphila melanogaster heads were found to behave kinetically similar (with regards to cholinergic ligand-induced 155 Eu: 3+ displacement from prelabeled proteins) to receptor proteins isolated from Torpedo californica electric tissue, providing additional biochemical evidence for the existence of a Drosophila acetylcholine receptor

RemBench: A Digital Workbench for Rembrandt Research

NARCIS (Netherlands)

Verberne, Suzan; Van Leeuwen, Rudie; Gerritsen, G.H.; Boves, Lou

2016-01-01

In this paper, we present RemBench, a search engine for research into the life and works of Rembrandt van Rijn. RemBench combines the data from four different databases behind one interface using federated search technology. Metadata filtering is enabled through faceted search. RemBench enables art

Chaoborus and gasterosteus anti-predator responses in Daphnia pulex are mediated by independent cholinergic and gabaergic neuronal signals.

Directory of Open Access Journals (Sweden)

Linda C Weiss

Full Text Available Many prey species evolved inducible defense strategies that protect effectively against predation threats. Especially the crustacean Daphnia emerged as a model system for studying the ecology and evolution of inducible defenses. Daphnia pulex e.g. shows different phenotypic adaptations against vertebrate and invertebrate predators. In response to the invertebrate phantom midge larvae Chaoborus (Diptera D. pulex develops defensive morphological defenses (neckteeth. Cues originating from predatory fish result in life history changes in which resources are allocated from somatic growth to reproduction. While there are hints that responses against Chaoborus cues are transmitted involving cholinergic neuronal pathways, nothing is known about the neurophysiology underlying the transmission of fish related cues. We investigated the neurophysiological basis underlying the activation of inducible defenses in D. pulex using induction assays with the invertebrate predator Chaoborus and the three-spined stickleback Gasterosteus aculeatus. Predator-specific cues were combined with neuro-effective substances that stimulated or inhibited the cholinergic and gabaergic nervous system. We show that cholinergic-dependent pathways are involved in the perception and transmission of Chaoborus cues, while GABA was not involved. Thus, the cholinergic nervous system independently mediates the development of morphological defenses in response to Chaoborus cues. In contrast, only the inhibitory effect of GABA significantly influence fish-induced life history changes, while the application of cholinergic stimulants had no effect in combination with fish related cues. Our results show that cholinergic stimulation mediates signal transmission of Chaoborus cues leading to morphological defenses. Fish cues, which are responsible for predator-specific life history adaptations involve gabaergic control. Our study shows that both pathways are independent and thus potentially

TASK Channels on Basal Forebrain Cholinergic Neurons Modulate Electrocortical Signatures of Arousal by Histamine.

Science.gov (United States)

Vu, Michael T; Du, Guizhi; Bayliss, Douglas A; Horner, Richard L

2015-10-07

Basal forebrain cholinergic neurons are the main source of cortical acetylcholine, and their activation by histamine elicits cortical arousal. TWIK-like acid-sensitive K(+) (TASK) channels modulate neuronal excitability and are expressed on basal forebrain cholinergic neurons, but the role of TASK channels in the histamine-basal forebrain cholinergic arousal circuit is unknown. We first expressed TASK channel subunits and histamine Type 1 receptors in HEK cells. Application of histamine in vitro inhibited the acid-sensitive K(+) current, indicating a functionally coupled signaling mechanism. We then studied the role of TASK channels in modulating electrocortical activity in vivo using freely behaving wild-type (n = 12) and ChAT-Cre:TASK(f/f) mice (n = 12), the latter lacking TASK-1/3 channels on cholinergic neurons. TASK channel deletion on cholinergic neurons significantly altered endogenous electroencephalogram oscillations in multiple frequency bands. We then identified the effect of TASK channel deletion during microperfusion of histamine into the basal forebrain. In non-rapid eye movement sleep, TASK channel deletion on cholinergic neurons significantly attenuated the histamine-induced increase in 30-50 Hz activity, consistent with TASK channels contributing to histamine action on basal forebrain cholinergic neurons. In contrast, during active wakefulness, histamine significantly increased 30-50 Hz activity in ChAT-Cre:TASK(f/f) mice but not wild-type mice, showing that the histamine response depended upon the prevailing cortical arousal state. In summary, we identify TASK channel modulation in response to histamine receptor activation in vitro, as well as a role of TASK channels on cholinergic neurons in modulating endogenous oscillations in the electroencephalogram and the electrocortical response to histamine at the basal forebrain in vivo. Attentive states and cognitive function are associated with the generation of γ EEG activity. Basal forebrain

REM behaviour disorder detection associated with neurodegenerative diseases

DEFF Research Database (Denmark)

Kempfner, Jacob; Sorensen, Gertrud; Zoetmulder, Marielle

2010-01-01

Abnormal skeleton muscle activity during REM sleep is characterized as REM Behaviour Disorder (RBD), and may be an early marker for different neurodegenerative diseases. Early detection of RBD is therefore highly important, and in this ongoing study a semi-automatic method for RBD detection......, a computerized algorithm has been attempted implemented. By analysing the REM and non-REM EMG activity, using advanced signal processing tools combined with a statistical classifier, it is possible to discriminate normal and abnormal EMG activity. Due to the small number of patients, the overall performance...

Selective REM Sleep Deprivation Improves Expectation-Related Placebo Analgesia.

Science.gov (United States)

Chouchou, Florian; Chauny, Jean-Marc; Rainville, Pierre; Lavigne, Gilles J

2015-01-01

The placebo effect is a neurobiological and psychophysiological process known to influence perceived pain relief. Optimization of placebo analgesia may contribute to the clinical efficacy and effectiveness of medication for acute and chronic pain management. We know that the placebo effect operates through two main mechanisms, expectations and learning, which is also influenced by sleep. Moreover, a recent study suggested that rapid eye movement (REM) sleep is associated with modulation of expectation-mediated placebo analgesia. We examined placebo analgesia following pharmacological REM sleep deprivation and we tested the hypothesis that relief expectations and placebo analgesia would be improved by experimental REM sleep deprivation in healthy volunteers. Following an adaptive night in a sleep laboratory, 26 healthy volunteers underwent classical experimental placebo analgesic conditioning in the evening combined with pharmacological REM sleep deprivation (clonidine: 13 volunteers or inert control pill: 13 volunteers). Medication was administered in a double-blind manner at bedtime, and placebo analgesia was tested in the morning. Results revealed that 1) placebo analgesia improved with REM sleep deprivation; 2) pain relief expectations did not differ between REM sleep deprivation and control groups; and 3) REM sleep moderated the relationship between pain relief expectations and placebo analgesia. These results support the putative role of REM sleep in modulating placebo analgesia. The mechanisms involved in these improvements in placebo analgesia and pain relief following selective REM sleep deprivation should be further investigated.

Cholinergic Neurons in the Basal Forebrain Promote Wakefulness by Actions on Neighboring Non-Cholinergic Neurons: An Opto-Dialysis Study.

Science.gov (United States)

Zant, Janneke C; Kim, Tae; Prokai, Laszlo; Szarka, Szabolcs; McNally, James; McKenna, James T; Shukla, Charu; Yang, Chun; Kalinchuk, Anna V; McCarley, Robert W; Brown, Ritchie E; Basheer, Radhika

2016-02-10

Understanding the control of sleep-wake states by the basal forebrain (BF) poses a challenge due to the intermingled presence of cholinergic, GABAergic, and glutamatergic neurons. All three BF neuronal subtypes project to the cortex and are implicated in cortical arousal and sleep-wake control. Thus, nonspecific stimulation or inhibition studies do not reveal the roles of these different neuronal types. Recent studies using optogenetics have shown that "selective" stimulation of BF cholinergic neurons increases transitions between NREM sleep and wakefulness, implicating cholinergic projections to cortex in wake promotion. However, the interpretation of these optogenetic experiments is complicated by interactions that may occur within the BF. For instance, a recent in vitro study from our group found that cholinergic neurons strongly excite neighboring GABAergic neurons, including the subset of cortically projecting neurons, which contain the calcium-binding protein, parvalbumin (PV) (Yang et al., 2014). Thus, the wake-promoting effect of "selective" optogenetic stimulation of BF cholinergic neurons could be mediated by local excitation of GABA/PV or other non-cholinergic BF neurons. In this study, using a newly designed opto-dialysis probe to couple selective optical stimulation with simultaneous in vivo microdialysis, we demonstrated that optical stimulation of cholinergic neurons locally increased acetylcholine levels and increased wakefulness in mice. Surprisingly, the enhanced wakefulness caused by cholinergic stimulation was abolished by simultaneous reverse microdialysis of cholinergic receptor antagonists into BF. Thus, our data suggest that the wake-promoting effect of cholinergic stimulation requires local release of acetylcholine in the basal forebrain and activation of cortically projecting, non-cholinergic neurons, including the GABAergic/PV neurons. Optogenetics is a revolutionary tool to assess the roles of particular groups of neurons in behavioral

Basal Forebrain Cholinergic Deficits Reduce Glucose Metabolism and Function of Cholinergic and GABAergic Systems in the Cingulate Cortex.

Science.gov (United States)

Jeong, Da Un; Oh, Jin Hwan; Lee, Ji Eun; Lee, Jihyeon; Cho, Zang Hee; Chang, Jin Woo; Chang, Won Seok

2016-01-01

Reduced brain glucose metabolism and basal forebrain cholinergic neuron degeneration are common features of Alzheimer's disease and have been correlated with memory function. Although regions representing glucose hypometabolism in patients with Alzheimer's disease are targets of cholinergic basal forebrain neurons, the interaction between cholinergic denervation and glucose hypometabolism is still unclear. The aim of the present study was to evaluate glucose metabolism changes caused by cholinergic deficits. We lesioned basal forebrain cholinergic neurons in rats using 192 immunoglobulin G-saporin. After 3 weeks, lesioned animals underwent water maze testing or were analyzed by ¹⁸F-2-fluoro-2-deoxyglucose positron emission tomography. During water maze probe testing, performance of the lesioned group decreased with respect to time spent in the target quadrant and platform zone. Cingulate cortex glucose metabolism in the lesioned group decreased, compared with the normal group. Additionally, acetylcholinesterase activity and glutamate decarboxylase 65/67 expression declined in the cingulate cortex. Our results reveal that spatial memory impairment in animals with selective basal forebrain cholinergic neuron damage is associated with a functional decline in the GABAergic and cholinergic system associated with cingulate cortex glucose hypometabolism.

Estrogen-cholinergic interactions: Implications for cognitive aging.

Science.gov (United States)

Newhouse, Paul; Dumas, Julie

2015-08-01

This article is part of a Special Issue "Estradiol and Cognition". While many studies in humans have investigated the effects of estrogen and hormone therapy on cognition, potential neurobiological correlates of these effects have been less well studied. An important site of action for estrogen in the brain is the cholinergic system. Several decades of research support the critical role of CNS cholinergic systems in cognition in humans, particularly in learning and memory formation and attention. In humans, the cholinergic system has been implicated in many aspects of cognition including the partitioning of attentional resources, working memory, inhibition of irrelevant information, and improved performance on effort-demanding tasks. Studies support the hypothesis that estradiol helps to maintain aspects of attention and verbal and visual memory. Such cognitive domains are exactly those modulated by cholinergic systems and extensive basic and preclinical work over the past several decades has clearly shown that basal forebrain cholinergic systems are dependent on estradiol support for adequate functioning. This paper will review recent human studies from our laboratories and others that have extended preclinical research examining estrogen-cholinergic interactions to humans. Studies examined include estradiol and cholinergic antagonist reversal studies in normal older women, examinations of the neural representations of estrogen-cholinergic interactions using functional brain imaging, and studies of the ability of selective estrogen receptor modulators such as tamoxifen to interact with cholinergic-mediated cognitive performance. We also discuss the implications of these studies for the underlying hypotheses of cholinergic-estrogen interactions and cognitive aging, and indications for prophylactic and therapeutic potential that may exploit these effects. Published by Elsevier Inc.

Impaired social interaction and enhanced sensitivity to phencyclidine-induced deficits in novel object recognition in rats with cortical cholinergic denervation.

Science.gov (United States)

Savage, S; Kehr, J; Olson, L; Mattsson, A

2011-11-10

Dysregulated cholinergic neurotransmission has been implicated in the pathophysiology of schizophrenia, particularly negative symptoms and cognitive deficits. The aim of the present study was to evaluate the role of neocortical cholinergic innervation and of the N-methyl-d-aspartate (NMDA) receptor antagonist phencyclidine (PCP) on social interaction and novel object recognition (NOR), a declarative memory task. The cholinergic corticopetal projection was lesioned by local infusion of the immunotoxin 192 IgG-saporin into nucleus basalis magnocellularis of adult male Lister hooded rats. Behavior was assessed 2.5 weeks later in a social interaction paradigm followed by the NOR task. We found that selective cholinergic denervation of neocortex led to a significant reduction in duration of social interaction, specifically active social interaction. Acute administration of PCP (1.0 mg/kg, s.c.) caused a marked decrease of active social interaction, such that there was no longer a difference between intact and denervated animals. Neither cholinergic denervation alone, nor PCP (1.0 mg/kg, s.c.) alone blocked the ability of rats to recognize a novel object. However, when animals lacking cortical cholinergic innervation were challenged by PCP, they were no longer able to recognize a novel object. This study indicates that rats lacking cholinergic innervation of neocortex have impaired social interaction and specifically that the duration of active contact is shortened. Animals with severe cortical cholinergic hypofunction maintain the ability to perform in a declarative memory test, although the task is carried out less intensively. However, a provocation of psychosis-like behavior by a dose of PCP that does not by itself impair performance in normal animals, will abolish the ability to recognize novel objects in animals lacking cortical cholinergic innervation. The present findings support a possible role for cortical cholinergic hypofunction in the negative and cognitive

A methodology for costing man-rem

International Nuclear Information System (INIS)

Bieber, C.

1976-03-01

An attempt is made to provide a methodology for costing man-rem in a way that can be applied to station conditions, based on 1974 Pickering G.S. data. Factors taken into account were social costs, exposure costs (dose accounting, training, dosimetry) temporary labour costs, and permanent replacement labour costs. A figure of $620/ man-rem was derived. (LL)

Levels of Interference in Long and Short-Term Memory Differentially Modulate Non-REM and REM Sleep.

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Fraize, Nicolas; Carponcy, Julien; Joseph, Mickaël Antoine; Comte, Jean-Christophe; Luppi, Pierre-Hervé; Libourel, Paul-Antoine; Salin, Paul-Antoine; Malleret, Gaël; Parmentier, Régis

2016-12-01

It is commonly accepted that sleep is beneficial to memory processes, but it is still unclear if this benefit originates from improved memory consolidation or enhanced information processing. It has thus been proposed that sleep may also promote forgetting of undesirable and non-essential memories, a process required for optimization of cognitive resources. We tested the hypothesis that non-rapid eye movement sleep (NREMS) promotes forgetting of irrelevant information, more specifically when processing information in working memory (WM), while REM sleep (REMS) facilitates the consolidation of important information. We recorded sleep patterns of rats trained in a radial maze in three different tasks engaging either the long-term or short-term storage of information, as well as a gradual level of interference. We observed a transient increase in REMS amount on the day the animal learned the rule of a long-term/reference memory task (RM), and, in contrast, a positive correlation between the performance of rats trained in a WM task involving an important processing of interference and the amount of NREMS or slow wave activity. Various oscillatory events were also differentially modulated by the type of training involved. Notably, NREMS spindles and REMS rapid theta increase with RM training, while sharp-wave ripples increase with all types of training. These results suggest that REMS, but also rapid oscillations occurring during NREMS would be specifically implicated in the long-term memory in RM, whereas NREMS and slow oscillations could be involved in the forgetting of irrelevant information required for WM. © 2016 Associated Professional Sleep Societies, LLC.

Obstructive Sleep Apnea during REM Sleep and Cardiovascular Disease.

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Aurora, R Nisha; Crainiceanu, Ciprian; Gottlieb, Daniel J; Kim, Ji Soo; Punjabi, Naresh M

2018-03-01

Obstructive sleep apnea (OSA) during REM sleep is a common disorder. Data on whether OSA that occurs predominantly during REM sleep is associated with health outcomes are limited. The present study examined the association between OSA during REM sleep and a composite cardiovascular endpoint in a community sample with and without prevalent cardiovascular disease. Full-montage home polysomnography was conducted as part of the Sleep Heart Health Study. The study cohort was followed for an average of 9.5 years, during which time cardiovascular events were assessed. Only participants with a non-REM apnea-hypopnea index (AHI) of less than 5 events/h were included. A composite cardiovascular endpoint was determined as the occurrence of nonfatal or fatal events, including myocardial infarction, coronary artery revascularization, congestive heart failure, and stroke. Proportional hazards regression was used to derive the adjusted hazards ratios for the composite cardiovascular endpoint. The sample consisted of 3,265 subjects with a non-REM AHI of less than 5.0 events/h. Using a REM AHI of less than 5.0 events/h as the reference group (n = 1,758), the adjusted hazards ratios for the composite cardiovascular endpoint in those with severe REM OSA (≥30 events/h; n = 180) was 1.35 (95% confidence interval, 0.98-1.85). Stratified analyses demonstrated that the association was most notable in those with prevalent cardiovascular disease and severe OSA during REM sleep with an adjusted hazards ratio of 2.56 (95% confidence interval, 1.46-4.47). Severe OSA that occurs primarily during REM sleep is associated with higher incidence of a composite cardiovascular endpoint, but in only those with prevalent cardiovascular disease.

Role of the thalamic parafascicular nucleus cholinergic system in the modulation of acute corneal nociception in rats

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Esmaeal Tamaddonfard

2011-11-01

Full Text Available The present study investigated the effects of microinjections of acetylcholine (a cholinergic agonist, physostigmine (a cholinesterase inhibitor, atropine (an antagonist of muscarinic cholinergic receptors and hexamethonium (an antagonist of nicotinic cholinergic receptors into the parafascicular nucleus of thalamus on the acute corneal nociception in rats. Acute corneal nociception was induced by putting a drop of 5 M NaCl solution onto the corneal surface of the eye and the number of eye wipes was counted during the first 30s. Both acetylcholine and physostigmine at the same doses of 0.5, 1 and 2 μg significantly (P < 0.05 reduced the number of eye wipes. The intensity of corneal nociception was not changed when atropine and hexamethonium were used alone. Atropine (4 μg, but not hexamethonium (4 μg significantly (P < 0.05 prevented acetylcholine (2 μg- and physostigmine (2 μg-induced antinociceptive effects. The results indicated that at the level of the parafascicular nucleus of thalamus, the muscarinic cholinergic receptors might be involved in the antinociceptive effects of acetylcholine and physostigmine.

Why REM sleep? Clues beyond the laboratory in a more challenging world.

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Horne, Jim

2013-02-01

REM sleep (REM) seems more likely to prepare for ensuing wakefulness rather than provides recovery from prior wakefulness, as happens with 'deeper' nonREM. Many of REM's characteristics are 'wake-like' (unlike nonREM), including several common to feeding. These, with recent findings outside sleep, provide perspectives on REM beyond those from the laboratory. REM can interchange with a wakefulness involving motor output, indicating that REM's atonia is integral to its function. Wakefulness for 'wild' mammals largely comprises exploration; a complex opportunistic behaviour mostly for foraging, involving: curiosity, minimising risks, (emotional) coping, navigation, when (including circadian timing) to investigate new destinations; all linked to 'purposeful, goal directed movement'. REM reflects these adaptive behaviours (including epigenesis), masked in laboratories having constrained, safe, unchanging, unchallenging, featureless, exploration-free environments with ad lib food. Similarly masked may be REM's functions for today's humans living safe, routine lives, with easy food accessibility. In these respects animal and human REM studies are not sufficiently 'ecological'. Copyright © 2012 Elsevier B.V. All rights reserved.

The role of muscarinic cholinergic signaling in cost-benefit decision making

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Fobbs, Wambura

Animals regularly face decisions that affect both their immediate success and long term survival. Such decisions typically involve some form of cost-benefit analysis and engage a number of high level cognitive processes, including learning, memory and motivational influences. While decision making has been a focus of study for over a century, it's only in the last 20 years that researchers have begun to identify functional neural circuits that subserve different forms of cost-benefit decision making. Even though the cholinergic system is both functionally and anatomically positioned to modulate cost-benefit decision circuits, the contribution of the cholinergic system to decision making has been little studied. In this thesis, I investigated the cognitive and neural contribution of muscarinic cholinergic signaling to cost-benefit decision making. I, first, re-examined the effects of systemic administration of 0.3 mg/kg atropine on delay and probability discounting tasks and found that blockade of muscarinic acetylcholine receptors by atropine induced suboptimal choices (impulsive and risky) in both tasks. Since the effect on delay discounting was restricted to the No Cue version of the delay discounting task, I concluded that muscarinic cholinergic signaling mediates both forms of cost-benefit decision making and is selectively engaged when decisions require valuation of reward options whose costs are not externally signified. Second, I assessed the impact of inactivating the nucleus basalis (NBM) on both forms decision making and the effect of injecting atropine locally into the orbitofrontal cortex (OFC), basolateral amygdala (BLA), or nucleus accumbens (NAc) core during the No Cue version of the delay discounting task. I discovered that although NBM inactivation failed to affect delay discounting, it induced risk aversion in the probability discounting task; and blockade of intra- NAc core, but not intra-OFC or intra-BLA, muscarinic cholinergic signaling lead to

REM sleep estimation only using respiratory dynamics

International Nuclear Information System (INIS)

Chung, Gih Sung; Choi, Byung Hoon; Lee, Jeong Su; Lee, Jin-Seong; Jeong, Do-Un; Park, Kwang Suk

2009-01-01

Polysomnography (PSG) is currently considered the gold standard for assessing sleep quality. However, the numerous sensors that must be attached to the subject can disturb sleep and limit monitoring to within hospitals and sleep clinics. If data could be obtained without such constraints, sleep monitoring would be more convenient and could be extended to ordinary homes. During rapid-eye-movement (REM) sleep, respiration rate and variability are known to be greater than in other sleep stages. Hence, we calculated the average rate and variability of respiration in an epoch (30 s) by applying appropriate smoothing algorithms. Increased and irregular respiratory patterns during REM sleep were extracted using adaptive and linear thresholds. When both parameters simultaneously showed higher values than the thresholds, the epochs were assumed to belong to REM sleep. Thermocouples and piezoelectric-type belts were used to acquire respiratory signals. Thirteen healthy adults and nine obstructive sleep apnea (OSA) patients participated in this study. Kappa statistics showed a substantial agreement (κ > 0.60) between the standard and respiration-based methods. One-way ANOVA analysis showed no significant difference between the techniques for total REM sleep. This approach can also be applied to the non-intrusive measurement of respiration signals, making it possible to automatically detect REM sleep without disturbing the subject

Why does serotonergic activity drastically decrease during REM sleep?

Science.gov (United States)

Sato, Kohji

2013-10-01

Here, I postulate two hypotheses that can explain the missing link between sleep and the serotonergic system in terms of spine homeostasis and memory consolidation. As dendritic spines contain many kinds of serotonin receptors, and the activation of serotonin receptors generally increases the number of spines in the cortex and hippocampus, I postulate that serotonin neurons are down-regulated during sleep to decrease spine number, which consequently maintains the total spine number at a constant level. Furthermore, since synaptic consolidation during REM sleep needs long-term potentiation (LTP), and serotonin is reported to inhibit LTP in the cortex, I postulate that serotonergic activity must drastically decrease during REM sleep to induce LTP and do memory consolidation. Until now, why serotonergic neurons show these dramatic changes in the sleep-wake cycle remains unexplained; however, making these hypotheses, I can confer physiological meanings on these dramatic changes of serotonergic neurons in terms of spine homeostasis and memory consolidation. Copyright © 2013. Published by Elsevier Ltd.

Management of REM sleep behavior disorder: An evidence based review

OpenAIRE

Preeti Devnani; Racheal Fernandes

2015-01-01

Rapid eye movement (REM) sleep behavior disorder (RBD) is characterized by dream enactment behavior resulting from a loss of REM skeletal muscle atonia. The neurobiology of REM sleep and the characteristic features of REM atonia have an important basis for understanding the aggravating etiologies the proposed pharmacological interventions in its management. This review outlines the evidence for behavioral and therapeutic measures along with evidence-based guidelines for their implementation, ...

Auditory Verbal Experience and Agency in Waking, Sleep Onset, REM, and Non-REM Sleep.

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Speth, Jana; Harley, Trevor A; Speth, Clemens

2017-04-01

We present one of the first quantitative studies on auditory verbal experiences ("hearing voices") and auditory verbal agency (inner speech, and specifically "talking to (imaginary) voices or characters") in healthy participants across states of consciousness. Tools of quantitative linguistic analysis were used to measure participants' implicit knowledge of auditory verbal experiences (VE) and auditory verbal agencies (VA), displayed in mentation reports from four different states. Analysis was conducted on a total of 569 mentation reports from rapid eye movement (REM) sleep, non-REM sleep, sleep onset, and waking. Physiology was controlled with the nightcap sleep-wake mentation monitoring system. Sleep-onset hallucinations, traditionally at the focus of scientific attention on auditory verbal hallucinations, showed the lowest degree of VE and VA, whereas REM sleep showed the highest degrees. Degrees of different linguistic-pragmatic aspects of VE and VA likewise depend on the physiological states. The quantity and pragmatics of VE and VA are a function of the physiologically distinct state of consciousness in which they are conceived. Copyright © 2016 Cognitive Science Society, Inc.

[Modulation of the cholinergic system during inflammation].

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Nezhinskaia, G I; Vladykin, A L; Sapronov, N S

2008-01-01

This review describes the effects of realization of the central and peripheral "cholinergic antiinflammatory pathway" in a model of endotoxic and anaphylactic shock. Under endotoxic shock conditions, a pharmacological correction by means of the central m-cholinomimetic action (electrical stimulation of the distal ends of nervus vagus after bilateral cervical vagotomy, surgical implantation of the stimulant devise, activation of efferent vagal neurons by means of muscarinic agonist) is directed toward the elimination of LPS-induced hypotension. During the anaphylaxis, peripheral effects of the cholinergic system induced by blocking m-AChR on the target cells (neuronal and non-neuronal lung cells) and acetylcholinesterase inhibition are related to suppression of the bronchoconstrictor response. The role of immune system in the pathogenesis of endotoxic shock is associated with the production of proinflammatory cytokines by macrophages, increase in IgM concentration, and complement activation, while the role in the pathogenesis of anaphylactic shock is associated with IgE, IgG1 augmentation. Effects of B cell stimulation may be important in hypoxia and in the prophylaxis of stress ulcers and other diseases. Plasma proteins can influence the effects of the muscarinic antagonist methacine: IgG enhance its action while albumin and CRP abolish it.

Striatal cholinergic interneurons and D2 receptor-expressing GABAergic medium spiny neurons regulate tardive dyskinesia.

Science.gov (United States)

Bordia, Tanuja; Zhang, Danhui; Perez, Xiomara A; Quik, Maryka

2016-12-01

Tardive dyskinesia (TD) is a drug-induced movement disorder that arises with antipsychotics. These drugs are the mainstay of treatment for schizophrenia and bipolar disorder, and are also prescribed for major depression, autism, attention deficit hyperactivity, obsessive compulsive and post-traumatic stress disorder. There is thus a need for therapies to reduce TD. The present studies and our previous work show that nicotine administration decreases haloperidol-induced vacuous chewing movements (VCMs) in rodent TD models, suggesting a role for the nicotinic cholinergic system. Extensive studies also show that D2 dopamine receptors are critical to TD. However, the precise involvement of striatal cholinergic interneurons and D2 medium spiny neurons (MSNs) in TD is uncertain. To elucidate their role, we used optogenetics with a focus on the striatum because of its close links to TD. Optical stimulation of striatal cholinergic interneurons using cholineacetyltransferase (ChAT)-Cre mice expressing channelrhodopsin2-eYFP decreased haloperidol-induced VCMs (~50%), with no effect in control-eYFP mice. Activation of striatal D2 MSNs using Adora2a-Cre mice expressing channelrhodopsin2-eYFP also diminished antipsychotic-induced VCMs, with no change in control-eYFP mice. In both ChAT-Cre and Adora2a-Cre mice, stimulation or mecamylamine alone similarly decreased VCMs with no further decline with combined treatment, suggesting nAChRs are involved. Striatal D2 MSN activation in haloperidol-treated Adora2a-Cre mice increased c-Fos + D2 MSNs and decreased c-Fos + non-D2 MSNs, suggesting a role for c-Fos. These studies provide the first evidence that optogenetic stimulation of striatal cholinergic interneurons and GABAergic MSNs modulates VCMs, and thus possibly TD. Moreover, they suggest nicotinic receptor drugs may reduce antipsychotic-induced TD. Copyright © 2016 Elsevier Inc. All rights reserved.

The role of REM theta activity in emotional memory

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Isabel Camilla Hutchison

2015-10-01

Full Text Available While NREM sleep has been strongly implicated in the reactivation and consolidation of memory traces, the role of REM sleep remains unclear. A growing body of research on humans and animals provide behavioral evidence for a role of REM sleep in the strengthening and modulation of emotional memories. Theta activity – which describes low frequency oscillations in the local field potential within the hippocampus, amygdala and neocortex – is a prominent feature of both wake and REM sleep in humans and rodents. Theta coherence between the hippocampus and amygdala drives large-scale PGO waves, the density of which predicts increases in plasticity-related gene expression. This could potentially facilitate the processing of emotional memory traces within the hippocampus during REM sleep. Further, the timing of hippocampal activity in relation to theta phase is vital in determining subsequent potentiation of neuronal activity. This could allow the emotionally modulated strengthening of novel and the gradual weakening of consolidated hippocampal memory traces observed in both wake and REM sleep. Hippocampal theta activity is also correlated with REM sleep acetylcholine levels – which are thought to reduce hippocampal afferent inputs in the neocortex. The additional low levels of noradrenaline during REM sleep, which facilitate recurrent activation within the neocortex, could allow the integration of novel memory traces previously consolidated during NREM sleep. We therefore propose that REM sleep mediates the prioritized processing of emotional memories within the hippocampus, the integration of previously consolidated memory traces within the neocortex, as well as the disengagement of consolidated neocortical memory traces from the hippocampus.

Basal Forebrain Cholinergic Deficits Reduce Glucose Metabolism and Function of Cholinergic and GABAergic Systems in the Cingulate Cortex

OpenAIRE

Jeong, Da Un; Oh, Jin Hwan; Lee, Ji Eun; Lee, Jihyeon; Cho, Zang Hee; Chang, Jin Woo; Chang, Won Seok

2015-01-01

Purpose Reduced brain glucose metabolism and basal forebrain cholinergic neuron degeneration are common features of Alzheimer's disease and have been correlated with memory function. Although regions representing glucose hypometabolism in patients with Alzheimer's disease are targets of cholinergic basal forebrain neurons, the interaction between cholinergic denervation and glucose hypometabolism is still unclear. The aim of the present study was to evaluate glucose metabolism changes caused ...

The Input-Output Relationship of the Cholinergic Basal Forebrain

Directory of Open Access Journals (Sweden)

Matthew R. Gielow

2017-02-01

Full Text Available Basal forebrain cholinergic neurons influence cortical state, plasticity, learning, and attention. They collectively innervate the entire cerebral cortex, differentially controlling acetylcholine efflux across different cortical areas and timescales. Such control might be achieved by differential inputs driving separable cholinergic outputs, although no input-output relationship on a brain-wide level has ever been demonstrated. Here, we identify input neurons to cholinergic cells projecting to specific cortical regions by infecting cholinergic axon terminals with a monosynaptically restricted viral tracer. This approach revealed several circuit motifs, such as central amygdala neurons synapsing onto basolateral amygdala-projecting cholinergic neurons or strong somatosensory cortical input to motor cortex-projecting cholinergic neurons. The presence of input cells in the parasympathetic midbrain nuclei contacting frontally projecting cholinergic neurons suggest that the network regulating the inner eye muscles are additionally regulating cortical state via acetylcholine efflux. This dataset enables future circuit-level experiments to identify drivers of known cortical cholinergic functions.

Rem uncouples excitation–contraction coupling in adult skeletal muscle fibers

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Beqollari, Donald; Romberg, Christin F.; Filipova, Dilyana; Meza, Ulises; Papadopoulos, Symeon

2015-01-01

In skeletal muscle, excitation–contraction (EC) coupling requires depolarization-induced conformational rearrangements in L-type Ca2+ channel (CaV1.1) to be communicated to the type 1 ryanodine-sensitive Ca2+ release channel (RYR1) of the sarcoplasmic reticulum (SR) via transient protein–protein interactions. Although the molecular mechanism that underlies conformational coupling between CaV1.1 and RYR1 has been investigated intensely for more than 25 years, the question of whether such signaling occurs via a direct interaction between the principal, voltage-sensing α1S subunit of CaV1.1 and RYR1 or through an intermediary protein persists. A substantial body of evidence supports the idea that the auxiliary β1a subunit of CaV1.1 is a conduit for this intermolecular communication. However, a direct role for β1a has been difficult to test because β1a serves two other functions that are prerequisite for conformational coupling between CaV1.1 and RYR1. Specifically, β1a promotes efficient membrane expression of CaV1.1 and facilitates the tetradic ultrastructural arrangement of CaV1.1 channels within plasma membrane–SR junctions. In this paper, we demonstrate that overexpression of the RGK protein Rem, an established β subunit–interacting protein, in adult mouse flexor digitorum brevis fibers markedly reduces voltage-induced myoplasmic Ca2+ transients without greatly affecting CaV1.1 targeting, intramembrane gating charge movement, or releasable SR Ca2+ store content. In contrast, a β1a-binding–deficient Rem triple mutant (R200A/L227A/H229A) has little effect on myoplasmic Ca2+ release in response to membrane depolarization. Thus, Rem effectively uncouples the voltage sensors of CaV1.1 from RYR1-mediated SR Ca2+ release via its ability to interact with β1a. Our findings reveal Rem-expressing adult muscle as an experimental system that may prove useful in the definition of the precise role of the β1a subunit in skeletal-type EC coupling. PMID:26078055

Cholinergic axon length reduced by 300 meters in the brain of an Alzheimer mouse model

DEFF Research Database (Denmark)

Nikolajsen, Gitte; Jensen, Morten Skovgaard; West, Mark J.

2011-01-01

Modern stereological techniques have been used to show that the total length of the cholinergic fibers in the cerebral cortex of the APPswe/PS1deltaE9 mouse is reduced by almost 300 meters at 18 months of age and has a nonlinear relationship to the amount of transgenetically-induced amyloidosis. ....... These data provide rigorous quantitative morphological evidence that Alzheimer's-like amyloidosis affects the axons of the cholinergic enervation of the cerebral cortex....

The cholinergic system, circadian rhythmicity, and time memory

NARCIS (Netherlands)

Hut, R. A.; Van der Zee, E. A.

2011-01-01

This review provides an overview of the interaction between the mammalian cholinergic system and circadian system, and its possible role in time memory. Several studies made clear that circadian (daily) fluctuations in acetylcholine (ACh) release, cholinergic enzyme activity and cholinergic receptor

Diagnostic thresholds for quantitative REM sleep phasic burst duration, phasic and tonic muscle activity, and REM atonia index in REM sleep behavior disorder with and without comorbid obstructive sleep apnea.

Science.gov (United States)

McCarter, Stuart J; St Louis, Erik K; Duwell, Ethan J; Timm, Paul C; Sandness, David J; Boeve, Bradley F; Silber, Michael H

2014-10-01

We aimed to determine whether phasic burst duration and conventional REM sleep without atonia (RSWA) methods could accurately diagnose REM sleep behavior disorder (RBD) patients with comorbid OSA. We visually analyzed RSWA phasic burst durations, phasic, "any," and tonic muscle activity by 3-s mini-epochs, phasic activity by 30-s (AASM rules) epochs, and conducted automated REM atonia index (RAI) analysis. Group RSWA metrics were analyzed and regression models fit, with receiver operating characteristic (ROC) curves determining the best diagnostic cutoff thresholds for RBD. Both split-night and full-night polysomnographic studies were analyzed. N/A. Parkinson disease (PD)-RBD (n = 20) and matched controls with (n = 20) and without (n = 20) OSA. N/A. All mean RSWA phasic burst durations and muscle activities were higher in PD-RBD patients than controls (P sleep without atonia diagnostic thresholds applicable in Parkinson disease-REM sleep behavior disorder (PD-RBD) patient populations with comorbid OSA that may be useful toward distinguishing PD-RBD in typical outpatient populations. © 2014 Associated Professional Sleep Societies, LLC.

Overnight improvements in two REM sleep-sensitive tasks are associated with both REM and NREM sleep changes, sleep spindle features, and awakenings for dream recall.

Science.gov (United States)

Nielsen, T; O'Reilly, C; Carr, M; Dumel, G; Godin, I; Solomonova, E; Lara-Carrasco, J; Blanchette-Carrière, C; Paquette, T

2015-07-01

Memory consolidation is associated with sleep physiology but the contribution of specific sleep stages remains controversial. To clarify the contribution of REM sleep, participants were administered two REM sleep-sensitive tasks to determine if associated changes occurred only in REM sleep. Twenty-two participants (7 men) were administered the Corsi Block Tapping and Tower of Hanoi tasks prior to and again after a night of sleep. Task improvers and non-improvers were compared for sleep structure, sleep spindles, and dream recall. Control participants (N = 15) completed the tasks twice during the day without intervening sleep. Overnight Corsi Block improvement was associated with more REM sleep whereas Tower of Hanoi improvement was associated with more N2 sleep. Corsi Block improvement correlated positively with %REM sleep and Tower of Hanoi improvement with %N2 sleep. Post-hoc analyses suggest Tower of Hanoi effects-but not Corsi Block effects-are due to trait differences. Sleep spindle density was associated with Tower of Hanoi improvement whereas spindle amplitude correlated with Corsi Block improvement. Number of REM awakenings for dream reporting (but not dream recall per se) was associated with Corsi Block, but not Tower of Hanoi, improvement but was confounded with REM sleep time. This non-replication of one of 2 REM-sensitive task effects challenges both 'dual-process' and 'sequential' or 'sleep organization' models of sleep-dependent learning and points rather to capacity limitations on REM sleep. Experimental awakenings for sampling dream mentation may not perturb sleep-dependent learning effects; they may even enhance them. Copyright © 2014 Elsevier Inc. All rights reserved.

Cholinergic innervation of human mesenteric lymphatic vessels.

Science.gov (United States)

D'Andrea, V; Bianchi, E; Taurone, S; Mignini, F; Cavallotti, C; Artico, M

2013-11-01

The cholinergic neurotransmission within the human mesenteric lymphatic vessels has been poorly studied. Therefore, our aim is to analyse the cholinergic nerve fibres of lymphatic vessels using the traditional enzymatic techniques of staining, plus the biochemical modifications of acetylcholinesterase (AChE) activity. Specimens obtained from human mesenteric lymphatic vessels were subjected to the following experimental procedures: 1) drawing, cutting and staining of tissues; 2) staining of total nerve fibres; 3) enzymatic staining of cholinergic nerve fibres; 4) homogenisation of tissues; 5) biochemical amount of proteins; 6) biochemical amount of AChE activity; 6) quantitative analysis of images; 7) statistical analysis of data. The mesenteric lymphatic vessels show many AChE positive nerve fibres around their wall with an almost plexiform distribution. The incubation time was performed at 1 h (partial activity) and 6 h (total activity). Moreover, biochemical dosage of the same enzymatic activity confirms the results obtained with morphological methods. The homogenates of the studied tissues contain strong AChE activity. In our study, the lymphatic vessels appeared to contain few cholinergic nerve fibres. Therefore, it is expected that perivascular nerve stimulation stimulates cholinergic nerves innervating the mesenteric arteries to release the neurotransmitter AChE, which activates muscarinic or nicotinic receptors to modulate adrenergic neurotransmission. These results strongly suggest, that perivascular cholinergic nerves have little or no effect on the adrenergic nerve function in mesenteric arteries. The cholinergic nerves innervating mesenteric arteries do not mediate direct vascular responses.

Vasoactive intestinal polypeptide excites medial pontine reticular formation neurons in the brainstem rapid eye movement sleep-induction zone

DEFF Research Database (Denmark)

Kohlmeier, Kristi Anne; Reiner, P B

1999-01-01

Although it has long been known that microinjection of the cholinergic agonist carbachol into the medial pontine reticular formation (mPRF) induces a state that resembles rapid eye movement (REM) sleep, it is likely that other transmitters contribute to mPRF regulation of behavioral states. A key...... candidate is the peptide vasoactive intestinal polypeptide (VIP), which innervates the mPRF and induces REM sleep when injected into this region of the brainstem. To begin understanding the cellular mechanisms underlying this phenomenon, we examined the effects of VIP on mPRF cells using whole-cell patch...... conclude that VIP excites mPRF neurons by activation of a sodium current. This effect is mediated at least in part by G-protein stimulation of adenylyl cyclase, cAMP, and protein kinase A. These data suggest that VIP may play a physiological role in REM induction by its actions on mPRF neurons....

Involvement of Cholinergic and Adrenergic Receptors in Pathogenesis and Inflammatory Response Induced by Alpha-Neurotoxin Bot III of Scorpion Venom.

Science.gov (United States)

Nakib, Imene; Martin-Eauclaire, Marie-France; Laraba-Djebari, Fatima

2016-10-01

Bot III neurotoxin is the most lethal α neurotoxin purified from Buthus occitanus tunetanus scorpion venom. This toxin binds to the voltage-gated sodium channel of excitable cells and blocks its inactivation, inducing an increased release of neurotransmitters (acetylcholine and catecholamines). This study aims to elucidate the involvement of cholinergic and adrenergic receptors in pathogenesis and inflammatory response triggered by this toxin. Injection of Bot III to animals induces an increase of peroxidase activities, an imbalance of oxidative status, tissue damages in lung parenchyma, and myocardium correlated with metabolic disorders. The pretreatment with nicotine (nicotinic receptor agonist) or atropine (muscarinic receptor antagonist) protected the animals from almost all disorders caused by Bot III toxin, especially the immunological alterations. Bisoprolol administration (selective β1 adrenergic receptor antagonist) was also efficient in the protection of animals, mainly on tissue damage. Propranolol (non-selective adrenergic receptor antagonist) showed less effect. These results suggest that both cholinergic and adrenergic receptors are activated in the cardiopulmonary manifestations induced by Bot III. Indeed, the muscarinic receptor appears to be more involved than the nicotinic one, and the β1 adrenergic receptor seems to dominate the β2 receptor. These results showed also that the activation of nicotinic receptor leads to a significant protection of animals against Bot III toxin effect. These findings supply a supplementary data leading to better understanding of the mechanism triggered by scorpionic neurotoxins and suggest the use of drugs targeting these receptors, especially the nicotinic one in order to counteract the inflammatory response observed in scorpion envenomation.

Cholinergic modulation of cognition: Insights from human pharmacological functional neuroimaging

Science.gov (United States)

Bentley, Paul; Driver, Jon; Dolan, Raymond J.

2011-01-01

Evidence from lesion and cortical-slice studies implicate the neocortical cholinergic system in the modulation of sensory, attentional and memory processing. In this review we consider findings from sixty-three healthy human cholinergic functional neuroimaging studies that probe interactions of cholinergic drugs with brain activation profiles, and relate these to contemporary neurobiological models. Consistent patterns that emerge are: (1) the direction of cholinergic modulation of sensory cortex activations depends upon top-down influences; (2) cholinergic hyperstimulation reduces top-down selective modulation of sensory cortices; (3) cholinergic hyperstimulation interacts with task-specific frontoparietal activations according to one of several patterns, including: suppression of parietal-mediated reorienting; decreasing ‘effort’-associated activations in prefrontal regions; and deactivation of a ‘resting-state network’ in medial cortex, with reciprocal recruitment of dorsolateral frontoparietal regions during performance-challenging conditions; (4) encoding-related activations in both neocortical and hippocampal regions are disrupted by cholinergic blockade, or enhanced with cholinergic stimulation, while the opposite profile is observed during retrieval; (5) many examples exist of an ‘inverted-U shaped’ pattern of cholinergic influences by which the direction of functional neural activation (and performance) depends upon both task (e.g. relative difficulty) and subject (e.g. age) factors. Overall, human cholinergic functional neuroimaging studies both corroborate and extend physiological accounts of cholinergic function arising from other experimental contexts, while providing mechanistic insights into cholinergic-acting drugs and their potential clinical applications. PMID:21708219

REM sleep and dreaming functions beyond reductionism.

Science.gov (United States)

Kirov, Roumen

2013-12-01

Brain activation patterns and mental, electrophysiological, and neurobiological features of rapid eye movement (REM) sleep suggest more functions than only elaborative encoding. Hence, the periodic occurrence of REM sleep episodes and dreaming may be regarded as a recurrent adaptive interference, which incorporates recent memories into a broader vital context comprising emotions, basic needs and individual genetic traits.

Monitoring of the prompt GRB afterglow with the REM telescope

International Nuclear Information System (INIS)

Covino, S.; Zerbi, F.; Chincarini, G.; Ghisellini, G.; Conconi, P.; Molinari, E.; Rodono, M.; Cutispoto, G.; Antonelli, L.A.; Nicastro, L.; Palazzi, E.

2003-01-01

In these pages we present REM (Rapid Eye Mount), a fully robotized fast slewing telescope equipped with a high throughput NIR (Z', J, H, K) camera and an Optical slitless spectrograph (ROSS) optimized for the monitoring of the prompt afterglow of Gamma Ray Bursts. Covering the NIR domain REM can discover objects at extremely high red-shift and trigger large telescopes to observe them when they are still bright. The synergy between REM-IR cam and ROSS makes REM a powerful observing tool for any kind of fast transient phenomena

The effect of REM sleep deprivation on motivation for food reward.

Science.gov (United States)

Hanlon, Erin C; Andrzejewski, Matthew E; Harder, Bridgette K; Kelley, Ann E; Benca, Ruth M

2005-08-30

Prolonged sleep deprivation in rats produces a characteristic syndrome consisting of an increase in food intake yet a decrease in weight. Moreover, the increase in food intake generally precedes the weight loss, suggesting that sleep deprivation may affect appetitive behaviors. Using the multiple platform method to produce rapid eye movement (REM) sleep deprivation, we investigated the effect of REM sleep deprivation (REMSD) on motivation for food reward utilizing food-reinforced operant tasks. In acquisition or maintenance of an operant task, REM sleep-deprived rats, with or without simultaneous food restriction, decreased responding for sucrose pellet reward in comparison to controls, despite the fact that all REM sleep-deprived rats lost weight. Furthermore, the overall response deficit of the REM sleep-deprived rats was due to a within-session decline in responding. REM sleep-deprived rats showed evidence of understanding the contingency of the task comparable to controls throughout deprivation period, suggesting that the decrements in responding were not primarily related to deficits in learning or memory. Rather, REM sleep deprivation appears to alter systems involved in motivational processes, reward, and/or attention.

Effects of chronic REM sleep restriction on D1 receptor and related signal pathways in rat prefrontal cortex.

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Han, Yan; Wen, Xiaosa; Rong, Fei; Chen, Xinmin; Ouyang, Ruying; Wu, Shuai; Nian, Hua; Ma, Wenling

2015-01-01

The prefrontal cortex (PFC) mediates cognitive function that is sensitive to disruption by sleep loss, and molecular mechanisms regulating neural dysfunction induced by chronic sleep restriction (CSR), particularly in the PFC, have yet to be completely understood. The aim of the present study was to investigate the effect of chronic REM sleep restriction (REM-CSR) on the D1 receptor (D1R) and key molecules in D1R' signal pathways in PFC. We employed the modified multiple platform method to create the REM-CSR rat model. The ultrastructure of PFC was observed by electron microscopy. HPLC was performed to measure the DA level in PFC. The expressions of genes and proteins of related molecules were assayed by real-time PCR and Western blot, respectively. The general state and morphology of PFC in rats were changed by CSR, and DA level and the expression of D1R in PFC were markedly decreased (P CSR rats (P CSR induced cognitive dysfunction, and the PKA pathway of D1R may play an important role in the impairment of advanced neural function.

An extended range neutron rem counter

International Nuclear Information System (INIS)

Birattari, C.; Nuccetelli, C.; Pelliccioni, M.; Silari, M.

1990-01-01

Extensive Monte Carlo calculations have been carried out to assess the possibility of extending the sensitivity of a neutron rem counter of the Andersson-Braun type up to several hundred MeV. The validity of the model adopted has first been checked by comparing with experimental data the calculated response curve and the angular dependence of the sensitivity for a well known commercial rem counter. Next, a number of modifications to the configuration of the moderator-attenuator have been investigated. The response functions and angular distributions produced by two simple solutions yielding an instrument with a sensitivity extended up to 400 MeV are presented. The response of the original rem counter and of its two modified versions to nine test spectra has also been calculated. The resulting instrument is transportable rather than portable, but the availability of an extended range neutron survey meter would be of great advantage at medium and high energy particle accelerator facilities. (orig.)

Vocabulary learning benefits from REM after slow-wave sleep.

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Batterink, Laura J; Westerberg, Carmen E; Paller, Ken A

2017-10-01

Memory reactivation during slow-wave sleep (SWS) influences the consolidation of recently acquired knowledge. This reactivation occurs spontaneously during sleep but can also be triggered by presenting learning-related cues, a technique known as targeted memory reactivation (TMR). Here we examined whether TMR can improve vocabulary learning. Participants learned the meanings of 60 novel words. Auditory cues for half the words were subsequently presented during SWS in an afternoon nap. Memory performance for cued versus uncued words did not differ at the group level but was systematically influenced by REM sleep duration. Participants who obtained relatively greater amounts of REM showed a significant benefit for cued relative to uncued words, whereas participants who obtained little or no REM demonstrated a significant effect in the opposite direction. We propose that REM after SWS may be critical for the consolidation of highly integrative memories, such as new vocabulary. Reactivation during SWS may allow newly encoded memories to be associated with other information, but this association can include disruptive linkages with pre-existing memories. Subsequent REM sleep may then be particularly beneficial for integrating new memories into appropriate pre-existing memory networks. These findings support the general proposition that memory storage benefits optimally from a cyclic succession of SWS and REM. Copyright © 2017 Elsevier Inc. All rights reserved.

Environmental risk factors for REM sleep behavior disorder

DEFF Research Database (Denmark)

Postuma, R B; Montplaisir, J Y; Pelletier, A

2012-01-01

Idiopathic REM sleep behavior disorder is a parasomnia characterized by dream enactment and is commonly a prediagnostic sign of parkinsonism and dementia. Since risk factors have not been defined, we initiated a multicenter case-control study to assess environmental and lifestyle risk factors...... for REM sleep behavior disorder....

Diagnostic REM sleep muscle activity thresholds in patients with idiopathic REM sleep behavior disorder with and without obstructive sleep apnea.

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McCarter, Stuart J; St Louis, Erik K; Sandness, David J; Duwell, Ethan J; Timm, Paul C; Boeve, Bradley F; Silber, Michael H

2017-05-01

We aimed to determine whether visual and automated rapid eye movement (REM) sleep without atonia (RSWA) methods could accurately diagnose patients with idiopathic REM sleep behavior disorder (iRBD) and comorbid obstructive sleep apnea (OSA). In iRBD patients (n = 15) and matched controls (n = 30) with and without OSA, we visually analyzed RSWA phasic burst durations, phasic, tonic, and "any" muscle activity by 3-s mini-epochs, phasic activity by 30-s (AASM rules) epochs, and automated REM atonia index (RAI). Group RSWA metrics were analyzed with regression models. Receiver operating characteristic (ROC) curves were used to determine the best diagnostic cutoff thresholds for REM sleep behavior disorder (RBD). Both split-night and full-night polysomnographic studies were analyzed. All mean RSWA phasic burst durations and muscle activities were higher in iRBD patients than in controls (p sleep behavior disorder (PD-RBD), consistent with a common mechanism and presumed underlying etiology of synucleinopathy in both groups. Copyright © 2016 Elsevier B.V. All rights reserved.

Pharmacological Mechanisms of Cortical Enhancement Induced by the Repetitive Pairing of Visual/Cholinergic Stimulation.

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Jun-Il Kang

Full Text Available Repetitive visual training paired with electrical activation of cholinergic projections to the primary visual cortex (V1 induces long-term enhancement of cortical processing in response to the visual training stimulus. To better determine the receptor subtypes mediating this effect the selective pharmacological blockade of V1 nicotinic (nAChR, M1 and M2 muscarinic (mAChR or GABAergic A (GABAAR receptors was performed during the training session and visual evoked potentials (VEPs were recorded before and after training. The training session consisted of the exposure of awake, adult rats to an orientation-specific 0.12 CPD grating paired with an electrical stimulation of the basal forebrain for a duration of 1 week for 10 minutes per day. Pharmacological agents were infused intracortically during this period. The post-training VEP amplitude was significantly increased compared to the pre-training values for the trained spatial frequency and to adjacent spatial frequencies up to 0.3 CPD, suggesting a long-term increase of V1 sensitivity. This increase was totally blocked by the nAChR antagonist as well as by an M2 mAChR subtype and GABAAR antagonist. Moreover, administration of the M2 mAChR antagonist also significantly decreased the amplitude of the control VEPs, suggesting a suppressive effect on cortical responsiveness. However, the M1 mAChR antagonist blocked the increase of the VEP amplitude only for the high spatial frequency (0.3 CPD, suggesting that M1 role was limited to the spread of the enhancement effect to a higher spatial frequency. More generally, all the drugs used did block the VEP increase at 0.3 CPD. Further, use of each of the aforementioned receptor antagonists blocked training-induced changes in gamma and beta band oscillations. These findings demonstrate that visual training coupled with cholinergic stimulation improved perceptual sensitivity by enhancing cortical responsiveness in V1. This enhancement is mainly mediated by n

REM sleep selectively prunes and maintains new synapses in development and learning.

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Li, Wei; Ma, Lei; Yang, Guang; Gan, Wen-Biao

2017-03-01

The functions and underlying mechanisms of rapid eye movement (REM) sleep remain unclear. Here we show that REM sleep prunes newly formed postsynaptic dendritic spines of layer 5 pyramidal neurons in the mouse motor cortex during development and motor learning. This REM sleep-dependent elimination of new spines facilitates subsequent spine formation during development and when a new motor task is learned, indicating a role for REM sleep in pruning to balance the number of new spines formed over time. Moreover, REM sleep also strengthens and maintains newly formed spines, which are critical for neuronal circuit development and behavioral improvement after learning. We further show that dendritic calcium spikes arising during REM sleep are important for pruning and strengthening new spines. Together, these findings indicate that REM sleep has multifaceted functions in brain development, learning and memory consolidation by selectively eliminating and maintaining newly formed synapses via dendritic calcium spike-dependent mechanisms.

A cholinergic contribution to the circulatory responses evoked at the onset of handgrip exercise in humans

DEFF Research Database (Denmark)

Vianna, Lauro C; Fadel, Paul J; Secher, Niels H

2015-01-01

A cholinergic (muscarinic) contribution to the initial circulatory response to exercise in humans remains controversial. Herein, we posit that this may be due to exercise mode with a cholinergic contribution being important during isometric handgrip exercise, where the hyperemic response......-induced fall in SVR and, thereby, augmented the pressor response (+13 ± 3 mmHg at 10 s; P exercise. These findings suggest that a cholinergic mechanism is important for the BP...... resistance (SVR) in young healthy males, while performing either 20 s of isometric handgrip contraction at 40% maximum voluntary contraction (protocol 1; n = 9) or 20 s of low-intensity leg cycling exercise (protocol 2; n = 8, 42 ± 8 W). Exercise trials were conducted under control (no drug) conditions...

THE NEUROBIOLOGY OF SLEEP AND WAKEFULNESS

Science.gov (United States)

Schwartz, Michael D.; Kilduff, Thomas S.

2015-01-01

SYNOPSIS Since the discovery of Rapid Eye Movement (REM) sleep in the late 1950s, identification of the neural circuitry underlying wakefulness, sleep onset and the alternation between REM and non-REM (NREM) sleep has been an active area of investigation. Synchronization and desynchronization of cortical activity as detected in the electroencephalogram (EEG) is due to a corticothalamocortical loop, intrinsic cortical oscillators, monoaminergic and cholinergic afferent input to the thalamus, and the basal forebrain cholinergic input directly to the cortex. The monoaminergic and cholinergic systems are largely wake-promoting; the brainstem cholinergic nuclei are also involved in REM sleep regulation. These wake-promoting systems receive excitatory input from the hypothalamic hypocretin/orexin system. Sleep-promoting nuclei are GABAergic in nature and found in the preoptic area, brainstem and lateral hypothalamus. Although the pons is critical for the expression of REM sleep, recent research has suggested that melanin-concentrating hormone/GABAergic cells in the lateral hypothalamus "gate" REM sleep. The temporal distribution of sleep and wakefulness is due to interaction between the circadian system and the sleep homeostatic system. Although the hypothalamic suprachiasmatic nuclei contain the circadian pacemaker, the neural circuitry underlying the sleep homeostat is less clear. Prolonged wakefulness results in the accumulation of extracellular adenosine, possibly from glial sources, which is an important feedback molecule for the sleep homeostatic system. Cortical neuronal nitric oxide (nNOS) neurons may also play a role in propagating slow waves through the cortex in NREM sleep. Several neuropeptides and other neurochemicals likely play important roles in sleep/wake control. Although the control of sleep and wakefulness seemingly involves multiple redundant systems, each of these systems provides a vulnerability that can result in sleep/wake dysfunction that may

Family history of idiopathic REM behavior disorder

DEFF Research Database (Denmark)

Dauvilliers, Yves; Postuma, Ronald B; Ferini-Strambi, Luigi

2013-01-01

To compare the frequency of proxy-reported REM sleep behavior disorder (RBD) among relatives of patients with polysomnogram-diagnosed idiopathic RBD (iRBD) in comparison to controls using a large multicenter clinic-based cohort.......To compare the frequency of proxy-reported REM sleep behavior disorder (RBD) among relatives of patients with polysomnogram-diagnosed idiopathic RBD (iRBD) in comparison to controls using a large multicenter clinic-based cohort....

Cholinergic Nociceptive Mechanisms in Rat Meninges and Trigeminal Ganglia: Potential Implications for Migraine Pain.

Science.gov (United States)

Shelukhina, Irina; Mikhailov, Nikita; Abushik, Polina; Nurullin, Leniz; Nikolsky, Evgeny E; Giniatullin, Rashid

2017-01-01

Parasympathetic innervation of meninges and ability of carbachol, acetylcholine (ACh) receptor (AChR) agonist, to induce headaches suggests contribution of cholinergic mechanisms to primary headaches. However, neurochemical mechanisms of cholinergic regulation of peripheral nociception in meninges, origin place for headache, are almost unknown. Using electrophysiology, calcium imaging, immunohistochemistry, and staining of meningeal mast cells, we studied effects of cholinergic agents on peripheral nociception in rat hemiskulls and isolated trigeminal neurons. Both ACh and carbachol significantly increased nociceptive firing in peripheral terminals of meningeal trigeminal nerves recorded by local suction electrode. Strong nociceptive firing was also induced by nicotine, implying essential role of nicotinic AChRs in control of excitability of trigeminal nerve endings. Nociceptive firing induced by carbachol was reduced by muscarinic antagonist atropine, whereas the action of nicotine was prevented by the nicotinic blocker d-tubocurarine but was insensitive to the TRPA1 antagonist HC-300033. Carbachol but not nicotine induced massive degranulation of meningeal mast cells known to release multiple pro-nociceptive mediators. Enzymes terminating ACh action, acetylcholinesterase (AChE) and butyrylcholinesterase, were revealed in perivascular meningeal nerves. The inhibitor of AChE neostigmine did not change the firing per se but induced nociceptive activity, sensitive to d-tubocurarine, after pretreatment of meninges with the migraine mediator CGRP. This observation suggested the pro-nociceptive action of endogenous ACh in meninges. Both nicotine and carbachol induced intracellular Ca 2+ transients in trigeminal neurons partially overlapping with expression of capsaicin-sensitive TRPV1 receptors. Trigeminal nerve terminals in meninges, as well as dural mast cells and trigeminal ganglion neurons express a repertoire of pro-nociceptive nicotinic and muscarinic AChRs, which

Automatic detection of REM sleep in subjects without atonia

DEFF Research Database (Denmark)

Kempfner, Jacob; Jennum, Poul; Nikolic, Miki

2012-01-01

Idiopathic Rapid-Rye-Movement (REM) sleep Behavior Disorder (iRBD) is a strong early marker of Parkinson's Disease and is characterized by REM sleep without atonia (RSWA) and increased phasic muscle activity. Current proposed methods for detecting RSWA assume the presence of a manually scored...... hypnogram. In this study a full automatic REM sleep detector, using the EOG and EEG channels, is proposed. Based on statistical features, combined with subject specific feature scaling and post-processing of the classifier output, it was possible to obtain an mean accuracy of 0.96 with a mean sensititvity...

Removal of ocular artifacts from the REM sleep EEG

NARCIS (Netherlands)

Waterman, D.; Woestenburg, J.C.; Elton, M.; Hofman, W.; Kok, A.

1992-01-01

The present report concerns the first study in which electrooculographic (EOG) contamination of electroencephalographic (EEG) recordings in rapid eye movement (REM) sleep is systematically investigated. Contamination of REM sleep EEG recordings in six subjects was evaluated in the frequency domain.

Olfactory impairment is related to REM sleep deprivation in rotenone model of Parkinson's disease

Directory of Open Access Journals (Sweden)

Mariana F. Aurich

Full Text Available Introduction: Olfactory dysfunction affects about 85-90% of Parkinson's disease (PD patients with severe deterioration in the ability of discriminate several types of odors. In addition, studies reported declines in olfactory performances during a short period of sleep deprivation. Besides, PD is also known to strongly affect the occurrence and maintenance of rapid eye movement (REM sleep. Methods: Therefore, we investigated the mechanisms involved on discrimination of a social odor (dependent on the vomeronasal system and a non-social odor (related to the main olfactory pathway in the rotenone model of PD. Also, a concomitant impairment in REM sleep was inflicted with the introduction of two periods (24 or 48 h of REM sleep deprivation (REMSD. Rotenone promoted a remarkable olfactory impairment in both social and non-social odors, with a notable modulation induced by 24 h of REMSD for the non-social odor. Results: Our findings demonstrated the occurrence of a strong association between the density of nigral TH-ir neurons and the olfactory discrimination capacity for both odorant stimuli. Specifically, the rotenone-induced decrease of these neurons tends to elicit reductions in the olfactory discrimination ability. Conclusions: These results are consistent with the participation of the nigrostriatal dopaminergic system mainly in the olfactory discrimination of a non-social odor, probably through the main olfactory pathway. Such involvement may have produce relevant impact in the preclinical abnormalities found in PD patients.

Cholinergic Septo-Hippocampal Innervation Is Required for Trace Eyeblink Classical Conditioning

Science.gov (United States)

Fontan-Lozano, Angela; Troncoso, Julieta; Munera, Alejandro; Carrion, Angel Manuel; Delgado-Garcia, Jose Maria

2005-01-01

We studied the effects of a selective lesion in rats, with 192-IgG-saporin, of the cholinergic neurons located in the medial septum/diagonal band (MSDB) complex on the acquisition of classical and instrumental conditioning paradigms. The MSDB lesion induced a marked deficit in the acquisition, but not in the retrieval, of eyeblink classical…

Cholinergic connectivity: it’s implications for psychiatric disorders.

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Elizabeth eScarr

2013-05-01

Full Text Available Acetylcholine has been implicated in both the pathophysiology and treatment of a number of psychiatric disorders, with most of the data related to its role and therapeutic potential focussing on schizophrenia. However, there is little thought given to the consequences of the documented changes in the cholinergic system and how they may affect the functioning of the brain. This review looks at the cholinergic system and its interactions with the intrinsic neurotransmitters glutamate and gamma-amino butyric acid as well as those with the projection neurotransmitters most implicated in the pathophysiologies of psychiatric disorders; dopamine and serotonin. In addition, with the recent focus on the role of factors normally associated with inflammation in the pathophysiologies of psychiatric disorders, links between the cholinergic system and these factors will also be examined. These interfaces are put into context, primarily for schizophrenia, by looking at the changes in each of these systems in the disorder and exploring, theoretically, whether the changes are interconnected with those seen in the cholinergic system. Thus, this review will provide a comprehensive overview of the connectivity between the cholinergic system and some of the major areas of research into the pathophysiologies of psychiatric disorders, resulting in a critical appraisal of the potential outcomes of a dysregulated central cholinergic system.

Risk evaluation and mitigation strategies (REMS): educating the prescriber.

Science.gov (United States)

Nicholson, Susan C; Peterson, Janet; Yektashenas, Behin

2012-02-01

The US FDA Amendments Act of 2007 was signed into law on 27 September 2007. A provision of this law granted the FDA new powers to enhance drug safety by requiring the pharmaceutical industry to develop Risk Evaluation and Mitigation Strategies (REMS). REMS are deemed necessary when a question exists as to whether the benefits of a drug outweigh its risks. REMS constitute a safety plan with several potential components, including a medication guide, a communication plan, elements to ensure safe use and an implementation system to help guide the prescribers, pharmacists and patients. This applies to existing drugs on the market, new drug applications (NDAs), abbreviated NDAs (generics) and biologics licence applications. REMS represent an 'upgrade' from previously required risk minimization action plans, based on the strengthening of FDA powers of authority and enforceability to incur monetary penalties against individuals representing the pharmaceutical industry who fail to comply. For illustrative purposes, we chose the drug romiplostim (Nplate®) to present an REMS, as all components were utilized to help assuage risks associated with the drug. Romiplostim is an FDA-approved drug used to treat thrombocytopenia in patients with chronic immune (idiopathic) thrombocytopenic purpura that has a significant adverse safety profile based on the risk of changes in bone marrow reticulin formation and bone marrow fibroses, and other associated risks. This review of current REMS policy is intended to provide the prescriber with a better understanding of current modalities in FDA-mandated drug safety programmes, which will impact day-to-day healthcare provider practices.

Respiration amplitude analysis for REM and NREM sleep classification

NARCIS (Netherlands)

Long, X.; Foussier, J.; Fonseca, P.; Haakma, R.; Aarts, R.M.

2013-01-01

In previous work, single-night polysomnography recordings (PSG) of respiratory effort and electrocardiogram (ECG) signals combined with actigraphy were used to classify sleep and wake states. In this study, we aim at classifying rapid-eye-movement (REM) and non-REM (NREM) sleep states. Besides the

Modulation of cholinergic airway reactivity and nitric oxide production by endogenous arginase activity

NARCIS (Netherlands)

Meurs, Herman; Hamer, M.A M; Pethe, S; Vadon-Le Goff, S; Boucher, J.-L; Zaagsma, Hans

1 Cholinergic airway constriction is functionally antagonized by agonist-induced constitutive nitric oxide synthase (cNOS)-derived nitric oxide (NO). Since cNOS and arginase, which hydrolyzes L-arginine to L-ornithine and urea, use L-arginine as a common substrate, competition between both enzymes

Modeling Parkinson's disease falls associated with brainstem cholinergic systems decline.

Science.gov (United States)

Kucinski, Aaron; Sarter, Martin

2015-04-01

In addition to the primary disease-defining symptoms, approximately half of patients with Parkinson's disease (PD) suffer from postural instability, impairments in gait control and a propensity for falls. Consistent with evidence from patients, we previously demonstrated that combined striatal dopamine (DA) and basal forebrain (BF) cholinergic cell loss causes falls in rats traversing dynamic surfaces. Because evidence suggests that degeneration of brainstem cholinergic neurons arising from the pedunculopontine nucleus (PPN) also contributes to impaired gait and falls, here we assessed the effects of selective cholinergic PPN lesions in combination with striatal DA loss or BF cholinergic cells loss as well as losses in all 3 regions. Results indicate that all combination losses that included the BF cholinergic system slowed traversal and increased slips and falls. However, the performance of rats with losses in all 3 regions (PPN, BF, and DA) was not more severely impaired than following combined BF cholinergic and striatal DA lesions. These results confirm the hypothesis that BF cholinergic-striatal disruption of attentional-motor interactions is a primary source of falls. Additional losses of PPN cholinergic neurons may worsen posture and gait control in situations not captured by the current testing conditions. (PsycINFO Database Record (c) 2015 APA, all rights reserved).

The basal forebrain cholinergic system in aging and dementia : Rescuing cholinergic neurons from neurotoxic amyloid-beta 42 with memantine

NARCIS (Netherlands)

Nyakas, Csaba; Granic, Ivica; Halmy, Laszlo G.; Banerjee, Pradeep; Luiten, Paul G. M.

2011-01-01

The dysfunction and loss of basal forebrain cholinergic neurons and their cortical projections are among the earliest pathological events in the pathogenesis of Alzheimer's disease (AD). The evidence pointing to cholinergic impairments come from studies that report a decline in the activity of

Change of cholinergic transmission and memory deficiency induced by injection of b-amyloid protein into NBM of rats

Institute of Scientific and Technical Information of China (English)

无

2001-01-01

The change of cholinergic transmission of b-amyloid protein (b-AP) treated rats was studied by intracerebral microdialysis sampling combined with HPLC analysis. b-AP1-40 was injected into nucleus basalis magnocellularis (NBM). Passive avoidance response test (step-down test) and delayed alternation task were used for memory testing. The impairment of memory after injection of b-AP1-40 into NBM exhibited mainly the deficiency of short-term working memory. One week after injection of b-AP1-40 the release of acetylcholine (ACh) from frontal cortex of freely-moving rats decreased significantly, and the response of cholinergic nerve ending to the action of high [K+] solution was rather weak. In control animals the percentage of increase of ACh- release during behavioral performance was 57%, while in b-AP1-40 - treated rats it was 34%. The temporary in-crease of the ACh-release of the rat put into a new place was also significantly diminished in b-AP1-40 -treated rats. The results show that the injection of b-AP1-40 into NBM impairs the cholinergic transmission in frontal cortex, and the impairment of cholinergic transmission may be the main cause of the deficit of working memory.

Representation of the Self in REM and NREM Dreams

Science.gov (United States)

McNamara, Patrick; McLaren, Deirdre; Durso, Kate

2008-01-01

The authors hypothesized that representations of the Self (or the dreamer) in dreams would change systematically, from a prereflective form of Self to more complex forms, as a function of both age and sleep state (REM vs. non-REM). These hypotheses were partially confirmed. While the authors found that all the self-concept-related dream content indexes derived from the Hall/Van de Castle dream content scoring system did not differ significantly between the dreams of children and adults, adult Selves were more likely to engage in “successful” social interactions. The Self never acted as aggressor in NREM dream states and was almost always the befriender in friendly interactions in NREM dreams. Conversely, the REM-related dream Self preferred aggressive encounters. Our results suggests that while prereflective forms of Self are the norm in children’s dreams, two highly complex forms of Self emerge in REM and NREM dreams. PMID:19169371

Brainstem circuitry regulating phasic activation of trigeminal motoneurons during REM sleep.

Directory of Open Access Journals (Sweden)

Christelle Anaclet

2010-01-01

Full Text Available Rapid eye movement sleep (REMS is characterized by activation of the cortical and hippocampal electroencephalogram (EEG and atonia of non-respiratory muscles with superimposed phasic activity or twitching, particularly of cranial muscles such as those of the eye, tongue, face and jaw. While phasic activity is a characteristic feature of REMS, the neural substrates driving this activity remain unresolved. Here we investigated the neural circuits underlying masseter (jaw phasic activity during REMS. The trigeminal motor nucleus (Mo5, which controls masseter motor function, receives glutamatergic inputs mainly from the parvocellular reticular formation (PCRt, but also from the adjacent paramedian reticular area (PMnR. On the other hand, the Mo5 and PCRt do not receive direct input from the sublaterodorsal (SLD nucleus, a brainstem region critical for REMS atonia of postural muscles. We hypothesized that the PCRt-PMnR, but not the SLD, regulates masseter phasic activity during REMS.To test our hypothesis, we measured masseter electromyogram (EMG, neck muscle EMG, electrooculogram (EOG and EEG in rats with cell-body specific lesions of the SLD, PMnR, and PCRt. Bilateral lesions of the PMnR and rostral PCRt (rPCRt, but not the caudal PCRt or SLD, reduced and eliminated REMS phasic activity of the masseter, respectively. Lesions of the PMnR and rPCRt did not, however, alter the neck EMG or EOG. To determine if rPCRt neurons use glutamate to control masseter phasic movements, we selectively blocked glutamate release by rPCRt neurons using a Cre-lox mouse system. Genetic disruption of glutamate neurotransmission by rPCRt neurons blocked masseter phasic activity during REMS.These results indicate that (1 premotor glutamatergic neurons in the medullary rPCRt and PMnR are involved in generating phasic activity in the masseter muscles, but not phasic eye movements, during REMS; and (2 separate brainstem neural circuits control postural and cranial muscle

Increased Motor Activity During REM Sleep Is Linked with Dopamine Function in Idiopathic REM Sleep Behavior Disorder and Parkinson Disease

DEFF Research Database (Denmark)

Zoetmulder, Marielle; Nikolic, Miki; Biernat, Heidi B

2016-01-01

STUDY OBJECTIVES: Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia characterized by impaired motor inhibition during REM sleep, and dream-enacting behavior. RBD is especially associated with α-synucleinopathies, such as Parkinson disease (PD). Follow-up studies have shown......-FP-CIT uptake in the putamen. In PD patients, EMG-activity was correlated to anti-Parkinson medication. CONCLUSIONS: Our results support the hypothesis that increased EMG-activity during REM sleep is at least partly linked to the nigrostriatal dopamine system in iRBD, and with dopamine function in PD....... the relation between this system and electromyographic (EMG) activity during sleep. The objective of this study was to investigate the relationship between the nigrostriatal dopamine system and muscle activity during sleep in iRBD and PD. METHODS: 10 iRBD patients, 10 PD patients with PD, 10 PD patients...

Increased Motor Activity During REM Sleep Is Linked with Dopamine Function in Idiopathic REM Sleep Behaviour Disorder and Parkinson Disease

DEFF Research Database (Denmark)

Zoetmulder, Marielle; Nikolic, Miki; Biernat, Heidi

2016-01-01

STUDY OBJECTIVES: Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia characterized by impaired motor inhibition during REM sleep, and dream-enacting behavior. RBD is especially associated with α-synucleinopathies, such as Parkinson disease (PD). Follow-up studies have shown...... in the putamen. In PD patients, EMG-activity was correlated to anti-Parkinson medication. CONCLUSIONS: Our results support the hypothesis that increased EMG-activity during REM sleep is at least partly linked to the nigrostriatal dopamine system in iRBD, and with dopamine function in PD....... the relation between this system and electromyographic (EMG) activity during sleep. The objective of this study was to investigate the relationship between the nigrostriatal dopamine system and muscle activity during sleep in iRBD and PD. METHODS: 10 iRBD patients, 10 PD patients with PD, 10 PD patients...

Asynchronous Cholinergic Drive Correlates with Excitation-Inhibition Imbalance via a Neuronal Ca2+ Sensor Protein

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Keming Zhou

2017-05-01

Full Text Available Excitation-inhibition imbalance in neural networks is widely linked to neurological and neuropsychiatric disorders. However, how genetic factors alter neuronal activity, leading to excitation-inhibition imbalance, remains unclear. Here, using the C. elegans locomotor circuit, we examine how altering neuronal activity for varying time periods affects synaptic release pattern and animal behavior. We show that while short-duration activation of excitatory cholinergic neurons elicits a reversible enhancement of presynaptic strength, persistent activation results to asynchronous and reduced cholinergic drive, inducing imbalance between endogenous excitation and inhibition. We find that the neuronal calcium sensor protein NCS-2 is required for asynchronous cholinergic release in an activity-dependent manner and dampens excitability of inhibitory neurons non-cell autonomously. The function of NCS-2 requires its Ca2+ binding and membrane association domains. These results reveal a synaptic mechanism implicating asynchronous release in regulation of excitation-inhibition balance.

Complex sound processing during human REM sleep by recovering information from long-term memory as revealed by the mismatch negativity (MMN).

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Atienza, M; Cantero, J L

2001-05-18

Perceptual learning is thought to be the result of neural changes that take place over a period of several hours or days, allowing information to be transferred to long-term memory. Evidence suggests that contents of long-term memory may improve attentive and pre-attentive sensory processing. Therefore, it is plausible to hypothesize that learning-induced neural changes that develop during wakefulness could improve automatic information processing during human REM sleep. The MMN, an objective measure of the automatic change detection in auditory cortex, was used to evaluate long-term learning effects on pre-attentive processing during wakefulness and REM sleep. When subjects learned to discriminate two complex auditory patterns in wakefulness, an increase in the MMN was obtained in both wake and REM states. The automatic detection of the infrequent complex auditory pattern may therefore be improved in both brain states by reactivating information from long-term memory. These findings suggest that long-term learning-related neural changes are accessible during REM sleep as well.

Differential actions of orexin receptors in brainstem cholinergic and monoaminergic neurons revealed by receptor knockouts: implications for orexinergic signaling in arousal and narcolepsy

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Kristi A Kohlmeier

2013-12-01

Full Text Available Orexin neuropeptides influence multiple homeostatic functions and play an essential role in the expression of normal sleep-wake behavior. While their two known receptors (OX1 and OX2 are targets for novel pharmacotherapeutics, the actions mediated by each receptor remain largely unexplored. Using brain slices from mice constitutively lacking either receptor, we used whole-cell and Ca2+ imaging methods to delineate the cellular actions of each receptor within cholinergic (laterodorsal tegmental nucleus; LDT and monoaminergic (dorsal raphe; DR and locus coeruleus; LC brainstem nuclei – where orexins promote arousal and suppress REM sleep. In slices from OX2-/- mice, orexin-A (300 nM elicited wild-type responses in LDT, DR and LC neurons consisting of a depolarizing current and augmented voltage-dependent Ca2+ transients. In slices from OX1-/- mice, the depolarizing current was absent in LDT and LC neurons and was attenuated in DR neurons, although Ca2+-transients were still augmented. Since orexin-A produced neither of these actions in slices lacking both receptors, our findings suggest that orexin-mediated depolarization is mediated by both receptors in DR, but is exclusively mediated by OX1 in LDT and LC neurons, even though OX2 is present and OX2 mRNA appears elevated in brainstems from OX1-/- mice. Considering published behavioral data, these findings support a model in which orexin-mediated excitation of mesopontine cholinergic and monoaminergic neurons contributes little to stabilizing spontaneous waking and sleep bouts, but functions in context-dependent arousal and helps restrict muscle atonia to REM sleep. The augmented Ca2± transients mediated by both receptors appeared mediated by influx via L-type Ca2+ channels, which is often linked to transcriptional signaling. This could provide an adaptive signal to compensate for receptor loss or prolonged antagonism and may contribute to the reduced severity of narcolepsy in single receptor

Clinical and polysomnographic characteristics of patients with REM sleep disordered breathing

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Cláudia Chaves Loureiro

2009-09-01

Full Text Available There is a 10–36% rate of obstructive sleep apnoea syndrome (OSAS associated with rapid eye movement (REM in the OSAS population. Prior studies have suggested an increased prevalence of psychiatric disorders and an effect of gender and age on these patients.Our aim was to study the clinical and polysomnograph (PSG characteristics of our patients with REM-related sleep disordered breathing (REM SDB.Inclusion criteria was the identification of REM SDB detected by PSG defined as apnea-hypopnea index (AHI in REM sleep ≥ 5 h, AHI in non-REM sleep (NREM ≤ 15 h and REM/NREM AHI ≥ 2.Several Sleep Disorders Questionnaire (SDQ version 1.02 parameters were analysed.The study comprised 19 patients with a mean age of 54.0 (SD ± 13.97, a mean BMI of 29.01 (SD ± 4.10 and a 0.58 female / male ratio. The mean Epworth Sleepiness Scale score was 12.74 (SD ± 4.86. Mean AHI was 9.16/h (SD 4.09; mean AHI in REM sleep 37.08/h (SD 25.87 and mean REM-AHI/NREM-AHI 8.86 (SD 8.63.The anxiety disorder rate was 33.3%; 44.4% in females, 16.7% in males.The average deep sleep was 20.7% (SD 10.42 and REM sleep 15.45% (SD 9.96, with a sleep efficiency of 85.3 (SD 8.70.No significant statistical correlation was found between the REM/NREM AHI index and anxiety symptoms, daytime sleepiness and sleep quality (REM and deep sleep percentages.These patients differ from the general OSAS population: on average, they are not obese, there are a greater number of females affected and they do not present a very significant diurnal hypersomnia. Reduced deep sleep and increased REM sleep were also present versus general population data, and sleep efficiency was just below the normal limit.Anxiety disorders were more prevalent in this group than described for the general population (3% and OSAS patients. Resumo: A síndroma de apneia obstrutiva do sono (SAOS associada ao sono REM tem uma incidência de 10–36% na

Visual hallucinations and pontine demyelination in a child: possible REM dissociation?

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Vita, Maria Gabriella; Batocchi, Anna Paola; Dittoni, Serena; Losurdo, Anna; Cianfoni, Alessandro; Stefanini, Maria Chiara; Vollono, Catello; Della Marca, Giacomo; Mariotti, Paolo

2008-12-15

An 11 year-old-boy acutely developed complex visual and acoustic hallucinations. Hallucinations, consisting of visions of a threatening, evil character of the Harry Potter saga, persisted for 3 days. Neurological and psychiatric examinations were normal. Ictal EEG was negative. MRI documented 3 small areas of hyperintense signal in the brainstem, along the paramedian and lateral portions of pontine tegmentum, one of which showed post-contrast enhancement. These lesions were likely of inflammatory origin, and treatment with immunoglobulins was started. Polysomnography was normal, multiple sleep latency test showed a mean sleep latency of 8 minutes, with one sleep-onset REM period. The pontine tegmentum is responsible for REM sleep regulation, and contains definite "REM-on" and "REM-off" regions. The anatomical distribution of the lesions permits us to hypothesize that hallucinations in this boy were consequent to a transient impairment of REM sleep inhibitory mechanisms, with the appearance of dream-like hallucinations during wake.

Modulation of Sleep Homeostasis by Corticotropin Releasing Hormone in REM Sleep-Deprived Rats

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Ricardo Borges Machado

2010-01-01

Full Text Available Studies have shown that sleep recovery following different protocols of forced waking varies according to the level of stress inherent to each method. Sleep deprivation activates the hypothalamic-pituitary-adrenal axis and increased corticotropin-releasing hormone (CRH impairs sleep. The purpose of the present study was to evaluate how manipulations of the CRH system during the sleep deprivation period interferes with subsequent sleep rebound. Throughout 96 hours of sleep deprivation, separate groups of rats were treated i.c.v. with vehicle, CRH or with alphahelical CRH9−41, a CRH receptor blocker, twice/day, at 07:00 h and 19:00 h. Both treatments impaired sleep homeostasis, especially in regards to length of rapid eye movement sleep (REM and theta/delta ratio and induced a later decrease in NREM and REM sleep and increased waking bouts. These changes suggest that activation of the CRH system impact negatively on the homeostatic sleep response to prolonged forced waking. These results indicate that indeed, activation of the HPA axis—at least at the hypothalamic level—is capable to reduce the sleep rebound induced by sleep deprivation.

Motivation and affect in REM sleep and the mentation reporting process.

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Smith, Mark R; Antrobus, John S; Gordon, Evelyn; Tucker, Matthew A; Hirota, Yasutaka; Wamsley, Erin J; Ross, Lars; Doan, Tieu; Chaklader, Annie; Emery, Rebecca N

2004-09-01

Although the emotional and motivational characteristics of dreaming have figured prominently in folk and psychoanalytic conceptions of dream production, emotions have rarely been systematically studied, and motivation, never. Because emotions during sleep lack the somatic components of waking emotions, and they change as the sleeper awakens, their properties are difficult to assess. Recent evidence of limbic system activation during REM sleep suggests a basis in brain architecture for the interaction of motivational and cognitive properties in dreaming. Motivational and emotional content in REM and NREM laboratory mentation reports from 25 participants were compared. Motivational and emotional content was significantly greater in REM than NREM sleep, even after controlling for the greater word count of REM reports.

Demodex canis regulates cholinergic system mediated immunosuppressive pathways in canine demodicosis.

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Kumari, P; Nigam, R; Singh, A; Nakade, U P; Sharma, A; Garg, S K; Singh, S K

2017-09-01

Demodex canis infestation in dogs remains one of the main challenges in veterinary dermatology. The exact pathogenesis of canine demodicosis is unknown but an aberration in immune status is considered very significant. No studies have underpinned the nexus between induction of demodicosis and neural immunosuppressive pathways so far. We have evaluated the involvement of cholinergic pathways in association with cytokines regulation as an insight into the immuno-pathogenesis of canine demodicosis in the present study. Remarkable elevations in circulatory immunosuppressive cytokine interleukin-10 and cholinesterase activity were observed in dogs with demodicosis. Simultaneously, remarkable reduction in circulatory pro-inflammatory cytokine tumour necrosis factor-alpha level was observed in dogs with demodicosis. Findings of the present study evidently suggest that Demodex mites might be affecting the cholinergic pathways to induce immunosuppression in their host and then proliferate incessantly in skin microenvironment to cause demodicosis.

Analysis of automated quantification of motor activity in REM sleep behaviour disorder

DEFF Research Database (Denmark)

Frandsen, Rune; Nikolic, Miki; Zoetmulder, Marielle

2015-01-01

Rapid eye movement (REM) sleep behaviour disorder (RBD) is characterized by dream enactment and REM sleep without atonia. Atonia is evaluated on the basis of visual criteria, but there is a need for more objective, quantitative measurements. We aimed to define and optimize a method for establishing...... baseline and all other parameters in automatic quantifying submental motor activity during REM sleep. We analysed the electromyographic activity of the submental muscle in polysomnographs of 29 patients with idiopathic RBD (iRBD), 29 controls and 43 Parkinson's (PD) patients. Six adjustable parameters...... were validated on PD patients. Automatic baseline estimation improved characterization of atonia during REM sleep, as it eliminates inter/intra-observer variability and can be standardized across diagnostic centres. We found an optimized method for quantifying motor activity during REM sleep...

Long-term relationships between cholinergic tone, synchronous bursting and synaptic remodeling.

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Maya Kaufman

Full Text Available Cholinergic neuromodulation plays key roles in the regulation of neuronal excitability, network activity, arousal, and behavior. On longer time scales, cholinergic systems play essential roles in cortical development, maturation, and plasticity. Presumably, these processes are associated with substantial synaptic remodeling, yet to date, long-term relationships between cholinergic tone and synaptic remodeling remain largely unknown. Here we used automated microscopy combined with multielectrode array recordings to study long-term relationships between cholinergic tone, excitatory synapse remodeling, and network activity characteristics in networks of cortical neurons grown on multielectrode array substrates. Experimental elevations of cholinergic tone led to the abrupt suppression of episodic synchronous bursting activity (but not of general activity, followed by a gradual growth of excitatory synapses over hours. Subsequent blockage of cholinergic receptors led to an immediate restoration of synchronous bursting and the gradual reversal of synaptic growth. Neither synaptic growth nor downsizing was governed by multiplicative scaling rules. Instead, these occurred in a subset of synapses, irrespective of initial synaptic size. Synaptic growth seemed to depend on intrinsic network activity, but not on the degree to which bursting was suppressed. Intriguingly, sustained elevations of cholinergic tone were associated with a gradual recovery of synchronous bursting but not with a reversal of synaptic growth. These findings show that cholinergic tone can strongly affect synaptic remodeling and synchronous bursting activity, but do not support a strict coupling between the two. Finally, the reemergence of synchronous bursting in the presence of elevated cholinergic tone indicates that the capacity of cholinergic neuromodulation to indefinitely suppress synchronous bursting might be inherently limited.

Long-term Relationships between Cholinergic Tone, Synchronous Bursting and Synaptic Remodeling

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Kaufman, Maya; Corner, Michael A.; Ziv, Noam E.

2012-01-01

Cholinergic neuromodulation plays key roles in the regulation of neuronal excitability, network activity, arousal, and behavior. On longer time scales, cholinergic systems play essential roles in cortical development, maturation, and plasticity. Presumably, these processes are associated with substantial synaptic remodeling, yet to date, long-term relationships between cholinergic tone and synaptic remodeling remain largely unknown. Here we used automated microscopy combined with multielectrode array recordings to study long-term relationships between cholinergic tone, excitatory synapse remodeling, and network activity characteristics in networks of cortical neurons grown on multielectrode array substrates. Experimental elevations of cholinergic tone led to the abrupt suppression of episodic synchronous bursting activity (but not of general activity), followed by a gradual growth of excitatory synapses over hours. Subsequent blockage of cholinergic receptors led to an immediate restoration of synchronous bursting and the gradual reversal of synaptic growth. Neither synaptic growth nor downsizing was governed by multiplicative scaling rules. Instead, these occurred in a subset of synapses, irrespective of initial synaptic size. Synaptic growth seemed to depend on intrinsic network activity, but not on the degree to which bursting was suppressed. Intriguingly, sustained elevations of cholinergic tone were associated with a gradual recovery of synchronous bursting but not with a reversal of synaptic growth. These findings show that cholinergic tone can strongly affect synaptic remodeling and synchronous bursting activity, but do not support a strict coupling between the two. Finally, the reemergence of synchronous bursting in the presence of elevated cholinergic tone indicates that the capacity of cholinergic neuromodulation to indefinitely suppress synchronous bursting might be inherently limited. PMID:22911726

Long-term relationships between cholinergic tone, synchronous bursting and synaptic remodeling.

Science.gov (United States)

Kaufman, Maya; Corner, Michael A; Ziv, Noam E

2012-01-01

Cholinergic neuromodulation plays key roles in the regulation of neuronal excitability, network activity, arousal, and behavior. On longer time scales, cholinergic systems play essential roles in cortical development, maturation, and plasticity. Presumably, these processes are associated with substantial synaptic remodeling, yet to date, long-term relationships between cholinergic tone and synaptic remodeling remain largely unknown. Here we used automated microscopy combined with multielectrode array recordings to study long-term relationships between cholinergic tone, excitatory synapse remodeling, and network activity characteristics in networks of cortical neurons grown on multielectrode array substrates. Experimental elevations of cholinergic tone led to the abrupt suppression of episodic synchronous bursting activity (but not of general activity), followed by a gradual growth of excitatory synapses over hours. Subsequent blockage of cholinergic receptors led to an immediate restoration of synchronous bursting and the gradual reversal of synaptic growth. Neither synaptic growth nor downsizing was governed by multiplicative scaling rules. Instead, these occurred in a subset of synapses, irrespective of initial synaptic size. Synaptic growth seemed to depend on intrinsic network activity, but not on the degree to which bursting was suppressed. Intriguingly, sustained elevations of cholinergic tone were associated with a gradual recovery of synchronous bursting but not with a reversal of synaptic growth. These findings show that cholinergic tone can strongly affect synaptic remodeling and synchronous bursting activity, but do not support a strict coupling between the two. Finally, the reemergence of synchronous bursting in the presence of elevated cholinergic tone indicates that the capacity of cholinergic neuromodulation to indefinitely suppress synchronous bursting might be inherently limited.

Why Does REM Sleep Occur? A Wake-up Hypothesis

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Dr. W. R. eKlemm

2011-09-01

Full Text Available Brain activity differs in the various sleep stages and in conscious wakefulness. Awakening from sleep requires restoration of the complex nerve impulse patterns in neuronal network assemblies necessary to re-create and sustain conscious wakefulness. Herein I propose that the brain uses REM to help wake itself up after it has had a sufficient amount of sleep. Evidence suggesting this hypothesis includes the facts that, 1 when first going to sleep, the brain plunges into Stage N3 (formerly called Stage IV, a deep abyss of sleep, and, as the night progresses, the sleep is punctuated by episodes of REM that become longer and more frequent toward morning, 2 conscious-like dreams are a reliable component of the REM state in which the dreamer is an active mental observer or agent in the dream, 3 the last awakening during a night’s sleep usually occurs in a REM episode during or at the end of a dream, 4 both REM and awake consciousness seem to arise out of a similar brainstem ascending arousal system 5 N3 is a functionally perturbed state that eventually must be corrected so that embodied brain can direct adaptive behavior, and 6 corticofugal projections to brainstem arousal areas provide a way to trigger increased cortical activity in REM to progressively raise the sleeping brain to the threshold required for wakefulness. This paper shows how the hypothesis conforms to common experience and has substantial predictive and explanatory power regarding the phenomenology of sleep in terms of ontogeny, aging, phylogeny, abnormal/disease states, cognition, and behavioral physiology. That broad range of consistency is not matched by competing theories, which are summarized herein. Specific ways to test this wake-up hypothesis are suggested. Such research could lead to a better understanding of awake consciousness.

Why does rem sleep occur? A wake-up hypothesis.

Science.gov (United States)

Klemm, W R

2011-01-01

Brain activity differs in the various sleep stages and in conscious wakefulness. Awakening from sleep requires restoration of the complex nerve impulse patterns in neuronal network assemblies necessary to re-create and sustain conscious wakefulness. Herein I propose that the brain uses rapid eye movement (REM) to help wake itself up after it has had a sufficient amount of sleep. Evidence suggesting this hypothesis includes the facts that, (1) when first going to sleep, the brain plunges into Stage N3 (formerly called Stage IV), a deep abyss of sleep, and, as the night progresses, the sleep is punctuated by episodes of REM that become longer and more frequent toward morning, (2) conscious-like dreams are a reliable component of the REM state in which the dreamer is an active mental observer or agent in the dream, (3) the last awakening during a night's sleep usually occurs in a REM episode during or at the end of a dream, (4) both REM and awake consciousness seem to arise out of a similar brainstem ascending arousal system (5) N3 is a functionally perturbed state that eventually must be corrected so that embodied brain can direct adaptive behavior, and (6) cortico-fugal projections to brainstem arousal areas provide a way to trigger increased cortical activity in REM to progressively raise the sleeping brain to the threshold required for wakefulness. This paper shows how the hypothesis conforms to common experience and has substantial predictive and explanatory power regarding the phenomenology of sleep in terms of ontogeny, aging, phylogeny, abnormal/disease states, cognition, and behavioral physiology. That broad range of consistency is not matched by competing theories, which are summarized herein. Specific ways to test this wake-up hypothesis are suggested. Such research could lead to a better understanding of awake consciousness.

GABAergic actions on cholinergic laterodorsal tegmental neurons

DEFF Research Database (Denmark)

Kohlmeier, K A; Kristiansen, Uffe

2010-01-01

Cholinergic neurons of the pontine laterodorsal tegmentum (LDT) play a critical role in regulation of behavioral state. Therefore, elucidation of mechanisms that control their activity is vital for understanding of how switching between wakefulness, sleep and anesthetic states is effectuated....... In vivo studies suggest that GABAergic mechanisms within the pons play a critical role in behavioral state switching. However, the postsynaptic, electrophysiological actions of GABA on LDT neurons, as well as the identity of GABA receptors present in the LDT mediating these actions is virtually unexplored...... neurons. Post-synaptic location of GABA(A) receptors was demonstrated by persistence of muscimol-induced inward currents in TTX and low Ca(2+) solutions. THIP, a selective GABA(A) receptor agonist with a preference for d-subunit containing GABA(A) receptors, induced inward currents, suggesting...

Nicotinic and muscarinic cholinergic receptors are recruited by acetylcholine-mediated neurotransmission within the locus coeruleus during the organisation of post-ictal antinociception.

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de Oliveira, Rithiele Cristina; de Oliveira, Ricardo; Biagioni, Audrey Franceschi; Falconi-Sobrinho, Luiz Luciano; Dos Anjos-Garcia, Tayllon; Coimbra, Norberto Cysne

2016-10-01

Post-ictal antinociception is characterised by an increase in the nociceptive threshold that accompanies tonic and tonic-clonic seizures (TCS). The locus coeruleus (LC) receives profuse cholinergic inputs from the pedunculopontine tegmental nucleus. Different concentrations (1μg, 3μg and 5μg/0.2μL) of the muscarinic cholinergic receptor antagonist atropine and the nicotinic cholinergic receptor antagonist mecamylamine were microinjected into the LC of Wistar rats to investigate the role of cholinergic mechanisms in the severity of TCS and the post-ictal antinociceptive response. Five minutes later, TCS were induced by systemic administration of pentylenetetrazole (PTZ) (64mg/kg). Seizures were recorded inside the open field apparatus for an average of 10min. Immediately after seizures, the nociceptive threshold was recorded for 130min using the tail-flick test. Pre-treatment of the LC with 1μg, 3μg and 5μg/0.2μL concentrations of both atropine and mecamylamine did not cause a significant effect on seizure severity. However, the same treatments decreased the post-ictal antinociceptive phenomenon. In addition, mecamylamine caused an earlier decrease in the post-ictal antinociception compared to atropine. These results suggest that muscarinic and mainly nicotinic cholinergic receptors of the LC are recruited to organise tonic-clonic seizure-induced antinociception. Copyright © 2016 Elsevier Inc. All rights reserved.

Effects of selective REM sleep deprivation on prefrontal gamma activity and executive functions.

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Corsi-Cabrera, M; Rosales-Lagarde, A; del Río-Portilla, Y; Sifuentes-Ortega, R; Alcántara-Quintero, B

2015-05-01

Given that the dorsolateral prefrontal cortex is involved in executive functions and is deactivated and decoupled from posterior associative regions during REM sleep, that Gamma temporal coupling involved in information processing is enhanced during REM sleep, and that adult humans spend about 90 min of every 24h in REM sleep, it might be expected that REM sleep deprivation would modify Gamma temporal coupling and have a deteriorating effect on executive functions. We analyzed EEG Gamma activity and temporal coupling during implementation of a rule-guided task before and after REM sleep deprivation and its effect on verbal fluency, flexible thinking and selective attention. After two nights in the laboratory for adaptation, on the third night subjects (n=18) were randomly assigned to either selective REM sleep deprivation effectuated by awakening them at each REM sleep onset or, the same number of NREM sleep awakenings as a control for unspecific effects of sleep interruptions. Implementation of abstract rules to guide behavior required greater activation and synchronization of Gamma activity in the frontopolar regions after REM sleep reduction from 20.6% at baseline to just 3.93% of total sleep time. However, contrary to our hypothesis, both groups showed an overall improvement in executive task performance and no effect on their capacity to sustain selective attention. These results suggest that after one night of selective REM sleep deprivation executive functions can be compensated by increasing frontal activation and they still require the participation of supervisory control by frontopolar regions. Copyright © 2015 Elsevier B.V. All rights reserved.

Estimate of man-rem expenditures for a mature CANDU 600 MW(e) station

International Nuclear Information System (INIS)

Kuperman, I.

1978-08-01

In recent years, man-rem expenditures at operating stations have come under close scrutiny in order to reduce operating personnel dosage. This increased awareness has led to concerted efforts to improve station design and to improve operating procedures to achieve lower man-rem expenditures. This paper is intended to highlight design improvements that have been made in the CANDU 600 MW(e) design and to show how these improvements will reduce man-rem expenditures. Other considerations, such as station decontaminations of the primary heat transport system and the fuelling machines and stricter chemistry control are presently available to help reduce man-rem consumption. Also, station management operating policy should emphasize man-rem awareness. (author)

Rapid Eye Movements (REMs) and visual dream recall in both congenitally blind and sighted subjects

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Bértolo, Helder; Mestre, Tiago; Barrio, Ana; Antona, Beatriz

2017-08-01

Our objective was to evaluate rapid eye movements (REMs) associated with visual dream recall in sighted subjects and congenital blind. During two consecutive nights polysomnographic recordings were performed at subjects home. REMs were detected by visual inspection on both EOG channels (EOG-H, EOG-V) and further classified as occurring isolated or in bursts. Dream recall was defined by the existence of a dream report. The two groups were compared using t-test and also the two-way ANOVA and a post-hoc Fisher test (for the features diagnosis (blind vs. sighted) and dream recall (yes or no) as a function of time). The average of REM awakenings per subject and the recall ability were identical in both groups. CB had a lower REM density than CS; the same applied to REM bursts and isolated eye movements. In the two-way ANOVA, REM bursts and REM density were significantly different for positive dream recall, mainly for the CB group and for diagnosis; furthermore for both features significant results were obtained for the interaction of time, recall and diagnosis; the interaction of recall and time was however, stronger. In line with previous findings the data show that blind have lower REMs density. However the ability of dream recall in congenitally blind and sighted controls is identical. In both groups visual dream recall is associated with an increase in REM bursts and density. REM bursts also show differences in the temporal profile. REM visual dream recall is associated with increased REMs activity.

Bovine pancreatic polypeptide as an antagonist of muscarinic cholinergic receptors

International Nuclear Information System (INIS)

Pan, G.Z.; Lu, L.; Qian, J.; Xue, B.G.

1987-01-01

In dispersed acini from rat pancreas, it was found that bovine pancreatic polypeptide (BPP) and its C-fragment hexapeptide amide (PP-6), at concentrations of 0.1 and 30 μM, respectively, could significantly inhibit amylase secretion stimulated by carbachol, and this inhibition by BPP was dose dependent. 45 Ca outflux induced by carbachol was also inhibited by BPP or PP-6, but they had no effect on cholecystokinin octapeptide- (CCK-8) or A23187-stimulated 45 Ca outflux. BPP was also capable of displacing the specific binding of [ 3 H]-quinuclidinyl benzilate to its receptors, and it possessed a higher affinity (K/sub i/35nM) than carbachol (K/sub i/ 1.8 μM) in binding with M-receptors. It is concluded from this study that BPP acts as an antagonist of muscarinic cholinergic receptors in rat pancreatic acini. In addition, BPP inhibited the potentiation of amylase secretion caused by the combination of carbachol plus secretin or vasoactive intestinal peptide. This may be a possible explanation of the inhibitory effect of BPP on secretin-induced pancreatic enzyme secretion shown in vivo, since pancreatic enzyme secretion stimulated by secretin under experimental conditions may be the result of potentiation of enzyme release produced by the peptide in combination with a cholinergic stimulant

Antidepressants Increase REM Sleep Muscle Tone in Patients with and without REM Sleep Behavior Disorder.

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McCarter, Stuart J; St Louis, Erik K; Sandness, David J; Arndt, Katlyn; Erickson, Maia; Tabatabai, Grace; Boeve, Bradley F; Silber, Michael H

2015-06-01

REM sleep behavior disorder (RBD) is associated with antidepressant treatment, especially in younger patients; but quantitative REM sleep without atonia (RSWA) analyses of psychiatric RBD patients remain limited. We analyzed RSWA in adults receiving antidepressants, with and without RBD. We comparatively analyzed visual, manual, and automated RSWA between RBD and control groups. RSWA metrics were compared between groups, and regression was used to explore associations with clinical variables. Tertiary-care sleep center. Participants included traditional RBD without antidepressant treatment (n = 30, 15 Parkinson disease [PD-RBD] and 15 idiopathic); psychiatric RBD receiving antidepressants (n = 30); and adults without RBD, including antidepressant-treated psychiatric (n = 30), untreated psychiatric (n = 15), and OSA (n = 60) controls. N/A. RSWA was highest in traditional and psychiatric RBD, intermediate in treated psychiatric controls, and lowest in untreated psychiatric and OSA controls (P sleep without atonia (RSWA) even without REM sleep behavior disorder (RBD), suggesting that antidepressants, not depression, promote RSWA. Differences in RSWA distribution and type were also seen, with higher anterior tibialis RSWA in antidepressant-treated patients and higher tonic RSWA in Parkinson disease-RBD patients, which could aid distinction between RBD subtypes. These findings suggest that antidepressants may mediate different RSWA mechanisms or, alternatively, that RSWA type and distribution evolve during progressive neurodegeneration. Further prospective RSWA analyses are necessary to clarify the relationships between antidepressant treatment, psychiatric disease, and RBD. © 2015 Associated Professional Sleep Societies, LLC.

In-vivo staging of pathology in REM sleep behaviour disorder

DEFF Research Database (Denmark)

Knudsen, Karoline; Fedorova, Tatyana D.; Hansen, Allan K.

2018-01-01

originating in the locus coeruleus, and 18F-dihydroxyphenylalanine (DOPA) PET to assess nigrostriatal dopamine storage capacity. For each imaging modality, we compared patients with idiopathic REM sleep behaviour disorder with previously published reference data of controls without neurological disorders...... or cognitive impairment and with symptomatic patients with Parkinson's disease. We assessed imaging data using one-way ANOVA corrected for multiple comparisons. Findings: Between June 3, 2016, and Dec 19, 2017, we recruited 22 consecutive patients with idiopathic REM sleep behaviour disorder to the study...... REM sleep behaviour disorder (pequal to that in diagnosed Parkinson's disease. These patients also showed noradrenergic...

REM sleep respiratory behaviours mental content in narcoleptic lucid dreamers.

Science.gov (United States)

Oudiette, Delphine; Dodet, Pauline; Ledard, Nahema; Artru, Emilie; Rachidi, Inès; Similowski, Thomas; Arnulf, Isabelle

2018-02-08

Breathing is irregular during rapid eye-movement (REM) sleep, whereas it is stable during non-REM sleep. Why this is so remains a mystery. We propose that irregular breathing has a cortical origin and reflects the mental content of dreams, which often accompany REM sleep. We tested 21 patients with narcolepsy who had the exceptional ability to lucid dream in REM sleep, a condition in which one is conscious of dreaming during the dream and can signal lucidity with an ocular code. Sleep and respiration were monitored during multiple naps. Participants were instructed to modify their dream scenario so that it involved vocalizations or an apnoea, -two behaviours that require a cortical control of ventilation when executed during wakefulness. Most participants (86%) were able to signal lucidity in at least one nap. In 50% of the lucid naps, we found a clear congruence between the dream report (e.g., diving under water) and the observed respiratory behaviour (e.g., central apnoea) and, in several cases, a preparatory breath before the respiratory behaviour. This suggests that the cortico-subcortical networks involved in voluntary respiratory movements are preserved during REM sleep and that breathing irregularities during this stage have a cortical/subcortical origin that reflects dream content.

Quantitative differences among EMG activities of muscles innervated by subpopulations of hypoglossal and upper spinal motoneurons during non-REM sleep - REM sleep transitions: a window on neural processes in the sleeping brain.

Science.gov (United States)

Rukhadze, I; Kamani, H; Kubin, L

2011-12-01

In the rat, a species widely used to study the neural mechanisms of sleep and motor control, lingual electromyographic activity (EMG) is minimal during non-rapid eye movement (non-REM) sleep and then phasic twitches gradually increase after the onset of REM sleep. To better characterize the central neural processes underlying this pattern, we quantified EMG of muscles innervated by distinct subpopulations of hypoglossal motoneurons and nuchal (N) EMG during transitions from non-REM sleep to REM sleep. In 8 chronically instrumented rats, we recorded cortical EEG, EMG at sites near the base of the tongue where genioglossal and intrinsic muscle fibers predominate (GG-I), EMG of the geniohyoid (GH) muscle, and N EMG. Sleep-wake states were identified and EMGs quantified relative to their mean levels in wakefulness in successive 10 s epochs. During non-REM sleep, the average EMG levels differed among the three muscles, with the order being N>GH>GG-I. During REM sleep, due to different magnitudes of phasic twitches, the order was reversed to GG-I>GH>N. GG-I and GH exhibited a gradual increase of twitching that peaked at 70-120 s after the onset of REM sleep and then declined if the REM sleep episode lasted longer. We propose that a common phasic excitatory generator impinges on motoneuron pools that innervate different muscles, but twitching magnitudes are different due to different levels of tonic motoneuronal hyperpolarization. We also propose that REM sleep episodes of average durations are terminated by intense activity of the central generator of phasic events, whereas long REM sleep episodes end as a result of a gradual waning of the tonic disfacilitatory and inhibitory processes.

Cholinergic imaging in dementia spectrum disorders

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Roy, Roman; Niccolini, Flavia; Pagano, Gennaro; Politis, Marios [Institute of Psychiatry, Psychology and Neuroscience, King' s College London, Neurodegeneration Imaging Group, Department of Basic and Clinical Neuroscience, London (United Kingdom)

2016-07-15

The multifaceted nature of the pathology of dementia spectrum disorders has complicated their management and the development of effective treatments. This is despite the fact that they are far from uncommon, with Alzheimer's disease (AD) alone affecting 35 million people worldwide. The cholinergic system has been found to be crucially involved in cognitive function, with cholinergic dysfunction playing a pivotal role in the pathophysiology of dementia. The use of molecular imaging such as SPECT and PET for tagging targets within the cholinergic system has shown promise for elucidating key aspects of underlying pathology in dementia spectrum disorders, including AD or parkinsonian dementias. SPECT and PET studies using selective radioligands for cholinergic markers, such as [{sup 11}C]MP4A and [{sup 11}C]PMP PET for acetylcholinesterase (AChE), [{sup 123}I]5IA SPECT for the α{sub 4}β{sub 2} nicotinic acetylcholine receptor and [{sup 123}I]IBVM SPECT for the vesicular acetylcholine transporter, have been developed in an attempt to clarify those aspects of the diseases that remain unclear. This has led to a variety of findings, such as cortical AChE being significantly reduced in Parkinson's disease (PD), PD with dementia (PDD) and AD, as well as correlating with certain aspects of cognitive function such as attention and working memory. Thalamic AChE is significantly reduced in progressive supranuclear palsy (PSP) and multiple system atrophy, whilst it is not affected in PD. Some of these findings have brought about suggestions for the improvement of clinical practice, such as the use of a thalamic/cortical AChE ratio to differentiate between PD and PSP, two diseases that could overlap in terms of initial clinical presentation. Here, we review the findings from molecular imaging studies that have investigated the role of the cholinergic system in dementia spectrum disorders. (orig.)

Cholinergic imaging in dementia spectrum disorders

International Nuclear Information System (INIS)

Roy, Roman; Niccolini, Flavia; Pagano, Gennaro; Politis, Marios

2016-01-01

The multifaceted nature of the pathology of dementia spectrum disorders has complicated their management and the development of effective treatments. This is despite the fact that they are far from uncommon, with Alzheimer's disease (AD) alone affecting 35 million people worldwide. The cholinergic system has been found to be crucially involved in cognitive function, with cholinergic dysfunction playing a pivotal role in the pathophysiology of dementia. The use of molecular imaging such as SPECT and PET for tagging targets within the cholinergic system has shown promise for elucidating key aspects of underlying pathology in dementia spectrum disorders, including AD or parkinsonian dementias. SPECT and PET studies using selective radioligands for cholinergic markers, such as [ 11 C]MP4A and [ 11 C]PMP PET for acetylcholinesterase (AChE), [ 123 I]5IA SPECT for the α 4 β 2 nicotinic acetylcholine receptor and [ 123 I]IBVM SPECT for the vesicular acetylcholine transporter, have been developed in an attempt to clarify those aspects of the diseases that remain unclear. This has led to a variety of findings, such as cortical AChE being significantly reduced in Parkinson's disease (PD), PD with dementia (PDD) and AD, as well as correlating with certain aspects of cognitive function such as attention and working memory. Thalamic AChE is significantly reduced in progressive supranuclear palsy (PSP) and multiple system atrophy, whilst it is not affected in PD. Some of these findings have brought about suggestions for the improvement of clinical practice, such as the use of a thalamic/cortical AChE ratio to differentiate between PD and PSP, two diseases that could overlap in terms of initial clinical presentation. Here, we review the findings from molecular imaging studies that have investigated the role of the cholinergic system in dementia spectrum disorders. (orig.)

Slow waves, sharp waves, ripples, and REM in sleeping dragons.

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Shein-Idelson, Mark; Ondracek, Janie M; Liaw, Hua-Peng; Reiter, Sam; Laurent, Gilles

2016-04-29

Sleep has been described in animals ranging from worms to humans. Yet the electrophysiological characteristics of brain sleep, such as slow-wave (SW) and rapid eye movement (REM) activities, are thought to be restricted to mammals and birds. Recording from the brain of a lizard, the Australian dragon Pogona vitticeps, we identified SW and REM sleep patterns, thus pushing back the probable evolution of these dynamics at least to the emergence of amniotes. The SW and REM sleep patterns that we observed in lizards oscillated continuously for 6 to 10 hours with a period of ~80 seconds. The networks controlling SW-REM antagonism in amniotes may thus originate from a common, ancient oscillator circuit. Lizard SW dynamics closely resemble those observed in rodent hippocampal CA1, yet they originate from a brain area, the dorsal ventricular ridge, that has no obvious hodological similarity with the mammalian hippocampus. Copyright © 2016, American Association for the Advancement of Science.

Differential effects of non-REM and REM sleep on memory consolidation?

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Ackermann Sandra; Rasch  Bjoern

2013-01-01

Sleep benefitsmemory consolidation. Previous theoretical accounts have proposed a differential role of slowwave sleep (SWS) rapid eye movement (REM) sleep and stage N2 sleep for different types of memories. For example the dual process hypothesis proposes that SWS is beneficial for declarative memories whereas REMsleep is important for consolidation of non declarative procedural and emotional memories. In fact numerous recent studies do provide further support for the crucial role of SWS (or ...

Development of a spherical neutron rem monitor

International Nuclear Information System (INIS)

Panchal, C.G.; Madhavi, V.; Bansode, P.Y.; Jakati, R.K.; Ghodgaonkar, M.D.; Desai, S.S.; Shaikh, A.M.; Sathian, V.

2007-01-01

A new neutron rem monitor based on spherical LINUS with the state of art electronic circuits has been designed in Electronics Division. This prototype instrument encompasses a spherical double polythene moderator to improve an isotropic response and a lead layer to extend its energy response compared to the conventional neutron rem monitors. A systematic testing and calibration of the energy and directional response of the prototype monitor have been carried out. Although the monitor is expected to perform satisfactorily upto an energy ∼ 55 MeV, at present its response has been tested upto 5 MeV. (author)

Acetylcholine content and viability of cholinergic neurons are influenced by the activity of protein histidine phosphatase

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2012-01-01

Background The first mammalian protein histidine phosphatase (PHP) was discovered in the late 90s of the last century. One of the known substrates of PHP is ATP-citrate lyase (ACL), which is responsible - amongst other functions - for providing acetyl-CoA for acetylcholine synthesis in neuronal tissues. It has been shown in previous studies that PHP downregulates the activity of ACL by dephosphorylation. According to this our present work focused on the influence of PHP activity on the acetylcholine level in cholinergic neurons. Results The amount of PHP in SN56 cholinergic neuroblastoma cells was increased after overexpression of PHP by using pIRES2-AcGFP1-PHP as a vector. We demonstrated that PHP overexpression reduced the acetylcholine level and induced cell death. The acetylcholine content of SN56 cells was measured by fast liquid chromatography-tandem mass spectrometry method. Overexpression of the inactive H53A-PHP mutant also induced cell damage, but in a significantly reduced manner. However, this overexpression of the inactive PHP mutant did not change the acetylcholine content of SN56 cells significantly. In contrast, PHP downregulation, performed by RNAi-technique, did not induce cell death, but significantly increased the acetylcholine content in SN56 cells. Conclusions We could show for the first time that PHP downregulation increased the acetylcholine level in SN56 cells. This might be a potential therapeutic strategy for diseases involving cholinergic deficits like Alzheimer's disease. PMID:22436051

Catalpol Induces Neuroprotection and Prevents Memory Dysfunction through the Cholinergic System and BDNF

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Dong Wan

2013-01-01

Full Text Available To investigate the role and mechanism of catalpol on neuroprotective effects and memory enhancing effects simultaneously, neuroprotective effects of catalpol were assessed by neurological deficits score, TTC staining, and cerebral blood flow detecting. Morris water maze was employed to investigate its effects on learning and memory and then clarify its possible mechanisms relating the central cholinergic system and BDNF. Edaravone and oxiracetam were used for positive control drugs based on its different action. Results showed that catalpol and edaravone significantly facilitated neurological function recovery, reduced infarction volume, and increased cerebral blood flow in stroke mice. Catalpol and oxiracetam decreased the escape latency significantly and increased the numbers of crossing platform obviously. The levels of ACh, ChAT, and BDNF in catalpol group were increased in a dose-dependent manner, and AChE declined with a U-shaped dose-response curve. Moreover, the levels of muscarinic AChR subtypes M1 and M2 in hippocampus were considerably raised by catalpol. These results demonstrated that catalpol may be useful for neuroprotection and memory enhancement, and the mechanism may be related to the central cholinergic system.

The motilin receptor agonist erythromycin stimulates hunger and food intake through a cholinergic pathway.

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Deloose, Eveline; Vos, Rita; Janssen, Pieter; Van den Bergh, Omer; Van Oudenhove, Lukas; Depoortere, Inge; Tack, Jan

2016-03-01

Motilin-induced phase III contractions have been identified as a hunger signal. These phase III contractions occur as part of the migrating motor complex (MMC), a contractility pattern of the gastrointestinal tract during fasting. The mechanism involved in this association between subjective hunger feelings and gastrointestinal motility during the MMC is largely unknown, however, as is its ability to stimulate food intake. We sought to 1) investigate the occurrence of hunger peaks and their relation to phase III contractions, 2) evaluate whether this relation was cholinergically driven, and 3) assess the ability of the motilin receptor agonist erythromycin to induce food intake. An algorithm was developed to detect hunger peaks. The association with phase III contractions was studied in 14 healthy volunteers [50% men; mean ± SEM age: 25 ± 2 y; mean ± SEM body mass index (BMI; in kg/m(2)): 23 ± 1]. The impact of pharmacologically induced phase III contractions on the occurrence of hunger peaks and the involvement of a cholinergic pathway were assessed in 14 healthy volunteers (43% men; age: 29 ± 3 y; BMI: 23 ± 1). Last, the effect of erythromycin administration on food intake was examined in 15 healthy volunteers (40% men; age: 28 ± 3 y; BMI: 22 ± 1). The occurrence of hunger peaks and their significant association with phase III contractions was confirmed (P hunger peaks (P hunger feelings through a cholinergic pathway. Moreover, erythromycin stimulated food intake, suggesting a physiologic role of motilin as an orexigenic signal from the gastrointestinal tract. This trial was registered at www.clinicaltrials.gov as NCT02633579. © 2016 American Society for Nutrition.

Reassessment of NRC's dollar per person-rem conversion factor policy

International Nuclear Information System (INIS)

1995-12-01

The US Nuclear Regulatory Commission (NRC) has completed a review and analysis of its dollar per person-rem conversion factor policy. As a result of this review, the NRC has decided to adopt a $2000 per person-rem conversion factor, subject it to present worth considerations, and limit its scope solely to health effects. This is in contrast to the previous policy and staff practice of using an undiscounted $1000 per person-rem conversion factor that served as a surrogate for all offsite consequences (health and offsite property). The policy shift has been incorporated in ''Regulatory Analysis Guidelines of the US Nuclear Regulatory Commission,'' NUREG/BR-0058, Revision 2, November 1995

Quantitative assessment of isolated rapid eye movement (REM) sleep without atonia without clinical REM sleep behavior disorder: clinical and research implications.

Science.gov (United States)

Sasai-Sakuma, Taeko; Frauscher, Birgit; Mitterling, Thomas; Ehrmann, Laura; Gabelia, David; Brandauer, Elisabeth; Inoue, Yuichi; Poewe, Werner; Högl, Birgit

2014-09-01

Rapid eye movement (REM) sleep without atonia (RWA) is observed in some patients without a clinical history of REM sleep behavior disorder (RBD). It remains unknown whether these patients meet the refined quantitative electromyographic (EMG) criteria supporting a clinical RBD diagnosis. We quantitatively evaluated EMG activity and investigated its overnight distribution in patients with isolated qualitative RWA. Fifty participants with an incidental polysomnographic finding of RWA (isolated qualitative RWA) were included. Tonic, phasic, and 'any' EMG activity during REM sleep on PSG were quantified retrospectively. Referring to the quantitative cut-off values for a polysomnographic diagnosis of RBD, 7/50 (14%) and 6/50 (12%) of the patients showed phasic and 'any' EMG activity in the mentalis muscle above the respective cut-off values. No patient was above the cut-off value for tonic EMG activity or phasic EMG activity in the anterior tibialis muscles. Patients with RWA above the cut-off value showed higher amounts of RWA during later REM sleep periods. This is the first study showing that some subjects with incidental RWA meet the refined quantitative EMG criteria for a diagnosis of RBD. Future longitudinal studies must investigate whether this subgroup with isolated qualitative RWA is at an increased risk of developing fully expressed RBD and/or neurodegenerative disease. Copyright © 2014 Elsevier B.V. All rights reserved.

Assessing the dream-lag effect for REM and NREM stage 2 dreams.

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Blagrove, Mark; Fouquet, Nathalie C; Henley-Einion, Josephine A; Pace-Schott, Edward F; Davies, Anna C; Neuschaffer, Jennifer L; Turnbull, Oliver H

2011-01-01

This study investigates evidence, from dream reports, for memory consolidation during sleep. It is well-known that events and memories from waking life can be incorporated into dreams. These incorporations can be a literal replication of what occurred in waking life, or, more often, they can be partial or indirect. Two types of temporal relationship have been found to characterize the time of occurrence of a daytime event and the reappearance or incorporation of its features in a dream. These temporal relationships are referred to as the day-residue or immediate incorporation effect, where there is the reappearance of features from events occurring on the immediately preceding day, and the dream-lag effect, where there is the reappearance of features from events occurring 5-7 days prior to the dream. Previous work on the dream-lag effect has used spontaneous home recalled dream reports, which can be from Rapid Eye Movement Sleep (REM) and from non-Rapid Eye Movement Sleep (NREM). This study addresses whether the dream-lag effect occurs only for REM sleep dreams, or for both REM and NREM stage 2 (N2) dreams. 20 participants kept a daily diary for over a week before sleeping in the sleep laboratory for 2 nights. REM and N2 dreams collected in the laboratory were transcribed and each participant rated the level of correspondence between every dream report and every diary record. The dream-lag effect was found for REM but not N2 dreams. Further analysis indicated that this result was not due to N2 dream reports being shorter, in terms of number of words, than the REM dream reports. These results provide evidence for a 7-day sleep-dependent non-linear memory consolidation process that is specific to REM sleep, and accord with proposals for the importance of REM sleep to emotional memory consolidation.

Assessing the Dream-Lag Effect for REM and NREM Stage 2 Dreams

Science.gov (United States)

Blagrove, Mark; Fouquet, Nathalie C.; Henley-Einion, Josephine A.; Pace-Schott, Edward F.; Davies, Anna C.; Neuschaffer, Jennifer L.; Turnbull, Oliver H.

2011-01-01

This study investigates evidence, from dream reports, for memory consolidation during sleep. It is well-known that events and memories from waking life can be incorporated into dreams. These incorporations can be a literal replication of what occurred in waking life, or, more often, they can be partial or indirect. Two types of temporal relationship have been found to characterize the time of occurrence of a daytime event and the reappearance or incorporation of its features in a dream. These temporal relationships are referred to as the day-residue or immediate incorporation effect, where there is the reappearance of features from events occurring on the immediately preceding day, and the dream-lag effect, where there is the reappearance of features from events occurring 5–7 days prior to the dream. Previous work on the dream-lag effect has used spontaneous home recalled dream reports, which can be from Rapid Eye Movement Sleep (REM) and from non-Rapid Eye Movement Sleep (NREM). This study addresses whether the dream-lag effect occurs only for REM sleep dreams, or for both REM and NREM stage 2 (N2) dreams. 20 participants kept a daily diary for over a week before sleeping in the sleep laboratory for 2 nights. REM and N2 dreams collected in the laboratory were transcribed and each participant rated the level of correspondence between every dream report and every diary record. The dream-lag effect was found for REM but not N2 dreams. Further analysis indicated that this result was not due to N2 dream reports being shorter, in terms of number of words, than the REM dream reports. These results provide evidence for a 7-day sleep-dependent non-linear memory consolidation process that is specific to REM sleep, and accord with proposals for the importance of REM sleep to emotional memory consolidation. PMID:22046336

Assessing the dream-lag effect for REM and NREM stage 2 dreams.

Directory of Open Access Journals (Sweden)

Mark Blagrove

Full Text Available This study investigates evidence, from dream reports, for memory consolidation during sleep. It is well-known that events and memories from waking life can be incorporated into dreams. These incorporations can be a literal replication of what occurred in waking life, or, more often, they can be partial or indirect. Two types of temporal relationship have been found to characterize the time of occurrence of a daytime event and the reappearance or incorporation of its features in a dream. These temporal relationships are referred to as the day-residue or immediate incorporation effect, where there is the reappearance of features from events occurring on the immediately preceding day, and the dream-lag effect, where there is the reappearance of features from events occurring 5-7 days prior to the dream. Previous work on the dream-lag effect has used spontaneous home recalled dream reports, which can be from Rapid Eye Movement Sleep (REM and from non-Rapid Eye Movement Sleep (NREM. This study addresses whether the dream-lag effect occurs only for REM sleep dreams, or for both REM and NREM stage 2 (N2 dreams. 20 participants kept a daily diary for over a week before sleeping in the sleep laboratory for 2 nights. REM and N2 dreams collected in the laboratory were transcribed and each participant rated the level of correspondence between every dream report and every diary record. The dream-lag effect was found for REM but not N2 dreams. Further analysis indicated that this result was not due to N2 dream reports being shorter, in terms of number of words, than the REM dream reports. These results provide evidence for a 7-day sleep-dependent non-linear memory consolidation process that is specific to REM sleep, and accord with proposals for the importance of REM sleep to emotional memory consolidation.

Neuropeptide glutamic acid-isoleucine (NEI)-induced paradoxical sleep in rats.

Science.gov (United States)

Fujimoto, Moe; Fukuda, Satoru; Sakamoto, Hidetoshi; Takata, Junko; Sawamura, Shigehito

2017-01-01

Neuropeptideglutamic acid-isoleucine (NEI) as well as melanin concentrating hormone (MCH) is cleaved from the 165 amino acid protein, prepro-melanin concentrating hormone (prepro-MCH). Among many physiological roles of MCH, we demonstrated that intracerebroventricular (icv) injection of MCH induced increases in REM sleep episodes as well as in non REM sleep episodes. However, there are no studies on the effect of NEI on the sleep-wake cycle. As for the sites of action of MCH for induction of REM sleep, the ventrolateral periaqueductal gray (vlPAG) has been reported to be one of its site of action. Although MCH neurons contain NEI, GABA, MCH, and other neuropeptides, we do not know which transmitter(s) might induce REM sleep by acting on the vlPAG. Thus, we first examined the effect of icv injection of NEI on the sleep-wake cycle, and investigated how microinjection of either NEI, MCH, or GABA into the vlPAG affected REM sleep in rats. Icv injection of NEI (0.61μg/5μl: n=7) significantly increased the time spent in REM episodes compared to control (saline: 5μl; n=6). Microinjection of either NEI (61ng/0.2μl: n=7), MCH (100ng/0.2μl: n=6) or GABA (250mM/0.2μl: n=7) into the vlPAG significantly increased the time spent in REM episodes and the AUC. Precise hourly analysis of REM sleep also revealed that after those microinjections, NEI and MCH increased REM episodes at the latter phase, compared to GABA which increased REM episodes at the earlier phase. This result suggests that NEI and MCH may induce sustained REM sleep, while GABA may initiate REM sleep. In conclusion, our findings demonstrate that NEI, a cleaved peptide from the same precursor, prepro-MCH, as MCH, induce REM sleep at least in part through acting on the vlPAG. Copyright © 2016 Elsevier Inc. All rights reserved.

Cholinergic innervation of the zebrafish olfactory bulb.

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Edwards, Jeffrey G; Greig, Ann; Sakata, Yoko; Elkin, Dimitry; Michel, William C

2007-10-20

A number of fish species receive forebrain cholinergic input but two recent reports failed to find evidence of cholinergic cell bodies or fibers in the olfactory bulbs (OBs) of zebrafish. In the current study we sought to confirm these findings by examining the OBs of adult zebrafish for choline acetyltransferase (ChAT) immunoreactivity. We observed a diffuse network of varicose ChAT-positive fibers associated with the nervus terminalis ganglion innervating the mitral cell/glomerular layer (MC/GL). The highest density of these fibers occurred in the anterior region of the bulb. The cellular targets of this cholinergic input were identified by exposing isolated OBs to acetylcholine receptor (AChR) agonists in the presence of agmatine (AGB), a cationic probe that permeates some active ion channels. Nicotine (50 microM) significantly increased the activity-dependent labeling of mitral cells and juxtaglomerular cells but not of tyrosine hydroxlase-positive dopaminergic neurons (TH(+) cells) compared to control preparations. The nAChR antagonist mecamylamine, an alpha7-nAChR subunit-specific antagonist, calcium-free artificial cerebrospinal fluid, or a cocktail of ionotropic glutamate receptor (iGluR) antagonists each blocked nicotine-stimulated labeling, suggesting that AGB does not enter the labeled neurons through activated nAChRs but rather through activated iGluRs following ACh-stimulated glutamate release. Deafferentation of OBs did not eliminate nicotine-stimulated labeling, suggesting that cholinergic input is primarily acting on bulbar neurons. These findings confirm the presence of a functioning cholinergic system in the zebrafish OB.

Cholinergic modulation of mesolimbic dopamine function and reward.

Science.gov (United States)

Mark, Gregory P; Shabani, Shkelzen; Dobbs, Lauren K; Hansen, Stephen T

2011-07-25

The substantial health risk posed by obesity and compulsive drug use has compelled a serious research effort to identify the neurobiological substrates that underlie the development these pathological conditions. Despite substantial progress, an understanding of the neurochemical systems that mediate the motivational aspects of drug-seeking and craving remains incomplete. Important work from the laboratory of Bart Hoebel has provided key information on neurochemical systems that interact with dopamine (DA) as potentially important components in both the development of addiction and the expression of compulsive behaviors such as binge eating. One such modulatory system appears to be cholinergic pathways that interact with DA systems at all levels of the reward circuit. Cholinergic cells in the pons project to DA-rich cell body regions in the ventral tegmental area (VTA) and substantial nigra (SN) where they modulate the activity of dopaminergic neurons and reward processing. The DA terminal region of the nucleus accumbens (NAc) contains a small but particularly important group of cholinergic interneurons, which have extensive dendritic arbors that make synapses with a vast majority of NAc neurons and afferents. Together with acetylcholine (ACh) input onto DA cell bodies, cholinergic systems could serve a vital role in gating information flow concerning the motivational value of stimuli through the mesolimbic system. In this report we highlight evidence that CNS cholinergic systems play a pivotal role in behaviors that are motivated by both natural and drug rewards. We argue that the search for underlying neurochemical substrates of compulsive behaviors, as well as attempts to identify potential pharmacotherapeutic targets to combat them, must include a consideration of central cholinergic systems. Copyright © 2011 Elsevier Inc. All rights reserved.

Differentiated NSC-34 motoneuron-like cells as experimental model for cholinergic neurodegeneration.

Science.gov (United States)

Maier, Oliver; Böhm, Julia; Dahm, Michael; Brück, Stefan; Beyer, Cordian; Johann, Sonja

2013-06-01

Alpha-motoneurons appear to be exceedingly affected in neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). Morphological and physiological degeneration of this neuronal phenotype is typically characterized by a marked decrease of neuronal markers and by alterations of cholinergic metabolism such as reduced choline acetyltransferase (ChAT) expression. The motoneuron-like cell line NSC-34 is a hybrid cell line produced by fusion of neuroblastoma with mouse motoneuron-enriched primary spinal cord cells. In order to further establish this cell line as a valid model system to investigate cholinergic neurodegeneration, NSC-34 cells were differentiated by serum deprivation and additional treatment with all-trans retinoic acid (atRA). Cell maturation was characterized by neurite outgrowth and increased expression of neuronal and cholinergic markers, including MAP2, GAP-43 and ChAT. Subsequently, we used differentiated NSC-34 cells to study early degenerative responses following exposure to various neurotoxins (H2O2, TNF-α, and glutamate). Susceptibility to toxin-induced cell death was determined by means of morphological changes, expression of neuronal marker proteins, and the ratio of pro-(Bax) to anti-(Bcl-2) apoptotic proteins. NSC-34 cells respond to low doses of neurotoxins with increased cell death of remaining undifferentiated cells with no obvious adverse effects on differentiated cells. Thus, the different vulnerability of differentiated and undifferentiated NSC-34 cells to neurotoxins is a key characteristic of NSC-34 cells and has to be considered in neurotoxic studies. Nonetheless, application of atRA induced differentiation of NSC-34 cells and provides a suitable model to investigate molecular events linked to neurodegeneration of differentiated neurons. Copyright © 2013 Elsevier Ltd. All rights reserved.

The spectrum of REM sleep-related episodes in children with type 1 narcolepsy.

Science.gov (United States)

Antelmi, Elena; Pizza, Fabio; Vandi, Stefano; Neccia, Giulia; Ferri, Raffaele; Bruni, Oliviero; Filardi, Marco; Cantalupo, Gaetano; Liguori, Rocco; Plazzi, Giuseppe

2017-06-01

Type 1 narcolepsy is a central hypersomnia due to the loss of hypocretin-producing neurons and characterized by cataplexy, excessive daytime sleepiness, sleep paralysis, hypnagogic hallucinations and disturbed nocturnal sleep. In children, close to the disease onset, type 1 narcolepsy has peculiar clinical features with severe cataplexy and a complex admixture of movement disorders occurring while awake. Motor dyscontrol during sleep has never been systematically investigated. Suspecting that abnormal motor control might affect also sleep, we systematically analysed motor events recorded by means of video polysomnography in 40 children with type 1 narcolepsy (20 females; mean age 11.8 ± 2.6 years) and compared these data with those recorded in 22 age- and sex-matched healthy controls. Motor events were classified as elementary movements, if brief and non-purposeful and complex behaviours, if simulating purposeful behaviours. Complex behaviours occurring during REM sleep were further classified as 'classically-defined' and 'pantomime-like' REM sleep behaviour disorder episodes, based on their duration and on their pattern (i.e. brief and vivid-energetic in the first case, longer and with subcontinuous gesturing mimicking daily life activity in the second case). Elementary movements emerging either from non-REM or REM sleep were present in both groups, even if those emerging from REM sleep were more numerous in the group of patients. Conversely, complex behaviours could be detected only in children with type 1 narcolepsy and were observed in 13 patients, with six having 'classically-defined' REM sleep behaviour disorder episodes and seven having 'pantomime-like' REM sleep behaviour disorder episodes. Complex behaviours during REM sleep tended to recur in a stereotyped fashion for several times during the night, up to be almost continuous. Patients displaying a more severe motor dyscontrol during REM sleep had also more severe motor disorder during daytime (i

Centrality of striatal cholinergic transmission in basal ganglia function

Directory of Open Access Journals (Sweden)

Paola eBonsi

2011-02-01

Full Text Available Work over the past two decades revealed a previously unexpected role for striatal cholinergic interneurons in the context of basal ganglia function. The recognition that these interneurons are essential in synaptic plasticity and motor learning represents a significant step ahead in deciphering how the striatum processes cortical inputs, and why pathological circumstances cause motor dysfunction.Loss of the reciprocal modulation between dopaminergic inputs and the intrinsic cholinergic innervation within the striatum appears to be the trigger for pathophysiological changes occurring in basal ganglia disorders. Accordingly, there is now compelling evidence showing profound changes in cholinergic markers in these disorders, in particular Parkinson’s disease and dystonia.Based on converging experimental and clinical evidence, we provide an overview of the role of striatal cholinergic transmission in physiological and pathological conditions, in the context of the pathogenesis of movement disorders.

Basic and modern concepts on cholinergic receptor: A review

Directory of Open Access Journals (Sweden)

Prashant Tiwari

2013-10-01

Full Text Available Cholinergic system is an important system and a branch of the autonomic nervous system which plays an important role in memory, digestion, control of heart beat, blood pressure, movement and many other functions. This article serves as both structural and functional sources of information regarding cholinergic receptors and provides a detailed understanding of the determinants governing specificity of muscarinic and nicotinic receptor to researchers. The study helps to give overall information about the fundamentals of the cholinergic system, its receptors and ongoing research in this field.

[Effects and mechanisms of the inflammatory reaction related to NASH and induced by activation of the cholinergic anti-inflammatory pathway].

Science.gov (United States)

Zhou, Zhou; Chen, Xiaomei; Li, Fuqiang; Tang, Cuilan

2015-01-01

To investigate the effects and mechanisms of the inflammatory reaction related to nonalcoholic steatohepatitis (NASH) and induced by activation of the cholinergic anti-inflammatory pathway. A mouse model of NASH was established by feeding a high-fat and high-sugar diet.Activation of the cholinergic anti-inflammatory pathway was achieved by nicotine administration to the NASH modeled mice and normal controls. Liver biopsies were taken and the concentrations of cytokines were measured. Isolated liver primary Kupffer cells and RAw264.7 cells were cultured, pre-treated or not with lipopolysaccharide (LPS) and exposed to nicotine, after which the supernatant concentrations of IL-6 and TNFa were determined by ELISA. The protein expression levels of phosphorylated (p)-NF-kB and I k B were detected in primary cultured Kupffer cells by western blotting. The mouse model of NASH was successfully established, as evidenced by findings from liver biopsy and serum liver function tests. The degree of liver inflammation in the NASH mice decreased after nicotine administration, and the level of serum TNFa also significantly decreased. The levels of serum TNFa were 21.95+/-0.8 pg/mL in nicotine-treated mice and 38.07+/-1.7 pg/mL in the non-nicotine-treated NASH mice (P less than 0.05). The nicotine treatment also significantly reduced the concentration of TNFa in the culture supernatants of Kupffer cells after LPS stimulation; moreover, the supernatant level of TNFa decreased significantly after the nicotine treatment (Pless than 0.05). LPS stimulation of the RAw264.7 cells led to an increased level ofp-NF-kB and a reduced level ofI-kB, suggesting that the NF-kB pathway had been activated; different doses of nicotine pre-treatment led to down-regulation of the p-NF-kB level and up-regulation of the I-kB level, both in dose-dependent manners. Activating the cholinergic anti-inflammatory pathway inhibits the NASH-related inflammatory reaction, and the mechanism for this inhibition

The hypocretins (orexins mediate the “phasic” components of REM sleep: A new hypothesis

Directory of Open Access Journals (Sweden)

Pablo Torterolo

2014-03-01

The hypocretinergic neurons are active during wakefulness in conjunction with the presence of motor activity that occurs during survival-related behaviors. These neurons decrease their firing rate during non-REM sleep; however there is still controversy upon the activity and role of these neurons during REM sleep. Hence, in the present report we conducted a critical review of the literature of the hypocretinergic system during REM sleep, and hypothesize a possible role of this system in the generation of REM sleep.

Protective role of rosmarinic acid on amyloid beta 42-induced echoic memory decline: Implication of oxidative stress and cholinergic impairment.

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Kantar Gok, Deniz; Hidisoglu, Enis; Ocak, Guzide Ayse; Er, Hakan; Acun, Alev Duygu; Yargıcoglu, Piraye

2018-04-13

In the present study, we examined whether rosmarinic acid (RA) reverses amyloid β (Aβ) induced reductions in antioxidant defense, lipid peroxidation, cholinergic damage as well as the central auditory deficits. For this purpose, Wistar rats were randomly divided into four groups; Sham(S), Sham + RA (SR), Aβ42 peptide (Aβ) and Aβ42 peptide + RA (AβR) groups. Rat model of Alzheimer was established by bilateral injection of Aβ42 peptide (2,2 nmol/10 μl) into the lateral ventricles. RA (50 mg/kg, daily) was administered orally by gavage for 14 days after intracerebroventricular injection. At the end of the experimental period, we recorded the auditory event related potentials (AERPs) and mismatch negativity (MMN) response to assess auditory functions followed by histological and biochemical analysis. Aβ42 injection led to a significant increase in the levels of thiobarbituric acid reactive substances (TBARS) and 4-Hydroxy-2-nonenal (4-HNE) but decreased the activity of antioxidant enzymes (SOD, CAT, GSH-Px) and glutathione levels. Moreover, Aβ42 injection resulted in a reduction in the acetylcholine content and acetylcholine esterase activity. RA treatment prevented the observed alterations in the AβR group. Furthermore, RA attenuated the increased Aβ staining and astrocyte activation. We also found that Aβ42 injection decreased the MMN response and theta power/coherence of AERPs, suggesting an impairing effect on auditory discrimination and echoic memory processes. RA treatment reversed the Aβ42 related alterations in AERP parameters. In conclusion, our study demonstrates that RA prevented Aβ-induced antioxidant-oxidant imbalance and cholinergic damage, which may contribute to the improvement of neural network dynamics of auditory processes in this rat model. Copyright © 2018. Published by Elsevier Ltd.

Cortical cholinergic innervation: Distribution and source in monkeys

International Nuclear Information System (INIS)

Struble, R.G.; Cork, L.C.; Coyle, J.T.; Lehmann, J.; Mitchell, S.J.; Price, D.L.

1986-01-01

In Alzheimer's disease (AD) and its late-life variant, senile dementia of the Alzheimer's type (SDAT), the predominant neurochemical abnormalities are marked decrements in the activities of ChAT and AChE, the high affinity uptake of tritium-choline, and synthesis of acetylcholine. Two studies are undertaken to delineate more clearly the variability of cortical cholinergic innervation and the contribution of the Ch system, particularly the Ch4, to this cholinergic innervation. In the first study, ChAT activity was assessed in multiple samples of neocortex from seven normal cynomolgus monkeys. In the second study, the nbM was lesioned in order to determine the contribution of the Ch system to cortical cholinergic innervation

Loss of Gnas imprinting differentially affects REM/NREM sleep and cognition in mice.

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Glenda Lassi

Full Text Available It has been suggested that imprinted genes are important in the regulation of sleep. However, the fundamental question of whether genomic imprinting has a role in sleep has remained elusive up to now. In this work we show that REM and NREM sleep states are differentially modulated by the maternally expressed imprinted gene Gnas. In particular, in mice with loss of imprinting of Gnas, NREM and complex cognitive processes are enhanced while REM and REM-linked behaviors are inhibited. This is the first demonstration that a specific overexpression of an imprinted gene affects sleep states and related complex behavioral traits. Furthermore, in parallel to the Gnas overexpression, we have observed an overexpression of Ucp1 in interscapular brown adipose tissue (BAT and a significant increase in thermoregulation that may account for the REM/NREM sleep phenotypes. We conclude that there must be significant evolutionary advantages in the monoallelic expression of Gnas for REM sleep and for the consolidation of REM-dependent memories. Conversely, biallelic expression of Gnas reinforces slow wave activity in NREM sleep, and this results in a reduction of uncertainty in temporal decision-making processes.

Nitric oxide and the non-adrenergic non-cholinergic neurotransmission

NARCIS (Netherlands)

Boeckxstaens, G. E.; Pelckmans, P. A.

1997-01-01

In the early 1960s, the first evidence was reported demonstrating neurally mediated responses in the presence of adrenergic and cholinergic antagonists, leading to the introduction of the concept of non-adrenergic non-cholinergic neurotransmission. The inhibitory component of this part of the

Surface-atmospheric water cycle at Gale crater through multi-year MSL/REMS observations

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Harri, A. M.; Genzer, M.; McConnochie, T. H.; Savijarvi, H. I.; Smith, M. D.; Martinez, G.; de la Torre Juarez, M.; Haberle, R. M.; Polkko, J.; Gomez-Elvira, J.; Renno, N. O.; Kemppinen, O.; Paton, M.; Richardson, M. I.; Newman, C. E.; Siili, T. T.; Mäkinen, T.

2017-12-01

The Mars Science laboratory (MSL) has been successfully operating for almost three Martian years. That includes an unprecedented long time series of atmospheric observations by the REMS instrument performing measurements of atmospheric pressure, relative humidity (REMS-H), temperature of the air, ground temperature, UV and wind speed and direction. The REMS-H relative humidity device is based on polymeric capacitive humidity sensors developed by Vaisala Inc. and it makes use of three (3) humidity sensor heads. The humidity device is mounted on the REMS boom providing ventilation with the ambient atmosphere through a filter protecting the device from airborne dust. The REMS-H humidity instrument has created an unprecedented data record of more than two full Martian. REMS-H measured the relative humidity and temperature at 1.6 m height for a period of 5 minutes every hour as part of the MSL/REMS instrument package. We focus on describing the annual in situ water cycle with the REMS-H instrument data for the period of almost three Martian years. The results will be constrained through comparison with independent indirect observations and through modeling efforts. We inferred the hourly atmospheric VMR from the REMS-H observations and compared these VMR measurements with predictions of VMR from our 1D column Martian atmospheric model and regolith to investigate the local water cycle, exchange processes and the local climate in Gale Crater. The strong diurnal variation suggests there are surface-atmosphere exchange processes at Gale Crater during all seasons, which depletes moisture to the ground in the evening and nighttime and release the moisture back to the atmosphere during the daytime. On the other hand, these processes do not seem to result in significant water deposition on the ground. Hence, our modelling results presumably indicate that adsorption processes take place during the nighttime and desorption during the daytime. Other processes, e.g. convective

Localization of rem2 in the central nervous system of the adult rainbow trout (Oncorhynchus mykiss).

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Downs, Anna G; Scholles, Katie R; Hollis, David M

2016-12-01

Rem2 is member of the RGK (Rem, Rad, and Gem/Kir) subfamily of the Ras superfamily of GTP binding proteins known to influence Ca 2+ entry into the cell. In addition, Rem2, which is found at high levels in the vertebrate brain, is also implicated in cell proliferation and synapse formation. Though the specific, regional localization of Rem2 in the adult mammalian central nervous system has been well-described, such information is lacking in other vertebrates. Rem2 is involved in neuronal processes where the capacities between adults of different vertebrate classes vary. Thus, we sought to localize the rem2 gene in the central nervous system of an adult anamniotic vertebrate, the rainbow trout (Oncorhynchus mykiss). In situ hybridization using a digoxigenin (DIG)-labeled RNA probe was used to identify the regional distribution of rem2 expression throughout the trout central nervous system, while real-time polymerase chain reaction (rtPCR) further supported these findings. Based on in situ hybridization, the regional distribution of rem2 occurred within each major subdivision of the brain and included large populations of rem2 expressing cells in the dorsal telencephalon of the cerebrum, the internal cellular layer of the olfactory bulb, and the optic tectum of the midbrain. In contrast, no rem2 expressing cells were resolved within the cerebellum. These results were corroborated by rtPCR, where differential rem2 expression occurred between the major subdivisions assayed with the highest levels being found in the cerebrum, while it was nearly absent in the cerebellum. These data indicate that rem2 gene expression is broadly distributed and likely influences diverse functions in the adult fish central nervous system. Copyright © 2016 Elsevier B.V. All rights reserved.

CHOLINERGIC NEUROPHARMACOLOGY - AN UPDATE

NARCIS (Netherlands)

PALACIOS, JM; BODDEKE, HWGM; POMBOVILLAR, E

1991-01-01

The current status of the pharmacology of central cholinergic transmission is reviewed. Particular attention is paid to the compounds that have been or are potential candidates as therapeutic agents for the treatment of mental disorders, particularly senile dementia. Compounds affecting

Activation of the mouse primary visual cortex by medial prefrontal subregion stimulation is not mediated by cholinergic basalo-cortical projections

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Hoang Nam eNguyen

2015-02-01

Full Text Available The medial prefrontal cortex (mPFC exerts top-down control of primary visual cortex (V1 activity. As there is no direct neuronal projection from mPFC to V1, this functional connection may use an indirect route, i.e., via basalo-cortical cholinergic projections. The cholinergic projections to V1 originate from neurons in the horizontal limb of the diagonal band of Broca (HDB, which receive neuronal projections from the ventral part of the mPFC, composed of prelimbic (PrL and infralimbic cortices (IL. Therefore, the objective of this study was to determine whether electrical stimulation of mice mPFC subregions activate 1 V1 neurons and 2 HDB cholinergic neurons, suggesting that the HDB serves as a relay point in the mPFC-V1 interaction. Neuronal activation was quantified using c-Fos immunocytochemistry or thallium autometallography for each V1 layer using automated particle analysis tools and optical density measurement. Stimulation of IL and PrL induced significantly higher c-Fos expression or thallium labelling in layers II/III and V of V1 in the stimulated hemisphere only. A HDB cholinergic neuron-specific lesion by saporin administration reduced IL-induced c-Fos expression in layers II/III of V1 but not in layer V. However, there was no c-Fos expression or thallium labelling in the HDB neurons, suggesting that this area was not activated by IL stimulation. Stimulation of another mPFC subarea, the anterior cingulate cortex (AC, which is involved in attention and receives input from V1, activated neither V1 nor HDB. The present results indicate that IL and PrL, but not AC, stimulation activates V1 with the minor involvement of the HDB cholinergic projections. These results suggest a functional link between the ventral mPFC and V1, but this function is only marginally supported by HDB cholinergic neurons and may involve other brain regions.

REM Sleep Behavior Disorder and Narcoleptic Features in Anti–Ma2-associated Encephalitis

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Compta, Yaroslau; Iranzo, Alex; Santamaría, Joan; Casamitjana, Roser; Graus, Francesc

2007-01-01

A 69-year-old man with anti-Ma2 paraneoplastic encephalitis presented with subacute onset of severe hypersomnia, memory loss, parkinsonism, and gaze palsy. A brain magnetic resonance imaging study showed bilateral damage in the dorsolateral midbrain, amygdala, and paramedian thalami. Videopolysomnography disclosed rapid eye movement (REM) sleep behavior disorder, and a Multiple Sleep Latency Test showed a mean sleep latency of 7 minutes and 4 sleep-onset REM periods. The level of hypocretin-1 in the cerebrospinal fluid was low (49 pg/mL). This observation illustrates that REM sleep behavior disorder and narcoleptic features are 2 REM-sleep abnormalities that (1) may share the same autoimmune-mediated origin affecting the brainstem, limbic, and diencephalic structures and (2) may occur in the setting of the paraneoplastic anti–Ma2-associated encephalitis. Citation: Compta Y; Iranzo A; Santamaría J et al. REM Sleep Behavior Disorder and Narcoleptic Features in Anti–Ma2-associated Encephalitis. SLEEP 2007;30(6):767-769. PMID:17580598

Phosphodiesterase 10A inhibition attenuates sleep deprivation-induced deficits in long-term fear memory.

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Guo, Lengqiu; Guo, Zhuangli; Luo, Xiaoqing; Liang, Rui; Yang, Shui; Ren, Haigang; Wang, Guanghui; Zhen, Xuechu

2016-12-02

Sleep, particularly rapid eye movement (REM) sleep, is implicated in the consolidation of emotional memories. In the present study, we investigated the protective effects of a phosphodiesterase 10A (PDE10A) inhibitor MP-10 on deficits in long-term fear memory induced by REM sleep deprivation (REM-SD). REM-SD caused deficits in long-term fear memory, however, MP-10 administration ameliorated the deleterious effects of REM-SD on long term fear memory. Brain-derived neurotropic factor (BDNF) and phosphorylated cAMP response element-binding protein (pCREB) were altered in specific brain regions associated with learning and memory in REM-SD rats. Accordingly, REM-SD caused a significant decrease of pCREB in hippocampus and striatum and a significant decrease of BDNF in the hippocampus, striatum and amygdala, however, MP-10 reversed the effects of REM-SD in a dose-dependent manner. Our findings suggest that REM-SD disrupts the consolidation of long-term fear memory and that administration of MP-10 protects the REM-SD-induced deficits in fear memory, which may be due to the MP-10-induced expression of BDNF in the hippocampus, striatum and amygdala, and phosphorylation of CREB in the hippocampus and striatum. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Sleep disorders in psychiatry.

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Costa e Silva, Jorge Alberto

2006-10-01

Sleep is an active state that is critical for our physical, mental, and emotional well-being. Sleep is also important for optimal cognitive functioning, and sleep disruption results in functional impairment. Insomnia is the most common sleep disorder in psychiatry. At any given time, 50% of adults are affected with 1 or more sleep problems such as difficulty in falling or staying asleep, in staying awake, or in adhering to a consistent sleep/wake schedule. Narcolepsy affects as many individuals as does multiple sclerosis or Parkinson disease. Sleep problems are especially prevalent in schizophrenia, depression, and other mental illnesses, and every year, sleep disorders, sleep deprivation, and sleepiness add billions to the national health care bill in industrialized countries. Although psychiatrists often treat patients with insomnia secondary to depression, most patients discuss their insomnia with general care physicians, making it important to provide this group with clear guidelines for the diagnosis and management of insomnia. Once the specific medical, behavioral, or psychiatric causes of the sleep problem have been identified, appropriate treatment can be undertaken. Chronic insomnia has multiple causes arising from medical disorders, psychiatric disorders, primary sleep disorders, circadian rhythm disorders, social or therapeutic use of drugs, or maladaptive behaviors. The emerging concepts of sleep neurophysiology are consistent with the cholinergic-aminergic imbalance hypothesis of mood disorders, which proposes that depression is associated with an increased ratio of central cholinergic to aminergic neurotransmission. The characteristic sleep abnormalities of depression may reflect a relative predominance of cholinergic activity. Antidepressant medications presumably reduce rapid eye movement (REM) sleep either by their anticholinergic properties or by enhancing aminergic neurotransmission. Intense and prolonged dreams often accompany abrupt withdrawal

The Time Course of the Probability of Transition Into and Out of REM Sleep

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Bassi, Alejandro; Vivaldi, Ennio A.; Ocampo-Garcés, Adrián

2009-01-01

Study Objectives: A model of rapid eye movement (REM) sleep expression is proposed that assumes underlying regulatory mechanisms operating as inhomogenous Poisson processes, the overt results of which are the transitions into and out of REM sleep. Design: Based on spontaneously occurring REM sleep episodes (“Episode”) and intervals without REM sleep (“Interval”), 3 variables are defined and evaluated over discrete 15-second epochs using a nonlinear logistic regression method: “Propensity” is the instantaneous rate of into-REM transition occurrence throughout an Interval, “Volatility” is the instantaneous rate of out-of-REM transition occurrence throughout an Episode, and “Opportunity” is the probability of being in non-REM (NREM) sleep at a given time throughout an Interval, a requisite for transition. Setting: 12:12 light:dark cycle, isolated boxes. Participants: Sixteen male Sprague-Dawley rats Interventions: None. Spontaneous sleep cycles. Measurements and Results: The highest levels of volatility and propensity occur, respectively, at the very beginning of Episodes and Intervals. The new condition stabilizes rapidly, and variables reach nadirs at minute 1.25 and 2.50, respectively. Afterward, volatility increases markedly, reaching values close to the initial level. Propensity increases moderately, the increment being stronger through NREM sleep bouts occurring at the end of long Intervals. Short-term homeostasis is evidenced by longer REM sleep episodes lowering propensity in the following Interval. Conclusions: The stabilization after transitions into Episodes or Intervals and the destabilization after remaining for some time in either condition may be described as resulting from continuous processes building up during Episodes and Intervals. These processes underlie the overt occurrence of transitions. Citation: Bassi A; Vivaldi EA; Ocampo-Garcées A. The time course of the probability of transition into and out of REM sleep. SLEEP 2009

Elevated Hippocampal Cholinergic Neurostimulating Peptide precursor protein (HCNP-pp) mRNA in the amygdala in major depression.

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Bassi, Sabrina; Seney, Marianne L; Argibay, Pablo; Sibille, Etienne

2015-04-01

The amygdala is innervated by the cholinergic system and is involved in major depressive disorder (MDD). Evidence suggests a hyper-activate cholinergic system in MDD. Hippocampal Cholinergic Neurostimulating Peptide (HCNP) regulates acetylcholine synthesis. The aim of the present work was to investigate expression levels of HCNP-precursor protein (HCNP-pp) mRNA and other cholinergic-related genes in the postmortem amygdala of MDD patients and matched controls (females: N = 16 pairs; males: N = 12 pairs), and in the mouse unpredictable chronic mild stress (UCMS) model that induced elevated anxiety-/depressive-like behaviors (females: N = 6 pairs; males: N = 6 pairs). Results indicate an up-regulation of HCNP-pp mRNA in the amygdala of women with MDD (p < 0.0001), but not males, and of UCMS-exposed mice (males and females; p = 0.037). HCNP-pp protein levels were investigated in the human female cohort, but no difference was found. There were no differences in gene expression of acetylcholinesterase (AChE), muscarinic (mAChRs) or nicotinic receptors (nAChRs) between MDD subjects and controls or UCMS and control mice, except for an up-regulation of AChE in UCMS-exposed mice (males and females; p = 0.044). Exploratory analyses revealed a baseline expression difference of cholinergic signaling-related genes between women and men (p < 0.0001). In conclusion, elevated amygdala HCNP-pp expression may contribute to mechanisms of MDD in women, potentially independently from regulating the cholinergic system. The differential expression of genes between women and men could also contribute to the increased vulnerability of females to develop MDD. Copyright © 2015 Elsevier Ltd. All rights reserved.

Nicotine protects kidney from renal ischemia/reperfusion injury through the cholinergic anti-inflammatory pathway.

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Claude Sadis

Full Text Available Kidney ischemia/reperfusion injury (I/R is characterized by renal dysfunction and tubular damages resulting from an early activation of innate immunity. Recently, nicotine administration has been shown to be a powerful inhibitor of a variety of innate immune responses, including LPS-induced toxaemia. This cholinergic anti-inflammatory pathway acts via the alpha7 nicotinic acetylcholine receptor (alpha7nAChR. Herein, we tested the potential protective effect of nicotine administration in a mouse model of renal I/R injury induced by bilateral clamping of kidney arteries. Renal function, tubular damages and inflammatory response were compared between control animals and mice receiving nicotine at the time of ischemia. Nicotine pretreatment protected mice from renal dysfunction in a dose-dependent manner and through the alpha7nAChR, as attested by the absence of protection in alpha7nAChR-deficient mice. Additionally, nicotine significantly reduced tubular damages, prevented neutrophil infiltration and decreased productions of the CXC-chemokine KC, TNF-alpha and the proinflammatory high-mobility group box 1 protein. Reduced tubular damage in nicotine pre-treated mice was associated with a decrease in tubular cell apoptosis and proliferative response as attested by the reduction of caspase-3 and Ki67 positive cells, respectively. All together, these data highlight that nicotine exerts a protective anti-inflammatory effect during kidney I/R through the cholinergic alpha7nAChR pathway. In addition, this could provide an opportunity to overcome the effect of surgical cholinergic denervation during kidney transplantation.

Analysis of the environmental conditions at Gale Crater from MSL/REMS measurements

Energy Technology Data Exchange (ETDEWEB)

Martinez, G.; Torre-Juarez, M. de la; Vicente-Retortillo, A.; Kemppinen, O.; Renno, N.; Lemmon, M.

2016-07-01

The environmental conditions at Gale Crater during the first 1160 sols of the Mars Science Laboratory (MSL) mission are assessed using measurements taken by the Rover Environmental Monitoring Station (REMS) on-board the MSL Curiosity rover. REMS is a suite of sensors developed to assess the environmental conditions along the rover traverse. In particular, REMS has been measuring atmospheric pressure, atmospheric and ground temperature, relative humidity, UV radiation flux and wind speed. Here we analyze processed data with the highest confidence possible of atmospheric pressure, atmospheric and ground temperature and relative humidity. In addition, we estimate the daily UV irradiation at the surface of Gale Crater using dust opacity values derived from the Mastcam instrument. REMS is still in operation, but it has already provided the most comprehensive coverage of surface environmental conditions recorded by a spacecraft landed on Mars. (Author)

The Effect of Exercise on Learning and Spatial Memory Following Stress-Induced Sleep Deprivation (Sleep REM in Rats

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Darkhah

2016-04-01

Full Text Available Background Stress induced by sleep deprivation can cause degradation of learning in the acquisition phase, and low-intensity exercise can prevent the negative effects of stress. Objectives The aim of this study was to investigate the moderating role of aerobic exercise on spatial memory and learning following stress-induced insomnia (sleep REM in animal models. Materials and Methods This experimental study was conducted on adult male Wistar rats that were randomly divided into two groups. Both groups were exposed to sleep deprivation induced stress, following which the experimental group was exposed to exercise training (experimental, n = 8; control, n = 8. The stress intervention was undertaken through 24 hours of sleep deprivation using a modified sleep deprivation platform (MMD. The exercise protocol included mild aerobic exercise on a treadmill (30 minutes a day, seven days, and Morris Water Maze (MWM protocols were applied to assess spatial memory and learning. Data were analyzed by an independent t-test and dependent t-test. Results The results showed that, after seven days of aerobic exercise on a treadmill, the experimental group showed better performance escape latency (P < 0.05 and distance traveled (P < 0.05 than the control group in the MWM, while there was no difference between these two groups in the pre-test. Conclusions The role of exercise is greater in the retention than the acquisition phase for recalling past experiences.

Elimination of the vesicular acetylcholine transporter in the striatum reveals regulation of behaviour by cholinergic-glutamatergic co-transmission.

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Monica S Guzman

2011-11-01

Full Text Available Cholinergic neurons in the striatum are thought to play major regulatory functions in motor behaviour and reward. These neurons express two vesicular transporters that can load either acetylcholine or glutamate into synaptic vesicles. Consequently cholinergic neurons can release both neurotransmitters, making it difficult to discern their individual contributions for the regulation of striatal functions. Here we have dissected the specific roles of acetylcholine release for striatal-dependent behaviour in mice by selective elimination of the vesicular acetylcholine transporter (VAChT from striatal cholinergic neurons. Analysis of several behavioural parameters indicates that elimination of VAChT had only marginal consequences in striatum-related tasks and did not affect spontaneous locomotion, cocaine-induced hyperactivity, or its reward properties. However, dopaminergic sensitivity of medium spiny neurons (MSN and the behavioural outputs in response to direct dopaminergic agonists were enhanced, likely due to increased expression/function of dopamine receptors in the striatum. These observations indicate that previous functions attributed to striatal cholinergic neurons in spontaneous locomotor activity and in the rewarding responses to cocaine are mediated by glutamate and not by acetylcholine release. Our experiments demonstrate how one population of neurons can use two distinct neurotransmitters to differentially regulate a given circuitry. The data also raise the possibility of using VAChT as a target to boost dopaminergic function and decrease high striatal cholinergic activity, common neurochemical alterations in individuals affected with Parkinson's disease.

CAN NON-REM SLEEP BE DEPRESSOGENIC

NARCIS (Netherlands)

BEERSMA, DGM; VANDENHOOFDAKKER, RH

Sleep and mood are clearly interrelated in major depression, as shown by the antidepressive effects of various experiments, such as total sleep deprivation, partial sleep deprivation, REM sleep deprivation, and temporal shifts of the sleep period. The prevailing hypotheses explaining these effects

Can non-REM sleep be depressogenic?

NARCIS (Netherlands)

Beersma, Domien G.M.; Hoofdakker, Rutger H. van den

1992-01-01

Sleep and mood are clearly interrelated in major depression, as shown by the antidepressive effects of various experiments, such as total sleep deprivation, partial sleep deprivation, REM sleep deprivation, and temporal shifts of the sleep period. The prevailing hypotheses explaining these effects

Cholinergic Modulation of Type 2 Immune Responses

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Goele Bosmans

2017-12-01

Full Text Available In recent years, the bidirectional relationship between the nervous and immune system has become increasingly clear, and its role in both homeostasis and inflammation has been well documented over the years. Since the introduction of the cholinergic anti-inflammatory pathway, there has been an increased interest in parasympathetic regulation of both innate and adaptive immune responses, including T helper 2 responses. Increasing evidence has been emerging suggesting a role for the parasympathetic nervous system in the pathophysiology of allergic diseases, including allergic rhinitis, asthma, food allergy, and atopic dermatitis. In this review, we will highlight the role of cholinergic modulation by both nicotinic and muscarinic receptors in several key aspects of the allergic inflammatory response, including barrier function, innate and adaptive immune responses, and effector cells responses. A better understanding of these cholinergic processes mediating key aspects of type 2 immune disorders might lead to novel therapeutic approaches to treat allergic diseases.

Endogenous cholinergic neurotransmission contributes to behavioral sensitization to morphine.

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Dusica Bajic

Full Text Available Neuroplasticity in the mesolimbic dopaminergic system is critical for behavioral adaptations associated with opioid reward and addiction. These processes may be influenced by cholinergic transmission arising from the laterodorsal tegmental nucleus (LDTg, a main source of acetylcholine to mesolimbic dopaminergic neurons. To examine this possibility we asked if chronic systemic morphine administration affects expression of genes in ventral and ventrolateral periaqueductal gray at the level of the LDTg using rtPCR. Specifically, we examined gene expression changes in the area of interest using Neurotransmitters and Receptors PCR array between chronic morphine and saline control groups. Analysis suggested that chronic morphine administration led to changes in expression of genes associated, in part, with cholinergic neurotransmission. Furthermore, using a quantitative immunofluorescent technique, we found that chronic morphine treatment produced a significant increase in immunolabeling of the cholinergic marker (vesicular acetylcholine transporter in neurons of the LDTg. Finally, systemic administration of the nonselective and noncompetitive neuronal nicotinic antagonist mecamylamine (0.5 or 2 mg/kg dose-dependently blocked the expression, and to a lesser extent the development, of locomotor sensitization. The same treatment had no effect on acute morphine antinociception, antinociceptive tolerance or dependence to chronic morphine. Taken together, the results suggest that endogenous nicotinic cholinergic neurotransmission selectively contributes to behavioral sensitization to morphine and this process may, in part, involve cholinergic neurons within the LDTg.

Development of myenteric cholinergic neurons in ChAT-Cre;R26R-YFP mice.

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Hao, Marlene M; Bornstein, Joel C; Young, Heather M

2013-10-01

Cholinergic neurons are the major excitatory neurons of the enteric nervous system (ENS), and include intrinsic sensory neurons, interneurons, and excitatory motor neurons. Cholinergic neurons have been detected in the embryonic ENS; however, the development of these neurons has been difficult to study as they are difficult to detect prior to birth using conventional immunohistochemistry. In this study we used ChAT-Cre;R26R-YFP mice to examine the development of cholinergic neurons in the gut of embryonic and postnatal mice. Cholinergic (YFP+) neurons were first detected at embryonic day (E)11.5, and the proportion of cholinergic neurons gradually increased during pre- and postnatal development. At birth, myenteric cholinergic neurons comprised less than half of their adult proportions in the small intestine (25% of myenteric neurons were YFP+ at P0 compared to 62% in adults). The earliest cholinergic neurons appear to mainly project anally. Projections into the presumptive circular muscle were first observed at E14.5. A subpopulation of cholinergic neurons coexpress calbindin through embryonic and postnatal development, but only a small proportion coexpressed neuronal nitric oxide synthase. Our study shows that cholinergic neurons in the ENS develop over a protracted period of time. © 2013 Wiley Periodicals, Inc.

Selective REM-sleep deprivation does not diminish emotional memory consolidation in young healthy subjects.

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Morgenthaler, Jarste; Wiesner, Christian D; Hinze, Karoline; Abels, Lena C; Prehn-Kristensen, Alexander; Göder, Robert

2014-01-01

Sleep enhances memory consolidation and it has been hypothesized that rapid eye movement (REM) sleep in particular facilitates the consolidation of emotional memory. The aim of this study was to investigate this hypothesis using selective REM-sleep deprivation. We used a recognition memory task in which participants were shown negative and neutral pictures. Participants (N=29 healthy medical students) were separated into two groups (undisturbed sleep and selective REM-sleep deprived). Both groups also worked on the memory task in a wake condition. Recognition accuracy was significantly better for negative than for neutral stimuli and better after the sleep than the wake condition. There was, however, no difference in the recognition accuracy (neutral and emotional) between the groups. In summary, our data suggest that REM-sleep deprivation was successful and that the resulting reduction of REM-sleep had no influence on memory consolidation whatsoever.

Management of REM sleep behavior disorder: An evidence based review.

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Devnani, Preeti; Fernandes, Racheal

2015-01-01

Rapid eye movement (REM) sleep behavior disorder (RBD) is characterized by dream enactment behavior resulting from a loss of REM skeletal muscle atonia. The neurobiology of REM sleep and the characteristic features of REM atonia have an important basis for understanding the aggravating etiologies the proposed pharmacological interventions in its management. This review outlines the evidence for behavioral and therapeutic measures along with evidence-based guidelines for their implementation, impact on falls, and effect on polysomnography (PSG) while highlighting the non-motor, autonomic, and cognitive impact of this entity. PubMed databases were reviewed upto May 2013 in peer-reviewed scientific literature regarding the pathophysiology and management of RBD in adults. The literature was graded according to the Oxford centre of evidence-based Medicine Levels. An early intervention that helps prevent consequences such as falls and provides a base for intervention with neuroprotective mechanisms and allocates a unique platform that RBD portrays with its high risk of disease conversion with a sufficiently long latency. RBD provides a unique platform with its high risk of disease conversion with a sufficiently long latency, providing an opportunity for early intervention both to prevent consequences such as falls and provide a base for intervention with neuroprotective mechanisms.

Management of REM sleep behavior disorder: An evidence based review

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Preeti Devnani

2015-01-01

Full Text Available Rapid eye movement (REM sleep behavior disorder (RBD is characterized by dream enactment behavior resulting from a loss of REM skeletal muscle atonia. The neurobiology of REM sleep and the characteristic features of REM atonia have an important basis for understanding the aggravating etiologies the proposed pharmacological interventions in its management. This review outlines the evidence for behavioral and therapeutic measures along with evidence-based guidelines for their implementation, impact on falls, and effect on polysomnography (PSG while highlighting the non-motor, autonomic, and cognitive impact of this entity. PubMed databases were reviewed upto May 2013 in peer-reviewed scientific literature regarding the pathophysiology and management of RBD in adults. The literature was graded according to the Oxford centre of evidence-based Medicine Levels. An early intervention that helps prevent consequences such as falls and provides a base for intervention with neuroprotective mechanisms and allocates a unique platform that RBD portrays with its high risk of disease conversion with a sufficiently long latency. RBD provides a unique platform with its high risk of disease conversion with a sufficiently long latency, providing an opportunity for early intervention both to prevent consequences such as falls and provide a base for intervention with neuroprotective mechanisms.

Sleep stability and transitions in patients with idiopathic REM sleep behavior disorder and patients with Parkinson's disease

DEFF Research Database (Denmark)

Christensen, Julie Anja Engelhard; Jennum, Poul; Koch, Henriette

2016-01-01

Objective: Patients with idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD) are at high risk of developing Parkinson's disease (PD). As wake/sleep-regulation is thought to involve neurons located in the brainstem and hypothalamic areas, we hypothesize that the neurodegeneration in i......RBD/PD is likely to affect wake/sleep and REM/non-REM (NREM) sleep transitions. Methods: We determined the frequency of wake/sleep and REM/NREM sleep transitions and the stability of wake (W), REM and NREM sleep as measured by polysomnography (PSG) in 27 patients with PD, 23 patients with iRBD, 25 patients...... with periodic leg movement disorder (PLMD) and 23 controls. Measures were computed based on manual scorings and data-driven labeled sleep staging. Results: Patients with PD showed significantly lower REM stability than controls and patients with PLMD. Patients with iRBD had significantly lower REM stability...

Cholinergic neurotransmission in human corpus cavernosum. II. Acetylcholine synthesis

International Nuclear Information System (INIS)

Blanco, R.; De Tejada, S.; Goldstein, I.; Krane, R.J.; Wotiz, H.H.; Cohen, R.A.

1988-01-01

Physiological and histochemical evidence indicates that cholinergic nerves may participate in mediating penile erection. Acetylcholine synthesis and release was studied in isolated human corporal tissue. Human corpus cavernosum incubated with [ 3 H]choline accumulated [ 3 H]choline and synthesized [ 3 H]acethylcholine in an concentration-dependent manner. [ 3 H]Acetylcholine accumulation by the tissue was inhibited by hemicholinium-3, a specific antagonist of the high-affinity choline transport in cholinergic nerves. Transmural electrical field stimulation caused release of [ 3 H]acetylcholine which was significantly diminished by inhibiting neurotransmission with calcium-free physiological salt solution or tetrodotoxin. These observations provide biochemical and physiological evidence for the existence of cholinergic innervation in human corpus cavernosum

REM sleep behavior disorder and narcoleptic features in anti-Ma2-associated encephalitis.

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Compta, Yaroslau; Iranzo, Alex; Santamaría, Joan; Casamitjana, Roser; Graus, Francesc

2007-06-01

A 69-year-old man with anti-Ma2 paraneoplastic encephalitis presented with subacute onset of severe hypersomnia, memory loss, parkinsonism, and gaze palsy. A brain magnetic resonance imaging study showed bilateral damage in the dorsolateral midbrain, amygdala, and paramedian thalami. Videopolysomnography disclosed rapid eye movement (REM) sleep behavior disorder, and a Multiple Sleep Latency Test showed a mean sleep latency of 7 minutes and 4 sleep-onset REM periods. The level of hypocretin-1 in the cerebrospinal fluid was low (49 pg/mL). This observation illustrates that REM sleep behavior disorder and narcoleptic features are 2 REM-sleep abnormalities that (1) may share the same autoimmune-mediated origin affecting the brainstem, limbic, and diencephalic structures and (2) may occur in the setting of the paraneoplastic anti-Ma2-associated encephalitis.

The cholinergic ligand binding material of axonal membranes

International Nuclear Information System (INIS)

Mautner, H.G.; Coronado, R.; Jumblatt, J.E.

1986-01-01

Choline acetyltransferase and acetylcholinesterase, the enzymes responsible for the synthesis and hydrolysis of ACh, are present in nerve fibers. In crustacean peripheral nerves, release of ACh from cut nerve fibers has been demonstrated. Previously closed membrane vesicles have been prepared from lobster walking leg nerve plasma membrane and saturable binding of cholinergic agonsist and antagonists to such membranes have been demonstrated. This paper studies this axonal cholinergic binding material, and elucidates its functions. The binding of tritium-nicotine to lobster nerve plasma membranes was antagonized by a series of cholinergic ligands as well as by a series of local anesthetics. This preparation was capable of binding I 125-alpha-bungarotoxin, a ligand widely believed to be a specific label for nicotinic ACh receptor. The labelling of 50 K petide band with tritium-MBTA following disulfide reduction is illustrated

Involvement of the cholinergic system of CA1 on harmane-induced amnesia in the step-down passive avoidance test.

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Nasehi, Mohammad; Sharifi, Shahrbano; Zarrindast, Mohammad Reza

2012-08-01

β-carboline alkaloids such as harmane (HA) are naturally present in the human food chain. They are derived from the plant Peganum harmala and have many cognitive effects. In the present study, effects of the nicotinic system of the dorsal hippocampus (CA1) on HA-induced amnesia and exploratory behaviors were examined. One-trial step-down and hole-board paradigms were used to assess memory retention and exploratory behaviors in adult male mice. Pre-training (15 mg/kg) but not pre-testing intraperitoneal (i.p.) administration of HA decreased memory formation but did not alter exploratory behaviors. Moreover, pre-testing administration of nicotine (0.5 µg/mouse, intra-CA1) decreased memory retrieval, but induced anxiogenic-like behaviors. On the other hand, pre-test intra-CA1 injection of ineffective doses of nicotine (0.1 and 0.25 µg/mouse) fully reversed HA-induced impairment of memory after pre-training injection of HA (15 mg/kg, i.p.) which did not alter exploratory behaviors. Furthermore, pre-testing administration of mecamylamine (0.5, 1 and 2 µg/mouse, intra-CA1) did not alter memory retrieval but fully reversed HA-induced impairment of memory after pre-training injection of HA (15 mg/kg, i.p.) which had no effect on exploratory behaviors. In conclusion, the present findings suggest the involvement of the nicotinic cholinergic system in the HA-induced impairment of memory formation.

Chronic Cerebral Ischaemia Forms New Cholinergic Mechanisms of Learning and Memory

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E. I. Zakharova

2010-01-01

Full Text Available The purpose of this research was a comparative analysis of cholinergic synaptic organization following learning and memory in normal and chronic cerebral ischaemic rats in the Morris water maze model. Choline acetyltransferase and protein content were determined in subpopulations of presynapses of “light” and “heavy” synaptosomal fractions of the cortex and the hippocampus, and the cholinergic projective and intrinsic systems of the brain structures were taken into consideration. We found a strong involvement of cholinergic systems, both projective and intrinsic, in all forms of cognition. Each form of cognition had an individual cholinergic molecular profile and the cholinergic synaptic compositions in the ischaemic rat brains differed significantly from normal ones. Our data demonstrated that under ischaemic conditions, instead of damaged connections new key synaptic relationships, which were stable against pathological influences and able to restore damaged cognitive functions, arose. The plasticity of neurochemical links in the individual organization of certain types of cognition gave a new input into brain pathology and can be used in the future for alternative corrections of vascular and other degenerative dementias.

From bench to bed: putative animal models of REM sleep behavior disorder (RBD).

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Krenzer, Martina; Lu, Jun; Mayer, Geert; Oertel, Wolfgang

2013-04-01

REM behavior disorder (RBD) is a parasomnia characterized by REM sleep without atonia, leading to abnormal and potentially injurious behavior during REM sleep. It is considered one of the most specific predictors of neurodegenerative disorders, such as Parkinson's disease. In this paper, we provide an overview of animal models contributing to our current understanding of REM-associated atonia, and, as a consequence, the pathophysiology of RBD. The generator of REM-associated atonia is located in glutamatergic neurons of the pontine sublaterodorsal nucleus (SLD), as shown in cats, rats and mice. These findings are supported by clinical cases of patients with lesions of the homologous structure in humans. Glutamatergic SLD neurons, presumably in conjunction with others, project to (a) the ventromedial medulla, where they either directly target inhibitory interneurons to alpha motor neurons or are relayed, and (b) the spinal cord directly. At the spinal level, alpha motor neurons are inhibited by GABAergic and glycinergic interneurons. Our current understanding is that lesions of the glutamatergic SLD are the key factor for REM sleep behavior disorder. However, open questions remain, e.g. other features of RBD (such as the typically aggressive dream content) or the frequent progression from idiopathic RBD to neurodegenerative disorders, to name only a few. In order to elucidate these questions, a constant interaction between basic and clinical researchers is required, which might, ultimately, create an early therapeutic window for neurodegenerative disorders.

Heavy metal uranium affects the brain cholinergic system in rat following sub-chronic and chronic exposure

International Nuclear Information System (INIS)

Bensoussan, Helene; Grancolas, Line; Dhieux-Lestaevel, Bernadette; Delissen, Olivia; Vacher, Claire-Marie; Dublineau, Isabelle; Voisin, Philippe; Gourmelon, Patrick; Taouis, Mohammed; Lestaevel, Philippe

2009-01-01

Uranium is a heavy metal naturally present in the environment that may be chronically ingested by the population. Previous studies have shown that uranium is present in the brain and alters behaviour, notably locomotor activity, sensorimotor ability, sleep/wake cycle and the memory process, but also metabolism of neurotransmitters. The cholinergic system mediates many cognitive systems, including those disturbed after chronic exposure to uranium i.e., spatial memory, sleep/wake cycle and locomotor activity. The objective of this study was to assess whether these disorders follow uranium-induced alteration of the cholinergic system. In comparison with 40 control rats, 40 rats drank 40 mg/L uranyl nitrate for 1.5 or 9 months. Cortex and hippocampus were removed and gene expression and protein level were analysed to determine potential changes in cholinergic receptors and acetylcholine levels. The expression of genes showed various alterations in the two brain areas after short- and long-term exposure. Nevertheless, protein levels of the choline acetyltransferase enzyme (ChAT), the vesicular transporter of acetylcholine (VAChT) and the nicotinic receptor β2 sub-unit (nAChRβ2) were unmodified in all cases of the experiment and muscarinic receptor type 1 (m1AChR) protein level was disturbed only after 9 months of exposure in the cortex (-30%). Acetylcholine levels were unchanged in the hippocampus after 1.5 and 9 months, but were decreased in the cortex after 1.5 months only (-22%). Acetylcholinesterase (AChE) activity was also unchanged in the hippocampus but decreased in the cortex after 1.5 and 9 months (-16% and -18%, respectively). Taken together, these data indicate that the cholinergic system is a target of uranium exposure in a structure-dependent and time-dependent manner. These cholinergic alterations could participate in behavioural impairments.

The involvement of cholinergic neurons in the spreading of tau pathology

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Diana eSimon

2013-06-01

Full Text Available Long time ago, it was described the selective loss of cholinergic neurons during the development of Alzheimer disease. Recently, it has been suggested that tau protein may play a role in that loss of cholinergic neurons through a mechanism involving the interaction of extracellular tau with M1/M3 muscarinic receptors present in the cholinergic neurons. This interaction between tau and muscarinic receptors may be a way, although not the only one, to explain the spreading of tau pathology occurring in Alzheimer disease.

Cholinergic Inputs from Basal Forebrain Add an Excitatory Bias to Odor Coding in the Olfactory Bulb

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Rothermel, Markus; Carey, Ryan M.; Puche, Adam; Shipley, Michael T.

2014-01-01

Cholinergic modulation of central circuits is associated with active sensation, attention, and learning, yet the neural circuits and temporal dynamics underlying cholinergic effects on sensory processing remain unclear. Understanding the effects of cholinergic modulation on particular circuits is complicated by the widespread projections of cholinergic neurons to telencephalic structures that themselves are highly interconnected. Here we examined how cholinergic projections from basal forebrain to the olfactory bulb (OB) modulate output from the first stage of sensory processing in the mouse olfactory system. By optogenetically activating their axons directly in the OB, we found that cholinergic projections from basal forebrain regulate OB output by increasing the spike output of presumptive mitral/tufted cells. Cholinergic stimulation increased mitral/tufted cell spiking in the absence of inhalation-driven sensory input and further increased spiking responses to inhalation of odorless air and to odorants. This modulation was rapid and transient, was dependent on local cholinergic signaling in the OB, and differed from modulation by optogenetic activation of cholinergic neurons in basal forebrain, which led to a mixture of mitral/tufted cell excitation and suppression. Finally, bulbar cholinergic enhancement of mitral/tufted cell odorant responses was robust and occurred independent of the strength or even polarity of the odorant-evoked response, indicating that cholinergic modulation adds an excitatory bias to mitral/tufted cells as opposed to increasing response gain or sharpening response spectra. These results are consistent with a role for the basal forebrain cholinergic system in dynamically regulating the sensitivity to or salience of odors during active sensing of the olfactory environment. PMID:24672011

The catecholaminergic-cholinergic balance hypothesis of bipolar disorder revisited

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van Enkhuizen, Jordy; Janowsky, David S; Olivier, Berend; Minassian, Arpi; Perry, William; Young, Jared W; Geyer, Mark A

2014-01-01

Bipolar disorder is a unique illness characterized by fluctuations between mood states of depression and mania. Originally, an adrenergic-cholinergic balance hypothesis was postulated to underlie these different affective states. In this review, we update this hypothesis with recent findings from human and animal studies, suggesting that a catecholaminergic-cholinergic hypothesis may be more relevant. Evidence from neuroimaging studies, neuropharmacological interventions, and genetic associations support the notion that increased cholinergic functioning underlies depression, whereas increased activations of the catecholamines (dopamine and norepinephrine) underlie mania. Elevated functional acetylcholine during depression may affect both muscarinic and nicotinic acetylcholine receptors in a compensatory fashion. Increased functional dopamine and norepinephrine during mania on the other hand may affect receptor expression and functioning of dopamine reuptake transporters. Despite increasing evidence supporting this hypothesis, a relationship between these two neurotransmitter systems that could explain cycling between states of depression and mania is missing. Future studies should focus on the influence of environmental stimuli and genetic susceptibilities that may affect the catecholaminergic-cholinergic balance underlying cycling between the affective states. Overall, observations from recent studies add important data to this revised balance theory of bipolar disorder, renewing interest in this field of research. PMID:25107282

Transmitter modulation of spike-evoked calcium transients in arousal related neurons

DEFF Research Database (Denmark)

Kohlmeier, Kristi Anne; Leonard, Christopher S

2006-01-01

Nitric oxide synthase (NOS)-containing cholinergic neurons in the laterodorsal tegmentum (LDT) influence behavioral and motivational states through their projections to the thalamus, ventral tegmental area and a brainstem 'rapid eye movement (REM)-induction' site. Action potential-evoked intracel......Nitric oxide synthase (NOS)-containing cholinergic neurons in the laterodorsal tegmentum (LDT) influence behavioral and motivational states through their projections to the thalamus, ventral tegmental area and a brainstem 'rapid eye movement (REM)-induction' site. Action potential......-evoked intracellular calcium transients dampen excitability and stimulate NO production in these neurons. In this study, we investigated the action of several arousal-related neurotransmitters and the role of specific calcium channels in these LDT Ca(2+)-transients by simultaneous whole-cell recording and calcium...... of cholinergic LDT neurons and that inhibition of spike-evoked Ca(2+)-transients is a common action of neurotransmitters that also activate GIRK channels in these neurons. Because spike-evoked calcium influx dampens excitability, our findings suggest that these 'inhibitory' transmitters could boost firing rate...

Selective retrograde labeling of cholinergic neurons with [3H]choline

International Nuclear Information System (INIS)

Bagnoli, P.; Beaudet, A.; Stella, M.; Cuenod, M.

1981-01-01

Evidence is presented which is consistent with a specific retrograde labeling of cholinergic neurons following [ 3 H]choline application in their zone of termination. [ 3 H]Choline injection in the rat hippocampus leads to perikaryal retrograde labeling in the ipsilateral medial septal nuclease and nucleus of the diagonal band, thus delineating an established cholinergic pathway, while only diffuse presumably anterograde labeling was observed in the lateral septum, the entorhinal cortex, and the opposite hippocampus. After [ 3 H]choline injection in the pigeon visual Wulst, only the ipsilateral thalamic relay, of all inputs, showed similar perikaryal retrograde labeling, an observation supporting the suggestion that at least some thalamo-Wulst neurons are cholinergic

Sleep stability and transitions in patients with idiopathic REM sleep behavior disorder and patients with Parkinson's disease.

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Christensen, Julie Anja Engelhard; Jennum, Poul; Koch, Henriette; Frandsen, Rune; Zoetmulder, Marielle; Arvastson, Lars; Christensen, Søren Rahn; Sorensen, Helge Bjarrup Dissing

2016-01-01

Patients with idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD) are at high risk of developing Parkinson's disease (PD). As wake/sleep-regulation is thought to involve neurons located in the brainstem and hypothalamic areas, we hypothesize that the neurodegeneration in iRBD/PD is likely to affect wake/sleep and REM/non-REM (NREM) sleep transitions. We determined the frequency of wake/sleep and REM/NREM sleep transitions and the stability of wake (W), REM and NREM sleep as measured by polysomnography (PSG) in 27 patients with PD, 23 patients with iRBD, 25 patients with periodic leg movement disorder (PLMD) and 23 controls. Measures were computed based on manual scorings and data-driven labeled sleep staging. Patients with PD showed significantly lower REM stability than controls and patients with PLMD. Patients with iRBD had significantly lower REM stability compared with controls. Patients with PD and RBD showed significantly lower NREM stability and significantly more REM/NREM transitions than controls. We conclude that W, NREM and REM stability and transitions are progressively affected in iRBD and PD, probably reflecting the successive involvement of brain stem areas from early on in the disease. Sleep stability and transitions determined by a data-driven approach could support the evaluation of iRBD and PD patients. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Effects of chronic alcohol consumption, withdrawal and nerve growth factor on neuropeptide Y expression and cholinergic innervation of the rat dentate hilus.

Science.gov (United States)

Pereira, Pedro A; Rocha, João P; Cardoso, Armando; Vilela, Manuel; Sousa, Sérgio; Madeira, M Dulce

2016-05-01

Several studies have demonstrated the vulnerability of the hippocampal formation (HF) to chronic alcohol consumption and withdrawal. Among the brain systems that appear to be particularly vulnerable to the effects of these conditions are the neuropeptide Y (NPY)-ergic and the cholinergic systems. Because these two systems seem to closely interact in the HF, we sought to study the effects of chronic alcohol consumption (6months) and subsequent withdrawal (2months) on the expression of NPY and on the cholinergic innervation of the rat dentate hilus. As such, we have estimated the areal density and the somatic volume of NPY-immunoreactive neurons, and the density of the cholinergic varicosities. In addition, because alcohol consumption and withdrawal are associated with impaired nerve growth factor (NGF) trophic support and the administration of exogenous NGF alters the effects of those conditions on various cholinergic markers, we have also estimated the same morphological parameters in withdrawn rats infused intracerebroventricularly with NGF. NPY expression increased after withdrawal and returned to control values after NGF treatment. Conversely, the somatic volume of these neurons did not differ among all groups. On other hand, the expression of vesicular acetylcholine transporter (VAChT) was reduced by 24% in ethanol-treated rats and by 46% in withdrawn rats. The administration of NGF to withdrawn rats increased the VAChT expression to values above control levels. These results show that the effects of prolonged alcohol intake and protracted withdrawal on the hilar NPY expression differ from those induced by shorter exposures to ethanol and by abrupt withdrawal. They also suggest that the normalizing effect of NGF on NPY expression might rely on the NGF-induced improvement of cholinergic neurotransmission in the dentate hilus. Copyright © 2016 Elsevier Inc. All rights reserved.

Evaluation of energy response of neutron rem monitor applied to high-energy accelerator facilities

Energy Technology Data Exchange (ETDEWEB)

Nakane, Yoshihiro; Harada, Yasunori; Sakamoto, Yukio [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment] [and others

2003-03-01

A neutron rem monitor was newly developed for applying to the high-intensity proton accelerator facility (J-PARC) that is under construction as a joint project between the Japan Atomic Energy Research Institute and the High Energy Accelerator Research Organization. To measure the dose rate accurately for wide energy range of neutrons from thermal to high-energy region, the neutron rem monitor was fabricated by adding a lead breeder layer to a conventional neutron rem monitor. The energy response of the monitor was evaluated by using neutron transport calculations for the energy range from thermal to 150 MeV. For verifying the results, the response was measured at neutron fields for the energy range from thermal to 65 MeV. The comparisons between the energy response and dose conversion coefficients show that the newly developed neutron rem monitor has a good performance in energy response up to 150 MeV, suggesting that the present study offered prospects of a practical fabrication of the rem monitor applicable to the high intensity proton accelerator facility. (author)

Role of REM Sleep, Melanin Concentrating Hormone and Orexin/Hypocretin Systems in the Sleep Deprivation Pre-Ischemia.

Science.gov (United States)

Pace, Marta; Adamantidis, Antoine; Facchin, Laura; Bassetti, Claudio

2017-01-01

Sleep reduction after stroke is linked to poor recovery in patients. Conversely, a neuroprotective effect is observed in animals subjected to acute sleep deprivation (SD) before ischemia. This neuroprotection is associated with an increase of the sleep, melanin concentrating hormone (MCH) and orexin/hypocretin (OX) systems. This study aims to 1) assess the relationship between sleep and recovery; 2) test the association between MCH and OX systems with the pathological mechanisms of stroke. Sprague-Dawley rats were assigned to four experimental groups: (i) SD_IS: SD performed before ischemia; (ii) IS: ischemia; (iii) SD_Sham: SD performed before sham surgery; (iv) Sham: sham surgery. EEG and EMG were recorded. The time-course of the MCH and OX gene expression was measured at 4, 12, 24 hours and 3, 4, 7 days following ischemic surgery by qRT-PCR. A reduction of infarct volume was observed in the SD_IS group, which correlated with an increase of REM sleep observed during the acute phase of stroke. Conversely, the IS group showed a reduction of REM sleep. Furthermore, ischemia induces an increase of MCH and OX systems during the acute phase of stroke, although, both systems were still increased for a long period of time only in the SD_IS group. Our data indicates that REM sleep may be involved in the neuroprotective effect of SD pre-ischemia, and that both MCH and OX systems were increased during the acute phase of stroke. Future studies should assess the role of REM sleep as a prognostic marker, and test MCH and OXA agonists as new treatment options in the acute phase of stroke.

Role of REM Sleep, Melanin Concentrating Hormone and Orexin/Hypocretin Systems in the Sleep Deprivation Pre-Ischemia.

Directory of Open Access Journals (Sweden)

Marta Pace

Full Text Available Sleep reduction after stroke is linked to poor recovery in patients. Conversely, a neuroprotective effect is observed in animals subjected to acute sleep deprivation (SD before ischemia. This neuroprotection is associated with an increase of the sleep, melanin concentrating hormone (MCH and orexin/hypocretin (OX systems. This study aims to 1 assess the relationship between sleep and recovery; 2 test the association between MCH and OX systems with the pathological mechanisms of stroke.Sprague-Dawley rats were assigned to four experimental groups: (i SD_IS: SD performed before ischemia; (ii IS: ischemia; (iii SD_Sham: SD performed before sham surgery; (iv Sham: sham surgery. EEG and EMG were recorded. The time-course of the MCH and OX gene expression was measured at 4, 12, 24 hours and 3, 4, 7 days following ischemic surgery by qRT-PCR.A reduction of infarct volume was observed in the SD_IS group, which correlated with an increase of REM sleep observed during the acute phase of stroke. Conversely, the IS group showed a reduction of REM sleep. Furthermore, ischemia induces an increase of MCH and OX systems during the acute phase of stroke, although, both systems were still increased for a long period of time only in the SD_IS group.Our data indicates that REM sleep may be involved in the neuroprotective effect of SD pre-ischemia, and that both MCH and OX systems were increased during the acute phase of stroke. Future studies should assess the role of REM sleep as a prognostic marker, and test MCH and OXA agonists as new treatment options in the acute phase of stroke.

Early presymptomatic cholinergic dysfunction in a murine model of amyotrophic lateral sclerosis

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Casas, Caty; Herrando-Grabulosa, Mireia; Manzano, Raquel; Mancuso, Renzo; Osta, Rosario; Navarro, Xavier

2013-01-01

Sporadic and familiar amyotrophic lateral sclerosis (ALS) cases presented lower cholinergic activity than in healthy individuals in their still preserved spinal motoneurons (MNs) suggesting that cholinergic reduction might occur before MN death. To unravel how and when cholinergic function is compromised, we have analyzed the spatiotemporal expression of choline acetyltransferase (ChAT) from early presymptomatic stages of the SOD1G93A ALS mouse model by confocal immunohistochemistry. The analysis showed an early reduction in ChAT content in soma and presynaptic boutons apposed onto MNs (to 76%) as well as in cholinergic interneurons in the lumbar spinal cord of the 30-day-old SOD1G93A mice. Cholinergic synaptic stripping occurred simultaneously to the presence of abundant surrounding major histocompatibility complex II (MHC-II)-positive microglia and the accumulation of nuclear Tdp-43 and the appearance of mild oxidative stress within MNs. Besides, there was a loss of neuronal MHC-I expression, which is necessary for balanced synaptic stripping after axotomy. These events occurred before the selective raise of markers of denervation such as ATF3. By the same time, alterations in postsynaptic cholinergic-related structures were also revealed with a loss of the presence of sigma-1 receptor, a Ca2+ buffering chaperone in the postsynaptic cisternae. By 2 months of age, ChAT seemed to accumulate in the soma of MNs, and thus efferences toward Renshaw interneurons were drastically diminished. In conclusion, cholinergic dysfunction in the local circuitry of the spinal cord may be one of the earliest events in ALS etiopathogenesis. PMID:23531559

Endosulfan and cholinergic (muscarinic) transmission: effect on electroencephalograms and [3H]quinuclidinyl benzilate in pigeon brain

International Nuclear Information System (INIS)

Anand, M.; Agrawal, A.K.; Gopal, K.; Sur, R.N.; Seth, P.K.

1986-01-01

Single exposure of endosulfan (5 mg/kg) to pigeons (Columbia livia) caused neuronal hyperexcitability as evidence by spike discharges of 200-500 μV in the electroencephalograms (EEG) from the telencephalon and hyperstriatum, but there was not effect on the ectostriatal area. Cholinergic (muscarinic) receptor binding study using [ 3 H]quinuclidinyl benzilate ([ 3 H]QNB) as a specific ligand indicated that a single exposure to 5 mg/kg of endosulfan caused a significant increase in [ 3 H]QNB binding to the striatal membrane. Behavior study further indicated that a single dose of 200 μg/kg of oxotremorine produced a significant induction in the tremor in endosulfan-pretreated pigeons. The results of this behavioral and biochemical study indicate the involvement of a cholinergic (muscarinic) transmitter system in endosulfan-induced neurotoxicity

A moderate increase of physiological CO2 in a critical range during stable NREM sleep episode: A potential gateway to REM sleep

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Vibha eMadan

2012-02-01

Full Text Available Sleep is characterized as rapid eye movement (REM and non-rapid eye movement (NREM sleep. Studies suggest that wake-related neurons in the basal forebrain, posterior hypothalamus and brainstem and NREM sleep-related neurons in the anterior-hypothalamic area inhibit each other, thus alternating sleep-wakefulness. Similarly, pontine REM-ON and REM-OFF neurons reciprocally inhibit each other for REM sleep modulation. It has been proposed that inhibition of locus coeruleus (LC REM-OFF neurons is pre-requisite for REM sleep genesis, but it remains ambiguous how REM-OFF neurons are hyperpolarized at REM sleep onset. The frequency of breathing pattern remains high during wake, slows down during NREM sleep but further escalates during REM sleep. As a result, brain CO2 level increases during NREM sleep, which may alter REM sleep manifestation. It has been reported that hypocapnia decreases REM sleep while hypercapnia increases REM sleep periods. The groups of brainstem chemosensory neurons, including those present in LC, sense the alteration in CO2 level and respond accordingly. For example; one group of LC neurons depolarize while other hyperpolarize during hypercapnia. In another group, hypercapnia initially depolarizes but later hyperpolarizes LC neurons. Besides chemosensory functions, LC’s REM-OFF neurons are an integral part of REM sleep executive machinery. We reason that increased CO2 level during a stable NREM sleep period may hyperpolarize LC neurons including REM-OFF, which may help initiate REM sleep. We propose that REM sleep might act as a sentinel to help maintain normal CO2 level for unperturbed sleep.

Walnut supplementation reverses the scopolamine-induced memory impairment by restoration of cholinergic function via mitigating oxidative stress in rats: a potential therapeutic intervention for age related neurodegenerative disorders.

Science.gov (United States)

Haider, Saida; Batool, Zehra; Ahmad, Saara; Siddiqui, Rafat Ali; Haleem, Darakhshan Jabeen

2018-02-01

The brain is highly susceptible to the damaging effects of oxidative reactive species. The free radicals which are produced as a consequence of aerobic respiration can cause cumulative oxygen damage which may lead to age-related neurodegeneration. Scopolamine, the anti-muscarinic agent, induces amnesia and oxidative stress similar to that observed in the older age. Studies suggest that antioxidants derived from plant products may provide protection against oxidative stress. Therefore, the present study was designed to investigate the attenuation of scopolamine-induced memory impairment and oxidative stress by walnut supplementation in rats. Rats in test group were administrated with walnut suspension (400 mg/kg/day) for four weeks. Both control and walnut-treated rats were then divided into saline and scopolamine-treated groups. Rats in the scopolamine group were injected with scopolamine (0.5 mg/kg dissolved in saline) five minutes before the start of each memory test. Memory was assessed by elevated plus maze (EPM), Morris water maze (MWM), and novel object recognition task (NOR) followed by estimation of regional acetylcholine levels and acetylcholinesterase activity. In the next phase, brain oxidative status was determined by assaying lipid peroxidation, and measuring superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) activities. Results showed that scopolamine-treatment impaired memory function, caused cholinergic dysfunction, and induced oxidative stress in rats compared to that saline-treated controls. These impairments were significantly restored by pre-administration of walnut. This study demonstrates that antioxidant properties of walnut may provide augmented effects on cholinergic function by reducing oxidative stress and thus improving memory performance.

The effect of selective REM-sleep deprivation on the consolidation and affective evaluation of emotional memories.

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Wiesner, Christian D; Pulst, Julika; Krause, Fanny; Elsner, Marike; Baving, Lioba; Pedersen, Anya; Prehn-Kristensen, Alexander; Göder, Robert

2015-07-01

Emotion boosts the consolidation of events in the declarative memory system. Rapid eye movement (REM) sleep is believed to foster the memory consolidation of emotional events. On the other hand, REM sleep is assumed to reduce the emotional tone of the memory. Here, we investigated the effect of selective REM-sleep deprivation, SWS deprivation, or wake on the affective evaluation and consolidation of emotional and neutral pictures. Prior to an 9-h retention interval, sixty-two healthy participants (23.5 ± 2.5 years, 32 female, 30 male) learned and rated their affect to 80 neutral and 80 emotionally negative pictures. Despite rigorous deprivation of REM sleep or SWS, the residual sleep fostered the consolidation of neutral and negative pictures. Furthermore, emotional arousal helped to memorize the pictures. The better consolidation of negative pictures compared to neutral ones was most pronounced in the SWS-deprived group where a normal amount of REM sleep was present. This emotional memory bias correlated with REM sleep only in the SWS-deprived group. Furthermore, emotional arousal to the pictures decreased over time, but neither sleep nor wake had any differential effect. Neither the comparison of the affective ratings (arousal, valence) during encoding and recognition, nor the affective ratings of the recognized targets and rejected distractors supported the hypothesis that REM sleep dampens the emotional reaction to remembered stimuli. The data suggest that REM sleep fosters the consolidation of emotional memories but has no effect on the affective evaluation of the remembered contents. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

A cellular and regulatory map of the cholinergic nervous system of C. elegans

Science.gov (United States)

Pereira, Laura; Kratsios, Paschalis; Serrano-Saiz, Esther; Sheftel, Hila; Mayo, Avi E; Hall, David H; White, John G; LeBoeuf, Brigitte; Garcia, L Rene; Alon, Uri; Hobert, Oliver

2015-01-01

Nervous system maps are of critical importance for understanding how nervous systems develop and function. We systematically map here all cholinergic neuron types in the male and hermaphrodite C. elegans nervous system. We find that acetylcholine (ACh) is the most broadly used neurotransmitter and we analyze its usage relative to other neurotransmitters within the context of the entire connectome and within specific network motifs embedded in the connectome. We reveal several dynamic aspects of cholinergic neurotransmitter identity, including a sexually dimorphic glutamatergic to cholinergic neurotransmitter switch in a sex-shared interneuron. An expression pattern analysis of ACh-gated anion channels furthermore suggests that ACh may also operate very broadly as an inhibitory neurotransmitter. As a first application of this comprehensive neurotransmitter map, we identify transcriptional regulatory mechanisms that control cholinergic neurotransmitter identity and cholinergic circuit assembly. DOI: http://dx.doi.org/10.7554/eLife.12432.001 PMID:26705699

Cholinergic Hypofunction in Presbycusis-Related Tinnitus With Cognitive Function Impairment: Emerging Hypotheses.

Science.gov (United States)

Ruan, Qingwei; Yu, Zhuowei; Zhang, Weibin; Ruan, Jian; Liu, Chunhui; Zhang, Ruxin

2018-01-01

Presbycusis (age-related hearing loss) is a potential risk factor for tinnitus and cognitive deterioration, which result in poor life quality. Presbycusis-related tinnitus with cognitive impairment is a common phenotype in the elderly population. In these individuals, the central auditory system shows similar pathophysiological alterations as those observed in Alzheimer's disease (AD), including cholinergic hypofunction, epileptiform-like network synchronization, chronic inflammation, and reduced GABAergic inhibition and neural plasticity. Observations from experimental rodent models indicate that recovery of cholinergic function can improve memory and other cognitive functions via acetylcholine-mediated GABAergic inhibition enhancement, nicotinic acetylcholine receptor (nAChR)-mediated anti-inflammation, glial activation inhibition and neurovascular protection. The loss of cholinergic innervation of various brain structures may provide a common link between tinnitus seen in presbycusis-related tinnitus and age-related cognitive impairment. We hypothesize a key component of the condition is the withdrawal of cholinergic input to a subtype of GABAergic inhibitory interneuron, neuropeptide Y (NPY) neurogliaform cells. Cholinergic denervation might not only cause the degeneration of NPY neurogliaform cells, but may also result in decreased AChR activation in GABAergic inhibitory interneurons. This, in turn, would lead to reduced GABA release and inhibitory regulation of neural networks. Reduced nAChR-mediated anti-inflammation due to the loss of nicotinic innervation might lead to the transformation of glial cells and release of inflammatory mediators, lowering the buffering of extracellular potassium and glutamate metabolism. Further research will provide evidence for the recovery of cholinergic function with the use of cholinergic input enhancement alone or in combination with other rehabilitative interventions to reestablish inhibitory regulation mechanisms of

Neuro-immune interactions via the cholinergic anti-inflammatory pathway

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Gallowitsch-Puerta, Margot; Pavlov, Valentin A.

2010-01-01

The overproduction of TNF and other cytokines can cause the pathophysiology of numerous diseases. Controlling cytokine synthesis and release is critical for preventing unrestrained inflammation and maintaining health. Recent studies identified an efferent vagus nerve-based mechanism termed “the cholinergic anti-inflammatory pathway” that controls cytokine production and inflammation. Here we review current advances related to the role of this pathway in neuro-immune interactions that prevent excessive inflammation. Experimental evidence indicates that vagus nerve cholinergic anti-inflammatory signaling requires alpha7 nicotinic acetylcholine receptors expressed on non-neuronal cytokine producing cells. Alpha7 nicotinic acetylcholine receptor agonists inhibit cytokine release and protect animals in a variety of experimental lethal inflammatory models. Knowledge related to the cholinergic anti-inflammatory pathway can be exploited in therapeutic approaches directed towards counteracting abnormal chronic and hyper-activated inflammatory responses. PMID:17289087

Cholinergic signalling in gut immunity

NARCIS (Netherlands)

Dhawan, Shobhit; Cailotto, Cathy; Harthoorn, Lucien F.; de Jonge, Wouter J.

2012-01-01

The gut immune system shares many signalling molecules and receptors with the autonomic nervous system. A good example is the vagal neurotransmitter acetylcholine (ACh), for which many immune cell types express cholinergic receptors (AChR). In the last decade the vagal nerve has emerged as an

20(S)-protopanaxadiol (PPD) alleviates scopolamine-induced memory impairment via regulation of cholinergic and antioxidant systems, and expression of Egr-1, c-Fos and c-Jun in mice.

Science.gov (United States)

Lu, Cong; Dong, Liming; Lv, Jingwei; Wang, Yan; Fan, Bei; Wang, Fengzhong; Liu, Xinmin

2018-01-05

20(S)-protopanaxadiol (PPD) possesses various biological properties, including anti-inflammatory, antitumor and anti-fatigue properties. Recent studies found that PPD functioned as a neurotrophic agent to ameliorate the sensory deficit caused by glutamate-induced excitotoxicity through its antioxidant effects and exhibited strong antidepressant-like effects in vivo. The objective of the present study was first to investigate the effect of PPD in scopolamine (SCOP)-induced memory deficit in mice and the potential mechanisms involved. In this study, mice were pretreated with PPD (20 and 40 μmol/kg) and donepezil (1.6 mg/kg) intraperitoneally (i.p) for 14 days. Then, open field test was used to assess the effect of PPD on the locomotor activity and mice were daily injected with SCOP (0.75 mg/kg) to induce cognitive deficits and then subjected to behavioral tests by object location recognition (OLR) experiment and Morris water maze (MWM) task. The cholinergic system function, oxidative stress biomarkers and protein expression of Egr-1, c-Fos, and c-Jun in mouse hippocampus were examined. PPD was found to significantly improve the performance of amnesia mice in OLR and MWM tests. PPD regulated cholinergic function by inhibiting SCOP-induced elevation of acetylcholinesterase (AChE) activity, decline of choline acetyltransferase (ChAT) activity and decrease of acetylcholine (Ach) level. PPD suppressed oxidative stress by increasing activities of antioxidant enzymes such as superoxide dismutase (SOD) and lowering maleic diadehyde (MDA) level. Additionally, PPD significantly elevated the expression of Egr-1, c-Fos, and c-Jun in hippocampus at protein level. Taken together, all these results suggested that 20(S)-protopanaxadiol (PPD) may be a candidate compound for the prevention against memory loss in some neurodegenerative diseases such as Alzheimer's disease (AD). Copyright © 2017. Published by Elsevier B.V.

Uranium chronic contamination effects on the cholinergic system: in vivo and in vitro approaches

International Nuclear Information System (INIS)

Bensoussan, H.

2009-01-01

Uranium (U) is a heavy metal which occurs naturally in the environment. It is both a chemical and a radiological toxicant. The aim of this work was: (i) to assess the effects of U chronic exposure on the cholinergic system (biosynthesis and breakdown enzymes, receptors and on behaviour of adult, young or predisposed to neuro-degenerative illness (ApoE KO) rodents; (ii) to grasp the neurotoxic effects of U on human neuronal cells. In vivo, this work shows a structure- (cortex more sensitive than hippocampus), rodent model- (young more sensitive than adults), time- (sub-chronic exposure more harmful than chronic exposure), exposure level- and isotope-dependent effect of U. In vitro, the study underlined the neuro-cytotoxic U potential and the presence of uranium precipitates in cells. These results show the deleterious impact of U on neuronal cells, and demonstrate that U induces impairments on the cholinergic system and the behaviour of rodents. (author)

The lateral paragigantocellular nucleus modulates parasympathetic cardiac neurons: a mechanism for rapid eye movement sleep-dependent changes in heart rate.

Science.gov (United States)

Dergacheva, Olga; Wang, Xin; Lovett-Barr, Mary R; Jameson, Heather; Mendelowitz, David

2010-08-01

Rapid eye movement (REM) sleep is generally associated with a withdrawal of parasympathetic activity and heart rate increases; however, episodic vagally mediated heart rate decelerations also occur during REM sleep. This alternating pattern of autonomic activation provides a physiological basis for REM sleep-induced cardiac arrhythmias. Medullary neurons within the lateral paragigantocellular nucleus (LPGi) are thought to be active after REM sleep recovery and play a role in REM sleep control. In proximity to the LPGi are parasympathetic cardiac vagal neurons (CVNs) within the nucleus ambiguus (NA), which are critical for controlling heart rate. This study examined brain stem pathways that may mediate REM sleep-related reductions in parasympathetic cardiac activity. Electrical stimulation of the LPGi evoked inhibitory GABAergic postsynaptic currents in CVNs in an in vitro brain stem slice preparation in rats. Because brain stem cholinergic mechanisms are involved in REM sleep regulation, we also studied the role of nicotinic neurotransmission in modulation of GABAergic pathway from the LGPi to CVNs. Application of nicotine diminished the GABAergic responses evoked by electrical stimulation. This inhibitory effect of nicotine was prevented by the alpha7 nicotinic receptor antagonist alpha-bungarotoxin. Moreover, hypoxia/hypercapnia (H/H) diminished LPGi-evoked GABAergic current in CVNs, and this inhibitory effect was also prevented by alpha-bungarotoxin. In conclusion, stimulation of the LPGi evokes an inhibitory pathway to CVNs, which may constitute a mechanism for the reduced parasympathetic cardiac activity and increase in heart rate during REM sleep. Inhibition of this pathway by nicotinic receptor activation and H/H may play a role in REM sleep-related and apnea-associated bradyarrhythmias.

Daytime REM sleep affects emotional experience but not decision choices in moral dilemmas.

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Cellini, Nicola; Lotto, Lorella; Pletti, Carolina; Sarlo, Michela

2017-09-11

Moral decision-making depends on the interaction between automatic emotional responses and rational cognitive control. A natural emotional regulator state seems to be sleep, in particular rapid eye movement (REM) sleep. We tested the impact of daytime sleep, either with or without REM, on moral decision. Sixty participants were presented with 12 sacrificial (6 Footbridge- and 6 Trolley-type) and 8 everyday-type moral dilemmas at 9 AM and at 5 PM. In sacrificial dilemmas, participants had to decide whether or not to kill one person to save more people (utilitarian choice), and to judge how morally acceptable the proposed choice was. In everyday-type dilemmas, participants had to decide whether to endorse moral violations involving dishonest behavior. At 12 PM, 40 participants took a 120-min nap (17 with REM and 23 with NREM only) while 20 participants remained awake. Mixed-model analysis revealed that participants judged the utilitarian choice as less morally acceptable in the afternoon, irrespective of sleep. We also observed a negative association between theta activity during REM and increased self-rated unpleasantness during moral decisions. Nevertheless, moral decision did not change across the day and between groups. These results suggest that although both time and REM sleep may affect the evaluation of a moral situation, these factors did not ultimately impact the individual moral choices.

Functional role of diverse changes in sympathetic nerve activity in regulating arterial pressure during REM sleep.

Science.gov (United States)

Yoshimoto, Misa; Yoshida, Ikue; Miki, Kenju

2011-08-01

This study aimed to investigate whether REM sleep evoked diverse changes in sympathetic outflows and, if so, to elucidate why REM sleep evokes diverse changes in sympathetic outflows. Male Wistar rats were chronically implanted with electrodes to measure renal (RSNA) and lumbar sympathetic nerve activity (LSNA), electroencephalogram, electromyogram, and electrocardiogram, and catheters to measure systemic arterial and central venous pressure; these parameters were measured simultaneously and continuously during the sleep-awake cycle in the same rat. REM sleep resulted in a step reduction in RNSA by 36.1% ± 2.7% (P sleep. In contrast to REM sleep, RSNA, LSNA, systemic arterial pressure, and heart rate increased in a unidirectional manner associated with increases in physical activity levels in the order from NREM sleep, quiet awake, moving, and grooming state. Thus, the relationship between RSNA vs. LSNA and systemic arterial pressure vs. heart rate observed during REM sleep was dissociated compared with that obtained during the other behavioral states. It is suggested that the diverse changes in sympathetic outflows during REM sleep may be needed to increase systemic arterial pressure by balancing vascular resistance between muscles and vegetative organs without depending on the heart.

Changes in the cholinergic system of rat sciatic nerve and skeletal muscle following suspension induced disuse

Science.gov (United States)

Gupta, R. C.; Misulis, K. E.; Dettbarn, W. D.

1984-01-01

Muscle disused induced changes in the cholinergic system of sciatic nerve, slow twitch soleus (SOL) and fast twitch extensor digitorum longus (EDL) muscle were studied in rats. Rats with hindlimbs suspended for 2 to 3 weeks showed marked elevation in the activity of choline acetyltransferase (ChAT) in sciatic nerve (38%), in SOL (108%) and in EDL (67%). Acetylcholinesterase (AChE) activity in SOL increased by 163% without changing the molecular forms pattern of 4S, 10S, 12S, and 16S. No significant changes in activity and molecular forms pattern of AChE were seen in EDL or in AChE activity of sciatic nerve. Nicotinic receptor binding of 3H-acetylcholine was increased in both muscles. When measured after 3 weeks of hindlimb suspension the normal distribution of type 1 fibers in SOL was reduced and a corresponding increase in type IIa and IIb fibers is seen. In EDL no significant change in fiber proportion is observed. Muscle activity, such as loadbearing, appears to have a greater controlling influence on the characteristics of the slow twitch SOL muscle than upon the fast twitch EDL muscle.

Thyroid hormone modulates the development of cholinergic terminal fields in the rat forebrain: relation to nerve growth factor receptor.

Science.gov (United States)

Oh, J D; Butcher, L L; Woolf, N J

1991-04-24

Hyperthyroidism, induced in rat pups by the daily intraperitoneal administration of 1 microgram/g body weight triiodothyronine, facilitated the development of ChAT fiber plexuses in brain regions innervated by basal forebrain cholinergic neurons, leading to an earlier and increased expression of cholinergic markers in those fibers in the cortex, hippocampus and amygdala. A similar enhancement was seen in the caudate-putamen complex. This histochemical profile was correlated with an accelerated appearance of ChAT-positive telencephalic puncta, as well as with a larger total number of cholinergic terminals expressed, which persisted throughout the eight postnatal week, the longest time examined in the present study. Hypothyroidism was produced in rat pups by adding 0.5% propylthiouracil to the dams' diet beginning the day after birth. This dietary manipulation resulted in the diminished expression of ChAT in forebrain fibers and terminals. Hypothyroid treatment also reduced the quantity of ChAT puncta present during postnatal weeks 2 and 3, and, from week 4 and continuing through week 6, the number of ChAT-positive terminals in the telencephalic regions examined was actually less than the amount extant during the former developmental epoch. Immunostaining for nerve growth factor receptor (NGF-R), which is associated almost exclusively with ChAT-positive somata and fibers in the basal forebrain, demonstrated a different time course of postnatal development. Forebrain fibers and terminals demonstrating NGF-R were maximally visualized 1 week postnatally, a time at which these same neuronal elements evinced minimal ChAT-like immunopositivity. Thereafter and correlated with increased immunoreactivity for ChAT, fine details of NGF-R stained fibers were observed less frequently. Although propylthiouracil administration decreased NGF-R immunodensity, no alteration in the development of that receptor was observed as a function of triiodothyronine treatment. Cholinergic

Hippocampal "cholinergic interneurons" visualized with the choline acetyltransferase promoter: anatomical distribution, intrinsic membrane properties, neurochemical characteristics, and capacity for cholinergic modulation.

Science.gov (United States)

Yi, Feng; Catudio-Garrett, Elizabeth; Gábriel, Robert; Wilhelm, Marta; Erdelyi, Ferenc; Szabo, Gabor; Deisseroth, Karl; Lawrence, Josh

2015-01-01

Release of acetylcholine (ACh) in the hippocampus (HC) occurs during exploration, arousal, and learning. Although the medial septum-diagonal band of Broca (MS-DBB) is the major extrinsic source of cholinergic input to the HC, cholinergic neurons intrinsic to the HC also exist but remain poorly understood. Here, ChAT-tauGFP and ChAT-CRE/Rosa26YFP (ChAT-Rosa) mice were examined in HC. The HC of ChAT-tauGFP mice was densely innervated with GFP-positive axons, often accompanied by large GFP-positive structures, some of which were Neurotrace/DAPI-negative and likely represent large axon terminals. In the HC of ChAT-Rosa mice, ChAT-YFP cells were Neurotrace-positive and more abundant in CA3 and dentate gyrus than CA1 with partial overlap with calretinin/VIP. Moreover, an anti-ChAT antibody consistently showed ChAT immunoreactivity in ChAT-YFP cells from MS-DBB but rarely from HC. Furthermore, ChAT-YFP cells from CA1 stratum radiatum/stratum lacunosum moleculare (SR/SLM) exhibited a stuttering firing phenotype but a delayed firing phenotype in stratum pyramidale (SP) of CA3. Input resistance and capacitance were also different between CA1 SR/LM and CA3 SP ChAT-YFP cells. Bath application of ACh increased firing frequency in all ChAT-YFP cells; however, cholinergic modulation was larger in CA1 SR/SLM than CA3 SP ChAT-YFP cells. Finally, CA3 SP ChAT-YFP cells exhibited a wider AP half-width and weaker cholinergic modulation than YFP-negative CA3 pyramidal cells. Consistent with CRE expression in a subpopulation of principal cells, optogenetic stimulation evoked glutamatergic postsynaptic currents in CA1 SR/SLM interneurons. In conclusion, the presence of fluorescently labeled hippocampal cells common to both ChAT-tauGFP and ChAT-Rosa mice are in good agreement with previous reports on the existence of cholinergic interneurons, but both transgenic mouse lines exhibited unexpected anatomical features that departed considerably from earlier observations.

Hippocampal cholinergic interneurons visualized with the choline acetyltransferase promoter: anatomical distribution, intrinsic membrane properties, neurochemical characteristics, and capacity for cholinergic modulation

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Feng eYi

2015-03-01

Full Text Available Release of acetylcholine (ACh in the hippocampus (HC occurs during exploration, arousal, and learning. Although the medial septum-diagonal band of Broca (MS-DBB is the major extrinsic source of cholinergic input to the HC, cholinergic neurons intrinsic to the HC also exist but remain poorly understood. Here, ChAT-tauGFP and ChAT-CRE/Rosa26YFP (ChAT-Rosa mice were examined in HC. The HC of ChAT-tauGFP mice was densely innervated with GFP-positive axons, often accompanied by large GFP-positive structures, some of which were Neurotrace/DAPI-negative and likely represent large axon terminals. In the HC of ChAT-Rosa mice, ChAT-YFP cells were Neurotrace-positive and more abundant in CA3 and dentate gyrus than CA1 with partial overlapping with calretinin/VIP. Moreover, an anti-ChAT antibody consistently showed ChAT immunoreactivity in ChAT-YFP cells from MS-DBB but rarely from HC. Furthermore, ChAT-YFP cells from CA1 stratum radiatum/stratum lacunosum moleculare (SR/SLM exhibited a stuttering firing phenotype but a delayed firing phenotype in stratum pyramidale (SP of CA3. Input resistance and capacitance were also different between CA1 SR/LM and CA3 SP ChAT-YFP cells. Bath application of ACh increased firing frequency in all ChAT-YFP cells; however, cholinergic modulation was larger in CA1 SR/SLM than CA3 SP ChAT-YFP cells. Finally, CA3 SP ChAT-YFP cells exhibited a wider AP half-width and weaker cholinergic modulation than YFP-negative CA3 pyramidal cells. Consistent with CRE expression in a subpopulation of principal cells, optogenetic stimulation evoked glutamatergic postsynaptic currents in CA1 SR/SLM interneurons. In conclusion, the presence of fluorescently labeled hippocampal cells common to both ChAT-Rosa and ChAT-tauGFP mice are in good agreement with previous reports on the existence of cholinergic interneurons, but both transgenic mouse lines exhibited unexpected anatomical features that departed considerably from earlier observations.

Cholinergic Hypofunction in Presbycusis-Related Tinnitus With Cognitive Function Impairment: Emerging Hypotheses

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Qingwei Ruan

2018-04-01

Full Text Available Presbycusis (age-related hearing loss is a potential risk factor for tinnitus and cognitive deterioration, which result in poor life quality. Presbycusis-related tinnitus with cognitive impairment is a common phenotype in the elderly population. In these individuals, the central auditory system shows similar pathophysiological alterations as those observed in Alzheimer’s disease (AD, including cholinergic hypofunction, epileptiform-like network synchronization, chronic inflammation, and reduced GABAergic inhibition and neural plasticity. Observations from experimental rodent models indicate that recovery of cholinergic function can improve memory and other cognitive functions via acetylcholine-mediated GABAergic inhibition enhancement, nicotinic acetylcholine receptor (nAChR-mediated anti-inflammation, glial activation inhibition and neurovascular protection. The loss of cholinergic innervation of various brain structures may provide a common link between tinnitus seen in presbycusis-related tinnitus and age-related cognitive impairment. We hypothesize a key component of the condition is the withdrawal of cholinergic input to a subtype of GABAergic inhibitory interneuron, neuropeptide Y (NPY neurogliaform cells. Cholinergic denervation might not only cause the degeneration of NPY neurogliaform cells, but may also result in decreased AChR activation in GABAergic inhibitory interneurons. This, in turn, would lead to reduced GABA release and inhibitory regulation of neural networks. Reduced nAChR-mediated anti-inflammation due to the loss of nicotinic innervation might lead to the transformation of glial cells and release of inflammatory mediators, lowering the buffering of extracellular potassium and glutamate metabolism. Further research will provide evidence for the recovery of cholinergic function with the use of cholinergic input enhancement alone or in combination with other rehabilitative interventions to reestablish inhibitory regulation

Lesions of the basal forebrain cholinergic system in mice disrupt idiothetic navigation.

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Adam S Hamlin

Full Text Available Loss of integrity of the basal forebrain cholinergic neurons is a consistent feature of Alzheimer's disease, and measurement of basal forebrain degeneration by magnetic resonance imaging is emerging as a sensitive diagnostic marker for prodromal disease. It is also known that Alzheimer's disease patients perform poorly on both real space and computerized cued (allothetic or uncued (idiothetic recall navigation tasks. Although the hippocampus is required for allothetic navigation, lesions of this region only mildly affect idiothetic navigation. Here we tested the hypothesis that the cholinergic medial septo-hippocampal circuit is important for idiothetic navigation. Basal forebrain cholinergic neurons were selectively lesioned in mice using the toxin saporin conjugated to a basal forebrain cholinergic neuronal marker, the p75 neurotrophin receptor. Control animals were able to learn and remember spatial information when tested on a modified version of the passive place avoidance test where all extramaze cues were removed, and animals had to rely on idiothetic signals. However, the exploratory behaviour of mice with cholinergic basal forebrain lesions was highly disorganized during this test. By contrast, the lesioned animals performed no differently from controls in tasks involving contextual fear conditioning and spatial working memory (Y maze, and displayed no deficits in potentially confounding behaviours such as motor performance, anxiety, or disturbed sleep/wake cycles. These data suggest that the basal forebrain cholinergic system plays a specific role in idiothetic navigation, a modality that is impaired early in Alzheimer's disease.

Computer models and output, Spartan REM: Appendix B

Science.gov (United States)

Marlowe, D. S.; West, E. J.

1984-01-01

A computer model of the Spartan Release Engagement Mechanism (REM) is presented in a series of numerical charts and engineering drawings. A crack growth analysis code is used to predict the fracture mechanics of critical components.

Comorbidity and medication in REM sleep behavior disorder

DEFF Research Database (Denmark)

Frauscher, Birgit; Jennum, Poul; Ju, Yo-El S

2014-01-01

OBJECTIVE: This controlled study investigated associations between comorbidity and medication in patients with polysomnographically confirmed idiopathic REM sleep behavior disorder (iRBD), using a large multicenter clinic-based cohort. METHODS: Data of a self-administered questionnaire...

Slow wave and REM sleep deprivation effects on explicit and implicit memory during sleep.

Science.gov (United States)

Casey, Sarah J; Solomons, Luke C; Steier, Joerg; Kabra, Neeraj; Burnside, Anna; Pengo, Martino F; Moxham, John; Goldstein, Laura H; Kopelman, Michael D

2016-11-01

It has been debated whether different stages in the human sleep cycle preferentially mediate the consolidation of explicit and implicit memories, or whether all of the stages in succession are necessary for optimal consolidation. Here we investigated whether the selective deprivation of slow wave sleep (SWS) or rapid eye movement (REM) sleep over an entire night would have a specific effect on consolidation in explicit and implicit memory tasks. Participants completed a set of explicit and implicit memory tasks at night, prior to sleep. They had 1 control night of undisturbed sleep and 2 experimental nights, during which either SWS or REM sleep was selectively deprived across the entire night (sleep conditions counterbalanced across participants). Polysomnography recordings quantified precisely the amount of SWS and REM sleep that occurred during each of the sleep conditions, and spindle counts were recorded. In the morning, participants completed the experimental tasks in the same sequence as the night before. SWS deprivation disrupted the consolidation of explicit memories for visuospatial information (ηp2 = .23), and both SWS (ηp2 = .53) and REM sleep (ηp2 = .52) deprivation adversely affected explicit verbal recall. Neither SWS nor REM sleep deprivation affected aspects of short-term or working memory, and did not affect measures of verbal implicit memory. Spindle counts did not correlate significantly with memory performance. These findings demonstrate the importance of measuring the sleep cycles throughout the entire night, and the contribution of both SWS and REM sleep to memory consolidation. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Synthesis of (±)-I-125-iodobenzovesamicol - A cholinergic neuron marker

International Nuclear Information System (INIS)

Jung, Y.W.; Van Dort, M.E.; Wieland, D.M.

1990-01-01

The authors are focusing efforts on developing markers for the cholinergic neuron. Vesamicol (VA) has been adopted as a basis for the design of a presynaptic cholinergic nerve marker. Benzovesamicol, an analog of VA, is equipotent with VA and displays remarkable bulk tolerance in the 5-position. They have synthesized (±)-[I-125]-5-iodobenzovesamicol, and have conducted in vivo screening with it in mice

Pinellia ternata (Thunb.) Makino Preparation promotes sleep by increasing REM sleep.

Science.gov (United States)

Lin, Sisi; Nie, Bo; Yao, Guihong; Yang, Hui; Ye, Ren; Yuan, Zhengzhong

2018-05-15

Pinellia ternata (Thunb.) Makino Preparation (PTP) is widely used to treat insomnia in traditional Chinese medicine; however, its specific role is not clear. In this study, PTP was prepared at three concentrations. For locomotor activity tests, mice were treated with PTP and evaluated for 14 days. For polygraph recordings, mice were treated for 14 days and recorded after treatment. The main chemical constituents in PTP were identified by Ultra performance liquid chromatography/quadrupole time spectrometry (UPLC/Q-TOF-MS). The results showed that 0.9 g/mL PTP significantly reduced locomotor activity. The effect was related to the time of treatment. PTP reduced wakefulness and increased sleep in mice. Furthermore, PTP promoted sleep by increasing the number of REM sleep episodes with a duration of 64-128s and increasing the number of transitions from NREM sleep to REM sleep and from REM sleep to wakefulness. A total of 17 compounds were identified.

Cholinergic drugs as therapeutic tools in inflammatory diseases: participation of neuronal and non-neuronal cholinergic systems.

Science.gov (United States)

Sales, María Elena

2013-01-01

Acetylcholine (ACh) is synthesized by choline acetyltransferase (ChAT) from acetylcoenzime A and choline. This reaction occurs not only in pre-ganglionic fibers of the autonomic nervous system and post-ganglionic parasympathetic nervous fibers but also in non neuronal cells. This knowledge led to expand the role of ACh as a neurotransmitter and to consider it as a "cytotransmitter" and also to evaluate the existence of a non-neuronal cholinergic system comprising ACh, ChAT, acetylcholinesterase, and the nicotinic and muscarinic ACh receptors, outside the nervous system. This review analyzes the participation of cholinergic system in inflammation and discusses the role of different muscarinic and nicotinic drugs that are being used to treat skin inflammatory disorders, asthma, and chronic obstructive pulmonary disease as well as, intestinal inflammation and systemic inflammatory diseases, among others, to assess the potential application of these compounds as therapeutic tools.

REM Behaviour Disorder Detection Associated with Neurodegerative Diseases

DEFF Research Database (Denmark)

Kempfner, Jacob; Sørensen, Gertrud Laura; Zoetmulder, Marielle

2010-01-01

Abnormal skeleton muscle activity during REM sleep is characterized as REM Behaviour Disorder (RBD), and may be an early marker for different neurodegenerative diseases. Early detection of RBD is therefore highly important, and in this ongoing study a semi-automatic method for RBD detection...... is proposed by analyzing the motor activity during sleep. Method: A total number of twelve patients have been involved in this study, six normal controls and six patients diagnosed with Parkinsons Disease (PD) with RBD. All subjects underwent at least one ambulant polysomnographic (PSG) recording. The sleep...... recordings were scored, according to the new sleep-scoring standard from the American Academy of Sleep Medicine, by two independent sleep specialists. A follow-up analysis of the scoring consensus between the two specialists has been conducted. Based on the agreement of the two manual scorings...

Transplantation of NSC-derived cholinergic neuron-like cells improves cognitive function in APP/PS1 transgenic mice.

Science.gov (United States)

Gu, G; Zhang, W; Li, M; Ni, J; Wang, P

2015-04-16

The ability to selectively control the differentiation of neural stem cells (NSCs) into cholinergic neurons in vivo would be an important step toward cell replacement therapy. First, green fluorescent protein (GFP)-NSCs were induced to differentiate into cholinergic neuron-like cells (CNLs) with retinoic acid (RA) pre-induction followed by nerve growth factor (NGF) induction. Then, these CNLs were transplanted into bilateral hippocampus of APP/PS1 transgenic mice. Behavioral parameters showed by Morris water maze (MWM) tests and the percentages of GFP-labeled cholinergic neurons of CNL transplanted mice were compared with those of controls. Brain levels of choline acetyltransferase (ChAT) mRNA and proteins were analyzed by quantitative real-time PCR and Western blotting, ChAT activity and acetylcholine (ACh) concentration were also evaluated by ChAT activity and ACh concentration assay kits. Immunofluorescence analysis showed that 80.3±1.5% NSCs differentiated into CNLs after RA pre-induction followed by NGF induction in vitro. Three months after transplantation, 82.4±6.3% CNLs differentiated into cholinergic neurons in vivo. APP/PS1 mice transplanted with CNLs showed a significant improvement in learning and memory ability compared with control groups at different time points. Furthermore, CNLs transplantation dramatically increased in the expressions of ChAT mRNA and protein, as well ChAT activity and ACh concentration in APP/PS1 mice. Our findings support the prospect of using NSC-derived CNLs in developing therapies for Alzheimer's disease (AD). Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Rev and Rex proteins of human complex retroviruses function with the MMTV Rem-responsive element

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Dudley Jaquelin P

2009-02-01

Full Text Available Abstract Background Mouse mammary tumor virus (MMTV encodes the Rem protein, an HIV Rev-like protein that enhances nuclear export of unspliced viral RNA in rodent cells. We have shown that Rem is expressed from a doubly spliced RNA, typical of complex retroviruses. Several recent reports indicate that MMTV can infect human cells, suggesting that MMTV might interact with human retroviruses, such as human immunodeficiency virus (HIV, human T-cell leukemia virus (HTLV, and human endogenous retrovirus type K (HERV-K. In this report, we test whether the export/regulatory proteins of human complex retroviruses will increase expression from vectors containing the Rem-responsive element (RmRE. Results MMTV Rem, HIV Rev, and HTLV Rex proteins, but not HERV-K Rec, enhanced expression from an MMTV-based reporter plasmid in human T cells, and this activity was dependent on the RmRE. No RmRE-dependent reporter gene expression was detectable using Rev, Rex, or Rec in HC11 mouse mammary cells. Cell fractionation and RNA quantitation experiments suggested that the regulatory proteins did not affect RNA stability or nuclear export in the MMTV reporter system. Rem had no demonstrable activity on export elements from HIV, HTLV, or HERV-K. Similar to the Rem-specific activity in rodent cells, the RmRE-dependent functions of Rem, Rev, or Rex in human cells were inhibited by a dominant-negative truncated nucleoporin that acts in the Crm1 pathway of RNA and protein export. Conclusion These data argue that many retroviral regulatory proteins recognize similar complex RNA structures, which may depend on the presence of cell-type specific proteins. Retroviral protein activity on the RmRE appears to affect a post-export function of the reporter RNA. Our results provide additional evidence that MMTV is a complex retrovirus with the potential for viral interactions in human cells.

Cholinergic depletion and basal forebrain volume in primary progressive aphasia

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Jolien Schaeverbeke

2017-01-01

In the PPA group, only LV cases showed decreases in AChE activity levels compared to controls. Surprisingly, a substantial number of SV cases showed significant AChE activity increases compared to controls. BF volume did not correlate with AChE activity levels in PPA. To conclude, in our sample of PPA patients, LV but not SV was associated with cholinergic depletion. BF atrophy in PPA does not imply cholinergic depletion.

Hippocampal “cholinergic interneurons” visualized with the choline acetyltransferase promoter: anatomical distribution, intrinsic membrane properties, neurochemical characteristics, and capacity for cholinergic modulation

Science.gov (United States)

Yi, Feng; Catudio-Garrett, Elizabeth; Gábriel, Robert; Wilhelm, Marta; Erdelyi, Ferenc; Szabo, Gabor; Deisseroth, Karl; Lawrence, Josh

2015-01-01

Release of acetylcholine (ACh) in the hippocampus (HC) occurs during exploration, arousal, and learning. Although the medial septum-diagonal band of Broca (MS-DBB) is the major extrinsic source of cholinergic input to the HC, cholinergic neurons intrinsic to the HC also exist but remain poorly understood. Here, ChAT-tauGFP and ChAT-CRE/Rosa26YFP (ChAT-Rosa) mice were examined in HC. The HC of ChAT-tauGFP mice was densely innervated with GFP-positive axons, often accompanied by large GFP-positive structures, some of which were Neurotrace/DAPI-negative and likely represent large axon terminals. In the HC of ChAT-Rosa mice, ChAT-YFP cells were Neurotrace-positive and more abundant in CA3 and dentate gyrus than CA1 with partial overlap with calretinin/VIP. Moreover, an anti-ChAT antibody consistently showed ChAT immunoreactivity in ChAT-YFP cells from MS-DBB but rarely from HC. Furthermore, ChAT-YFP cells from CA1 stratum radiatum/stratum lacunosum moleculare (SR/SLM) exhibited a stuttering firing phenotype but a delayed firing phenotype in stratum pyramidale (SP) of CA3. Input resistance and capacitance were also different between CA1 SR/LM and CA3 SP ChAT-YFP cells. Bath application of ACh increased firing frequency in all ChAT-YFP cells; however, cholinergic modulation was larger in CA1 SR/SLM than CA3 SP ChAT-YFP cells. Finally, CA3 SP ChAT-YFP cells exhibited a wider AP half-width and weaker cholinergic modulation than YFP-negative CA3 pyramidal cells. Consistent with CRE expression in a subpopulation of principal cells, optogenetic stimulation evoked glutamatergic postsynaptic currents in CA1 SR/SLM interneurons. In conclusion, the presence of fluorescently labeled hippocampal cells common to both ChAT-tauGFP and ChAT-Rosa mice are in good agreement with previous reports on the existence of cholinergic interneurons, but both transgenic mouse lines exhibited unexpected anatomical features that departed considerably from earlier observations. PMID:25798106

Effect of bite-raised condition on the hippocampal cholinergic system of aged SAMP8 mice.

Science.gov (United States)

Katayama, Tasuku; Mori, Daisuke; Miyake, Hidekazu; Fujiwara, Shuu; Ono, Yumie; Takahashi, Toru; Onozuka, Minoru; Kubo, Kin-Ya

2012-06-27

Occlusal disharmony induces chronic stress, which results in learning deficits in association with the morphologic changes in the hippocampus, e.g., neuronal degeneration and increased hypertrophied glial fibrillary acidic protein-positive cells. To investigate the mechanisms underlying impaired hippocampal function resulting from occlusal disharmony, we examined the effects of the bite-raised condition on the septohippocampal cholinergic system by assessing acetylcholine release in the hippocampus and choline acetyltransferase immunoreactivity in the medial septal nucleus in aged SAMP8 mice that underwent the bite raising procedure. Aged bite-raised mice showed decreased acetylcholine release in the hippocampus and a reduced number of choline acetyltransferase-immunopositive neurons in the medial septal nucleus compared to age-matched control mice. These findings suggest that the bite-raised condition in aged SAMP8 mice enhances the age-related decline in the septohippocampal cholinergic system, leading to impaired learning. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Catecholaminergic and cholinergic systems of mouse brain are modulated by LMN diet, rich in theobromine, polyphenols and polyunsaturated fatty acids.

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Fernández-Fernández, Laura; Esteban, Gerard; Giralt, Mercedes; Valente, Tony; Bolea, Irene; Solé, Montse; Sun, Ping; Benítez, Susana; Morelló, José Ramón; Reguant, Jordi; Ramírez, Bartolomé; Hidalgo, Juan; Unzeta, Mercedes

2015-04-01

The possible modulatory effect of the functional LMN diet, rich in theobromine, polyphenols and polyunsaturated fatty acids, on the catecholaminergic and cholinergic neurotransmission, affecting cognition decline during aging has been studied. 129S1/SvlmJ mice were fed for 10, 20, 30 and 40 days with either LMN or control diets. The enzymes involved in catecholaminergic and cholinergic metabolism were determined by both immunohistological and western blot analyses. Noradrenalin, dopamine and other metabolites were quantified by HPLC analysis. Theobromine, present in cocoa, the main LMN diet component, was analysed in parallel using SH-SY5Y and PC12 cell lines. An enhanced modulatory effect on both cholinergic and catecholaminergic transmissions was observed on 20 day fed mice. Similar effect was observed with theobromine, besides its antioxidant capacity inducing SOD-1 and GPx expression. The enhancing effect of the LMN diet and theobromine on the levels of acetylcholine-related enzymes, dopamine and specially noradrenalin confirms the beneficial role of this diet on the "cognitive reserve" and hence a possible reducing effect on cognitive decline underlying aging and Alzheimer's disease.

Inhaled ammonium persulphate inhibits non-adrenergic, non-cholinergic relaxations in the guinea pig isolated trachea.

Science.gov (United States)

Dellabianca, A; Faniglione, M; De Angelis, S; Colucci, M; Cervio, M; Balestra, B; Tonini, S; Candura, S M

2010-01-01

Persulphates can act both as irritants and sensitizers in inducing occupational asthma. A dysfunction of nervous control regulating the airway tone has been hypothesized as a mechanism underlying bronchoconstriction in asthma. It was the aim of this study to investigate whether inhaled ammonium persulphate affects the non-adrenergic, non-cholinergic (NANC) inhibitory innervation, the cholinergic nerve-mediated contraction or the muscular response to the spasmogens, carbachol or histamine, in the guinea pig epithelium-free, isolated trachea. Male guinea pigs inhaled aerosols containing ammonium persulphate (10 mg/m(3) for 30 min for 5 days during 3 weeks). Control animals inhaled saline aerosol. NANC relaxations to electrical field stimulation at 3 Hz were evaluated in whole tracheal segments as intraluminal pressure changes. Drugs inactivating peptide transmission, nitric oxide synthase, carbon monoxide production by haem oxygenase-2 and soluble guanylyl cyclase were used to assess the involvement of various inhibitory neurotransmitters. Carbachol and histamine cumulative concentration-response curves were obtained. In both groups, nitric oxide and carbon monoxide participated to the same extent as inhibitory neurotransmitters. In exposed animals, the tracheal NANC relaxations were reduced to 45.9 +/- 12.1% (p guinea pig airways. This may represent a novel mechanism contributing to persulphate-induced asthma. Copyright 2009 S. Karger AG, Basel.

Beta-amyloid and cholinergic neurons

Czech Academy of Sciences Publication Activity Database

Doležal, Vladimír; Kašparová, Jana

2003-01-01

Roč. 28, 3-4 (2003), s. 499-506 ISSN 0364-3190 R&D Projects: GA ČR GA305/01/0283; GA AV ČR IAA5011206 Institutional research plan: CEZ:AV0Z5011922 Keywords : cholinergic neurons * AlzheimerŽs disease * beta-amyloid Subject RIV: FH - Neurology Impact factor: 1.511, year: 2003

Variable expression of GFP in different populations of peripheral cholinergic neurons of ChATBAC-eGFP transgenic mice.

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Brown, T Christopher; Bond, Cherie E; Hoover, Donald B

2018-03-01

Immunohistochemistry is used widely to identify cholinergic neurons, but this approach has some limitations. To address these problems, investigators developed transgenic mice that express enhanced green fluorescent protein (GFP) directed by the promoter for choline acetyltransferase (ChAT), the acetylcholine synthetic enzyme. Although, it was reported that these mice express GFP in all cholinergic neurons and non-neuronal cholinergic cells, we could not detect GFP in cardiac cholinergic nerves in preliminary experiments. Our goals for this study were to confirm our initial observation and perform a qualitative screen of other representative autonomic structures for the presences of GFP in cholinergic innervation of effector tissues. We evaluated GFP fluorescence of intact, unfixed tissues and the cellular localization of GFP and vesicular acetylcholine transporter (VAChT), a specific cholinergic marker, in tissue sections and intestinal whole mounts. Our experiments identified two major tissues where cholinergic neurons and/or nerve fibers lacked GFP: 1) most cholinergic neurons of the intrinsic cardiac ganglia and all cholinergic nerve fibers in the heart and 2) most cholinergic nerve fibers innervating airway smooth muscle. Most cholinergic neurons in airway ganglia stained for GFP. Cholinergic systems in the bladder and intestines were fully delineated by GFP staining. GFP labeling of input to ganglia with long preganglionic projections (vagal) was sparse or weak, while that to ganglia with short preganglionic projections (spinal) was strong. Total absence of GFP might be due to splicing out of the GFP gene. Lack of GFP in nerve projections from GFP-positive cell bodies might reflect a transport deficiency. Copyright © 2017 Elsevier B.V. All rights reserved.

The Antarctic permafrost as a testbed for REMS (Rover Environmental Monitoring Station-Mars Science Laboratory)

Science.gov (United States)

Esteban, B.; Ramos, M.; Sebastián, E.; Armiens, C.; Gómez-Elvira, J.; Cabos, W.; de Pablo, M. A.

2009-04-01

The present climatic characteristics of Mars favor the presence of extense permafrost areas in this lonely planet. Therefore environmental parameters that are included in Martian Rover missions are also used for monitoring thermal soil surface evolution in order to study the permafrost active layer thickness and the energy balance in the soil-atmosphere boundary limit layer. The REMS (Rover Environmental Monitoring Station) is an environmental station designed by the Centro de Astrobiología (CAB- Spain) with the collaboration of national and international partners (CRISA/EADS, UPC and FMI), which is part of the payload of the MSL (Mars Science Laboratory) NASA mission to Mars (http://mars.jpl.nasa.gov/msl/overview/). This mission is expected to be launched in the final months of 2009, and mainly consists of a Rover, with a complete set of scientific instruments; the Rover will carry the biggest, most advanced suite of instruments for scientific studies ever sent to the Martian surface. Five sensors compose the REMS instrument: ground (GT-REMS) and air temperatures, wind speed and direction, pressure, humidity and ultraviolet radiation (UV-REMS). A simplified setup of the REMS was deployed on Antarctica in the surroundings of the Spanish Antarctic Stations on Livingston and Deception Islands (Maritime Antarctica), where the permafrost distribution is well-known. The aim of the experiment was to check REMS's sensors response against hard environmental conditions and calibrates their measures with standard Antarctic devices. The experimental apparatuses included some standard meteorological and thermopiles sensors corresponding to the REMS. All the sensors are mounted in a 1.8 m mast and include a Pt100 air temperature sensor with shield solar protection on the mast top, a Kipp and Zonnen CNR1 net radiometer for measuring infrared (5-50 μm) and short wave solar (305-2800 nm) radiation at 1.5 m high, GT-REMS sensor and its amplification box at 0.7 m high and finally

Choline metabolism as a basis for the selective vulnerability of cholinergic neurons

Science.gov (United States)

Wurtman, R. J.

1992-01-01

The unique propensity of cholinergic neurons to use choline for two purposes--ACh and membrane phosphatidylcholine synthesis--may contribute to their selective vulnerability in Alzheimer's disease and other cholinergic neurodegenerative disorders. When physiologically active, the neurons use free choline taken from the 'reservoir' in membrane phosphatidylcholine to synthesize ACh; this can lead to an actual decrease in the quantity of membrane per cell. Alzheimer's disease (but not Down's syndrome, or other neurodegenerative disorders) is associated with characteristic neurochemical lesions involving choline and ethanolamine: brain levels of these compounds are diminished, while those of glycerophosphocholine and glycerophosphoethanolamine (breakdown products of their respective membrane phosphatides) are increased, both in cholinergic and noncholinergic brain regions. Perhaps this metabolic disturbance and the tendency of cholinergic neurons to 'export' choline--in the form of ACh--underlie the selective vulnerability of the neurons. Resulting changes in membrane composition could abnormally expose intramembraneous proteins such as amyloid precursor protein to proteases.

Spatial and reversal learning in the Morris water maze are largely resistant to six hours of REM sleep deprivation following training

Science.gov (United States)

Walsh, Christine M.; Booth, Victoria; Poe, Gina R.

2011-01-01

This first test of the role of REM (rapid eye movement) sleep in reversal spatial learning is also the first attempt to replicate a much cited pair of papers reporting that REM sleep deprivation impairs the consolidation of initial spatial learning in the Morris water maze. We hypothesized that REM sleep deprivation following training would impair both hippocampus-dependent spatial learning and learning a new target location within a familiar environment: reversal learning. A 6-d protocol was divided into the initial spatial learning phase (3.5 d) immediately followed by the reversal phase (2.5 d). During the 6 h following four or 12 training trials/day of initial or reversal learning phases, REM sleep was eliminated and non-REM sleep left intact using the multiple inverted flowerpot method. Contrary to our hypotheses, REM sleep deprivation during four or 12 trials/day of initial spatial or reversal learning did not affect training performance. However, some probe trial measures indicated REM sleep-deprivation–associated impairment in initial spatial learning with four trials/day and enhancement of subsequent reversal learning. In naive animals, REM sleep deprivation during normal initial spatial learning was followed by a lack of preference for the subsequent reversal platform location during the probe. Our findings contradict reports that REM sleep is essential for spatial learning in the Morris water maze and newly reveal that short periods of REM sleep deprivation do not impair concurrent reversal learning. Effects on subsequent reversal learning are consistent with the idea that REM sleep serves the consolidation of incompletely learned items. PMID:21677190

El trastorno de conducta del sueño rem

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Alex Iranzo De Riquer, Dr.

2013-05-01

Full Text Available El trastorno de conducta durante el sueño REM (TCSR se caracteriza por conductas motoras vigorosas, pesadillas y ausencia de atonía muscular durante el sueño REM. Se debe a la disfunción directa o indirecta de las estructuras del tronco cerebral que regulan el sueño REM, especialmente el núcleo subceruleus. El TCSR puede ser idiopático o asociado a enfermedades neurológicas como la enfermedad de Parkinson (EP, la demencia con cuerpos de Lewy (DCL, la atrofia multisistémica (AMS y la narcolepsia. Los pacientes con la forma idiopática, especialmente los que tienen alterados el SPECT del transportador de la dopamina, la sonografía de la sustancia negra, los test de olfato y de la visión de colores, tienen un elevado riesgo de desarrollar la E P, DCL y AMS. El TCSR no debe considerarse como un simple trastorno del sueño, sino como una manifestación de una enfermedad neurológica. El clonazepam (0.25-4 mg y la melatonina (3-12 mg a la hora de acostarse mejoran los síntomas del TCSR pero no evitan, en la forma idiopática, la conversión a una enfermedad neurodegenerativa.

Differential modulation of global and local neural oscillations in REM sleep by homeostatic sleep regulation.

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Kim, Bowon; Kocsis, Bernat; Hwang, Eunjin; Kim, Youngsoo; Strecker, Robert E; McCarley, Robert W; Choi, Jee Hyun

2017-02-28

Homeostatic rebound in rapid eye movement (REM) sleep normally occurs after acute sleep deprivation, but REM sleep rebound settles on a persistently elevated level despite continued accumulation of REM sleep debt during chronic sleep restriction (CSR). Using high-density EEG in mice, we studied how this pattern of global regulation is implemented in cortical regions with different functions and network architectures. We found that across all areas, slow oscillations repeated the behavioral pattern of persistent enhancement during CSR, whereas high-frequency oscillations showed progressive increases. This pattern followed a common rule despite marked topographic differences. The findings suggest that REM sleep slow oscillations may translate top-down homeostatic control to widely separated brain regions whereas fast oscillations synchronizing local neuronal ensembles escape this global command. These patterns of EEG oscillation changes are interpreted to reconcile two prevailing theories of the function of sleep, synaptic homeostasis and sleep dependent memory consolidation.

Single-Cell Gene Expression Analysis of Cholinergic Neurons in the Arcuate Nucleus of the Hypothalamus.

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Jae Hoon Jeong

Full Text Available The cholinoceptive system in the hypothalamus, in particular in the arcuate nucleus (ARC, plays a role in regulating food intake. Neurons in the ARC contain multiple neuropeptides, amines, and neurotransmitters. To study molecular and neurochemical heterogeneity of ARC neurons, we combine single-cell qRT-PCR and single-cell whole transcriptome amplification methods to analyze expression patterns of our hand-picked 60 genes in individual neurons in the ARC. Immunohistochemical and single-cell qRT-PCR analyses show choline acetyltransferase (ChAT-expressing neurons in the ARC. Gene expression patterns are remarkably distinct in each individual cholinergic neuron. Two-thirds of cholinergic neurons express tyrosine hydroxylase (Th mRNA. A large subset of these Th-positive cholinergic neurons is GABAergic as they express the GABA synthesizing enzyme glutamate decarboxylase and vesicular GABA transporter transcripts. Some cholinergic neurons also express the vesicular glutamate transporter transcript gene. POMC and POMC-processing enzyme transcripts are found in a subpopulation of cholinergic neurons. Despite this heterogeneity, gene expression patterns in individual cholinergic cells appear to be highly regulated in a cell-specific manner. In fact, membrane receptor transcripts are clustered with their respective intracellular signaling and downstream targets. This novel population of cholinergic neurons may be part of the neural circuitries that detect homeostatic need for food and control the drive to eat.

The role of REM sleep in the processing of emotional memories: evidence from behavior and event-related potentials.

Science.gov (United States)

Groch, S; Wilhelm, I; Diekelmann, S; Born, J

2013-01-01

Emotional memories are vividly remembered for the long-term. Rapid eye movement (REM) sleep has been repeatedly proposed to support the superior retention of emotional memories. However, its exact contribution and, specifically, whether its effect is mainly on the consolidation of the contents or the processing of the affective component of emotional memories is not clear. Here, we investigated the effects of sleep rich in slow wave sleep (SWS) or REM sleep on the consolidation of emotional pictures and the accompanying changes in affective tone, using event-related potentials (ERPs) together with subjective ratings of valence and arousal. Sixteen healthy, young men learned 50 negative and 50 neutral pictures before 3-h retention sleep intervals that were filled with either SWS-rich early or REM sleep-rich late nocturnal sleep. In accordance with our hypothesis, recognition was better for emotional pictures than neutral pictures after REM compared to SWS-rich sleep. This emotional enhancement after REM-rich sleep expressed itself in an increased late positive potential of the ERP over the frontal cortex 300-500 ms after stimulus onset for correctly classified old emotional pictures compared with new emotional and neutral pictures. Valence and arousal ratings of emotional pictures were not differentially affected by REM or SWS-rich sleep after learning. Our results corroborate that REM sleep contributes to the consolidation of emotional contents in memory, but suggest that the affective tone is preserved rather than reduced by the processing of emotional memories during REM sleep. Copyright © 2012 Elsevier Inc. All rights reserved.

Illuminating the role of cholinergic signaling in circuits of attention and emotionally salient behaviors

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Antonio eLuchicchi

2014-10-01

Full Text Available Acetylcholine (ACh signaling underlies specific aspects of cognitive functions and behaviors, including attention, learning, memory and motivation. Alterations in ACh signaling are involved in the pathophysiology of multiple neuropsychiatric disorders. In the central nervous system, ACh transmission is mainly guaranteed by dense innervation of select cortical and subcortical regions from disperse groups of cholinergic neurons within the basal forebrain (e.g. diagonal band, medial septal, nucleus basalis and the pontine-mesencephalic nuclei, respectively. Despite the fundamental role of cholinergic signaling in the CNS and the long standing knowledge of the organization of cholinergic circuitry, remarkably little is known about precisely how ACh release modulates cortical and subcortical neural activity and the behaviors these circuits subserve. Growing interest in cholinergic signaling in the CNS focuses on the mechanism(s of action by which endogenously released ACh regulates cognitive functions, acting as a neuromodulator and /or as a direct transmitter via nicotinic and muscarinic receptors. The development of optogenetic techniques has provided a valuable toolbox with which we can address these questions, as it allows the selective manipulation of the excitability of cholinergic inputs to the diverse array of cholinergic target fields within cortical and subcortical domains. Here, we review recent papers that use the light-sensitive opsins in the cholinergic system to elucidate the role of ACh in circuits related to attention and emotionally salient behaviors. In particular, we highlight recent optogenetic studies which have tried to disentangle the precise role of ACh in the modulation of cortical-, hippocampal- and striatal-dependent functions.

The monetary value of the collective dose equivalent unit (person-rem)

International Nuclear Information System (INIS)

Rodgers, Reginald C.

1978-01-01

In the design and operation of nuclear power reactor facilities, it is recommended that radiation exposures to the workers and the general public be kept as 'low as reasonably achievable' (ALARA). In the process of implementing this principle cost-benefit evaluations are part of the decision making process. For this reason a monetary value has to be assigned to the collective dose equivalent unit (person-rem). The various factors such as medical health care, societal penalty and manpower replacement/saving are essential ingredients to determine a monetary value for the person-rem. These factors and their dependence on the level of risk (or exposure level) are evaluated. Monetary values of well under $100 are determined for the public dose equivalent unit. The occupational worker person-rem value is determined to be in the range of $500 to about $5000 depending on the exposure level and the type of worker and his affiliation, i.e., temporary or permanent. A discussion of the variability and the range of the monetary values will be presented. (author)

Observations on muscle activity in REM sleep behavior disorder assessed with a semi-automated scoring algorithm

DEFF Research Database (Denmark)

Jeppesen, Jesper; Otto, Marit; Frederiksen, Yoon

2018-01-01

OBJECTIVES: Rapid eye movement (REM) sleep behavior disorder (RBD) is defined by dream enactment due to a failure of normal muscle atonia. Visual assessment of this muscle activity is time consuming and rater-dependent. METHODS: An EMG computer algorithm for scoring 'tonic', 'phasic' and 'any......' submental muscle activity during REM sleep was evaluated compared with human visual ratings. Subsequently, 52 subjects were analyzed with the algorithm. Duration and maximal amplitude of muscle activity, and self-awareness of RBD symptoms were assessed. RESULTS: The computer algorithm showed high congruency...... sleep without atonia. CONCLUSIONS: Our proposed algorithm was able to detect and rate REM sleep without atonia allowing identification of RBD. Increased duration and amplitude of muscle activity bouts were characteristics of RBD. Quantification of REM sleep without atonia represents a marker of RBD...

Brain Cholinergic Function and Response to Rivastigmine in Patients With Chronic Sequels of Traumatic Brain Injury

DEFF Research Database (Denmark)

Östberg, Anna; Virta, Jere; Rinne, Juha O

2018-01-01

subjects for more than 1 year after at least moderate traumatic brain injury. Ten of the subjects were respondents and 7 nonrespondents to cholinergic medication. DESIGN:: Cholinergic function was assessed with [methyl-C] N-methylpiperidyl-4-acetate-PET (C-MP4A-PET), which reflects the activity...... was notably lower throughout the cortex in both respondents and nonrespondents, without significant differences between them. CONCLUSION:: Our study suggests that frontal cholinergic dysfunction is associated with the clinical response to cholinergic stimulation in patients with traumatic brain injury....

Optogenetic stimulation of cholinergic projection neurons as an alternative for deep brain stimulation for Alzheimer's treatment

Science.gov (United States)

Mancuso, James; Chen, Yuanxin; Zhao, Zhen; Li, Xuping; Xue, Zhong; Wong, Stephen T. C.

2013-03-01

Deep brain stimulation (DBS) of the cholinergic nuclei has emerged as a powerful potential treatment for neurodegenerative disease and is currently in a clinical trial for Alzheimer's therapy. While effective in treatment for a number of conditions from depression to epilepsy, DBS remains somewhat unpredictable due to the heterogeneity of the projection neurons that are activated, including glutamatergic, GABAergic, and cholinergic neurons, leading to unacceptable side effects ranging from apathy to depression or even suicidal behavior. It would be highly advantageous to confine stimulation to specific populations of neurons, particularly in brain diseases involving complex network interactions such as Alzheimer's. Optogenetics, now firmly established as an effective approach to render genetically-defined populations of cells sensitive to light activation including mice expressing Channelrhodopsin-2 specifically in cholinergic neurons, provides just this opportunity. Here we characterize the light activation properties and cell density of cholinergic neurons in healthy mice and mouse models of Alzheimer's disease in order to evaluate the feasibility of using optogenetic modulation of cholinergic synaptic activity to slow or reverse neurodegeneration. This paper is one of the very first reports to suggest that, despite the anatomical depth of their cell bodies, cholinergic projection neurons provide a better target for systems level optogenetic modulation than cholinergic interneurons found in various brain regions including striatum and the cerebral cortex. Additionally, basal forebrain channelrhodopsin-expressing cholinergic neurons are shown to exhibit normal distribution at 60 days and normal light activation at 40 days, the latest timepoints observed. The data collected form the basis of ongoing computational modeling of light stimulation of entire populations of cholinergic neurons.

Electroacupuncture at Zusanli Prevents Severe Scalds-Induced Gut Ischemia and Paralysis by Activating the Cholinergic Pathway

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Huan Wang

2015-01-01

Full Text Available Severe burn injuries may result in gastrointestinal paralysis, and barrier dysfunction due to gut ischemia and lowered vagus excitability. In this study we investigate whether electroacupuncture (EA at Zusanli (ST36 could prevent severe scalds-induced gut ischemia, paralysis, and barrier dysfunction and whether the protective role of EA at ST36 is related to the vagus nerve. 35% burn area rats were divided into six groups: (a EAN: EA nonchannel acupoints followed by scald injury; (b EA: EA at ST36 after scald injury; (c VGX/EA: vagotomy (VGX before EA at ST36 and scald injury; (d VGX/EAN: VGX before EAN and scald injury; (e atropine/EA: applying atropine before scald injury and then EA at ST36; (f atropine/EAN: applying atropine before scald injury and then EA at nonchannel acupoints. EA at the Zusanli point significantly promoted the intestinal impelling ratio and increased the amount of mucosal blood flow after scald injury. The plasma diamine oxidase (DAO and intestinal permeability decreased significantly after scald injury in the EA group compared with others. However, EA after atropine injection or cervical vagotomy failed to improve intestinal motility and mucosa blood flow suggesting that the mechanism of EA may be related to the activation of the cholinergic nerve pathway.

Spartan Release Engagement Mechanism (REM) stress and fracture analysis

Science.gov (United States)

Marlowe, D. S.; West, E. J.

1984-01-01

The revised stress and fracture analysis of the Spartan REM hardware for current load conditions and mass properties is presented. The stress analysis was performed using a NASTRAN math model of the Spartan REM adapter, base, and payload. Appendix A contains the material properties, loads, and stress analysis of the hardware. The computer output and model description are in Appendix B. Factors of safety used in the stress analysis were 1.4 on tested items and 2.0 on all other items. Fracture analysis of the items considered fracture critical was accomplished using the MSFC Crack Growth Analysis code. Loads and stresses were obtaind from the stress analysis. The fracture analysis notes are located in Appendix A and the computer output in Appendix B. All items analyzed met design and fracture criteria.

Effects of cholinergic deafferentation of the rhinal cortex on visual recognition memory in monkeys.

Science.gov (United States)

Turchi, Janita; Saunders, Richard C; Mishkin, Mortimer

2005-02-08

Excitotoxic lesion studies have confirmed that the rhinal cortex is essential for visual recognition ability in monkeys. To evaluate the mnemonic role of cholinergic inputs to this cortical region, we compared the visual recognition performance of monkeys given rhinal cortex infusions of a selective cholinergic immunotoxin, ME20.4-SAP, with the performance of monkeys given control infusions into this same tissue. The immunotoxin, which leads to selective cholinergic deafferentation of the infused cortex, yielded recognition deficits of the same magnitude as those produced by excitotoxic lesions of this region, providing the most direct demonstration to date that cholinergic activation of the rhinal cortex is essential for storing the representations of new visual stimuli and thereby enabling their later recognition.

REM-sleep alterations in children with co-existence of tic disorders and attention-deficit/hyperactivity disorder: impact of hypermotor symptoms.

Science.gov (United States)

Kirov, Roumen; Banaschewski, Tobias; Uebel, Henrik; Kinkelbur, Jörg; Rothenberger, Aribert

2007-06-01

To characterize precisely the sleep pattern in children with co-existence of TD + ADHD. By means of polysomnography, sleep pattern was investigated in 19 children with TD + ADHD unmedicated before and during study and 19 healthy controls, matched for age, gender, and intelligence. Compared with healthy controls, children with TD + ADHD displayed shorter REM sleep latency and increased REM sleep duration. There was a negative correlational relationship between these REM-sleep alterations and they were determined by hyperactivity symptoms. Sleep in children with coexistence of TD + ADHD may be characterized by an elevated REM sleep drive. Common mechanisms are suggested to underpin hypermotor symptoms and REM sleep regulation.

Cholinergic neurons in the dorsomedial hypothalamus regulate mouse brown adipose tissue metabolism

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Jae Hoon Jeong

2015-06-01

Conclusion: DMH cholinergic neurons directly send efferent signals to sympathetic premotor neurons in the Rpa. Elevated cholinergic input to this area reduces BAT activity through activation of M2 mAChRs on serotonergic neurons. Therefore, the direct DMHACh–Rpa5-HT pathway may mediate physiological heat-defense responses to elevated environmental temperature.

Yokukansan and Yokukansankachimpihange Ameliorate Aggressive Behaviors in Rats with Cholinergic Degeneration in the Nucleus Basalis of Meynert

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Masahiro Tabuchi

2017-04-01

Full Text Available Yokukansan (YKS and yokukansankachimpihange (YKSCH are traditional Japanese Kampo medicines. The latter comprises YKS along with the medicinal herbs Citrus unshiu peel and Pinellia tuber. Both of these Kampo medicines are indicated for the treatment of night crying and irritability in children and for neurosis and insomnia in adults. In recent clinical trials, YKS exhibited ameliorative effects on the behavioral and psychological symptoms of dementia, such as aggressiveness, excitement, and irritability. In the present study, we aimed to clarify the involvement of cholinergic degeneration in the nucleus basalis of Meynert (NBM in the development of aggressiveness in rats. Subsequently, using this animal model, the effects of YKS and YKSCH on aggressiveness were compared and the mechanisms underlying these effects were investigated. L-Glutamic acid (Glu was injected into the right NBM of rats to induce deterioration of cholinergic neurons. On day 8 after Glu injection, aggressive behaviors were evaluated using resident–intruder tests. After the evaluation, YKS or YKSCH was administered to rats with aggressive behaviors daily for 7 days. In some groups, the 5-HT1A receptor antagonist WAY-100635 was coadministered with YKS or YKSCH over the same period. In other groups, locomotor activity was measured on days 12–14 after Glu injection. On day 15, immunohistochemistry was then performed to examine choline acetyltransferase (ChAT activities in the NBM. Aggressive behaviors had developed on day 8 after Glu injection and were maintained until day 15. YKS and YKSCH significantly ameliorated the aggressive behaviors. These suppressive effects were entirely abolished following coadministration of WAY-100635. Finally, the number of ChAT-positive cells in the right NBM was significantly reduced on day 15 after Glu injection, and treatment with YKS or YKSCH did not ameliorate these reduced cell numbers. Our results show that unilateral Glu injections

Development of cardiac parasympathetic neurons, glial cells, and regional cholinergic innervation of the mouse heart.

Science.gov (United States)

Fregoso, S P; Hoover, D B

2012-09-27

Very little is known about the development of cardiac parasympathetic ganglia and cholinergic innervation of the mouse heart. Accordingly, we evaluated the growth of cholinergic neurons and nerve fibers in mouse hearts from embryonic day 18.5 (E18.5) through postnatal day 21(P21). Cholinergic perikarya and varicose nerve fibers were identified in paraffin sections immunostained for the vesicular acetylcholine transporter (VAChT). Satellite cells and Schwann cells in adjacent sections were identified by immunostaining for S100β calcium binding protein (S100) and brain-fatty acid binding protein (B-FABP). We found that cardiac ganglia had formed in close association to the atria and cholinergic innervation of the atrioventricular junction had already begun by E18.5. However, most cholinergic innervation of the heart, including the sinoatrial node, developed postnatally (P0.5-P21) along with a doubling of the cross-sectional area of cholinergic perikarya. Satellite cells were present throughout neonatal cardiac ganglia and expressed primarily B-FABP. As they became more mature at P21, satellite cells stained strongly for both B-FABP and S100. Satellite cells appeared to surround most cardiac parasympathetic neurons, even in neonatal hearts. Mature Schwann cells, identified by morphology and strong staining for S100, were already present at E18.5 in atrial regions that receive cholinergic innervation at later developmental times. The abundance and distribution of S100-positive Schwann cells increased postnatally along with nerve density. While S100 staining of cardiac Schwann cells was maintained in P21 and older mice, Schwann cells did not show B-FABP staining at these times. Parallel development of satellite cells and cholinergic perikarya in the cardiac ganglia and the increase in abundance of Schwann cells and varicose cholinergic nerve fibers in the atria suggest that neuronal-glial interactions could be important for development of the parasympathetic nervous

Cholinergic systems are essential for late-stage maturation and refinement of motor cortical circuits

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Ramanathan, Dhakshin S.; Conner, James M.; Anilkumar, Arjun A.

2014-01-01

Previous studies reported that early postnatal cholinergic lesions severely perturb early cortical development, impairing neuronal cortical migration and the formation of cortical dendrites and synapses. These severe effects of early postnatal cholinergic lesions preclude our ability to understand the contribution of cholinergic systems to the later-stage maturation of topographic cortical representations. To study cholinergic mechanisms contributing to the later maturation of motor cortical circuits, we first characterized the temporal course of cortical motor map development and maturation in rats. In this study, we focused our attention on the maturation of cortical motor representations after postnatal day 25 (PND 25), a time after neuronal migration has been accomplished and cortical volume has reached adult size. We found significant maturation of cortical motor representations after this time, including both an expansion of forelimb representations in motor cortex and a shift from proximal to distal forelimb representations to an extent unexplainable by simple volume enlargement of the neocortex. Specific cholinergic lesions placed at PND 24 impaired enlargement of distal forelimb representations in particular and markedly reduced the ability to learn skilled motor tasks as adults. These results identify a novel and essential role for cholinergic systems in the late refinement and maturation of cortical circuits. Dysfunctions in this system may constitute a mechanism of late-onset neurodevelopmental disorders such as Rett syndrome and schizophrenia. PMID:25505106

From the skyscraper to the ground-scraper. Rem Koolhaas’s Japanese Kasbah

OpenAIRE

Álvarez Arce, Raquel

2016-01-01

Rem Koolhaas, as a contemporary architect, draws from the proposals which were devel-oped by the architects who reacted to the ideas formulated on the International Congresses of Modern Architecture, like the Team 10 members. Woods, along with Candilis and Josic, worked out a new type of building that he called ground-scrapper, although it is better known by the name given by Alison Smithson: the mat-building. Rem Koolhaas, in the Nexus World building in Fukuoka, propose, as he says in S,M,L,...

Calculations of dosimetric parameter and REM meter response for BE(d, n) source

International Nuclear Information System (INIS)

Chen Changmao

1988-01-01

Based on the recent data about neutron spectra, the average energy, effictive energy and conversion coefficient of fluence to dose equivalent are calculated for some Be (α, n) neutron sources which have differene types and structures. The responses of 2202D and 0075 REM meter for thses spectral neutrons are also estimated. The results indicate that the relationship between average energy and conversion coefficient or REM meter responses can be described by simple functions

Co-expression of Cholinergic and Noradrenergic Phenotypes in Human and Non-Human Autonomic Nervous System

OpenAIRE

Weihe, Eberhard; Schütz, Burkhard; Hartschuh, Wolfgang; Anlauf, Martin; Schäfer, Martin K.; Eiden, Lee E.

2005-01-01

It has long been known that the sympathetic innervation of the sweat glands is cholinergic in most mammalian species, and that during development, rodent sympathetic cholinergic sweat gland innervation transiently expresses noradrenergic traits. We show here that some noradrenergic traits persist in cholinergic sympathetic innervation of the sweat glands in rodents, but that lack of expression of the vesicular monoamine transporter renders these cells functionally non-noradrenergic. Adult hum...

Internal cholinergic regulation of learning and recall in a model of olfactory processing

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Licurgo Benemann Almeida

2016-11-01

Full Text Available In the olfactory system, cholinergic modulation has been associated with contrast modulation and changes in receptive fields in the olfactory bulb, as well the learning of odor associations in olfactory cortex. Computational modeling and behavioral studies suggest that cholinergic modulation could improve sensory processing and learning while preventing pro-active interference when task demands are high. However, how sensory inputs and/or learning regulate incoming modulation has not yet been elucidated. We here use a computational model of the olfactory bulb, piriform cortex (PC and horizontal limb of the diagonal band of Broca (HDB to explore how olfactory learning could regulate cholinergic inputs to the system in a closed feedback loop. In our model, the novelty of an odor is reflected in firing rates and sparseness of cortical neurons in response to that odor and these firing rates can directly regulate learning in the system by modifying cholinergic inputs to the system. In the model, cholinergic neurons reduce their firing in response to familiar odors – reducing plasticity in the PC, but increase their firing in response to novel odor – increasing PC plasticity. Recordings from HDB neurons in awake behaving rats reflect predictions from the model by showing that a subset of neurons decrease their firing as an odor becomes familiar.

Modeling Parkinson’s Disease Falls Associated With Brainstem Cholinergic Systems Decline

OpenAIRE

Kucinski, Aaron; Sarter, Martin

2015-01-01

In addition to the primary disease-defining symptoms, approximately half of patients with Parkinson’s disease (PD) suffer from postural instability, impairments in gait control and a propensity for falls. Consistent with evidence from patients, we previously demonstrated that combined striatal dopamine (DA) and basal forebrain (BF) cholinergic cell loss causes falls in rats traversing dynamic surfaces. Because evidence suggests that degeneration of brainstem cholinergic neurons arising from t...

Cholinergic enhancement modulates neural correlates of selective attention and emotional processing.

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Bentley, Paul; Vuilleumier, Patrik; Thiel, Christiane M; Driver, Jon; Dolan, Raymond J

2003-09-01

Neocortical cholinergic afferents are proposed to influence both selective attention and emotional processing. In a study of healthy adults we used event-related fMRI while orthogonally manipulating attention and emotionality to examine regions showing effects of cholinergic modulation by the anticholinesterase physostigmine. Either face or house pictures appeared at task-relevant locations, with the alternative picture type at irrelevant locations. Faces had either neutral or fearful expressions. Physostigmine increased relative activity within the anterior fusiform gyrus for faces at attended, versus unattended, locations, but decreased relative activity within the posterolateral occipital cortex for houses in attended, versus unattended, locations. A similar pattern of regional differences in the effect of physostigmine on cue-evoked responses was also present in the absence of stimuli. Cholinergic enhancement augmented the relative neuronal response within the middle fusiform gyrus to fearful faces, whether at attended or unattended locations. By contrast, physostigmine influenced responses in the orbitofrontal, intraparietal and cingulate cortices to fearful faces when faces occupied task-irrelevant locations. These findings suggest that acetylcholine may modulate both selective attention and emotional processes through independent, region-specific effects within the extrastriate cortex. Furthermore, cholinergic inputs to the frontoparietal cortex may influence the allocation of attention to emotional information.

Acute food deprivation reverses morphine-induced locomotion deficits in M5 muscarinic receptor knockout mice.

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Steidl, Stephan; Lee, Esther; Wasserman, David; Yeomans, John S

2013-09-01

Lesions of the pedunculopontine tegmental nucleus (PPT), one of two sources of cholinergic input to the ventral tegmental area (VTA), block conditioned place preference (CPP) for morphine in drug-naïve rats. M5 muscarinic cholinergic receptors, expressed by midbrain dopamine neurons, are critical for the ability of morphine to increase nucleus accumbens dopamine levels and locomotion, and for morphine CPP. This suggests that M5-mediated PPT cholinergic inputs to VTA dopamine neurons critically contribute to morphine-induced dopamine activation, reward and locomotion. In the current study we tested whether food deprivation, which reduces PPT contribution to morphine CPP in rats, could also reduce M5 contributions to morphine-induced locomotion in mice. Acute 18-h food deprivation reversed the phenotypic differences usually seen between non-deprived wild-type and M5 knockout mice. That is, food deprivation increased morphine-induced locomotion in M5 knockout mice but reduced morphine-induced locomotion in wild-type mice. Food deprivation increased saline-induced locomotion equally in wild-type and M5 knockout mice. Based on these findings, we suggest that food deprivation reduces the contribution of M5-mediated PPT cholinergic inputs to the VTA in morphine-induced locomotion and increases the contribution of a PPT-independent pathway. The contributions of cholinergic, dopaminergic and GABAergic neurons to the effects of acute food deprivation are discussed. Copyright © 2013 Elsevier B.V. All rights reserved.

Reversal of androgen inhibition of estrogen-activated sexual behavior by cholinergic agents.

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Dohanich, G P; Cada, D A

1989-12-01

Androgens have been found to inhibit lordosis activated by estrogen treatment of ovariectomized female rats. In the present experiments, dihydrotestosterone propionate (200 micrograms for 3 days) inhibited the incidence of lordosis in ovariectomized females treated with estradiol benzoate (1 microgram for 3 days). This inhibition of lordosis was reversed 15 min after bilateral intraventricular infusion of physostigmine (10 micrograms/cannula), an acetylcholinesterase inhibitor, or carbachol (0.5 microgram/cannula), a cholinergic receptor agonist. This reversal of inhibition appears to be mediated by cholinergic muscarinic receptors since pretreatment with scopolamine (4 mg/kg, ip), a muscarinic receptor blocker, prevented the reversal of androgen inhibition by physostigmine. These results indicate that androgens may inhibit estrogen-activated lordosis through interference with central cholinergic muscarinic mechanisms.

Increased Ventricular Premature Contraction Frequency During REM Sleep in Patients with Coronary Artery Disease and Obstructive Sleep Apnea

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Mari A. Watanabe

2008-11-01

Full Text Available Background Patients with obstructive sleep apnea are reported to have a peak of sudden cardiac death at night, in contrast to patients without apnea whose peak is in the morning. We hypothesized that ventricular premature contraction (VPC frequency would correlate with measures of apnea and sympathetic activity.Methods Electrocardiograms from a sleep study of 125 patients with coronary artery disease were evaluated. Patients were categorized by apnea-hypopnea index (AHI into Moderate (AHI 15 apnea groups. Sleep stages studied were Wake, S1, S2, S34, and rapid eye movement (REM. Parameters of a potent autonomically-based risk predictor for sudden cardiac death called heart rate turbulence were calculated.Results There were 74 Moderate and 51 Severe obstructive sleep apnea patients. VPC frequency was affected significantly by sleep stage (Wake, S2 and REM, F=5.8, p<.005 and by AHI (F=8.7, p<.005. In Severe apnea patients, VPC frequency was higher in REM than in Wake (p=.011. In contrast, patients with Moderate apnea had fewer VPCs and exhibited no sleep stage dependence (p=.19. Oxygen desaturation duration per apnea episode correlated positively with AHI (r2=.71, p<.0001, and was longer in REM than in non-REM (p<.0001. The heart rate turbulence parameter TS correlated negatively with oxygen desaturation duration in REM (r2=.06, p=.014.Conclusions Higher VPC frequency coupled with higher sympathetic activity caused by longer apnea episodes in REM sleep may be one reason for increased nocturnal death in apneic patients.

Cholinergic markers in the cortex and hippocampus of some animal species and their correlation to Alzheimer's disease.

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Orta-Salazar, E; Cuellar-Lemus, C A; Díaz-Cintra, S; Feria-Velasco, A I

2014-10-01

The cholinergic system includes neurons located in the basal forebrain and their long axons that reach the cerebral cortex and the hippocampus. This system modulates cognitive function. In Alzheimer's disease (AD) and ageing, cognitive impairment is associated with progressive damage to cholinergic fibres, which leads us to the cholinergic hypothesis for AD. The AD produces alterations in the expression and activity of acetyltransferase (ChAT) and acetyl cholinesterase (AChE), enzymes specifically related to cholinergic system function. Both proteins play a role in cholinergic transmission, which is altered in both the cerebral cortex and the hippocampus due to ageing and AD. Dementia disorders are associated with the severe destruction and disorganisation of the cholinergic projections extending to both structures. Specific markers, such as anti-ChAT and anti-AChE antibodies, have been used in light immunohistochemistry and electron microscopy assays to study this system in adult members of certain animal species. This paper reviews the main immunomorphological studies of the cerebral cortex and hippocampus in some animal species with particular emphasis on the cholinergic system and its relationship with the AD. Copyright © 2012 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

Changes in EEG power density of non-REM sleep in depressed patients during treatment with trazodone

NARCIS (Netherlands)

Bemmel, Alex L. van; Beersma, Domien G.M.; Hoofdakker, Rutger H. van den

1995-01-01

Recently, it was hypothesized that acute or cumulative suppression of non-REM sleep intensity might be related to the therapeutic effects of antidepressants. This intensity has been proposed to be expressed in the EEG power density in non-REM sleep. In the present study, the relationship was

Rapid expansion method (REM) for time‐stepping in reverse time migration (RTM)

KAUST Repository

Pestana, Reynam C.

2009-01-01

We show that the wave equation solution using a conventional finite‐difference scheme, derived commonly by the Taylor series approach, can be derived directly from the rapid expansion method (REM). After some mathematical manipulation we consider an analytical approximation for the Bessel function where we assume that the time step is sufficiently small. From this derivation we find that if we consider only the first two Chebyshev polynomials terms in the rapid expansion method we can obtain the second order time finite‐difference scheme that is frequently used in more conventional finite‐difference implementations. We then show that if we use more terms from the REM we can obtain a more accurate time integration of the wave field. Consequently, we have demonstrated that the REM is more accurate than the usual finite‐difference schemes and it provides a wave equation solution which allows us to march in large time steps without numerical dispersion and is numerically stable. We illustrate the method with post and pre stack migration results.

Cholinergic modulation of the hippocampal region and memory function.

Science.gov (United States)

Haam, Juhee; Yakel, Jerrel L

2017-08-01

Acetylcholine (ACh) plays an important role in memory function and has been implicated in aging-related dementia, in which the impairment of hippocampus-dependent learning strongly manifests. Cholinergic neurons densely innervate the hippocampus, mediating the formation of episodic as well as semantic memory. Here, we will review recent findings on acetylcholine's modulation of memory function, with a particular focus on hippocampus-dependent learning, and the circuits involved. In addition, we will discuss the complexity of ACh actions in memory function to better understand the physiological role of ACh in memory. This is an article for the special issue XVth International Symposium on Cholinergic Mechanisms. © 2017 International Society for Neurochemistry.

Relabeling exchange method (REM) for learning in neural networks

Science.gov (United States)

Wu, Wen; Mammone, Richard J.

1994-02-01

The supervised training of neural networks require the use of output labels which are usually arbitrarily assigned. In this paper it is shown that there is a significant difference in the rms error of learning when `optimal' label assignment schemes are used. We have investigated two efficient random search algorithms to solve the relabeling problem: the simulated annealing and the genetic algorithm. However, we found them to be computationally expensive. Therefore we shall introduce a new heuristic algorithm called the Relabeling Exchange Method (REM) which is computationally more attractive and produces optimal performance. REM has been used to organize the optimal structure for multi-layered perceptrons and neural tree networks. The method is a general one and can be implemented as a modification to standard training algorithms. The motivation of the new relabeling strategy is based on the present interpretation of dyslexia as an encoding problem.

Hallucinations and REM sleep behaviour disorder in Parkinson's disease: dream imagery intrusions and other hypotheses.

Science.gov (United States)

Manni, Raffaele; Terzaghi, Michele; Ratti, Pietro-Luca; Repetto, Alessandra; Zangaglia, Roberta; Pacchetti, Claudio

2011-12-01

REM sleep behaviour disorder (RBD) is a REM sleep-related parasomnia which may be considered a "dissociated state of wakefulness and sleep", given that conflicting elements of REM sleep (dreaming) and of wakefulness (sustained muscle tone and movements) coexist during the episodes, leading to motor and behavioural manifestations reminiscent of an enacted dream. RBD has been reported in association with α-synucleinopathies: around a third of patients with Parkinson's disease (PD) have full-blown RBD. Recent data indicate that PD patients with RBD are more prone to hallucinations than PD patients without this parasomnia. However it is still not clear why RBD in PD is associated with an increased prevalence of VHs. Data exist which suggest that visual hallucinations in PD may be the result of untimely intrusions of REM visual imagery into wakefulness. RBD, which is characterised by a REM sleep dissociation pattern, might be a condition that particularly favours such intrusions. However, other hypotheses may be advanced. In fact, deficits in attentional, executive, visuoperceptual and visuospatial abilities have been documented in RBD and found to occur far more frequently in PD with RBD than in PD without RBD. Neuropsychological deficits involving visual perception and attentional processes are thought to play an important role in the pathophysiology of VHs. On this basis, RBD in PD could be viewed as a contributory risk factor for VHs. Copyright © 2010 Elsevier Inc. All rights reserved.

Visual short-term memory deficits in REM sleep behaviour disorder mirror those in Parkinson's disease.

Science.gov (United States)

Rolinski, Michal; Zokaei, Nahid; Baig, Fahd; Giehl, Kathrin; Quinnell, Timothy; Zaiwalla, Zenobia; Mackay, Clare E; Husain, Masud; Hu, Michele T M

2016-01-01

Individuals with REM sleep behaviour disorder are at significantly higher risk of developing Parkinson's disease. Here we examined visual short-term memory deficits--long associated with Parkinson's disease--in patients with REM sleep behaviour disorder without Parkinson's disease using a novel task that measures recall precision. Visual short-term memory for sequentially presented coloured bars of different orientation was assessed in 21 patients with polysomnography-proven idiopathic REM sleep behaviour disorder, 26 cases with early Parkinson's disease and 26 healthy controls. Three tasks using the same stimuli controlled for attentional filtering ability, sensorimotor and temporal decay factors. Both patients with REM sleep behaviour disorder and Parkinson's disease demonstrated a deficit in visual short-term memory, with recall precision significantly worse than in healthy controls with no deficit observed in any of the control tasks. Importantly, the pattern of memory deficit in both patient groups was specifically explained by an increase in random responses. These results demonstrate that it is possible to detect the signature of memory impairment associated with Parkinson's disease in individuals with REM sleep behaviour disorder, a condition associated with a high risk of developing Parkinson's disease. The pattern of visual short-term memory deficit potentially provides a cognitive marker of 'prodromal' Parkinson's disease that might be useful in tracking disease progression and for disease-modifying intervention trials. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain.

Therapeutic potential of a non-steroidal bifunctional anti-inflammatory and anti-cholinergic agent against skin injury induced by sulfur mustard

Energy Technology Data Exchange (ETDEWEB)

Chang, Yoke-Chen; Wang, James D.; Hahn, Rita A.; Gordon, Marion K.; Joseph, Laurie B. [Department of Pharmacology and Toxicology, Rutgers University, Piscataway, NJ (United States); Heck, Diane E. [Department of Environmental Science, New York Medical College, Valhalla, NY (United States); Heindel, Ned D. [Department of Chemistry, Lehigh University, Bethlehem, PA (United States); Young, Sherri C. [Department of Chemistry, Muhlenberg College, Allentown, PA (United States); Sinko, Patrick J. [Department of Pharmaceutics, Rutgers University, Piscataway, NJ (United States); Casillas, Robert P. [MRIGlobal, Kansas City, MO (United States); Laskin, Jeffrey D. [Environmental and Occupational Medicine, Robert Wood Johnson Medical School, Rutgers University, Piscataway, NJ (United States); Laskin, Debra L. [Department of Pharmacology and Toxicology, Rutgers University, Piscataway, NJ (United States); Gerecke, Donald R., E-mail: gerecke@eohsi.rutgers.edu [Department of Pharmacology and Toxicology, Rutgers University, Piscataway, NJ (United States)

2014-10-15

Sulfur mustard (bis(2-chloroethyl) sulfide, SM) is a highly reactive bifunctional alkylating agent inducing edema, inflammation, and the formation of fluid-filled blisters in the skin. Medical countermeasures against SM-induced cutaneous injury have yet to be established. In the present studies, we tested a novel, bifunctional anti-inflammatory prodrug (NDH 4338) designed to target cyclooxygenase 2 (COX2), an enzyme that generates inflammatory eicosanoids, and acetylcholinesterase, an enzyme mediating activation of cholinergic inflammatory pathways in a model of SM-induced skin injury. Adult SKH-1 hairless male mice were exposed to SM using a dorsal skin vapor cup model. NDH 4338 was applied topically to the skin 24, 48, and 72 h post-SM exposure. After 96 h, SM was found to induce skin injury characterized by edema, epidermal hyperplasia, loss of the differentiation marker, keratin 10 (K10), upregulation of the skin wound marker keratin 6 (K6), disruption of the basement membrane anchoring protein laminin 322, and increased expression of epidermal COX2. NDH 4338 post-treatment reduced SM-induced dermal edema and enhanced skin re-epithelialization. This was associated with a reduction in COX2 expression, increased K10 expression in the suprabasal epidermis, and reduced expression of K6. NDH 4338 also restored basement membrane integrity, as evidenced by continuous expression of laminin 332 at the dermal–epidermal junction. Taken together, these data indicate that a bifunctional anti-inflammatory prodrug stimulates repair of SM induced skin injury and may be useful as a medical countermeasure. - Highlights: • Bifunctional anti-inflammatory prodrug (NDH4338) tested on SM exposed mouse skin • The prodrug NDH4338 was designed to target COX2 and acetylcholinesterase. • The application of NDH4338 improved cutaneous wound repair after SM induced injury. • NDH4338 treatment demonstrated a reduction in COX2 expression on SM injured skin. • Changes of skin repair

Cholinergic Neurons - Keeping Check on Amyloid beta in the Cerebral Cortex

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Saak V. Ovsepian

2013-12-01

Full Text Available The physiological relevance of the uptake of ligands with no apparent trophic functions via the p75 neurotrophin receptor (p75NTR remains unclear. Herein, we propose a homeostatic role for this in clearance of amyloid β (Aβ in the brain. We hypothesize that uptake of Aβ in conjunction with p75NTR followed by its degradation in lysosomes endows cholinergic basalo-cortical projections enriched in this receptor a facility for maintaining physiological levels of Aβ in target areas. Thus, in addition to the diffuse modulator influence and channeling of extra-thalamic signals, cholinergic innervations could supply the cerebral cortex with an elaborate system for Aβ drainage. Interpreting the emerging relationship of new molecular data with established role of cholinergic modulator system in regulating cortical network dynamics should provide new insights into the brain physiology and mechanisms of neuro-degenerative diseases.

PET study of cholinergic system in the brain

Energy Technology Data Exchange (ETDEWEB)

Shinotoh, Hitoshi [Chiba Univ. (Japan). School of Medicine

1999-01-01

Recently, we have developed a method to measure acetylcholinesterase (AChE) activity, a functional marker for cholinergic system, by positron emission tomography (PET) and carbon-11 labeled N-methyl-4-piperidyl acetate. Kinetic analysis of the radioactivity in the brain and the plasma yielded a rate constant ``k 3`` as an index of AChE activity. The ratios for the k 3 values for the cerebral cortex/thalamus/cerebellum/striatum found in healthy participants were 1/ 3/ 8/ 10, respectively, corresponding well with AChE activity ratios in the brain at necropsy (1/ 3/ 8/ 38), except for the striatum. In 23 healthy volunteers (age range: 24-89 years), there was no age-related decline of k 3 values in the cerebral cortex, suggesting AChE activity is preserved in aged cerebral cortex. In 11 patients with Alzheimer`s disease, there was a significant reduction (-24%) of k 3 values in the cerebral cortex and hippocampus, suggesting a loss of ascending cholinergic system from the basal forebrain to the cerebral cortex and hippocampus. In 16 patients with Parkinson`s disease, there was a significant reduction (-18%) of k 3 values in the cerebral cortex. In 10 patients with progressive supra nuclear palsy, there was a significant reduction (-38%) of k 3 values in the thalamus. This technique is useful for investigating central cholinergic system in neuro degenerative disorders with dementia. (author)

PET study of cholinergic system in the brain

International Nuclear Information System (INIS)

Shinotoh, Hitoshi

1999-01-01

Recently, we have developed a method to measure acetylcholinesterase (AChE) activity, a functional marker for cholinergic system, by positron emission tomography (PET) and carbon-11 labeled N-methyl-4-piperidyl acetate. Kinetic analysis of the radioactivity in the brain and the plasma yielded a rate constant ''k 3'' as an index of AChE activity. The ratios for the k 3 values for the cerebral cortex/thalamus/cerebellum/striatum found in healthy participants were 1/ 3/ 8/ 10, respectively, corresponding well with AChE activity ratios in the brain at necropsy (1/ 3/ 8/ 38), except for the striatum. In 23 healthy volunteers (age range: 24-89 years), there was no age-related decline of k 3 values in the cerebral cortex, suggesting AChE activity is preserved in aged cerebral cortex. In 11 patients with Alzheimer's disease, there was a significant reduction (-24%) of k 3 values in the cerebral cortex and hippocampus, suggesting a loss of ascending cholinergic system from the basal forebrain to the cerebral cortex and hippocampus. In 16 patients with Parkinson's disease, there was a significant reduction (-18%) of k 3 values in the cerebral cortex. In 10 patients with progressive supra nuclear palsy, there was a significant reduction (-38%) of k 3 values in the thalamus. This technique is useful for investigating central cholinergic system in neuro degenerative disorders with dementia. (author)

Myotropic Effects of Cholinergic Muscarinic Agonists and Antagonists in the Beetle Tenebrio molitor L.

Science.gov (United States)

Chowanski, Szymon; Rosinski, Grzegorz

2017-01-01

In mammals, the cholinergic nervous system plays a crucial role in neuronal regulation of physiological processes. It acts on cells by two types of receptors - nicotinic and muscarinic receptors. Both signal transmission pathways also operate in the central and peripheral cholinergic nervous system of insects. In our pharmacological experiments, we studied the effects of two muscarinic agonists (carbachol, pilocarpine) and two muscarinic antagonists (atropine, scopolamine) on the muscle contractile activity of visceral organs in the beetle, Tenebrio molitor. Both antagonists, when injected to haemolymph at concentration 10-5 M, caused delayed and prolonged cardioinhibitory effects on heart contractility in ortho- and antidromic phases of heart activity in T. molitor pupa what was observed as negative chrono- and inotropic effects. Agonist of muscarinic receptors - carbachol evoked opposite effect and increased contraction rate but only in antidromic phase. Pilocarpine, the second agonist induced weak negative chronotropic effects in the antiand orthodromic phases of heart activity. However, neither agonists had an effect on semi-isolated beetle heart in vitro. Only atropine at the highest tested concentrations slightly decreased the frequency of myocardial contractions. These suggest the regulation of heart activity by muscarinic system indirectly. The tested compounds also affected the contractility of the oviduct and hindgut, but the responses of these organs were varied and depended on the concentration of the applied compounds. These pharmacological experiments suggest the possible modulation of insect visceral muscle contractility by the cholinergic nervous system and indirectly indicate the presence of muscarinic receptor(s) in the visceral organs of the beetle T. molitor. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Materials properties, loads, and stress analysis, Spartan REM: Appendix A

Science.gov (United States)

Marlowe, D. S.; West, E. J.

1984-01-01

The mechanical properties, load tests, and stress analysis of the Spartan Release Engagement Mechanism (REM) is presented. The fracture properties of the components of the unit are also discussed. Detailed engineering drawings are included.

Replay of conditioned stimuli during late REM and stage N2 sleep influences affective tone rather than emotional memory strength.

Science.gov (United States)

Rihm, Julia S; Rasch, Björn

2015-07-01

Emotional memories are reprocessed during sleep, and it is widely assumed that this reprocessing occurs mainly during rapid eye movement (REM) sleep. In support for this notion, vivid emotional dreams occur mainly during REM sleep, and several studies have reported emotional memory enhancement to be associated with REM sleep or REM sleep-related parameters. However, it is still unknown whether reactivation of emotional memories during REM sleep strengthens emotional memories. Here, we tested whether re-presentation of emotionally learned stimuli during REM sleep enhances emotional memory. In a split-night design, participants underwent Pavlovian conditioning after the first half of the night. Neutral sounds served as conditioned stimuli (CS) and were either paired with a negative odor (CS+) or an odorless vehicle (CS-). During sound replay in subsequent late REM or N2 sleep, half of the CS+ and half of the CS- were presented again. In contrast to our hypothesis, replay during sleep did not affect emotional memory as measured by the differentiation between CS+ and CS- in expectancy, arousal and valence ratings. However, replay unspecifically decreased subjective arousal ratings of both emotional and neutral sounds and increased positive valence ratings also for both CS+ and CS- sounds, respectively. These effects were slightly more pronounced for replay during REM sleep. Our results suggest that re-exposure to previously conditioned stimuli during late sleep does not affect emotional memory strength, but rather influences the affective tone of both emotional and neutral memories. Copyright © 2015 Elsevier Inc. All rights reserved.

REM sleep behavior disorder in Parkinson′s disease: A case from India confirmed with polysomnographic data

Directory of Open Access Journals (Sweden)

Ravi Gupta

2013-01-01

Full Text Available Rapid eye movement (REM sleep behavior disorder is a condition characterized by dream enactment. This condition may accompany neurodegenerative disorders. However, only a few reports from India are available, that too, without any polysomnographic evidence. We are reporting a case of REM sleep behavior disorder with polysomnographic evidence.

Daytime Ayahuasca administration modulates REM and slow-wave sleep in healthy volunteers.

Science.gov (United States)

Barbanoj, Manel J; Riba, Jordi; Clos, S; Giménez, S; Grasa, E; Romero, S

2008-02-01

Ayahuasca is a traditional South American psychoactive beverage and the central sacrament of Brazilian-based religious groups, with followers in Europe and the United States. The tea contains the psychedelic indole N,N-dimethyltryptamine (DMT) and beta-carboline alkaloids with monoamine oxidase-inhibiting properties that render DMT orally active. DMT interacts with serotonergic neurotransmission acting as a partial agonist at 5-HT(1A) and 5-HT(2A/2C) receptor sites. Given the role played by serotonin in the regulation of the sleep/wake cycle, we investigated the effects of daytime ayahuasca consumption in sleep parameters. Subjective sleep quality, polysomnography (PSG), and spectral analysis were assessed in a group of 22 healthy male volunteers after the administration of a placebo, an ayahuasca dose equivalent to 1 mg DMT kg(-1) body weight, and 20 mg d-amphetamine, a proaminergic drug, as a positive control. Results show that ayahuasca did not induce any subjectively perceived deterioration of sleep quality or PSG-measured disruptions of sleep initiation or maintenance, in contrast with d-amphetamine, which delayed sleep initiation, disrupted sleep maintenance, induced a predominance of 'light' vs 'deep' sleep and significantly impaired subjective sleep quality. PSG analysis also showed that similarly to d-amphetamine, ayahuasca inhibits rapid eye movement (REM) sleep, decreasing its duration, both in absolute values and as a percentage of total sleep time, and shows a trend increase in its onset latency. Spectral analysis showed that d-amphetamine and ayahuasca increased power in the high frequency range, mainly during stage 2. Remarkably, whereas slow-wave sleep (SWS) power in the first night cycle, an indicator of sleep pressure, was decreased by d-amphetamine, ayahuasca enhanced power in this frequency band. Results show that daytime serotonergic psychedelic drug administration leads to measurable changes in PSG and sleep power spectrum and suggest an

BMP9 ameliorates amyloidosis and the cholinergic defect in a mouse model of Alzheimer's disease.

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Burke, Rebecca M; Norman, Timothy A; Haydar, Tarik F; Slack, Barbara E; Leeman, Susan E; Blusztajn, Jan Krzysztof; Mellott, Tiffany J

2013-11-26

Bone morphogenetic protein 9 (BMP9) promotes the acquisition of the cholinergic phenotype in basal forebrain cholinergic neurons (BFCN) during development and protects these neurons from cholinergic dedifferentiation following axotomy when administered in vivo. A decline in BFCN function occurs in patients with Alzheimer's disease (AD) and contributes to the AD-associated memory deficits. We infused BMP9 intracerebroventricularly for 7 d in transgenic AD model mice expressing green fluorescent protein specifically in cholinergic neurons (APP.PS1/CHGFP) and in wild-type littermate controls (WT/CHGFP). We used 5-mo-old mice, an age when the AD transgenics display early amyloid deposition and few cholinergic defects, and 10-mo-old mice, by which time these mice exhibit established disease. BMP9 infusion reduced the number of Aβ42-positive amyloid plaques in the hippocampus and cerebral cortex of 5- and 10-mo-old APP.PS1/CHGFP mice and reversed the reductions in choline acetyltransferase protein levels in the hippocampus of 10-mo-old APP.PS1/CHGFP mice. The treatment increased cholinergic fiber density in the hippocampus of both WT/CHGFP and APP.PS1/CHGFP mice at both ages. BMP9 infusion also increased hippocampal levels of neurotrophin 3, insulin-like growth factor 1, and nerve growth factor and of the nerve growth factor receptors, tyrosine kinase receptor A and p75/NGFR, irrespective of the genotype of the mice. These data show that BMP9 administration is effective in reducing the Aβ42 amyloid plaque burden, reversing cholinergic neuron abnormalities, and generating a neurotrophic milieu for BFCN in a mouse model of AD and provide evidence that the BMP9-signaling pathway may constitute a therapeutic target for AD.

Transcriptional Profiling of Cholinergic Neurons From Basal Forebrain Identifies Changes in Expression of Genes Between Sleep and Wake.

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Nikonova, Elena V; Gilliland, Jason DA; Tanis, Keith Q; Podtelezhnikov, Alexei A; Rigby, Alison M; Galante, Raymond J; Finney, Eva M; Stone, David J; Renger, John J; Pack, Allan I; Winrow, Christopher J

2017-06-01

To assess differences in gene expression in cholinergic basal forebrain cells between sleeping and sleep-deprived mice sacrificed at the same time of day. Tg(ChAT-eGFP)86Gsat mice expressing enhanced green fluorescent protein (eGFP) under control of the choline acetyltransferase (Chat) promoter were utilized to guide laser capture of cholinergic cells in basal forebrain. Messenger RNA expression levels in these cells were profiled using microarrays. Gene expression in eGFP(+) neurons was compared (1) to that in eGFP(-) neurons and to adjacent white matter, (2) between 7:00 am (lights on) and 7:00 pm (lights off), (3) between sleep-deprived and sleeping animals at 0, 3, 6, and 9 hours from lights on. There was a marked enrichment of ChAT and other markers of cholinergic neurons in eGFP(+) cells. Comparison of gene expression in these eGFP(+) neurons between 7:00 am and 7:00 pm revealed expected differences in the expression of clock genes (Arntl2, Per1, Per2, Dbp, Nr1d1) as well as mGluR3. Comparison of expression between spontaneous sleep and sleep-deprived groups sacrificed at the same time of day revealed a number of transcripts (n = 55) that had higher expression in sleep deprivation compared to sleep. Genes upregulated in sleep deprivation predominantly were from the protein folding pathway (25 transcripts, including chaperones). Among 42 transcripts upregulated in sleep was the cold-inducible RNA-binding protein. Cholinergic cell signatures were characterized. Whether the identified genes are changing as a consequence of differences in behavioral state or as part of the molecular regulatory mechanism remains to be determined. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

Serotonin 5-HT4 receptors and forebrain cholinergic system: receptor expression in identified cell populations.

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Peñas-Cazorla, Raúl; Vilaró, M Teresa

2015-11-01

Activation of serotonin 5-HT4 receptors has pro-cognitive effects on memory performance. The proposed underlying neurochemical mechanism is the enhancement of acetylcholine release in frontal cortex and hippocampus elicited by 5-HT4 agonists. Although 5-HT4 receptors are present in brain areas related to cognition, e.g., hippocampus and cortex, the cellular localization of the receptors that might modulate acetylcholine release is unknown at present. We have analyzed, using dual label in situ hybridization, the cellular localization of 5-HT4 receptor mRNA in identified neuronal populations of the rat basal forebrain, which is the source of the cholinergic innervation to cortex and hippocampus. 5-HT4 receptor mRNA was visualized with isotopically labeled oligonucleotide probes, whereas cholinergic, glutamatergic, GABAergic and parvalbumin-synthesizing neurons were identified with digoxigenin-labeled oligonucleotide probes. 5-HT4 receptor mRNA was not detected in the basal forebrain cholinergic cell population. In contrast, basal forebrain GABAergic, parvalbumin synthesizing, and glutamatergic cells contained 5-HT4 receptor mRNA. Hippocampal and cortical glutamatergic neurons also express this receptor. These results indicate that 5-HT4 receptors are not synthesized by cholinergic cells, and thus would be absent from cholinergic terminals. In contrast, several non-cholinergic cell populations within the basal forebrain and its target hippocampal and cortical areas express these receptors and are thus likely to mediate the enhancement of acetylcholine release elicited by 5-HT4 agonists.

Interaction of basal forebrain cholinergic neurons with the glucocorticoid system in stress regulation and cognitive impairment

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Saswati ePaul

2015-04-01

Full Text Available A substantial number of studies on basal forebrain cholinergic neurons (BFCN have provided compelling evidence for their role in the etiology of stress, cognitive aging, Alzheimer’s disease (AD, and other neurodegenerative diseases. BFCN project to a broad range of cortical sites and limbic structures, including the hippocampus, and are involved in stress and cognition. In particular, the hippocampus, the primary target tissue of the glucocorticoid stress hormones, is associated with cognitive function in tandem with hypothalamic-pituitary-adrenal (HPA axis modulation. The present review summarizes glucocorticoid and HPA axis research to date in an effort to establish the manner in which stress affects the release of acetylcholine, glucocorticoids, and their receptor in the context of cognitive processes. We attempt to provide the molecular interactive link between the glucocorticoids and cholinergic system that contributes to BFCN degeneration in stress-induced acceleration of cognitive decline in aging and AD. We also discuss the importance of animal models in facilitating such studies for pharmacological use, which could help decipher disease states and propose leads for pharmacological intervention.

Using the relational event model (REM) to investigate the temporal dynamics of animal social networks.

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Tranmer, Mark; Marcum, Christopher Steven; Morton, F Blake; Croft, Darren P; de Kort, Selvino R

2015-03-01

Social dynamics are of fundamental importance in animal societies. Studies on nonhuman animal social systems often aggregate social interaction event data into a single network within a particular time frame. Analysis of the resulting network can provide a useful insight into the overall extent of interaction. However, through aggregation, information is lost about the order in which interactions occurred, and hence the sequences of actions over time. Many research hypotheses relate directly to the sequence of actions, such as the recency or rate of action, rather than to their overall volume or presence. Here, we demonstrate how the temporal structure of social interaction sequences can be quantified from disaggregated event data using the relational event model (REM). We first outline the REM, explaining why it is different from other models for longitudinal data, and how it can be used to model sequences of events unfolding in a network. We then discuss a case study on the European jackdaw, Corvus monedula , in which temporal patterns of persistence and reciprocity of action are of interest, and present and discuss the results of a REM analysis of these data. One of the strengths of a REM analysis is its ability to take into account different ways in which data are collected. Having explained how to take into account the way in which the data were collected for the jackdaw study, we briefly discuss the application of the model to other studies. We provide details of how the models may be fitted in the R statistical software environment and outline some recent extensions to the REM framework.

A remorin gene SiREM6, the target gene of SiARDP, from foxtail millet (Setaria italica) promotes high salt tolerance in transgenic Arabidopsis.

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Yue, Jing; Li, Cong; Liu, Yuwei; Yu, Jingjuan

2014-01-01

Remorin proteins (REMs) form a plant-specific protein family, with some REMs being responsive to abiotic stress. However, the precise functions of REMs in abiotic stress tolerance are not clear. In this study, we identified 11 remorin genes from foxtail millet (Setaria italica) and cloned a remorin gene, SiREM6, for further investigation. The transcript level of SiREM6 was increased by high salt stress, low temperature stress and abscisic acid (ABA) treatment, but not by drought stress. The potential oligomerization of SiREM6 was examined by negative staining electron microscopy. The overexpression of SiREM6 improved high salt stress tolerance in transgenic Arabidopsis at the germination and seedling stages as revealed by germination rate, survival rate, relative electrolyte leakage and proline content. The SiREM6 promoter contains two dehydration responsive elements (DRE) and one ABA responsive element (ABRE). An ABA responsive DRE-binding transcription factor, SiARDP, and an ABRE-binding transcription factor, SiAREB1, were cloned from foxtail millet. SiARDP could physically bind to the DREs, but SiAREB1 could not. These results revealed that SiREM6 is a target gene of SiARDP and plays a critical role in high salt stress tolerance.

A remorin gene SiREM6, the target gene of SiARDP, from foxtail millet (Setaria italica promotes high salt tolerance in transgenic Arabidopsis.

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Jing Yue

Full Text Available Remorin proteins (REMs form a plant-specific protein family, with some REMs being responsive to abiotic stress. However, the precise functions of REMs in abiotic stress tolerance are not clear. In this study, we identified 11 remorin genes from foxtail millet (Setaria italica and cloned a remorin gene, SiREM6, for further investigation. The transcript level of SiREM6 was increased by high salt stress, low temperature stress and abscisic acid (ABA treatment, but not by drought stress. The potential oligomerization of SiREM6 was examined by negative staining electron microscopy. The overexpression of SiREM6 improved high salt stress tolerance in transgenic Arabidopsis at the germination and seedling stages as revealed by germination rate, survival rate, relative electrolyte leakage and proline content. The SiREM6 promoter contains two dehydration responsive elements (DRE and one ABA responsive element (ABRE. An ABA responsive DRE-binding transcription factor, SiARDP, and an ABRE-binding transcription factor, SiAREB1, were cloned from foxtail millet. SiARDP could physically bind to the DREs, but SiAREB1 could not. These results revealed that SiREM6 is a target gene of SiARDP and plays a critical role in high salt stress tolerance.

A new view of “dream enactment” in REM sleep behavior disorder

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Blumberg, Mark S.; Plumeau, Alan M.

2015-01-01

SUMMARY REM sleep behavior disorder (RBD) is a disorder in which patients exhibit increased muscle tone and exaggerated myoclonic twitching during REM sleep. In addition, violent movements of the limbs, and complex behaviors that can sometimes appear to involve the enactment of dreams, are associated with RBD. These behaviors are widely thought to result from a dysfunction involving atonia-producing neural circuitry in the brainstem, thereby unmasking cortically generated dreams. Here we scrutinize the assumptions that led to this interpretation of RBD. In particular, we challenge the assumption that motor cortex produces twitches during REM sleep, thus calling into question the related assumption that motor cortex is primarily responsible for all of the pathological movements of RBD. Moreover, motor cortex is not even necessary to produce complex behavior; for example, stimulation of some brainstem structures can produce defensive and aggressive behaviors in rats and monkeys that are striking similar to those reported in human patients with RBD. Accordingly, we suggest an interpretation of RBD that focuses increased attention on the brainstem as a source of the pathological movements and that considers sensory feedback from moving limbs as an important influence on the content of dream mentation. PMID:26802823

Flurbiprofen in rapid eye movement sleep deprivation induced hyperalgesia.

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Gürel, Elif Ezgi; Ural, Keremcan; Öztürk, Gülnur; Öztürk, Levent

2014-04-10

Rapid eye movement (REM) sleep deprivation induces hyperalgesia in healthy rats. Here, we evaluated the effects of flurbiprofen, an anti-inflammatory and neuroprotective agent, on the increased thermal responses observed in REM sleep deprived rats. Forty female rats were divided into four groups following 96-hour REM sleep deprivation: intraperitoneal injections of placebo, and flurbiprofen 5 mg/kg, 15 mg/kg and 40 mg/kg were made in CONT (n=10), FBP5, FBP15 and FBP40 groups respectively. Pain threshold measurements were performed three times at baseline (0.hour), at the end of REM sleep deprivation (96.hour) and at 1 h after injections (97.hour) by hot plate and tail-flick tests. REM sleep deprivation induced a significant decrease in pain thresholds of all rats (hotplate: 0.hour vs 96.hour, 9.75±2.85 vs 5.10±2.02, pFlurbiprofen in 15 mg/kg and 40 mg/kg doses significantly improved pain tolerance measured by tail flick test (tail flick in FBP15 and FBP40 groups: 96.hour vs 97.hour, 7.01±4.97 vs 8.34±3.61 and 5.06±1.57 vs 7.04±2.49, pFlurbiprofen was used for the first time in a rat model of REM sleep deprivation, and it provided anti-nociceptive effects in 15 mg/kg and 40 mg/kg doses. Flurbiprofen may have the potential for treatment of painful syndromes accompanying insomnia or sleep loss. Copyright © 2014 Elsevier Inc. All rights reserved.

Pauses in Striatal Cholinergic Interneurons: What is Revealed by Their Common Themes and Variations?

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Yan-Feng Zhang

2017-10-01

Full Text Available Striatal cholinergic interneurons, the so-called tonically active neurons (TANs, pause their firing in response to sensory cues and rewards during classical conditioning and instrumental tasks. The respective pause responses observed can demonstrate many commonalities, such as constant latency and duration, synchronous occurrence in a population of cells, and coincidence with phasic activities of midbrain dopamine neurons (DANs that signal reward predictions and errors. Pauses can however also show divergent properties. Pause latencies and durations can differ in a given TAN between appetitive vs. aversive outcomes in classical conditioning, initial excitation can be present or absent, and a second pause can variably follow a rebound. Despite more than 20 years of study, the functions of these pause responses are still elusive. Our understanding of pause function is hindered by an incomplete understanding of how pauses are generated. In this mini-review article, we compare pause types, as well as current key hypotheses for inputs underlying pauses that include dopamine-induced inhibition through D2-receptors, a GABA input from ventral tegmental area, and a prolonged afterhyperpolarization induced by excitatory input from the cortex or from the thalamus. We review how each of these mechanisms alone explains some but not all aspects of pause responses. These mechanisms might need to operate in specific but variable sets of sequences to generate a full range of pause responses. Alternatively, these mechanisms might operate in conjunction with an underlying control mechanism within cholinergic interneurons which could potentially provide a framework to generate the common themes and variations seen amongst pause responses.

Hypothalamic L-Histidine Decarboxylase Is Up-Regulated During Chronic REM Sleep Deprivation of Rats.

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Gloria E Hoffman

Full Text Available A competition of neurobehavioral drives of sleep and wakefulness occurs during sleep deprivation. When enforced chronically, subjects must remain awake. This study examines histaminergic neurons of the tuberomammillary nucleus of the posterior hypothalamus in response to enforced wakefulness in rats. We tested the hypothesis that the rate-limiting enzyme for histamine biosynthesis, L-histidine decarboxylase (HDC, would be up-regulated during chronic rapid eye movement sleep deprivation (REM-SD because histamine plays a major role in maintaining wakefulness. Archived brain tissues of male Sprague Dawley rats from a previous study were used. Rats had been subjected to REM-SD by the flowerpot paradigm for 5, 10, or 15 days. For immunocytochemistry, rats were transcardially perfused with acrolein-paraformaldehyde for immunodetection of L-HDC; separate controls used carbodiimide-paraformaldehyde for immunodetection of histamine. Immunolocalization of histamine within the tuberomammillary nucleus was validated using carbodiimide. Because HDC antiserum has cross-reactivity with other decarboxylases at high antibody concentrations, titrations localized L-HDC to only tuberomammillary nucleus at a dilution of ≥ 1:300,000. REM-SD increased immunoreactive HDC by day 5 and it remained elevated in both dorsal and ventral aspects of the tuberomammillary complex. Our results suggest that up-regulation of L-HDC within the tuberomammillary complex during chronic REM-SD may be responsible for maintaining wakefulness.

Measurement of functional cholinergic innervation in rat heart with a novel vesamicol receptor ligand

International Nuclear Information System (INIS)

Coffeen, Paul R.; Efange, S.M.N.; Haidet, George C.; McKnite, Scott; Langason, Rosemary B.; Khare, A.B.; Pennington, Jennifer; Lurie, Keith G.

1996-01-01

Regional differences in cholinergic activity in the cardiac conduction system have been difficult to study. We tested the utility of (+)-m-[ 125 I]iodobenzyl)trozamicol(+)-[ 125 I]MIBT), a novel radioligand that binds to the vesamicol receptor located on the synaptic vesicle in presynaptic cholinergic neurons, as a functional marker of cholinergic activity in the conduction system. The (+)-[ 125 I]MIBT was injected intravenously into four rats. Three hours later, the rats were killed and their hearts were frozen. Quantitative autoradiography was performed on 20-micron-thick sections that were subsequently stained for acetylcholinesterase to identify specific conduction-system elements. Marked similarities existed between (+)-[ 125 I]MIBT uptake and acetylcholinesterase-positive regions. Optical densitometric analysis of regional (+)-[ 125 I]MIBT uptake revealed significantly greater (+)-[ 125 I]MIBT binding (nCi/mg) in the atrioventricular node (AVN) and His bundle regions compared with other conduction and contractile elements (AVN: 3.43 ± 0.37; His bundle: 2.16 ± 0.30; right bundle branch: 0.95 ± 0.13; right atrium: 0.68 ± 0.05; right ventricle: 0.57 ± 0.03; and left ventricle: 0.57 ± 0.03; p 125 I]MIBT binds avidly to cholinergic nerve tissue innervating specific conduction-system elements. Thus, (+)-[ 125 I]MIBT may be a useful functional marker in studies on cholinergic innervation in the cardiac conduction system

Cholinergic effects of HI-6 in Soman poisoning

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Shih, T.M.; Lockwood, P.A.; Lundy, P.M.; Valdes, J.J.; Whalley, C.E.

1986-01-01

The authors conduct studies to determine the role of cholinergic mechanisms in the antidotal effects of HI-6 in soman poisoning. The effects of HI-6 were studied in discrete brain areas and elevation of acetylcholine or choline levels in vivo as well as on muscarinic receptor binding and high affinity Ch uptake (HAChT) in vitro. The effect of pralidoxime chloride was studied on the same cholinergic mechanisms to compare its effects with HI-6. Methyl-tritium-choline chloride and tritium-quinuclidinyl benzilate were used in the experiments on male Wistar rats. The influence of antidotal treatments on time to death in soman intoxicated rats is shown. The effects of soman and its antidotal treatments on regional bain ChE activity are shown. The most significant protection was afforded by simultaneous treatment with both HI-6 and ATS

Spatial and Reversal Learning in the Morris Water Maze Are Largely Resistant to Six Hours of REM Sleep Deprivation Following Training

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Walsh, Christine M.; Booth, Victoria; Poe, Gina R.

2011-01-01

This first test of the role of REM (rapid eye movement) sleep in reversal spatial learning is also the first attempt to replicate a much cited pair of papers reporting that REM sleep deprivation impairs the consolidation of initial spatial learning in the Morris water maze. We hypothesized that REM sleep deprivation following training would impair…

Facilitation and inhibition by capsaicin of cholinergic neurotransmission in the guinea-pig small intestine.

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Geber, Christian; Mang, Christian F; Kilbinger, Heinz

2006-01-01

The effects of capsaicin on [3H]acetylcholine release and muscle contraction were studied on the myenteric plexus-longitudinal muscle preparation of the guinea-pig ileum preincubated with [3H]choline. Capsaicin concentration-dependently increased both basal [3H]acetylcholine release (pEC50 7.0) and muscle tone (pEC50 6.1). The facilitatory effects of capsaicin were antagonized by 1 microM capsazepine (pK (B) 7.0 and 7.6), and by the combined blockade of NK1 and NK3 tachykinin receptors with the antagonists CP99994 plus SR142801 (each 0.1 microM). This suggests that stimulation by capsaicin of TRPV1 receptors on primary afferent fibres causes a release of tachykinins which, in turn, mediate via NK1 and NK3 receptors an increase in acetylcholine release. The capsaicin-induced acetylcholine release was significantly enhanced by the NO synthase inhibitor L-NG-nitroarginine (100 microM). This indicates that tachykinins released from sensory neurons also stimulate nitrergic neurons and thus lead, via NO release, to inhibition of acetylcholine release. Capsaicin concentration-dependently reduced the electrically-evoked [3H]acetylcholine release (pEC50 6.4) and twitch contractions (pEC50 5.9). The inhibitory effects were not affected by either capsazepine, NK1 and NK3 receptor antagonists, the cannabinoid CB1 antagonist SR141716A or by L-NG-nitroarginine. Desensitization of TRPV1 receptors by a short exposure to 3 microM capsaicin abolished the facilitatory responses to a subsequent administration, but did not modify the inhibitory effects. In summary, capsaicin has a dual effect on cholinergic neurotransmission. The facilitatory effect is indirect and involves tachykinin release and excitation of NK1 and NK3 receptors on cholinergic neurons. The inhibition of acetylcholine release may be due to a decrease of Ca2+ influx into cholinergic neurons.

Cholinergic dysfunction and amnesia in patients with Wernicke-Korsakoff syndrome: a transcranial magnetic stimulation study.

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Nardone, Raffaele; Bergmann, Jürgen; De Blasi, Pierpaolo; Kronbichler, Martin; Kraus, Jörg; Caleri, Francesca; Tezzon, Frediano; Ladurner, Gunther; Golaszewski, Stefan

2010-03-01

The specific neurochemical substrate underlying the amnesia in patients with Wernicke-Korsakoff syndrome (WKS) is still poorly defined. Memory impairment has been linked to dysfunction of neurons in the cholinergic system. A transcranial magnetic stimulation (TMS) protocol, the short latency afferent inhibition (SAI), may give direct information about the function of some cholinergic pathways in the human motor cortex. In the present study, we measured SAI in eight alcoholics with WKS and compared the data with those from a group of age-matched healthy individuals; furthermore, we correlated the individual SAI values of the WKS patients with memory and other cognitive functions. Mean SAI was significantly reduced in WKS patients when compared with the controls. SAI was increased after administration of a single dose of donezepil in a subgroup of four patients. The low score obtained in the Rey Complex Figure delayed recall test, the Digit Span subtest of the Wechsler Adult Intelligence Scale-Revised (WAIS-R) and the Corsi's Block Span subtest of the WAIS-R documented a severe impairment in the anterograde memory and short-term memory. None of the correlations between SAI values and these neuropsychological tests reached significance. We provide physiological evidence of cholinergic involvement in WKS. However, this putative marker of central cholinergic activity did not significantly correlate with the memory deficit in our patients. These findings suggest that the cholinergic dysfunction does not account for the memory disorder and that damage to the cholinergic system is not sufficient to cause a persisting amnesic syndrome in WKS.

REM Sleep Behavior Disorder and Prodromal Neurodegeneration - Where are We Headed?

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Ronald B. Postuma

2013-04-01

Full Text Available Rapid eye movement (REM sleep behavior disorder (RBD is characterized by loss of normal atonia during REM sleep, such that patients appear to act out their dreams. The most important implication of research into this area is that patients with idiopathic RBD are at very high risk of developing synucleinmediated neurodegenerative disease (Parkinson's disease [PD], dementia with Lewy bodies [DLB], and multiple system atrophy, with risk estimates that approximate 40–65% at 10 years. Thus, RBD disorder is a very strong feature of prodromal synucleinopathy. This provides several opportunities for future research. First, patients with REM sleep behavior disorder can be studied to test other predictors of disease, which could potentially be applied to the general population. These studies have demonstrated that olfactory loss, decreased color vision, slowing on quantitative motor testing, and abnormal substantia nigra neuroimaging findings can predict clinical synucleinopathy. Second, prospectively studying patients with RBD allows a completely unprecedented opportunity to directly evaluate patients as they transition into clinical neurodegenerative disease. Studies assessing progression of markers of neurodegeneration in prodromal PD are beginning to appear. Third, RBD are very promising subjects for neuroprotective therapy trials because they have a high risk of disease conversion with a sufficiently long latency, which provides an opportunity for early intervention. As RBD research expands, collaboration between centers will become increasingly essential.

Cholinergic denervation of the hippocampal formation does not produce long-term changes in glucose metabolism

International Nuclear Information System (INIS)

Harrell, L.E.; Davis, J.N.

1984-01-01

Decreased glucose metabolism is found in Alzheimer's disease associated with a loss of cholinergic neurons. The relationship between the chronic cholinergic denervation produced by medial septal lesions and glucose metabolism was studied using 2-deoxy-D-[ 3 H]glucose in the rat hippocampal formation. Hippocampal glucose metabolism was increased 1 week after medial septal lesions. Three weeks after lesions, glucose metabolism was profoundly suppressed in all regions. By 3 months, intraregional hippocampal glucose metabolism had returned to control values. Our results demonstrate that chronic cholinergic denervation of the hippocampal formation does not result in permanent alterations of metabolic activity

REM optical/NIR observations of MAXI J1659-152

NARCIS (Netherlands)

D'Avanzo, P.; Goldoni, P.; Patruno, A.; Casella, P.; Campana, S.; Russell, D.M.; Belloni, T.M.

2010-01-01

We observed the optical and NIR counterpart of the recently discovered X-ray transient MAXI J1659-152 (Negoro et al. 2010, ATel #2873; Mangano et al. 2010, GCN #11296) with the REM telescope located in La Silla (Chile) in imaging mode using the V, R, I, J, H and K filters.

Enhancement of learning capacity and cholinergic synaptic function by carnitine in aging rats.

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Ando, S; Tadenuma, T; Tanaka, Y; Fukui, F; Kobayashi, S; Ohashi, Y; Kawabata, T

2001-10-15

The effects of a carnitine derivative, acetyl-L-carnitine (ALCAR), on the cognitive and cholinergic activities of aging rats were examined. Rats were given ALCAR (100 mg/kg) per os for 3 months and were subjected to the Hebb-Williams tasks and a new maze task, AKON-1, to assess their learning capacity. The learning capacity of the ALCAR-treated group was superior to that of the control. Cholinergic activities were determined with synaptosomes isolated from the cortices. The high-affinity choline uptake by synaptosomes, acetylcholine synthesis in synaptosomes, and acetylcholine release from synaptosomes on membrane depolarization were all enhanced in the ALCAR group. This study indicates that chronic administration of ALCAR increases cholinergic synaptic transmission and consequently enhances learning capacity as a cognitive function in aging rats. Copyright 2001 Wiley-Liss, Inc.

Cholinergic stimulation enhances Bayesian belief updating in the deployment of spatial attention.

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Vossel, Simone; Bauer, Markus; Mathys, Christoph; Adams, Rick A; Dolan, Raymond J; Stephan, Klaas E; Friston, Karl J

2014-11-19

The exact mechanisms whereby the cholinergic neurotransmitter system contributes to attentional processing remain poorly understood. Here, we applied computational modeling to psychophysical data (obtained from a spatial attention task) under a psychopharmacological challenge with the cholinesterase inhibitor galantamine (Reminyl). This allowed us to characterize the cholinergic modulation of selective attention formally, in terms of hierarchical Bayesian inference. In a placebo-controlled, within-subject, crossover design, 16 healthy human subjects performed a modified version of Posner's location-cueing task in which the proportion of validly and invalidly cued targets (percentage of cue validity, % CV) changed over time. Saccadic response speeds were used to estimate the parameters of a hierarchical Bayesian model to test whether cholinergic stimulation affected the trial-wise updating of probabilistic beliefs that underlie the allocation of attention or whether galantamine changed the mapping from those beliefs to subsequent eye movements. Behaviorally, galantamine led to a greater influence of probabilistic context (% CV) on response speed than placebo. Crucially, computational modeling suggested this effect was due to an increase in the rate of belief updating about cue validity (as opposed to the increased sensitivity of behavioral responses to those beliefs). We discuss these findings with respect to cholinergic effects on hierarchical cortical processing and in relation to the encoding of expected uncertainty or precision. Copyright © 2014 the authors 0270-6474/14/3415735-08$15.00/0.

Control of cerebral cortical blood flow by stimulation of basal forebrain cholinergic areas in mice.

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Hotta, Harumi; Uchida, Sae; Kagitani, Fusako; Maruyama, Naoki

2011-05-01

We examined whether activity of the nucleus basalis of Meynert (NBM) regulates regional cerebral cortical blood flow (rCBF) in mice, using laser speckle and laser Doppler flowmetry. In anesthetized mice, unilateral focal stimulation, either electrical or chemical, of the NBM increased rCBF of the ipsilateral cerebral cortex in the frontal, parietal and occipital lobes, independent of changes in systemic blood pressure. Most of vasodilative responses to low intensity stimuli (2 times threshold intensity: 2T) were abolished by atropine (a muscarinic cholinergic blocker), whereas responses to higher intensity stimuli (3T) were abolished by atropine and mecamylamine (a nicotinic cholinergic blocker). Blood flow changes were largest when the tip of the electrode was located within the area containing cholinergic neurons shown by choline acetyltransferase-immunocytochemistry. These results suggest that cholinergic projections from basal forebrain neurons in mice cause vasodilation in the ipsilateral cerebral cortex by a combination of muscarinic and nicotinic mechanisms, as previously found in rats and cats.

Spontaneous Vesicle Fusion Is Differentially Regulated at Cholinergic and GABAergic Synapses

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Haowen Liu

2018-02-01

Full Text Available The locomotion of C. elegans is balanced by excitatory and inhibitory neurotransmitter release at neuromuscular junctions. However, the molecular mechanisms that maintain the balance of synaptic transmission remain enigmatic. Here, we investigated the function of voltage-gated Ca2+ channels in triggering spontaneous release at cholinergic and GABAergic synapses. Recordings of the miniature excitatory/inhibitory postsynaptic currents (mEPSCs and mIPSCs, respectively showed that UNC-2/CaV2 and EGL-19/CaV1 channels are the two major triggers for spontaneous release. Notably, however, Ca2+-independent spontaneous release was observed at GABAergic but not cholinergic synapses. Functional screening led to the identification of hypomorphic unc-64/Syntaxin-1A and snb-1/VAMP2 mutants in which mEPSCs are severely impaired, whereas mIPSCs remain unaltered, indicating differential regulation of these currents at cholinergic and GABAergic synapses. Moreover, Ca2+-independent spontaneous GABA release was nearly abolished in the hypomorphic unc-64 and snb-1 mutants, suggesting distinct mechanisms for Ca2+-dependent and Ca2+-independent spontaneous release.

REM-Enriched Naps Are Associated with Memory Consolidation for Sad Stories and Enhance Mood-Related Reactivity.

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Gilson, Médhi; Deliens, Gaétane; Leproult, Rachel; Bodart, Alice; Nonclercq, Antoine; Ercek, Rudy; Peigneux, Philippe

2015-12-29

Emerging evidence suggests that emotion and affect modulate the relation between sleep and cognition. In the present study, we investigated the role of rapid-eye movement (REM) sleep in mood regulation and memory consolidation for sad stories. In a counterbalanced design, participants (n = 24) listened to either a neutral or a sad story during two sessions, spaced one week apart. After listening to the story, half of the participants had a short (45 min) morning nap. The other half had a long (90 min) morning nap, richer in REM and N2 sleep. Story recall, mood evolution and changes in emotional response to the re-exposure to the story were assessed after the nap. Although recall performance was similar for sad and neutral stories irrespective of nap duration, sleep measures were correlated with recall performance in the sad story condition only. After the long nap, REM sleep density positively correlated with retrieval performance, while re-exposure to the sad story led to diminished mood and increased skin conductance levels. Our results suggest that REM sleep may not only be associated with the consolidation of intrinsically sad material, but also enhances mood reactivity, at least on the short term.

Upregulating Nonneuronal Cholinergic Activity Decreases TNF Release from Lipopolysaccharide-Stimulated RAW264.7 Cells

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Yi Lv

2014-01-01

Full Text Available Nonneuronal cholinergic system plays a primary role in maintaining homeostasis. It has been proved that endogenous neuronal acetylcholine (ACh could play an anti-inflammatory role, and exogenous cholinergic agonists could weaken macrophages inflammatory response to lipopolysaccharide (LPS stimulation through activation of α7 subunit-containing nicotinic acetylcholine receptor (α7nAChR. We assumed that nonneuronal cholinergic system existing in macrophages could modulate inflammation through autocrine ACh and expressed α7nAChR on the cells. Therefore, we explored whether LPS continuous stimulation could upregulate the nonneuronal cholinergic activity in macrophages and whether increasing autocrine ACh could decrease TNF release from the macrophages. The results showed that, in RAW264.7 cells incubated with LPS for 20 hours, the secretion of ACh was significantly decreased at 4 h and then gradually increased, accompanied with the enhancement of α7nAChR expression level. The release of TNF was greatly increased from RAW264.7 cells at 4 h and 8 h exposure to LPS; however, it was suppressed at 20 h. Upregulating choline acetyltransferase (ChAT expression through ChAT gene transfection could enhance ACh secretion and reduce TNF release from the infected RAW264. 7cells. The results indicated that LPS stimulation could modulate the activity of nonneuronal cholinergic system of RAW264.7 cells. Enhancing autocrine ACh production could attenuate TNF release from RAW264.7 cells.

Selective effects of cholinergic modulation on task performance during selective attention.

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Furey, Maura L; Pietrini, Pietro; Haxby, James V; Drevets, Wayne C

2008-03-01

The cholinergic neurotransmitter system is critically linked to cognitive functions including attention. The current studies were designed to evaluate the effect of a cholinergic agonist and an antagonist on performance during a selective visual attention task where the inherent salience of attended/unattended stimuli was modulated. Two randomized, placebo-controlled, crossover studies were performed, one (n=9) with the anticholinesterase physostigmine (1.0 mg/h), and the other (n=30) with the anticholinergic scopolamine (0.4 mc/kg). During the task, two double-exposure pictures of faces and houses were presented side by side. Subjects were cued to attend to either the face or the house component of the stimuli, and were instructed to perform a matching task with the two exemplars from the attended category. The cue changed every 4-7 trials to instruct subjects to shift attention from one stimulus component to the other. During placebo in both studies, reaction time (RT) associated with the first trial following a cued shift in attention was longer than RT associated with later trials (pattention to houses condition (pattention to faces. Scopolamine increased RT relative to placebo selectively during trials greater than one (pattention to faces condition (pselective attention (ie trials greater than 1). Moreover, effects of cholinergic manipulation depend on the selective attention condition (ie faces vs houses), which may suggest that cholinergic activity interacts with stimulus salience. The findings are discussed within the context of the role of acetylcholine both in stimulus processing and stimulus salience, and in establishing attention biases through top-down and bottom-up mechanisms of attention.

[Involvement of cross interaction between central cholinergic and histaminergic systems in the nucleus tractus solitarius in regulating carotid sinus baroreceptor reflex].

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Hu, Li-Xun; Zhang, Guo-Xing; Zhang, Yu-Ying; Zhao, Hong-Fen; Yu, Kang-Ying; Wang, Guo-Qing

2013-12-25

The carotid sinus baroreceptor reflex (CSR) is an important approach for regulating arterial blood pressure homeostasis instantaneously and physiologically. Activation of the central histaminergic or cholinergic systems results in CSR functional inhibitory resetting. However, it is unclear whether two systems at the nucleus tractus solitarius (NTS) level display cross interaction to regulate the CSR or not. In the present study, the left or right carotid sinus region was isolated from the systemic circulation in Sprague-Dawley rats (sinus nerve was reserved) anesthetized with pentobarbital sodium. Respective intubation was conducted into one side isolated carotid sinus and into the femoral artery for recording the intracarotid sinus pressure (ISP) and mean arterial pressure (MAP) simultaneously with pressure transducers connection in vivo. ISP was set at the level of 0 mmHg to eliminate the effect of initial internal pressure of the carotid sinus on the CSR function. To trigger CSR, the ISP was quickly elevated from 0 mmHg to 280 mmHg in a stepwise manner (40 mmHg) which was added at every step for over 4 s, and then ISP returned to 0 mmHg in similar steps. The original data of ISP and corresponding MAP were fitted to a modified logistic equation with five parameters to obtain the ISP-MAP, ISP-Gain relationship curves and the CSR characteristic parameters, which were statistically compared and analyzed separately. Under the precondition of no influence on the basic levels of the artery blood pressure, the effects and potential regulatory mechanism of preceding microinjection with different cholinoceptor antagonists, the selective cholinergic M1 receptor antagonist, i.e., pirenzepine (PRZ), the M2 receptor antagonist, i.e., methoctramine (MTR) or the N1 receptor antagonist, i.e., hexamethonium (HEX) into the NTS on the changes in function of CSR induced by intracerebroventricular injection (i.c.v.) of histamine (HA) in rats were observed. Meanwhile, the actions and

Hypocretin-2 saporin lesions of the ventrolateral periaquaductal gray (vlPAG increase REM sleep in hypocretin knockout mice.

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Satvinder Kaur

2009-07-01

Full Text Available Ten years ago the sleep disorder narcolepsy was linked to the neuropeptide hypocretin (HCRT, also known as orexin. This disorder is characterized by excessive day time sleepiness, inappropriate triggering of rapid-eye movement (REM sleep and cataplexy, which is a sudden loss of muscle tone during waking. It is still not known how HCRT regulates REM sleep or muscle tone since HCRT neurons are localized only in the lateral hypothalamus while REM sleep and muscle atonia are generated from the brainstem. To identify a potential neuronal circuit, the neurotoxin hypocretin-2-saporin (HCRT2-SAP was used to lesion neurons in the ventral lateral periaquaductal gray (vlPAG. The first experiment utilized hypocretin knock-out (HCRT-ko mice with the expectation that deletion of both HCRT and its target neurons would exacerbate narcoleptic symptoms. Indeed, HCRT-ko mice (n = 8 given the neurotoxin HCRT2-SAP (16.5 ng/23nl/sec each side in the vlPAG had levels of REM sleep and sleep fragmentation that were considerably higher compared to HCRT-ko given saline (+39%; n = 7 or wildtype mice (+177%; n = 9. However, cataplexy attacks did not increase, nor were levels of wake or non-REM sleep changed. Experiment 2 determined the effects in mice where HCRT was present but the downstream target neurons in the vlPAG were deleted by the neurotoxin. This experiment utilized an FVB-transgenic strain of mice where eGFP identifies GABA neurons. We verified this and also determined that eGFP neurons were immunopositive for the HCRT-2 receptor. vlPAG lesions in these mice increased REM sleep (+79% versus saline controls and it was significantly correlated (r = 0.89 with loss of eGFP neurons. These results identify the vlPAG as one site that loses its inhibitory control over REM sleep, but does not cause cataplexy, as a result of hypocretin deficiency.

Augmented In Situ Subsurface Bioremediation Process™BIO-REM, Inc. - Demonstration Bulletin

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The Augmented In Situ Subsurface Bioremediation Process™ developed by BIO-REM, Inc., uses microaerophilic bacteria and micronutrients (H-10) and surface tension depressants/penetrants for the treatment of hydrocarbon contaminated soils and groundwater. The bacteria utilize hydroc...

Autonomic symptoms in idiopathic REM behavior disorder

DEFF Research Database (Denmark)

Ferini-Strambi, Luigi; Oertel, Wolfgang; Dauvilliers, Yves

2014-01-01

Patients with idiopathic REM sleep behavior disorder (iRBD) are at very high risk of developing neurodegenerative synucleinopathies, which are disorders with prominent autonomic dysfunction. Several studies have documented autonomic dysfunction in iRBD, but large-scale assessment of autonomic...... symptoms has never been systematically performed. Patients with polysomnography-confirmed iRBD (318 cases) and controls (137 healthy volunteers and 181 sleep center controls with sleep diagnoses other than RBD) were recruited from 13 neurological centers in 10 countries from 2008 to 2011. A validated scale...

Lesions of cholinergic pedunculopontine tegmental nucleus neurons fail to affect cocaine or heroin self-administration or conditioned place preference in rats.

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Stephan Steidl

Full Text Available Cholinergic input to the ventral tegmental area (VTA is known to contribute to reward. Although it is known that the pedunculopontine tegmental nucleus (PPTg provides an important source of excitatory input to the dopamine system, the specific role of PPTg cholinergic input to the VTA in cocaine reward has not been previously determined. We used a diphtheria toxin conjugated to urotensin-II (Dtx::UII, the endogenous ligand for urotensin-II receptors expressed by PPTg cholinergic but not glutamatergic or GABAergic cells, to lesion cholinergic PPTg neurons. Dtx::UII toxin infusion resulted in the loss of 95.78 (±0.65% of PPTg cholinergic cells but did not significantly alter either cocaine or heroin self-administration or the development of cocaine or heroin conditioned place preferences. Thus, cholinergic cells originating in PPTg do not appear to be critical for the rewarding effects of cocaine or of heroin.

Involvement of Striatal Cholinergic Interneurons and M1 and M4 Muscarinic Receptors in Motor Symptoms of Parkinson's Disease.

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Ztaou, Samira; Maurice, Nicolas; Camon, Jeremy; Guiraudie-Capraz, Gaëlle; Kerkerian-Le Goff, Lydia; Beurrier, Corinne; Liberge, Martine; Amalric, Marianne

2016-08-31

Over the last decade, striatal cholinergic interneurons (ChIs) have reemerged as key actors in the pathophysiology of basal-ganglia-related movement disorders. However, the mechanisms involved are still unclear. In this study, we address the role of ChI activity in the expression of parkinsonian-like motor deficits in a unilateral nigrostriatal 6-hydroxydopamine (6-OHDA) lesion model using optogenetic and pharmacological approaches. Dorsal striatal photoinhibition of ChIs in lesioned ChAT(cre/cre) mice expressing halorhodopsin in ChIs reduces akinesia, bradykinesia, and sensorimotor neglect. Muscarinic acetylcholine receptor (mAChR) blockade by scopolamine produces similar anti-parkinsonian effects. To decipher which of the mAChR subtypes provides these beneficial effects, systemic and intrastriatal administration of the selective M1 and M4 mAChR antagonists telenzepine and tropicamide, respectively, were tested in the same model of Parkinson's disease. The two compounds alleviate 6-OHDA lesion-induced motor deficits. Telenzepine produces its beneficial effects by blocking postsynaptic M1 mAChRs expressed on medium spiny neurons (MSNs) at the origin of the indirect striatopallidal and direct striatonigral pathways. The anti-parkinsonian effects of tropicamide were almost completely abolished in mutant lesioned mice that lack M4 mAChRs specifically in dopamine D1-receptor-expressing neurons, suggesting that postsynaptic M4 mAChRs expressed on direct MSNs mediate the antiakinetic action of tropicamide. The present results show that altered cholinergic transmission via M1 and M4 mAChRs of the dorsal striatum plays a pivotal role in the occurrence of motor symptoms in Parkinson's disease. The striatum, where dopaminergic and cholinergic systems interact, is the pivotal structure of basal ganglia involved in pathophysiological changes underlying Parkinson's disease. Here, using optogenetic and pharmacological approaches, we investigated the involvement of striatal

Cholinergic enhancement reduces functional connectivity and BOLD variability in visual extrastriate cortex during selective attention.

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Ricciardi, Emiliano; Handjaras, Giacomo; Bernardi, Giulio; Pietrini, Pietro; Furey, Maura L

2013-01-01

Enhancing cholinergic function improves performance on various cognitive tasks and alters neural responses in task specific brain regions. We have hypothesized that the changes in neural activity observed during increased cholinergic function reflect an increase in neural efficiency that leads to improved task performance. The current study tested this hypothesis by assessing neural efficiency based on cholinergically-mediated effects on regional brain connectivity and BOLD signal variability. Nine subjects participated in a double-blind, placebo-controlled crossover fMRI study. Following an infusion of physostigmine (1 mg/h) or placebo, echo-planar imaging (EPI) was conducted as participants performed a selective attention task. During the task, two images comprised of superimposed pictures of faces and houses were presented. Subjects were instructed periodically to shift their attention from one stimulus component to the other and to perform a matching task using hand held response buttons. A control condition included phase-scrambled images of superimposed faces and houses that were presented in the same temporal and spatial manner as the attention task; participants were instructed to perform a matching task. Cholinergic enhancement improved performance during the selective attention task, with no change during the control task. Functional connectivity analyses showed that the strength of connectivity between ventral visual processing areas and task-related occipital, parietal and prefrontal regions reduced significantly during cholinergic enhancement, exclusively during the selective attention task. Physostigmine administration also reduced BOLD signal temporal variability relative to placebo throughout temporal and occipital visual processing areas, again during the selective attention task only. Together with the observed behavioral improvement, the decreases in connectivity strength throughout task-relevant regions and BOLD variability within stimulus

Blockade of central nicotine acetylcholine receptor signaling attenuate ghrelin-induced food intake in rodents.

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Dickson, S L; Hrabovszky, E; Hansson, C; Jerlhag, E; Alvarez-Crespo, M; Skibicka, K P; Molnar, C S; Liposits, Z; Engel, J A; Egecioglu, E

2010-12-29

Here we sought to determine whether ghrelin's central effects on food intake can be interrupted by nicotine acetylcholine receptor (nAChR) blockade. Ghrelin regulates mesolimbic dopamine neurons projecting from the ventral tegmental area (VTA) to the nucleus accumbens, partly via cholinergic VTA afferents originating in the laterodorsal tegmental area (LDTg). Given that these cholinergic projections to the VTA have been implicated in natural as well as drug-induced reinforcement, we sought to investigate the role of cholinergic signaling in ghrelin-induced food intake as well as fasting-induced food intake, for which endogenous ghrelin has been implicated. We found that i.p. treatment with the non-selective centrally active nAChR antagonist, mecamylamine decreased fasting-induced food intake in both mice and rats. Moreover, central administration of mecamylamine decreased fasting-induced food intake in rats. I.c.v. ghrelin-induced food intake was suppressed by mecamylamine i.p. but not by hexamethonium i.p., a peripheral nAChR antagonist. Furthermore, mecamylamine i.p. blocked food intake following ghrelin injection into the VTA. Expression of the ghrelin receptor, the growth hormone secretagogue receptor 1A, was found to co-localize with choline acetyltransferase, a marker of cholinergic neurons, in the LDTg. Finally, mecamylamine treatment i.p. decreased the ability of palatable food to condition a place preference. These data suggest that ghrelin-induced food intake is partly mediated via nAChRs and that nicotinic blockade decreases the rewarding properties of food. Copyright © 2010 IBRO. Published by Elsevier Ltd. All rights reserved.

Non-REM sleep EEG power distribution in fatigue and sleepiness.

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Neu, Daniel; Mairesse, Olivier; Verbanck, Paul; Linkowski, Paul; Le Bon, Olivier

2014-04-01

The aim of this study is to contribute to the sleep-related differentiation between daytime fatigue and sleepiness. 135 subjects presenting with sleep apnea-hypopnea syndrome (SAHS, n=58) or chronic fatigue syndrome (CFS, n=52) with respective sleepiness or fatigue complaints and a control group (n=25) underwent polysomnography and psychometric assessments for fatigue, sleepiness, affective symptoms and perceived sleep quality. Sleep EEG spectral analysis for ultra slow, delta, theta, alpha, sigma and beta power bands was performed on frontal, central and occipital derivations. Patient groups presented with impaired subjective sleep quality and higher affective symptom intensity. CFS patients presented with highest fatigue and SAHS patients with highest sleepiness levels. All groups showed similar total sleep time. Subject groups mainly differed in sleep efficiency, wake after sleep onset, duration of light sleep (N1, N2) and slow wave sleep, as well as in sleep fragmentation and respiratory disturbance. Relative non-REM sleep power spectra distributions suggest a pattern of power exchange in higher frequency bands at the expense of central ultra slow power in CFS patients during all non-REM stages. In SAHS patients, however, we found an opposite pattern at occipital sites during N1 and N2. Slow wave activity presents as a crossroad of fatigue and sleepiness with, however, different spectral power band distributions during non-REM sleep. The homeostatic function of sleep might be compromised in CFS patients and could explain why, in contrast to sleepiness, fatigue does not resolve with sleep in these patients. The present findings thus contribute to the differentiation of both phenomena. Copyright © 2014 Elsevier Inc. All rights reserved.

Perinatal exposure to methadone affects central cholinergic activity in the weanling rat.

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Robinson, S E; Mo, Q; Maher, J R; Wallace, M J; Kunko, P M

1996-06-01

Pregnant rats were implanted with osmotic minipumps containing either methadone hydrochloride (initial dose, 9 mg/kg/day) or sterile water. Their offspring were cross-fostered so that they were exposed to methadone prenatally and/or postnatally. Perinatal methadone exposure disrupted cholinergic activity on postnatal day 21 as measured by the turnover rate of acetylcholine (TRACh) in both female and male rats, although there were some sexually-dimorphic responses. The most profoundly affected brain region was the striatum, where prenatal exposure to methadone increased ACh turnover, whether or not the rats continued to be exposed to methadone postnatally. It appears unlikely that neonatal withdrawal contributes to brain regional changes in ACh turnover, as continued postnatal exposure to methadone did not prevent the prenatal methadone induced changes.

Effects of acute administration of nicotinic and muscarinic cholinergic agonists and antagonists on performance in different cost-benefit decision making tasks in rats.

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Mendez, Ian A; Gilbert, Ryan J; Bizon, Jennifer L; Setlow, Barry

2012-12-01

Alterations in cost-benefit decision making accompany numerous neuropsychiatric conditions, including schizophrenia, attention deficit hyperactivity disorder, and addiction. Central cholinergic systems have been linked to the etiology and/or treatment of many of these conditions, but little is known about the role of cholinergic signaling in cost-benefit decision making. The goal of these experiments was to determine how cholinergic signaling is involved in cost-benefit decision making, using a behavioral pharmacological approach. Male Long-Evans rats were trained in either "probability discounting" or "delay discounting" tasks, in which rats made discrete-trial choices between a small food reward and a large food reward associated with either varying probabilities of omission or varying delays to delivery, respectively. The effects of acute administration of different doses of nicotinic and muscarinic acetylcholine receptor agonists and antagonists were assessed in each task. In the probability discounting task, acute nicotine administration (1.0 mg/kg) significantly increased choice of the large risky reward, and control experiments suggested that this was due to robust nicotine-induced impairments in behavioral flexibility. In the delay discounting task, the muscarinic antagonists scopolamine (0.03, 0.1, and 0.3 mg/kg) and atropine (0.3 mg/kg) both significantly increased choice of the small immediate reward. Neither mecamylamine nor oxotremorine produced reliable effects on either of the decision making tasks. These data suggest that cholinergic receptors play multiple roles in decision making contexts which include consideration of reward delay or probability. These roles should be considered when targeting these receptors for therapeutic purposes.

REM-Enriched Naps Are Associated with Memory Consolidation for Sad Stories and Enhance Mood-Related Reactivity

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Médhi Gilson

2015-12-01

Full Text Available Emerging evidence suggests that emotion and affect modulate the relation between sleep and cognition. In the present study, we investigated the role of rapid-eye movement (REM sleep in mood regulation and memory consolidation for sad stories. In a counterbalanced design, participants (n = 24 listened to either a neutral or a sad story during two sessions, spaced one week apart. After listening to the story, half of the participants had a short (45 min morning nap. The other half had a long (90 min morning nap, richer in REM and N2 sleep. Story recall, mood evolution and changes in emotional response to the re-exposure to the story were assessed after the nap. Although recall performance was similar for sad and neutral stories irrespective of nap duration, sleep measures were correlated with recall performance in the sad story condition only. After the long nap, REM sleep density positively correlated with retrieval performance, while re-exposure to the sad story led to diminished mood and increased skin conductance levels. Our results suggest that REM sleep may not only be associated with the consolidation of intrinsically sad material, but also enhances mood reactivity, at least on the short term.

A cholinergic hypothesis of the unconscious in affective disorders.

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Costa eVakalopoulos

2013-11-01

Full Text Available The interactions between distinct pharmacological systems are proposed as a key dynamic in the formation of unconscious memories underlying rumination and mood disorder, but also reflect the plastic capacity of neural networks that can aid recovery. An inverse and reciprocal relationship is postulated between cholinergic and monoaminergic receptor subtypes. M1-type muscarinic receptor transduction facilitates encoding of unconscious, prepotent behavioural repertoires at the core of affective disorders and ADHD. Behavioural adaptation to new contingencies is mediated by the classic prototype receptor: 5-HT1A (Gi/o and its modulation of m1-plasticity. Reversal of learning is dependent on increased phasic activation of midbrain monoaminergic nuclei and is a function of hippocampal theta. Acquired hippocampal dysfunction due to abnormal activation of the hypothalamic-pituitary-adrenal (HPA axis predicts deficits in hippocampal-dependent memory and executive function and further impairments to cognitive inhibition. Encoding of explicit memories is mediated by Gq/11 and Gs signalling of monoamines only. A role is proposed for the phasic activation of the basal forebrain cholinergic nucleus by cortical projections from the complex consisting of the insula and claustrum. Although controversial. recent studies suggest a common ontogenetic origin of the two structures and a functional coupling. Lesions of the region result in loss of motivational behaviour and familiarity based judgements. A major hypothesis of the paper is that these lost faculties result indirectly, from reduced cholinergic tone.

Cholinergic and dopaminergic activities in senile dementia of Lewy body type.

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Perry, E K; Marshall, E; Perry, R H; Irving, D; Smith, C J; Blessed, G; Fairbairn, A F

1990-01-01

Analyses of brain tissue in a recently identified group of elderly demented patients suggest a neurochemical basis for some of the clinical features. Senile dementia of the Lewy body type (SDLT) can be distinguished from classical Alzheimer disease (AD) clinically by its acute presentation with confusion frequently accompanied by visual hallucinations, and neuropathologically by the presence of Lewy bodies and senile plaques (but not generally neurofibrillary tangles) in the cerebral cortex. Reductions in the cortical cholinergic enzyme choline acetyltransferase were more pronounced in individuals with (80%) compared to those without (50%) hallucinations and correlated strongly with mental test scores in the group as a whole. In the caudate nucleus, dopamine levels were related to the number of neurons in the substantia nigra, there being a 40-60% loss of both in SDLT--probably accounting for mild extrapyramidal features in some of these cases--compared with an 80% loss in Parkinson disease and no change in AD. The cholinergic correlates of mental impairment in SDLT together with the relative absence of cortical neurofibrillary tangles and evidence for postsynaptic cholinergic receptor compensation raise the question of whether this type of dementia may be more amenable to cholinotherapy than classical AD.

Optogenetic activation of septal cholinergic neurons suppresses sharp wave ripples and enhances theta oscillations in the hippocampus.

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Vandecasteele, Marie; Varga, Viktor; Berényi, Antal; Papp, Edit; Barthó, Péter; Venance, Laurent; Freund, Tamás F; Buzsáki, György

2014-09-16

Theta oscillations in the limbic system depend on the integrity of the medial septum. The different populations of medial septal neurons (cholinergic and GABAergic) are assumed to affect different aspects of theta oscillations. Using optogenetic stimulation of cholinergic neurons in ChAT-Cre mice, we investigated their effects on hippocampal local field potentials in both anesthetized and behaving mice. Cholinergic stimulation completely blocked sharp wave ripples and strongly suppressed the power of both slow oscillations (0.5-2 Hz in anesthetized, 0.5-4 Hz in behaving animals) and supratheta (6-10 Hz in anesthetized, 10-25 Hz in behaving animals) bands. The same stimulation robustly increased both the power and coherence of theta oscillations (2-6 Hz) in urethane-anesthetized mice. In behaving mice, cholinergic stimulation was less effective in the theta (4-10 Hz) band yet it also increased the ratio of theta/slow oscillation and theta coherence. The effects on gamma oscillations largely mirrored those of theta. These findings show that medial septal cholinergic activation can both enhance theta rhythm and suppress peri-theta frequency bands, allowing theta oscillations to dominate.

Cholinergic Potentiation and Audiovisual Repetition-Imitation Therapy Improve Speech Production and Communication Deficits in a Person with Crossed Aphasia by Inducing Structural Plasticity in White Matter Tracts.

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Berthier, Marcelo L; De-Torres, Irene; Paredes-Pacheco, José; Roé-Vellvé, Núria; Thurnhofer-Hemsi, Karl; Torres-Prioris, María J; Alfaro, Francisco; Moreno-Torres, Ignacio; López-Barroso, Diana; Dávila, Guadalupe

2017-01-01

Donepezil (DP), a cognitive-enhancing drug targeting the cholinergic system, combined with massed sentence repetition training augmented and speeded up recovery of speech production deficits in patients with chronic conduction aphasia and extensive left hemisphere infarctions (Berthier et al., 2014). Nevertheless, a still unsettled question is whether such improvements correlate with restorative structural changes in gray matter and white matter pathways mediating speech production. In the present study, we used pharmacological magnetic resonance imaging to study treatment-induced brain changes in gray matter and white matter tracts in a right-handed male with chronic conduction aphasia and a right subcortical lesion (crossed aphasia). A single-patient, open-label multiple-baseline design incorporating two different treatments and two post-treatment evaluations was used. The patient received an initial dose of DP (5 mg/day) which was maintained during 4 weeks and then titrated up to 10 mg/day and administered alone (without aphasia therapy) during 8 weeks (Endpoint 1). Thereafter, the drug was combined with an audiovisual repetition-imitation therapy (Look-Listen-Repeat, LLR) during 3 months (Endpoint 2). Language evaluations, diffusion weighted imaging (DWI), and voxel-based morphometry (VBM) were performed at baseline and at both endpoints in JAM and once in 21 healthy control males. Treatment with DP alone and combined with LLR therapy induced marked improvement in aphasia and communication deficits as well as in selected measures of connected speech production, and phrase repetition. The obtained gains in speech production remained well-above baseline scores even 4 months after ending combined therapy. Longitudinal DWI showed structural plasticity in the right frontal aslant tract and direct segment of the arcuate fasciculus with both interventions. VBM revealed no structural changes in other white matter tracts nor in cortical areas linked by these tracts. In

Cholinergic Potentiation and Audiovisual Repetition-Imitation Therapy Improve Speech Production and Communication Deficits in a Person with Crossed Aphasia by Inducing Structural Plasticity in White Matter Tracts

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Marcelo L. Berthier

2017-06-01

Full Text Available Donepezil (DP, a cognitive-enhancing drug targeting the cholinergic system, combined with massed sentence repetition training augmented and speeded up recovery of speech production deficits in patients with chronic conduction aphasia and extensive left hemisphere infarctions (Berthier et al., 2014. Nevertheless, a still unsettled question is whether such improvements correlate with restorative structural changes in gray matter and white matter pathways mediating speech production. In the present study, we used pharmacological magnetic resonance imaging to study treatment-induced brain changes in gray matter and white matter tracts in a right-handed male with chronic conduction aphasia and a right subcortical lesion (crossed aphasia. A single-patient, open-label multiple-baseline design incorporating two different treatments and two post-treatment evaluations was used. The patient received an initial dose of DP (5 mg/day which was maintained during 4 weeks and then titrated up to 10 mg/day and administered alone (without aphasia therapy during 8 weeks (Endpoint 1. Thereafter, the drug was combined with an audiovisual repetition-imitation therapy (Look-Listen-Repeat, LLR during 3 months (Endpoint 2. Language evaluations, diffusion weighted imaging (DWI, and voxel-based morphometry (VBM were performed at baseline and at both endpoints in JAM and once in 21 healthy control males. Treatment with DP alone and combined with LLR therapy induced marked improvement in aphasia and communication deficits as well as in selected measures of connected speech production, and phrase repetition. The obtained gains in speech production remained well-above baseline scores even 4 months after ending combined therapy. Longitudinal DWI showed structural plasticity in the right frontal aslant tract and direct segment of the arcuate fasciculus with both interventions. VBM revealed no structural changes in other white matter tracts nor in cortical areas linked by these

Is a purpose of REM sleep atonia to help regenerate intervertebral disc volumetric loss?

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Fryer Jerome CJ

2009-01-01

Full Text Available Abstract The nature of atonia in sleep continues to be enigmatic. This article discusses a new hypothesis for complete core muscle relaxation in REM sleep, suggesting a bottom-up recuperative perspective. That is, does the atonia in REM sleep provide a utility to help restore the mechanobiology and respective diurnal intervertebral disc hydraulic loss? By combining the effects of gravity with current compressive concepts in spinal stability, this article looks at vertebral approximation as a deleterious experience with an intrinsic biological need to keep vertebrae separated. Methods using polysomnography and recumbent MRI are discussed.

Hypo Activity of Cholinergic System in Patients with Early Stage of Alzheimer's Disease

International Nuclear Information System (INIS)

Davidescu, L.; Codorean, I.; Matei, C.; Barret, O.; Mazere, J.; Guyot, M.; Rimbu, A.; Allard, M.

2006-01-01

Full text: Objective A cholinergic dysfunction was documented in advanced stages of Alzheimer's disease. In order to specify the cholinergic involvement in early stages, we performed a presynaptic imaging study of the cholinergic system using a vesicular Acetylcholine transporter ligand labelled with iodine 123 ( 123 I-IBVM - Iodobenzovesamicol) Materials And Methods Eight patients (5 women and 3 men, 74-89 years, MMS>23) and 8 controls (6 women and 2 men, 72-80 years, MMS>30) have been evaluated using the neuropsychological tests; cerebral SPECT was performed 6 hours after intravenous injection of 218±19 MBq of 123 I - IBVM (30 min, 3 volume, 128x128) and the 3D MRI (T1 weighted images). Acquisition data were processed by filtered retroprojection (Butterworth 5.35) and analysed with SPM software. Each examination was co-registered with the MRI of the patient, normalised in the MNI template and smoothed (10mm). Results The analyse of the group (two sample T-test, p 123 I-IBVM has been detected in the patients group, compared to the control. Conclusions Our results indicate that cholinergic dysfunctions appear very early in the development of Alzheimer's disease and affect the cortical structures involved in the attention process. Some studies are in progress to analyze imaging data with cognitive impairments of each patient. (author)

Brain Region–Specific Alterations in the Gene Expression of Cytokines, Immune Cell Markers and Cholinergic System Components during Peripheral Endotoxin–Induced Inflammation

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Silverman, Harold A; Dancho, Meghan; Regnier-Golanov, Angelique; Nasim, Mansoor; Ochani, Mahendar; Olofsson, Peder S; Ahmed, Mohamed; Miller, Edmund J; Chavan, Sangeeta S; Golanov, Eugene; Metz, Christine N; Tracey, Kevin J; Pavlov, Valentin A

2014-01-01

Inflammatory conditions characterized by excessive peripheral immune responses are associated with diverse alterations in brain function, and brain-derived neural pathways regulate peripheral inflammation. Important aspects of this bidirectional peripheral immune–brain communication, including the impact of peripheral inflammation on brain region–specific cytokine responses, and brain cholinergic signaling (which plays a role in controlling peripheral cytokine levels), remain unclear. To provide insight, we studied gene expression of cytokines, immune cell markers and brain cholinergic system components in the cortex, cerebellum, brainstem, hippocampus, hypothalamus, striatum and thalamus in mice after an intraperitoneal lipopolysaccharide injection. Endotoxemia was accompanied by elevated serum levels of interleukin (IL)-1β, IL-6 and other cytokines and brain region–specific increases in Il1b (the highest increase, relative to basal level, was in cortex; the lowest increase was in cerebellum) and Il6 (highest increase in cerebellum; lowest increase in striatum) mRNA expression. Gene expression of brain Gfap (astrocyte marker) was also differentially increased. However, Iba1 (microglia marker) mRNA expression was decreased in the cortex, hippocampus and other brain regions in parallel with morphological changes, indicating microglia activation. Brain choline acetyltransferase (Chat ) mRNA expression was decreased in the striatum, acetylcholinesterase (Ache) mRNA expression was decreased in the cortex and increased in the hippocampus, and M1 muscarinic acetylcholine receptor (Chrm1) mRNA expression was decreased in the cortex and the brainstem. These results reveal a previously unrecognized regional specificity in brain immunoregulatory and cholinergic system gene expression in the context of peripheral inflammation and are of interest for designing future antiinflammatory approaches. PMID:25299421

Modulation of Specific Sensory Cortical Areas by Segregated Basal Forebrain Cholinergic Neurons Demonstrated by Neuronal Tracing and Optogenetic Stimulation in Mice.

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Chaves-Coira, Irene; Barros-Zulaica, Natali; Rodrigo-Angulo, Margarita; Núñez, Ángel

2016-01-01

Neocortical cholinergic activity plays a fundamental role in sensory processing and cognitive functions. Previous results have suggested a refined anatomical and functional topographical organization of basal forebrain (BF) projections that may control cortical sensory processing in a specific manner. We have used retrograde anatomical procedures to demonstrate the existence of specific neuronal groups in the BF involved in the control of specific sensory cortices. Fluoro-Gold (FlGo) and Fast Blue (FB) fluorescent retrograde tracers were deposited into the primary somatosensory (S1) and primary auditory (A1) cortices in mice. Our results revealed that the BF is a heterogeneous area in which neurons projecting to different cortical areas are segregated into different neuronal groups. Most of the neurons located in the horizontal limb of the diagonal band of Broca (HDB) projected to the S1 cortex, indicating that this area is specialized in the sensory processing of tactile stimuli. However, the nucleus basalis magnocellularis (B) nucleus shows a similar number of cells projecting to the S1 as to the A1 cortices. In addition, we analyzed the cholinergic effects on the S1 and A1 cortical sensory responses by optogenetic stimulation of the BF neurons in urethane-anesthetized transgenic mice. We used transgenic mice expressing the light-activated cation channel, channelrhodopsin-2, tagged with a fluorescent protein (ChR2-YFP) under the control of the choline-acetyl transferase promoter (ChAT). Cortical evoked potentials were induced by whisker deflections or by auditory clicks. According to the anatomical results, optogenetic HDB stimulation induced more extensive facilitation of tactile evoked potentials in S1 than auditory evoked potentials in A1, while optogenetic stimulation of the B nucleus facilitated either tactile or auditory evoked potentials equally. Consequently, our results suggest that cholinergic projections to the cortex are organized into segregated

REM Desensitization as a New Therapeutic Method for Post- Traumatic Stress Disorder: A Randomized Controlled Trial

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Khodabakhsh Ahmadi

2016-05-01

Full Text Available Aim: to evaluate potential efficacy of a new therapeutic approach in posttraumatic stress disorder in comparison with eye movement desensitization and reprocessing (EMDR, a standard treatment approach and controls. Methods: the study was designed using a randomized controlled trial methodology. Participants were recruited from military servicemen aged between 25 to 50 years who were admitting hospitals of Bushehr, Iran, with the final diagnosis of PTSD. Finally 33 male patients were devided into three subgroups: G1: EMDR; G2: REM Desensitization; and group 3: controls who received no therapy. Mississippi Scale for Posttraumatic Stress Disorder, Pittsburgh Sleep Quality Index (PSQI and a 37 item death anxiety questionnaire were used for measures. Results: multiple comparisons showed that intrusive thoughts were significantly more likely to improve with REM Desensitization versus EMDR (P=0.03, while depression was more responsive to EMDR (p=0.03. Among the Pittsburgh scale for the quality of sleep items, sleep quality (p=0.02, sleep duration (p=0.001, and total sleep quality score (p=0.002 were significantly more likely to improve in the REM Desensitization group. Change in the absolute death anxiety scores was not different between subgroups excepting EMDR versus control group (p=0.05. Conclusion: REM, desensitization, the new therapeutic approach to PTSD is a highly effective strategy, even more than EMDR, the standard treatment, in most of the evaluated subjects, with special emphasis on sleep symptoms, and also in the management of intrusive thoughts. Depression is the only factor in which, REM Desensitization was significantly less likely to represent a superior therapeutic effect than EMDR. Key words: post traumatic stress disorder (PTSD, eye movement desensitization and reprocessing, new treatment.

Cognitive performance as a zeitgeber: cognitive oscillators and cholinergic modulation of the SCN entrain circadian rhythms.

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Howard J Gritton

Full Text Available The suprachiasmatic nucleus (SCN is the primary circadian pacemaker in mammals that can synchronize or entrain to environmental cues. Although light exerts powerful influences on SCN output, other non-photic stimuli can modulate the SCN as well. We recently demonstrated that daily performance of a cognitive task requiring sustained periods of attentional effort that relies upon basal forebrain (BF cholinergic activity dramatically alters circadian rhythms in rats. In particular, normally nocturnal rats adopt a robust diurnal activity pattern that persists for several days in the absence of cognitive training. Although anatomical and pharmacological data from non-performing animals support a relationship between cholinergic signaling and circadian rhythms, little is known about how endogenous cholinergic signaling influences SCN function in behaving animals. Here we report that BF cholinergic projections to the SCN provide the principal signal allowing for the expression of cognitive entrainment in light-phase trained animals. We also reveal that oscillator(s outside of the SCN drive cognitive entrainment as daily timed cognitive training robustly entrains SCN-lesioned arrhythmic animals. Ablation of the SCN, however, resulted in significant impairments in task acquisition, indicating that SCN-mediated timekeeping benefits new learning and cognitive performance. Taken together, we conclude that cognition entrains non-photic oscillators, and cholinergic signaling to the SCN serves as a temporal timestamp attenuating SCN photic-driven rhythms, thereby permitting cognitive demands to modulate behavior.

Cholinergic nicotinic and muscarinic receptors in dementia of Alzheimer, Parkinson and Lewy body types.

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Perry, E K; Smith, C J; Court, J A; Perry, R H

1990-01-01

Cholinergic nicotinic and muscarinic receptor binding were measured in post mortem human brain tissue, using low (nM) concentrations of (3H)-nicotine to detect predominately the high affinity nicotinic site and (3H)-N-methylscopolamine in the presence and absence of 3 x 10(-4) M carbachol to measure both the low and high affinity agonist subtypes of the muscarinic receptor group. Consistent with most previous reports, the nicotinic but not muscarinic binding was reduced in the different forms of dementia associated with cortical cholinergic deficits, including Alzheimer's and Parkinson's disease, senile dementia of Lewy body type (SDLT) and Down's syndrome (over 50 years). Analysis of (3H)-nicotine binding displaced by a range of carbachol concentrations (10(-9)-10(-3) M) indicated 2 binding sites for nicotine and that the high affinity rather than low affinity site was reduced in Alzheimer's disease. In all 3 cortical areas investigated (temporal, parietal and occipital) there were increases in the low affinity muscarinic site in Parkinson's disease and SDLT but not Alzheimer's disease or middle-aged Down's syndrome. This observation raised the question of whether the presence of neurofibrillary tangles (evident in the latter but not former 2 disorders) is incompatible with denervation-induced muscarinic supersensitivity in cholinoceptive neurons which include cortical pyramids generally affeted by tangle formation.

A point mutation in the hair cell nicotinic cholinergic receptor prolongs cochlear inhibition and enhances noise protection.

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Julian Taranda

2009-01-01

Full Text Available The transduction of sound in the auditory periphery, the cochlea, is inhibited by efferent cholinergic neurons projecting from the brainstem and synapsing directly on mechanosensory hair cells. One fundamental question in auditory neuroscience is what role(s this feedback plays in our ability to hear. In the present study, we have engineered a genetically modified mouse model in which the magnitude and duration of efferent cholinergic effects are increased, and we assess the consequences of this manipulation on cochlear function. We generated the Chrna9L9'T line of knockin mice with a threonine for leucine change (L9'T at position 9' of the second transmembrane domain of the alpha9 nicotinic cholinergic subunit, rendering alpha9-containing receptors that were hypersensitive to acetylcholine and had slower desensitization kinetics. The Chrna9L9'T allele produced a 3-fold prolongation of efferent synaptic currents in vitro. In vivo, Chrna9L9'T mice had baseline elevation of cochlear thresholds and efferent-mediated inhibition of cochlear responses was dramatically enhanced and lengthened: both effects were reversed by strychnine blockade of the alpha9alpha10 hair cell nicotinic receptor. Importantly, relative to their wild-type littermates, Chrna9(L9'T/L9'T mice showed less permanent hearing loss following exposure to intense noise. Thus, a point mutation designed to alter alpha9alpha10 receptor gating has provided an animal model in which not only is efferent inhibition more powerful, but also one in which sound-induced hearing loss can be restrained, indicating the ability of efferent feedback to ameliorate sound trauma.

Schiphol - üks saar muudab Hollandi / Rem Koolhaas ; tõlk. Inga Raukas

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Koolhaas, Rem, 1944-

2000-01-01

Schipholi lennuvälja ümberpaigutamine kunstlikule saarele meres. Hollandi arhitektuuribüroo OMA arhitektuurse projekti kirjeldus. Projekteerijad Rem Koolhaas, Reinier de Graaf, Jens Hommert, Mateo Poli, Adam Kurdahl, Anna Little, Bert Karel Deuten. 23 ill

A relationship between REM sleep measures and the duration of posttraumatic stress disorder in a young adult urban minority population.

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Mellman, Thomas A; Kobayashi, Ihori; Lavela, Joseph; Wilson, Bryonna; Hall Brown, Tyish S

2014-08-01

To determine relationships of polysomnographic (PSG) measures with posttraumatic stress disorder (PTSD) in a young adult, urban African American population. Cross-sectional, clinical and laboratory evaluation. Community recruitment, evaluation in the clinical research unit of an urban University hospital. Participants (n = 145) were Black, 59.3% female, with a mean age of 23.1 y (SD = 4.8). One hundred twenty-one participants (83.4%) met criteria for trauma exposure, the most common being nonsexual violence. Thirty-nine participants (26.9%) met full (n = 19) or subthreshold criteria (n = 20) for current PTSD, 41 (28.3%) had met lifetime PTSD criteria and were recovered, and 65 (45%) were negative for PTSD. Evaluations included the Clinician Administered PTSD Scale (CAPS) and 2 consecutive nights of overnight PSG. Analysis of variance did not reveal differences in measures of sleep duration and maintenance, percentage of sleep stages, and the latency to and duration of uninterrupted segments of rapid eye movement (REM) sleep by study group. There were significant relationships between the duration of PTSD and REM sleep percentage (r = 0.53, P = 0.001), REM segment length (r = 0.43, P = 0.006), and REM sleep latency (r = -0.34, P sleep with posttraumatic stress disorder (PTSD) relatively proximate to trauma exposure and nondisrupted or increased REM sleep with chronic PTSD. Mellman TA, Kobayashi I, Lavela J, Wilson B, Hall Brown TS. A relationship between REM sleep measures and the duration of posttraumatic stress disorder in a young adult urban minority population.

Regulation of drugs affecting striatal cholinergic activity by corticostriatal projections

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Ladinsky, H.

1986-01-01

Research demonstrates that the chronic degeneration of the corticostriatal excitatory pathway makes the cholinergic neurons of the striatum insensitive to the neuropharmacological action of a number of different drugs. Female rats were used; they were killed and after the i.v. infusion of tritium-choline precursor, choline acetyltransferase activity was measured. Striatal noradrenaline, dopamine and serotonin content was measured by electrochemical detection coupled with high pressure liquid chromatography. Uptake of tritium-glutamic acid was estimated. The data were analyzed statistically. It is shown that there is evidence that the effects of a number of drugs capable of depressing cholinergic activity through receptor-mediated responses are operative only if the corticostriatal pathway is integral. Neuropharmacological responses in the brain appear to be the result of an interaction between several major neurotransmitter systems

Adenosine Inhibits the Excitatory Synaptic Inputs to Basal Forebrain Cholinergic, GABAergic and Parvalbumin Neurons in mice

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Chun eYang

2013-06-01

Full Text Available Coffee and tea contain the stimulants caffeine and theophylline. These compounds act as antagonists of adenosine receptors. Adenosine promotes sleep and its extracellular concentration rises in association with prolonged wakefulness, particularly in the basal forebrain (BF region involved in activating the cerebral cortex. However, the effect of adenosine on identified BF neurons, especially non-cholinergic neurons, is incompletely understood. Here we used whole-cell patch-clamp recordings in mouse brain slices prepared from two validated transgenic mouse lines with fluorescent proteins expressed in GABAergic or parvalbumin (PV neurons to determine the effect of adenosine. Whole-cell recordings were made BF cholinergic neurons and from BF GABAergic & PV neurons with the size (>20 µm and intrinsic membrane properties (prominent H-currents corresponding to cortically projecting neurons. A brief (2 min bath application of adenosine (100 μM decreased the frequency but not the amplitude of spontaneous excitatory postsynaptic currents in all groups of BF cholinergic, GABAergic and PV neurons we recorded. In addition, adenosine decreased the frequency of miniature EPSCs in BF cholinergic neurons. Adenosine had no effect on the frequency of spontaneous inhibitory postsynaptic currents in cholinergic neurons or GABAergic neurons with large H-currents but reduced them in a group of GABAergic neurons with smaller H-currents. All effects of adenosine were blocked by a selective, adenosine A1 receptor antagonist, cyclopentyltheophylline (CPT, 1 μM. Adenosine had no postsynaptic effects. Taken together, our work suggests that adenosine promotes sleep by an A1-receptor mediated inhibition of glutamatergic inputs to cortically-projecting cholinergic and GABA/PV neurons. Conversely, caffeine and theophylline promote attentive wakefulness by inhibiting these A1 receptors in BF thereby promoting the high-frequency oscillations in the cortex required for

Effects of acute administration of nicotinic and muscarinic cholinergic agonists and antagonists on performance in different cost–benefit decision making tasks in rats

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Mendez, Ian A.; Gilbert, Ryan J.; Bizon, Jennifer L.

2012-01-01

Rationale Alterations in cost–benefit decision making accompany numerous neuropsychiatric conditions, including schizophrenia, attention deficit hyperactivity disorder, and addiction. Central cholinergic systems have been linked to the etiology and/or treatment of many of these conditions, but little is known about the role of cholinergic signaling in cost–benefit decision making. Objectives The goal of these experiments was to determine how cholinergic signaling is involved in cost–benefit decision making, using a behavioral pharmacological approach. Methods Male Long-Evans rats were trained in either “probability discounting” or “delay discounting” tasks, in which rats made discrete-trial choices between a small food reward and a large food reward associated with either varying probabilities of omission or varying delays to delivery, respectively. The effects of acute administration of different doses of nicotinic and muscarinic acetylcholine receptor agonists and antagonists were assessed in each task. Results In the probability discounting task, acute nicotine administration (1.0 mg/kg) significantly increased choice of the large risky reward, and control experiments suggested that this was due to robust nicotine-induced impairments in behavioral flexibility. In the delay discounting task, the muscarinic antagonists scopolamine (0.03, 0.1, and 0.3 mg/kg) and atropine (0.3 mg/kg) both significantly increased choice of the small immediate reward. Neither mecamylamine nor oxotremorine produced reliable effects on either of the decision making tasks. Conclusions These data suggest that cholinergic receptors play multiple roles in decision making contexts which include consideration of reward delay or probability. These roles should be considered when targeting these receptors for therapeutic purposes. PMID:22760484

The benefits of cholinergic enhancement during perceptual learning are long-lasting

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Ariel eRokem

2013-05-01

Full Text Available The neurotransmitter acetylcholine (ACh regulates many aspects of cognition, including attention and memory. Previous research in animal models has shown that plasticity in sensory systems often depends on the behavioral relevance of a stimulus and/or task. However, experimentally increasing ACh release in the cortex can result in experience-dependent plasticity, even in the absence of behavioral relevance. In humans, the pharmacological enhancement of ACh transmission by administration of the cholinesterase inhibitor donepezil during performance of a perceptual task increases the magnitude of perceptual learning (PL and its specificity to physical parameters of the stimuli used for training. Behavioral effects of PL have previously been shown to persist for many months. In the present study, we tested whether enhancement of PL by donepezil is also long-lasting. Healthy human subjects were trained on a motion direction discrimination task during cholinergic enhancement, and follow-up testing was performed 5-15 months after the end of training and without additional drug administration. Increases in performance associated with training under donepezil were evident in follow-up retesting, indicating that cholinergic enhancement has beneficial long-term effects on PL. These findings suggest that cholinergic enhancement of training procedures used to treat clinical disorders should improve long-term outcomes of these procedures.

The cholinergic pathway alleviates acute oxygen and glucose deprivation induced renal tubular cell injury by reducing the secretion of inflammatory medium of macrophages

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Ming WU

2017-10-01

Full Text Available Objective To investigate the effects of cholinergic pathway on acute renal tubular cell injury induced by acute oxygen and glucose deprivation. Methods Rat kidney macrophages were isolated and cultured for constructing macrophages and renal epithelial cells co-cultivating model of oxygen-glucose deprivation (OGD, and the model cells were divided into three groups: OGD alone group, acetylcholine (ACh 100μmol/L+OGD group and ACh + galantamine (Gal 10μmol/L+OGD group. The cells underwent OGD treatment for 1 hour, and normally cultured for 24 hours. The expressions of TNF alpha, IL-1 beta, and IL-10 in supernatant fluid were detected by ELISA, the renal tubular cell viability was determined by MTT assay, the expression of acetylcholine esterase (AChE mRNA and protein were determined by RT-qPCR and Western blotting. The activity of AChE was determined by colorimetric method. Results The expressions of TNF alpha (pg/ml in OGD, Ach+OGD group, Ach+Gal+OGD groups were 140.2±44.81, 119.46±4.42 and 103.31±1.62 respectively (P0.05; The values of renal tubular cell proliferation were 55.02%±6.28%, 66.65%±6.47%, and 79.75%±4.22% respectively (P0.05; those of AchE protein were 0.66±0.07, 0.74±0.04 and 0.67±0.06 respectively (P>0.05; The activity of AChE (kU/L was 0.51±0.02, 0.35±0.05 and 0.32±0.04 respectively (P=0.001, 0.001 and 0.368. Conclusions ACh and Gal could inhibit the secretion of inflammatory mediators and cholinesterase activity and can reduce the acute hypoxic renal tubular cell injury. The modulation of the cholinergic pathway in macrophages may be the important treatment method for acute renal injury in the future. DOI: 10.11855/j.issn.0577-7402.2017.08.01

Glycopyrrolate abolishes the exercise-induced increase in cerebral perfusion in humans

DEFF Research Database (Denmark)

Seifert, Thomas; Fisher, James P; Young, Colin N

2010-01-01

Brain blood vessels contain muscarinic receptors that are important for cerebral blood flow (CBF) regulation, but whether a cholinergic receptor mechanism is involved in the exercise-induced increase in cerebral perfusion or affects cerebral metabolism remains unknown. We evaluated CBF and cerebral......(mean) during ergometer cycling (n = 8). Separate, randomized and counterbalanced trials were performed in control (no drug) conditions and following muscarinic cholinergic receptor blockade by glycopyrrolate. Glycopyrrolate increased resting heart rate from approximately 60 to approximately 110 beats min(-1...... abolished by glycopyrrolate (P important for the exercise-induced increase in cerebral perfusion without affecting the cerebral metabolic rate for oxygen....

Muscarinic M4 Receptors on Cholinergic and Dopamine D1 Receptor-Expressing Neurons Have Opposing Functionality for Positive Reinforcement and Influence Impulsivity

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Anna M. Klawonn

2018-04-01

Full Text Available The neurotransmitter acetylcholine has been implicated in reward learning and drug addiction. However, the roles of the various cholinergic receptor subtypes on different neuron populations remain elusive. Here we study the function of muscarinic M4 receptors (M4Rs in dopamine D1 receptor (D1R expressing neurons and cholinergic neurons (expressing choline acetyltransferase; ChAT, during various reward-enforced behaviors and in a “waiting”-impulsivity test. We applied cell-type-specific gene deletions targeting M4Rs in D1RCre or ChATCre mice. Mice lacking M4Rs in D1R-neurons displayed greater cocaine seeking and drug-primed reinstatement than their littermate controls in a Pavlovian conditioned place preference (CPP paradigm. Furthermore, the M4R-D1RCre mice initiated significantly more premature responses (PRs in the 5-choice-serial-reaction-time-task (5CSRTT than their littermate controls, indicating impaired waiting impulse control. In contrast, mice lacking M4Rs in cholinergic neurons did not acquire cocaine Pavlovian conditioning. The M4R-ChATCre mice were also unable to learn positive reinforcement to either natural reward or cocaine in an operant runway paradigm. Immediate early gene (IEG expression (cFos and FosB induced by repeated cocaine injections was significantly increased in the forebrain of M4R-D1RCre mice, whereas it remained normal in the M4R-ChATCre mice. Our study illustrates that muscarinic M4Rs on specific neural populations, either cholinergic or D1R-expressing, are pivotal for learning processes related to both natural reward and drugs of abuse, with opposing functionality. Furthermore, we found that neurons expressing both M4Rs and D1Rs are important for signaling impulse control.

Muscarinic M4 Receptors on Cholinergic and Dopamine D1 Receptor-Expressing Neurons Have Opposing Functionality for Positive Reinforcement and Influence Impulsivity.

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Klawonn, Anna M; Wilhelms, Daniel B; Lindström, Sarah H; Singh, Anand Kumar; Jaarola, Maarit; Wess, Jürgen; Fritz, Michael; Engblom, David

2018-01-01

The neurotransmitter acetylcholine has been implicated in reward learning and drug addiction. However, the roles of the various cholinergic receptor subtypes on different neuron populations remain elusive. Here we study the function of muscarinic M4 receptors (M4Rs) in dopamine D1 receptor (D1R) expressing neurons and cholinergic neurons (expressing choline acetyltransferase; ChAT), during various reward-enforced behaviors and in a "waiting"-impulsivity test. We applied cell-type-specific gene deletions targeting M4Rs in D1RCre or ChATCre mice. Mice lacking M4Rs in D1R-neurons displayed greater cocaine seeking and drug-primed reinstatement than their littermate controls in a Pavlovian conditioned place preference (CPP) paradigm. Furthermore, the M4R-D1RCre mice initiated significantly more premature responses (PRs) in the 5-choice-serial-reaction-time-task (5CSRTT) than their littermate controls, indicating impaired waiting impulse control. In contrast, mice lacking M4Rs in cholinergic neurons did not acquire cocaine Pavlovian conditioning. The M4R-ChATCre mice were also unable to learn positive reinforcement to either natural reward or cocaine in an operant runway paradigm. Immediate early gene (IEG) expression ( cFos and FosB ) induced by repeated cocaine injections was significantly increased in the forebrain of M4R-D1RCre mice, whereas it remained normal in the M4R-ChATCre mice. Our study illustrates that muscarinic M4Rs on specific neural populations, either cholinergic or D1R-expressing, are pivotal for learning processes related to both natural reward and drugs of abuse, with opposing functionality. Furthermore, we found that neurons expressing both M4Rs and D1Rs are important for signaling impulse control.

Sleep disturbances in Parkinsonism.

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Askenasy, J J M

2003-02-01

The present article is meant to suggest an approach to the guidelines for the therapy of sleep disturbances in Parkinson's Disease (PD) patients.The factors affecting the quality of life in PD patients are depression, sleep disturbances and dependence. A large review of the literature on sleep disturbances in PD patients, provided the basis for the following classification of the sleep-arousal disturbances in PD patients. We suggest a model based on 3 steps in the treatment of sleep disturbances in PD patients. This model allowing the patient, the spouse or the caregiver a quiet sleep at night, may postpone the retirement and the institutionalization of the PD patient. I. Correct diagnosis of sleep disorders based on detailed anamnesis of the patient and of the spouse or of the caregiver. One week recording on a symptom diary (log) by the patient or the caregiver. Correct diagnosis of sleep disorders co morbidities. Selection of the most appropriate sleep test among: polysomnography (PSG), multiple sleep latency test (MSLT), multiple wake latency test (MWLT), Epworth Sleepiness Scale, actigraphy or video-PSG. II. The nonspecific therapeutic approach consists in: a) Checking the sleep effect on motor performance, is it beneficial, worse or neutral. b) Psycho-physical assistance. c) Dopaminergic adjustment is necessary owing to the progression of the nigrostriatal degeneration and the increased sensitivity of the terminals, which alter the normal modulator mechanisms of the motor centers in PD patients. Among the many neurotransmitters of the nigro-striatal pathway one can distinguish two with a major influence on REM and NonREM sleep. REM sleep corresponds to an increased cholinergic receptor activity and a decreased dopaminergic activity. This is the reason why REM sleep deprivation by suppressing cholinergic receptor activity ameliorates PD motor symptoms. L-Dopa and its agonists by suppressing cholinergic receptors suppress REM sleep. The permanent adjustment

Pedunculopontine Nucleus Gamma Band Activity-Preconscious Awareness, Waking, and REM Sleep

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Francisco J Urbano

2014-10-01

Full Text Available The pedunculopontine nucleus (PPN is a major component of the reticular activating system (RAS that regulates waking and REM sleep, states of high frequency EEG activity. Recently, we described the presence of high threshold, voltage-dependent N- and P/Q-type calcium channels in RAS nuclei that subserve gamma band oscillations in the mesopontine pedunculopontine nucleus (PPN, intralaminar parafascicular nucleus (Pf, and pontine Subcoeruleus nucleus dorsalis (SubCD. Cortical gamma band activity participates in sensory perception, problem solving, and memory. Rather than participating in the temporal binding of sensory events as in the cortex, gamma band activity in the RAS may participate in the processes of preconscious awareness, and provide the essential stream of information for the formulation of many of our actions. That is, the RAS may play an early permissive role in volition. Our latest results suggest that, 1 the manifestation of gamma band activity during waking may employ a separate intracellular pathway compared to that during REM sleep, 2 neuronal calcium sensor (NCS-1 protein, which is over expressed in schizophrenia and bipolar disorder, modulates gamma band oscillations in the PPN in a concentration-dependent manner, 3 leptin, which undergoes resistance in obesity resulting in sleep dysregulation, decreases sodium currents in PPN neurons, accounting for its normal attenuation of waking, and 4 following our discovery of electrical coupling in the RAS, we hypothesize that there are cell clusters within the PPN that may act in concert. These results provide novel information on the mechanisms controlling high frequency activity related to waking and REM sleep by elements of the RAS.

Why are seizures rare in rapid eye movement sleep? Review of the frequency of seizures in different sleep stages.

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Ng, Marcus; Pavlova, Milena

2013-01-01

Since the formal characterization of sleep stages, there have been reports that seizures may preferentially occur in certain phases of sleep. Through ascending cholinergic connections from the brainstem, rapid eye movement (REM) sleep is physiologically characterized by low voltage fast activity on the electroencephalogram, REMs, and muscle atonia. Multiple independent studies confirm that, in REM sleep, there is a strikingly low proportion of seizures (~1% or less). We review a total of 42 distinct conventional and intracranial studies in the literature which comprised a net of 1458 patients. Indexed to duration, we found that REM sleep was the most protective stage of sleep against focal seizures, generalized seizures, focal interictal discharges, and two particular epilepsy syndromes. REM sleep had an additional protective effect compared to wakefulness with an average 7.83 times fewer focal seizures, 3.25 times fewer generalized seizures, and 1.11 times fewer focal interictal discharges. In further studies REM sleep has also demonstrated utility in localizing epileptogenic foci with potential translation into postsurgical seizure freedom. Based on emerging connectivity data in sleep, we hypothesize that the influence of REM sleep on seizures is due to a desynchronized EEG pattern which reflects important connectivity differences unique to this sleep stage.

A differentiating empirical linguistic analysis of dreamer activity in reports of EEG-controlled REM-dreams and hypnagogic hallucinations.

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Speth, Jana; Frenzel, Clemens; Voss, Ursula

2013-09-01

We present Activity Analysis as a new method for the quantification of subjective reports of altered states of consciousness with regard to the indicated level of simulated motor activity. Empirical linguistic activity analysis was conducted with dream reports conceived immediately after EEG-controlled periods of hypnagogic hallucinations and REM-sleep in the sleep laboratory. Reports of REM-dreams exhibited a significantly higher level of simulated physical dreamer activity, while hypnagogic hallucinations appear to be experienced mostly from the point of passive observer. This study lays the groundwork for clinical research on the level of simulated activity in pathologically altered states of subjective experience, for example in the REM-dreams of clinically depressed patients, or in intrusions and dreams of patients diagnosed with PTSD. Copyright © 2013 Elsevier Inc. All rights reserved.

Personal dose assessment using region of interest analysis compared with harshaw TLD WinREMS software evaluation

International Nuclear Information System (INIS)

Adjei, D.

2010-06-01

Personal dose equivalents, Hp(10), have been evaluated manually using Region of Interest (ROI) analysis and compared with the automated computerized WinREMS software for the occupationally exposed in medical, industrial and research/teaching applications for 2008 and 2009. The mean annual effective dose estimated by the WinREMS software for medical, industrial and research/teaching applications for the study period are 0.459 mSv, 0.549mSv and 0.447 mSv, respectively compared with ROI analysis are 0.424 mSv, 0.520 mSv and 0.407 mSv respectively. The mean annual collective doses evaluated by the WinREMS software for medical, industrial and research/teaching applications for the two-year study period are 0.258 man-Sv, 0.084 man-Sv and 0.032 man-Sv respectively, compared with the ROI analysis with values: 0.238 man-Sv, 0.080 man-Sv and 0.029 man-Sv respectively. The individual doses for the occupationally exposed in Ghana fall within the typical range of individual doses in the UNSCEAR 2008 report. In calibration mode, the WinREMS method overestimated the personal dose equivalent by 51.3% for doses below 1 mSv and 12.0% above 1 mSv. The corresponding values for the Region of Interest analysis method are 13.2% and 6.5%. The results from the study indicate that the ROI analysis provides a better alternative to estimating the personal doses (au).

Methodology and results of the impacts of modeling electric utilities: a comparative evaluation of MEMM and REM

International Nuclear Information System (INIS)

1981-09-01

This study compares two models of the US electric utility industry including the EIA's electric utility submodel in the Midterm Energy Market Model (MEMM), and the Baughman-Joskow Regionalized Electricity Model (REM). The method of comparison emphasizes reconciliation of differences in data common to both models, and the performance of simulation experiments to evaluate the empirical significance of certain structural differences in the models. The major research goal was to contrast and compare the effects of alternative modeling structures and data assumptions on model results; and, particularly to considered each model's approach to the impacts of generation technology and fuel use choices on electric utilities. The methodology used was to run the REM model first without and, then, with a representation of the Power Plant and Industrial Fuel Act of 1978, assuming medium supply and demand curves and varying fuel prices. The models and data structures of the two models are described. The original 1978 data used in MEMM and REM are analyzed and compared. The computations and effects of different assumptions on fuel use decisions are discussed. The adjusted REM data required for the experiments are presented. Simulation results of the two models are compared. These results represent projections for 1985, 1990, and 1995 of: US power generation by plant type; amounts of each type of fuel used for power generation; average electricity prices; and the effects of additional or fewer nuclear and coal-fired plants. A significant result is that the REM model exhibits about 7 times as much gas and oil consumption in 1995 as the MEMM model. Continuing simulation experiments on MEMM are recommended to determine whether the input data to MEMM are reasonable and properly adjusted

Moringa oleifera Seed Extract Alleviates Scopolamine-Induced Learning and Memory Impairment in Mice

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Juan Zhou

2018-04-01

Full Text Available The extract of Moringa oleifera seeds has been shown to possess various pharmacological properties. In the present study, we assessed the neuropharmacological effects of 70% ethanolic M. oleifera seed extract (MSE on cognitive impairment caused by scopolamine injection in mice using the passive avoidance and Morris water maze (MWM tests. MSE (250 or 500 mg/kg was administered to mice by oral gavage for 7 or 14 days, and cognitive impairment was induced by intraperitoneal injection of scopolamine (4 mg/kg for 1 or 6 days. Mice that received scopolamine alone showed impaired learning and memory retention and considerably decreased cholinergic system reactivity and neurogenesis in the hippocampus. MSE pretreatment significantly ameliorated scopolamine-induced cognitive impairment and enhanced cholinergic system reactivity and neurogenesis in the hippocampus. Additionally, the protein expressions of phosphorylated Akt, ERK1/2, and CREB in the hippocampus were significantly decreased by scopolamine, but these decreases were reversed by MSE treatment. These results suggest that MSE-induced ameliorative cognitive effects are mediated by enhancement of the cholinergic neurotransmission system and neurogenesis via activation of the Akt, ERK1/2, and CREB signaling pathways. These findings suggest that MSE could be a potent neuropharmacological drug against amnesia, and its mechanism might be modulation of cholinergic activity via the Akt, ERK1/2, and CREB signaling pathways.

Short-Term Total Sleep-Deprivation Impairs Contextual Fear Memory, and Contextual Fear-Conditioning Reduces REM Sleep in Moderately Anxious Swiss Mice

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Munazah F. Qureshi

2017-11-01

Full Text Available The conditioning tasks have been widely used to model fear and anxiety and to study their association with sleep. Many reports suggest that sleep plays a vital role in the consolidation of fear memory. Studies have also demonstrated that fear-conditioning influences sleep differently in mice strains having a low or high anxiety level. It is, therefore, necessary to know, how sleep influences fear-conditioning and how fear-conditioning induces changes in sleep architecture in moderate anxious strains. We have used Swiss mice, a moderate anxious strain, to study the effects of: (i sleep deprivation on contextual fear conditioned memory, and also (ii contextual fear conditioning on sleep architecture. Animals were divided into three groups: (a non-sleep deprived (NSD; (b stress control (SC; and (c sleep-deprived (SD groups. The SD animals were SD for 5 h soon after training. We found that the NSD and SC animals showed 60.57% and 58.12% freezing on the testing day, while SD animals showed significantly less freezing (17.13% only; p < 0.001 on the testing day. Further, we observed that contextual fear-conditioning did not alter the total amount of wakefulness and non-rapid eye movement (NREM sleep. REM sleep, however, significantly decreased in NSD and SC animals on the training and testing days. Interestingly, REM sleep did not decrease in the SD animals on the testing day. Our results suggest that short-term sleep deprivation impairs fear memory in moderate anxious mice. It also suggests that NREM sleep, but not REM sleep, may have an obligatory role in memory consolidation.

Cholinergic Modulation of Cortical Microcircuits Is Layer-Specific: Evidence from Rodent, Monkey and Human Brain

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Joshua Obermayer

2017-12-01

Full Text Available Acetylcholine (ACh signaling shapes neuronal circuit development and underlies specific aspects of cognitive functions and behaviors, including attention, learning, memory and motivation. During behavior, activation of muscarinic and nicotinic acetylcholine receptors (mAChRs and nAChRs by ACh alters the activation state of neurons, and neuronal circuits most likely process information differently with elevated levels of ACh. In several brain regions, ACh has been shown to alter synaptic strength as well. By changing the rules for synaptic plasticity, ACh can have prolonged effects on and rearrange connectivity between neurons that outlasts its presence. From recent discoveries in the mouse, rat, monkey and human brain, a picture emerges in which the basal forebrain (BF cholinergic system targets the neocortex with much more spatial and temporal detail than previously considered. Fast cholinergic synapses acting on a millisecond time scale are abundant in the mammalian cerebral cortex, and provide BF cholinergic neurons with the possibility to rapidly alter information flow in cortical microcircuits. Finally, recent studies have outlined novel mechanisms of how cholinergic projections from the BF affect synaptic strength in several brain areas of the rodent brain, with behavioral consequences. This review highlights these exciting developments and discusses how these findings translate to human brain circuitries.

Cholinergic stimulation prevents the development of autoimmune diabetes: Evidence for the modulation of Th17 effector cells via an IFNgamma-dependent mechanism

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Junu George

2016-10-01

Full Text Available Type I diabetes (T1D results from T cell-mediated damage of pancreatic β-cells and loss of insulin production. The cholinergic anti-inflammatory pathway represents a physiological link connecting the central nervous and immune systems via vagus nerve, and functions to control the release of proinflammatory cytokines. Using the multiple-low-dose streptozotocin (MLD-STZ model to induce experimental autoimmune diabetes, we investigated the potential of regulating the development of hyperglycemia through administration of paraoxon, a highly specific acetylcholinesterase inhibitor (AChEI. We demonstrate that pretreatment with paraoxon prevented hyperglycemia in STZ-treated C57BL/6 mice. This correlated with a reduction in T cell infiltration into pancreatic islets and preservation of the structure and functionality of β-cells. Gene expression analysis of pancreatic tissue revealed that increased peripheral cholinergic activity prevented STZ-mediated loss of insulin production, this being associated with a reduction in IL-1β, IL-6, and IL-17 proinflammatory cytokines. Intracellular cytokine analysis in splenic T cells demonstrated that inhibition of AChE led to a shift in STZ-induced immune response from a predominantly disease-causing IL-17-expressing Th17 cells to IFNγ-positive Th1 cells. Consistent with this conclusion, inhibition of AChE failed to prevent STZ-induced hyperglycemia in IFNγ-deficient mice. Our results provide mechanistic evidence for the prevention of murine T1D by inhibition of AChE and suggest a promising strategy for modulating disease severity.

Privação de sono REM em um modelo experimental da doença de Parkinson

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Luiz A. F. Andrade

1987-09-01

Full Text Available Investigação prévia mostrou que ratos privados de sono (REM SD mostram acentuação de resposta a agonistas dopaminérgicos. As evidências indicam que essa ação parece ser mediada por supersensibilização de receptores dopaminérgicos pós-sinápticos. Com base nisso, foi feita REM SD em ratos com modelo experimental da doença de Parkinson, nos quais foi feita lesão eletrolítica bilateral de ambas as vias nigro-estriatais. Sete dias após a cirurgia os animais eram submetidos a REM SD por 72 horas. Imediatamente após o final deste período era feita observação em campo aberto para a ambulação, "rearing", "grooming" e latência. Em comparação com ratos não-privados foi observado aumento significativo na ambulação e "rearing", resposta que reapareceu após um segundo período de REM SD, realizado 21 dias após a cirurgia. Estes dados, de melhora de dois parâmetros de modelo experimental da doença de Parkinson, sugerem que a privação de sono pode ser útil nesta doença.

Chronic Treatment with Squid Phosphatidylserine Activates Glucose Uptake and Ameliorates TMT-Induced Cognitive Deficit in Rats via Activation of Cholinergic Systems

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Hyun-Jung Park

2012-01-01

Full Text Available The present study examined the effects of squid phosphatidylserine (Squid-PS on the learning and memory function and the neural activity in rats with TMT-induced memory deficits. The rats were administered saline or squid derived Squid-PS (Squid-PS 50 mg kg−1, p.o. daily for 21 days. The cognitive improving efficacy of Squid-PS on the amnesic rats, which was induced by TMT, was investigated by assessing the passive avoidance task and by performing choline acetyltransferase (ChAT and acetylcholinesterase (AchE immunohistochemistry. 18F-Fluorodeoxyglucose and performed a positron emission tomography (PET scan was also performed. In the passive avoidance test, the control group which were injected with TMT showed a markedly lower latency time than the non-treated normal group (P<0.05. However, treatment of Squid-PS significantly recovered the impairment of memory compared to the control group (P<0.05. Consistent with the behavioral data, Squid-PS significantly alleviated the loss of ChAT immunoreactive neurons in the hippocampal CA3 compared to that of the control group (P<0.01. Also, Squid-PS significantly increased the AchE positive neurons in the hippocampal CA1 and CA3. In the PET analysis, Squid-PS treatment increased the glucose uptake more than twofold in the frontal lobe and the hippocampus (P<0.05, resp.. These results suggest that Squid-PS may be useful for improving the cognitive function via regulation of cholinergic enzyme activity and neural activity.

Histamine H3 Receptors Decrease Dopamine Release in the Ventral Striatum by Reducing the Activity of Striatal Cholinergic Interneurons.

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Varaschin, Rafael Koerich; Osterstock, Guillaume; Ducrot, Charles; Leino, Sakari; Bourque, Marie-Josée; Prado, Marco A M; Prado, Vania Ferreira; Salminen, Outi; Rannanpää Née Nuutinen, Saara; Trudeau, Louis-Eric

2018-04-15

Histamine H 3 receptors are widely distributed G i -coupled receptors whose activation reduces neuronal activity and inhibits release of numerous neurotransmitters. Although these receptors are abundantly expressed in the striatum, their modulatory role on activity-dependent dopamine release is not well understood. Here, we observed that histamine H 3 receptor activation indirectly diminishes dopamine overflow in the ventral striatum by reducing cholinergic interneuron activity. Acute brain slices from C57BL/6 or channelrhodopsin-2-transfected DAT-cre mice were obtained, and dopamine transients evoked either electrically or optogenetically were measured by fast-scan cyclic voltammetry. The H 3 agonist α-methylhistamine significantly reduced electrically- evoked dopamine overflow, an effect blocked by the nicotinic acetylcholine receptor antagonist dihydro-β-erythroidine, suggesting involvement of cholinergic interneurons. None of the drug treatments targeting H 3 receptors affected optogenetically evoked dopamine overflow, indicating that direct H 3 -modulation of dopaminergic axons is unlikely. Next, we used qPCR and confirmed the expression of histamine H 3 receptor mRNA in cholinergic interneurons, both in ventral and dorsal striatum. Activation of H 3 receptors by α-methylhistamine reduced spontaneous firing of cholinergic interneurons in the ventral, but not in the dorsal striatum. Resting membrane potential and number of spontaneous action potentials in ventral-striatal cholinergic interneurons were significantly reduced by α-methylhistamine. Acetylcholine release from isolated striatal synaptosomes, however, was not altered by α-methylhistamine. Together, these results indicate that histamine H 3 receptors are important modulators of dopamine release, specifically in the ventral striatum, and that they do so by decreasing the firing rate of cholinergic neurons and, consequently, reducing cholinergic tone on dopaminergic axons. Copyright © 2018 IBRO

Maternal exposure to hexachlorophene targets intermediate-stage progenitor cells of the hippocampal neurogenesis in rat offspring via dysfunction of cholinergic inputs by myelin vacuolation

International Nuclear Information System (INIS)

Itahashi, Megu; Abe, Hajime; Tanaka, Takeshi; Mizukami, Sayaka; Kimura, Masayuki; Yoshida, Toshinori; Shibutani, Makoto

2015-01-01

Highlights: • The effect of maternal exposure to HCP on rat hippocampal neurogenesis was examined. • HCP induces myelin vacuolation of nerve tracts in the septal–hippocampal pathway. • Myelin changes suppress Chrnb2-mediated cholinergic inputs to the dentate gyrus. • SGZ apoptosis occurs via the mitochondrial pathway and targets type-2b cells. • Dysfunction of cholinergic inputs is related to type-2b SGZ cell apoptosis. - Abstract: Hexachlorophene (HCP) is known to induce myelin vacuolation corresponding to intramyelinic edema of nerve fibers in the central and peripheral nervous system in animals. This study investigated the effect of maternal exposure to HCP on hippocampal neurogenesis in rat offspring using pregnant rats supplemented with 0 (controls), 100, or 300 ppm HCP in the diet from gestational day 6 to day 21 after delivery. On postnatal day (PND) 21, the numbers of T box brain 2 + progenitor cells and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling + apoptotic cells in the hippocampal subgranular zone (SGZ) decreased in female offspring at 300 ppm, which was accompanied by myelin vacuolation and punctate tubulin beta-3 chain staining of nerve fibers in the hippocampal fimbria. In addition, transcript levels of the cholinergic receptor, nicotinic beta 2 (Chrnb2) and B-cell CLL/lymphoma 2 (Bcl2) decreased in the dentate gyrus. HCP-exposure did not alter the numbers of SGZ proliferating cells and reelin- or calcium-binding protein-expressing γ-aminobutyric acid (GABA)-ergic interneuron subpopulations in the dentate hilus on PND 21 and PND 77. Although some myelin vacuolation remained, all other changes observed in HCP-exposed offspring on PND 21 disappeared on PND 77. These results suggest that maternal HCP exposure reversibly decreases type-2b intermediate-stage progenitor cells via the mitochondrial apoptotic pathway in offspring hippocampal neurogenesis at 300 ppm HCP. Neurogenesis may be affected by dysfunction

Caffeine attenuates scopolamine-induced memory impairment in humans.

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Riedel, W; Hogervorst, E; Leboux, R; Verhey, F; van Praag, H; Jolles, J

1995-11-01

Caffeine consumption can be beneficial for cognitive functioning. Although caffeine is widely recognized as a mild CNS stimulant drug, the most important consequence of its adenosine antagonism is cholinergic stimulation, which might lead to improvement of higher cognitive functions, particularly memory. In this study, the scopolamine model of amnesia was used to test the cholinergic effects of caffeine, administered as three cups of coffee. Subjects were 16 healthy volunteers who received 250 mg caffeine and 2 mg nicotine separately, in a placebo-controlled double-blind cross-over design. Compared to placebo, nicotine attenuated the scopolamine-induced impairment of storage in short-term memory and attenuated the scopolamine-induced slowing of speed of short-term memory scanning. Nicotine also attenuated the scopolamine-induced slowing of reaction time in a response competition task. Caffeine attenuated the scopolamine-induced impairment of free recall from short- and long-term memory, quality and speed of retrieval from long-term memory in a word learning task, and other cognitive and non-cognitive measures, such as perceptual sensitivity in visual search, reading speed, and rate of finger-tapping. On the basis of these results it was concluded that caffeine possesses cholinergic cognition enhancing properties. Caffeine could be used as a control drug in studies using the scopolamine paradigm and possibly also in other experimental studies of cognitive enhancers, as the effects of a newly developed cognition enhancing drug should at least be superior to the effects of three cups of coffee.

Seizures induced by carbachol, morphine, and leucine-enkephalin: a comparison.

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Snead, O C

1983-04-01

The electrical, behavioral, and pharmacological properties of seizures induced by morphine, leucine-enkephalin, and the muscarinic cholinergic agonist carbachol were examined and compared. Low-dose carbachol given intracerebroventricularly (ICV) produced seizures similar electrically to those produced by ICV morphine and leucine-enkephalin, although there was some difference in site of subcortical origin of onset. Carbachol and morphine were similar in that they had the same anticonvulsant profile, produced similar behavioral changes, caused generalized absence seizures in low doses and generalized convulsive seizures in high doses, and were capable of chemical kindling. However, opiate-induced seizures were not overcome by cholinergic antagonists, nor were carbachol seizures blocked by opiate antagonists. These data suggest that there may be a common noncholinergic, nonopiatergic system involved in mediating carbachol- and morphine-induced seizures but not enkephalin seizures.

Disappearance of "phantom limb" and amputated arm usage during dreaming in REM sleep behaviour disorder.

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Vetrugno, Roberto; Arnulf, Isabelle; Montagna, Pasquale

2009-01-01

Limb amputation is followed, in approximately 90% of patients, by "phantom limb" sensations during wakefulness. When amputated patients dream, however, the phantom limb may be present all the time, part of the time, intermittently or not at all. Such dreaming experiences in amputees have usually been obtained only retrospectively in the morning and, moreover, dreaming is normally associated with muscular atonia so the motor counterpart of the phantom limb experience cannot be observed directly. REM sleep behaviour disorder (RBD), in which muscle atonia is absent during REM sleep and patients act out their dreams, allows a more direct analysis of the "phantom limb" phenomena and their modifications during sleep.

Sleep board review questions: sleep disordered breathing that improves in REM

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Budhiraja R

2012-08-01

Full Text Available No abstract available. Article truncated at end of question. Which of the following breathing disorders is usually less severe in rapid eye movement (REM sleep compared to non-rapid eye movement (NREM sleep?1.Sleep-related hypoxemia in COPD2.Obstructive Sleep Apnea3.Cheyne Stokes Breathing4.Hypoxemia in Pulmonary Hypertension

Dynamic changes in GABAA receptors on basal forebrain cholinergic neurons following sleep deprivation and recovery

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Jones Barbara E

2007-02-01

Full Text Available Abstract Background The basal forebrain (BF cholinergic neurons play an important role in cortical activation and arousal and are active in association with cortical activation of waking and inactive in association with cortical slow wave activity of sleep. In view of findings that GABAA receptors (Rs and inhibitory transmission undergo dynamic changes as a function of prior activity, we investigated whether the GABAARs on cholinergic cells might undergo such changes as a function of their prior activity during waking vs. sleep. Results In the brains of rats under sleep control (SC, sleep deprivation (SD or sleep recovery (SR conditions in the 3 hours prior to sacrifice, we examined immunofluorescent staining for β2–3 subunit GABAARs on choline acetyltransferase (ChAT immunopositive (+ cells in the magnocellular BF. In sections also stained for c-Fos, β2–3 GABAARs were present on ChAT+ neurons which expressed c-Fos in the SD group alone and were variable or undetectable on other ChAT+ cells across groups. In dual-immunostained sections, the luminance of β2–3 GABAARs over the membrane of ChAT+ cells was found to vary significantly across conditions and to be significantly higher in SD than SC or SR groups. Conclusion We conclude that membrane GABAARs increase on cholinergic cells as a result of activity during sustained waking and reciprocally decrease as a result of inactivity during sleep. These changes in membrane GABAARs would be associated with increased GABA-mediated inhibition of cholinergic cells following prolonged waking and diminished inhibition following sleep and could thus reflect a homeostatic process regulating cholinergic cell activity and thereby indirectly cortical activity across the sleep-waking cycle.

Cholinergic Machinery as Relevant Target in Acute Lymphoblastic T Leukemia

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Oxana Dobrovinskaya

2016-08-01

Full Text Available Various types of non-neuronal cells, including tumors, are able to produce acetylcholine (ACh, which acts as an autocrine/paracrine growth factor. T lymphocytes represent a key component of the non-neuronal cholinergic system. T cells-derived ACh is involved in a stimulation of their activation and proliferation, and acts as a regulator of immune response. The aim of the present work was to summarize the data about components of cholinergic machinery in T lymphocytes, with an emphasis on the comparison of healthy and leukemic T cells. Cell lines derived from acute lymphoblastic leukemias of T lineage (T-ALL were found to produce a considerably higher amount of ACh than healthy T lumphocytes. Additionally, ACh produced by T-ALL is not efficiently hydrolyzed, because acetylcholinesterase (AChE activity is drastically decreased in these cells. Up-regulation of muscarinic ACh receptors was also demonstrated at expression and functional level, whereas nicotinic ACh receptors seem to play a less important role and not form functional channels in cells derived from T-ALL. We hypothesized that ACh over-produced in T-ALL may act as an autocrine growth factor and play an important role in leukemic clonal expansion through shaping of intracellular Ca2+ signals. We suggest that cholinergic machinery may be attractive targets for new drugs against T-ALL. Specifically, testing of high affinity antagonists of muscarinic ACh receptors as well as antagomiRs, which interfere with miRNAs involved in the suppression of AChE expression, may be the first choice options.

Increased cholinergic contractions of jejunal smooth muscle caused by a high cholesterol diet are prevented by the 5-HT4 agonist – tegaserod

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Shaffer Eldon

2006-02-01

Full Text Available Abstract Background Excess cholesterol in bile and in blood is a major risk factor for the respective development of gallbladder disease and atherosclerosis. This lipid in excess negatively impacts the functioning of other smooth muscles, including the intestine. Serotonin is an important mediator of the contractile responses of the small intestine. Drugs targeting the serotonin receptor are used as prokinetic agents to manage intestinal motor disorders, in particular irritable bowel syndrome. Thus, tegaserod, acting on 5-HT4 receptor, ideally should obviate detrimental effects of excessive cholesterol on gastrointestinal smooth muscle. In this study we examined the effect of tegaserod on cholesterol-induced changes in the contractile responses of intestinal smooth muscle. Methods The effects of a high cholesterol (1% diet on the in vitro contractile responses of jejunal longitudinal smooth muscle from Richardson ground squirrels to the cholinergic agonist carbachol were examined in the presence or absence of tetrodrodotoxin (TTX. Two groups of animals, fed either low (0.03% or high cholesterol rat chow diet, were further divided into two subgroups and treated for 28 days with either vehicle or tegaserod. Results The high cholesterol diet increased, by nearly 2-fold, contractions of the jejunal longitudinal smooth muscle elicited by carbachol. These cholinergic contractions were mediated by muscarinic receptors since they were blocked by scopolamine, a muscarinic receptor antagonist, but not by the nicotinic receptor antagonist, hexamethonium. Tegaserod treatment, which did not affect cholinergic contractions of tissues from low cholesterol fed animals, abrogated the increase caused by the high cholesterol diet. With low cholesterol diet TTX enhanced carbachol-evoked contractions, whereas this action potential blocker did not affect the augmented cholinergic contractions seen with tissues from animals on the high cholesterol diet. Tegaserod

Reduced upper obstructions in N3 and increased lower obstructions in REM sleep stage detected with manometry.

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Wirth, Markus; Schramm, Juliane; Bautz, Maximilian; Hofauer, Benedikt; Edenharter, Günther; Ott, Armin; Heiser, Clemens

2018-01-01

In obstructive sleep apnea (OSA), airway obstruction occurs at different anatomic levels. The frequency and location of obstructions play a crucial role in the planning of surgical treatment. The aim of this study was to evaluate the pharyngeal obstruction levels in different sleep stages with manometry in OSA patients. In addition, the manometry results were compared with drug-induced sleep endoscopy (DISE). Forty-one patients with OSA received manometry measurements during one night of sleep. All patients were simultaneously evaluated with polysomnography. The frequency of obstructions in different sleep stages was assessed. Twenty patients were additionally studied with DISE. Obstruction levels detected with manometry were compared with DISE. The frequency of upper and to a lesser extent lower obstructions decreased in sleep stage N3. In rapid eye movement (REM) sleep, lower obstructions increased. The overall proportion of upper and lower obstructions detected with manometry corresponded with DISE in 13 of 20 cases. A significant change in the obstruction levels was detected with manometry in N3 and REM sleep. The reduction of both upper and to a lesser extent lower obstructions in N3 suggests more stable airways in slow-wave sleep. Relevant lower obstructions were not detected in DISE compared to manometry in 5 out of 20 examinations. This could be a potential reason for treatment failure of site-specific surgical OSA treatment when only performing DISE preoperatively. Therefore, manometry could be a useful complementary tool in the preoperative evaluation for OSA.

Beneficial Effects of Gagam-Palmultang on Scopolamine-Induced Memory Deficits in Mice

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Yu Ri Kim

2018-01-01

Full Text Available From text mining of Dongeuibogam, the 7 herbs in Palmultang can be considered effective candidates for memory enhancement. We sought to determine whether Gagam-Palmultang, comprising these 7 herbs, ameliorates scopolamine-induced memory impairment in mice, by focusing on the central cholinergic system and memory-related signaling molecules. Behavioral tests were performed after inducing memory impairment by scopolamine administration. The cholinergic system activity and memory-related molecules were examined in the hippocampus by enzyme-linked immunosorbent, western blot, and immunofluorescence assays. Gagam-Palmultang ameliorated scopolamine-induced memory impairment in the Morris water maze test, producing a significant improvement in the mean time required to find the hidden platform. Treatment with Gagam-Palmultang reduced acetylcholinesterase activity and expression in the hippocampus induced by scopolamine. The diminished phosphorylated phosphatidylinositide 3-kinase (PI3K, extracellular signal-regulated kinase (ERK, cAMP response element-binding protein (CREB, and mature brain-derived neurotrophic factor (mBDNF expressions caused by scopolamine administration were attenuated by treatment with Gagam-Palmultang. This treatment also promoted neuronal cell proliferation in the hippocampus. Gagam-Palmultang has beneficial effects against scopolamine-induced memory impairments, which are exerted via modulation of the cholinergic system as well as the PI3K and ERK/CREB/BDNF signaling pathway. Therefore, this multiherb formula may be a useful therapeutic agent for diseases associated with memory impairments.

Central cholinergic dysfunction could be associated with oropharyngeal dysphagia in early Parkinson's disease.

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Lee, Kyung Duck; Koo, Jung Hoi; Song, Sun Hong; Jo, Kwang Deog; Lee, Moon Kyu; Jang, Wooyoung

2015-11-01

Dysphagia is an important issue in the prognosis of Parkinson's disease (PD). Although several studies have reported that oropharyngeal dysphagia may be associated with cognitive dysfunction, the exact relationship between cortical function and swallowing function in PD patients is unclear. Therefore, we investigated the association between an electrophysiological marker of central cholinergic function, which reflected cognitive function, and swallowing function, as measured by videofluoroscopic studies (VFSS). We enrolled 29 early PD patients. Using the Swallowing Disturbance Questionnaire (SDQ), we divided the enrolled patients into two groups: PD with dysphagia and PD without dysphagia. The videofluoroscopic dysphagia scale (VDS) was applied to explore the nature of the dysphagia. To assess central cholinergic dysfunction, short latency afferent inhibition (SAI) was evaluated. We analyzed the relationship between central cholinergic dysfunction and oropharyngeal dysphagia and investigated the characteristics of the dysphagia. The SAI values were significantly different between the two groups. The comparison of each VFSS component between the PD with dysphagia group and the PD without dysphagia group showed statistical significance for most of the oral phase components and for a single pharyngeal phase component. The total score on the VDS was higher in the PD with dysphagia group than in the PD without dysphagia group. The Mini-Mental State Examination and SAI values showed significant correlations with the total score of the oral phase components. According to binary logistic regression analysis, SAI value independently contributed to the presence of dysphagia in PD patients. Our findings suggest that cholinergic dysfunction is associated with dysphagia in early PD and that an abnormal SAI value is a good biomarker for predicting the risk of dysphagia in PD patients.

Localization of pre- and postsynaptic cholinergic markers in rodent forebrain : A brief history and comparison of rat and mouse

NARCIS (Netherlands)

Van der Zee, E. A.; Keijser, J.N.

2011-01-01

Rat and mouse models are widely used for studies in cognition and pathophysiology, among others. Here, we sought to determine to what extent these two model species differ for cholinergic and cholinoceptive features. For this purpose, we focused on cholinergic innervation patterns based on choline

Rapid-Eye-Movement-Sleep (REM Associated Enhancement of Working Memory Performance after a Daytime Nap.

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Esther Yuet Ying Lau

Full Text Available The main objective was to study the impact of a daytime sleep opportunity on working memory and the mechanism behind such impact. This study adopted an experimental design in a sleep research laboratory. Eighty healthy college students (Age:17-23, 36 males were randomized to either have a polysomnography-monitored daytime sleep opportunity (Nap-group, n=40 or stay awake (Wake-group, n=40 between the two assessment sessions. All participants completed a sleep diary and wore an actigraph-watch for 5 days before and one day after the assessment sessions. They completed the state-measurement of sleepiness and affect, in addition to a psychomotor vigilance test and a working memory task before and after the nap/wake sessions. The two groups did not differ in their sleep characteristics prior to and after the lab visit. The Nap-group had higher accuracy on the working memory task, fewer lapses on the psychomotor vigilance test and lower state-sleepiness than the Wake-group. Within the Nap-group, working memory accuracy was positively correlated with duration of rapid eye movement sleep (REM and total sleep time during the nap. Our findings suggested that "sleep gain" during a daytime sleep opportunity had significant positive impact on working memory performance, without affecting subsequent nighttime sleep in young adult, and such impact was associated with the duration of REM. While REM abnormality has long been noted in pathological conditions (e.g. depression, which are also presented with cognitive dysfunctions (e.g. working memory deficits, this was the first evidence showing working memory enhancement associated with REM in daytime napping in college students, who likely had habitual short sleep duration but were otherwise generally healthy.

Rapid-Eye-Movement-Sleep (REM) Associated Enhancement of Working Memory Performance after a Daytime Nap

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Lau, Kristy Nga Ting; Hui, Florence Wai Ying; Tseng, Chia-huei

2015-01-01

The main objective was to study the impact of a daytime sleep opportunity on working memory and the mechanism behind such impact. This study adopted an experimental design in a sleep research laboratory. Eighty healthy college students (Age:17-23, 36 males) were randomized to either have a polysomnography-monitored daytime sleep opportunity (Nap-group, n=40) or stay awake (Wake-group, n=40) between the two assessment sessions. All participants completed a sleep diary and wore an actigraph-watch for 5 days before and one day after the assessment sessions. They completed the state-measurement of sleepiness and affect, in addition to a psychomotor vigilance test and a working memory task before and after the nap/wake sessions. The two groups did not differ in their sleep characteristics prior to and after the lab visit. The Nap-group had higher accuracy on the working memory task, fewer lapses on the psychomotor vigilance test and lower state-sleepiness than the Wake-group. Within the Nap-group, working memory accuracy was positively correlated with duration of rapid eye movement sleep (REM) and total sleep time during the nap. Our findings suggested that “sleep gain” during a daytime sleep opportunity had significant positive impact on working memory performance, without affecting subsequent nighttime sleep in young adult, and such impact was associated with the duration of REM. While REM abnormality has long been noted in pathological conditions (e.g. depression), which are also presented with cognitive dysfunctions (e.g. working memory deficits), this was the first evidence showing working memory enhancement associated with REM in daytime napping in college students, who likely had habitual short sleep duration but were otherwise generally healthy. PMID:25970511

Young Human Cholinergic Neurons Respond to Physiological Regulators and Improve Cognitive Symptoms in an Animal Model of Alzheimer’s Disease

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Annamaria Morelli

2017-10-01

Full Text Available The degeneration of cholinergic neurons of the nucleus basalis of Meynert (NBM in the basal forebrain (BF is associated to the cognitive decline of Alzheimer’s disease (AD patients. To date no resolutive therapies exist. Cell-based replacement therapy is a strategy currently under consideration, although the mechanisms underlying the generation of stem cell-derived NBM cholinergic neurons able of functional integration remain to be clarified. Since fetal brain is an optimal source of neuronal cells committed towards a specific phenotype, this study is aimed at isolating cholinergic neurons from the human fetal NBM (hfNBMs in order to study their phenotypic, maturational and functional properties. Extensive characterization confirmed the cholinergic identity of hfNBMs, including positivity for specific markers (such as choline acetyltransferase and acetylcholine (Ach release. Electrophysiological measurements provided the functional validation of hfNBM cells, which exhibited the activation of peculiar sodium (INa and potassium (IK currents, as well as the presence of functional cholinergic receptors. Accordingly, hfNBMs express both nicotinic and muscarinic receptors, which were activated by Ach. The hfNBMs cholinergic phenotype was regulated by the nerve growth factor (NGF, through the activation of the high-affinity NGF receptor TrkA, as well as by 17-β-estradiol through a peculiar recruitment of its own receptors. When intravenously administered in NBM-lesioned rats, hfNBMs determined a significant improvement in memory functions. Histological examination of brain sections showed that hfNBMs (labeled with PKH26 fluorescent dye prior to administration reached the damaged brain areas. The study provides a useful model to study the ontogenetic mechanisms regulating the development and maintenance of the human brain cholinergic system and to assess new lines of research, including disease modeling, drug discovery and cell-based therapy for AD.

Why Does REM Sleep Occur? A Wake-up Hypothesis

OpenAIRE

Dr. W. R. eKlemm

2011-01-01

Brain activity differs in the various sleep stages and in conscious wakefulness. Awakening from sleep requires restoration of the complex nerve impulse patterns in neuronal network assemblies necessary to re-create and sustain conscious wakefulness. Herein I propose that the brain uses REM to help wake itself up after it has had a sufficient amount of sleep. Evidence suggesting this hypothesis includes the facts that, 1) when first going to sleep, the brain plunges into Stage N3 (formerly ca...

Olfactory impairment in the rotenone model of Parkinson's disease is associated with bulbar dopaminergic D2 activity after REM sleep deprivation

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Laís Soares Rodrigues

2014-12-01

Full Text Available Olfactory and rapid eye movement (REM sleep deficits are commonly found in untreated subjects with a recent diagnosis of Parkinson's disease (PD. Besides different studies reported declines in olfactory performances during a short period of sleep deprivation. Mechanisms underlying these clinical manifestations are poorly understood although the impairment in the dopamine (DA neurotransmission in the olfactory bulb and in the nigrostriatal pathway may have important roles in olfactory as well as in REM sleep disturbances. Therefore, we have led to the hypothesis that a modulation of the dopaminergic D2 receptors in the olfactory bulb could provide a more comprehensive understanding of the olfactory deficits in PD and after a short period of REM sleep deprivation (REMSD. We decided to investigate the olfactory, neurochemical and histological alterations generated by the administration of piribedil (a selective D2 agonist or raclopride (a selective D2 antagonist, within the glomerular layer of the olfactory bulb, in rats submitted to intranigral rotenone and REMSD. Our findings provided a remarkable evidence of the occurrence of a negative correlation (r = - 0.52, P = 0.04 between the number of periglomerular TH-ir neurons and the bulbar levels of DA in the rotenone, but not sham groups. A significant positive correlation (r = 0.34, P = 0.03 was observed between nigral DA and olfactory discrimination index (DI, for the sham groups, indicating that increased DA levels in the substantia nigra pars compacta (SNpc are associated to enhanced olfactory discrimination performance. Also, increased levels in bulbar and striatal DA induced by piribedil in the rotenone control and rotenone REMSD groups were consistent with reduced amounts of DI. The present evidence reinforce that DA produced by periglomerular neurons, and particularly the bulbar dopaminergic D2 receptors, are essential participants in the olfactory discrimination processes, as well as SNpc

Selective Activation of Cholinergic Interneurons Enhances Accumbal Phasic Dopamine Release: Setting the Tone for Reward Processing

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Roger Cachope

2012-07-01

Full Text Available Dopamine plays a critical role in motor control, addiction, and reward-seeking behaviors, and its release dynamics have traditionally been linked to changes in midbrain dopamine neuron activity. Here, we report that selective endogenous cholinergic activation achieved via in vitro optogenetic stimulation of nucleus accumbens, a terminal field of dopaminergic neurons, elicits real-time dopamine release. This mechanism occurs via direct actions on dopamine terminals, does not require changes in neuron firing within the midbrain, and is dependent on glutamatergic receptor activity. More importantly, we demonstrate that in vivo selective activation of cholinergic interneurons is sufficient to elicit dopamine release in the nucleus accumbens. Therefore, the control of accumbal extracellular dopamine levels by endogenous cholinergic activity results from a complex convergence of neurotransmitter/neuromodulator systems that may ultimately synergize to drive motivated behavior.

Transplantation of Human Chorion-Derived Cholinergic Progenitor Cells: a Novel Treatment for Neurological Disorders.

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Mohammadi, Alireza; Maleki-Jamshid, Ali; Sanooghi, Davood; Milan, Peiman Brouki; Rahmani, Arash; Sefat, Farshid; Shahpasand, Koorosh; Soleimani, Mansoureh; Bakhtiari, Mehrdad; Belali, Rafie; Faghihi, Faezeh; Joghataei, Mohammad Taghi; Perry, George; Mozafari, Masoud

2018-03-16

A neurological disorder is any disorder or abnormality in the nervous system. Among different neurological disorders, Alzheimer's disease (AD) is recognized as the sixth leading cause of death globally. Considerable research has been conducted to find pioneer treatments for this devastating disorder among which cell therapy has attracted remarkable attentions over the last decade. Up to now, targeted differentiation into specific desirable cell types has remained a major obstacle to clinical application of cell therapy. Also, potential risks including uncontrolled growth of stem cells could be disastrous. In our novel protocol, we used basal forebrain cholinergic progenitor cells (BFCN) derived from human chorion-derived mesenchymal stem cells (hC-MSCs) which made it possible to obtain high-quality population of cholinergic neurons and in vivo in much shorter time period than previous established methods. Remarkably, the transplanted progenitors fully differentiated to cholinergic neurons which in turn integrated in higher cortical networks of host brains, resulting in significant improvement in cognitive assessments. This method may have profound implications in cell therapies for any other neurodegenerative disorders. Graphical Abstract ᅟ.

Cholinergic receptor binding in the frontal cortex of suicide victims

International Nuclear Information System (INIS)

Stanley, M.

1986-01-01

Because there is a high incidence of individuals diagnosed as having an affective disorder who subsequently commit suicide, the author thought it would be of interest to determine QNB binding in the brains of a large sample of suicide victims, and to compare the findings with a well-matched control group. Brain samples were obtained at autopsy from 22 suicide victims and 22 controls. Frontal cortex samples were diseected, frozen, and stored until assayed. Samples of tissue homogenate were incubated in duplicate with 10 concentrations of tritium-QNB. Specific binding was determined with and without atropine. The results confirmed previous studies in which no changes were noted in suicide versus control brains. While the findings neither disprove nor support the cholinergic hypothesis of depression, they do suggest that the neurochemical basis for the in vivo observations of increased responsivity of depressed individuals to muscarinic cholinergic agents might not involve changes in receptors estimated by QNB binding

Pharmacological identification of cholinergic receptor subtypes on Drosophila melanogaster larval heart.

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Malloy, Cole A; Ritter, Kyle; Robinson, Jonathan; English, Connor; Cooper, Robin L

2016-01-01

The Drosophila melanogaster heart is a popular model in which to study cardiac physiology and development. Progress has been made in understanding the role of endogenous compounds in regulating cardiac function in this model. It is well characterized that common neurotransmitters act on many peripheral and non-neuronal tissues as they flow through the hemolymph of insects. Many of these neuromodulators, including acetylcholine (ACh), have been shown to act directly on the D. melanogaster larval heart. ACh is a primary neurotransmitter in the central nervous system (CNS) of vertebrates and at the neuromuscular junctions on skeletal and cardiac tissue. In insects, ACh is the primary excitatory neurotransmitter of sensory neurons and is also prominent in the CNS. A full understanding regarding the regulation of the Drosophila cardiac physiology by the cholinergic system remains poorly understood. Here we use semi-intact D. melanogaster larvae to study the pharmacological profile of cholinergic receptor subtypes, nicotinic acetylcholine receptors (nAChRs) and muscarinic acetylcholine receptors (mAChRs), in modulating heart rate (HR). Cholinergic receptor agonists, nicotine and muscarine both increase HR, while nAChR agonist clothianidin exhibits no significant effect when exposed to an open preparation at concentrations as low as 100 nM. In addition, both nAChR and mAChR antagonists increase HR as well but also display capabilities of blocking agonist actions. These results provide evidence that both of these receptor subtypes display functional significance in regulating the larval heart's pacemaker activity.

Reorganization of Motor Cortex by Vagus Nerve Stimulation Requires Cholinergic Innervation.

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Hulsey, Daniel R; Hays, Seth A; Khodaparast, Navid; Ruiz, Andrea; Das, Priyanka; Rennaker, Robert L; Kilgard, Michael P

2016-01-01

Vagus nerve stimulation (VNS) paired with forelimb training drives robust, specific reorganization of movement representations in the motor cortex. The mechanisms that underlie VNS-dependent enhancement of map plasticity are largely unknown. The cholinergic nucleus basalis (NB) is a critical substrate in cortical plasticity, and several studies suggest that VNS activates cholinergic circuitry. We examined whether the NB is required for VNS-dependent enhancement of map plasticity in the motor cortex. Rats were trained to perform a lever pressing task and then received injections of the immunotoxin 192-IgG-saporin to selectively lesion cholinergic neurons of the NB. After lesion, rats underwent five days of motor training during which VNS was paired with successful trials. At the conclusion of behavioral training, intracortical microstimulation was used to document movement representations in motor cortex. VNS paired with forelimb training resulted in a substantial increase in the representation of proximal forelimb in rats with an intact NB compared to untrained controls. NB lesions prevent this VNS-dependent increase in proximal forelimb area and result in representations similar to untrained controls. Motor performance was similar between groups, suggesting that differences in forelimb function cannot account for the difference in proximal forelimb representation. Together, these findings indicate that the NB is required for VNS-dependent enhancement of plasticity in the motor cortex and may provide insight into the mechanisms that underlie the benefits of VNS therapy. Copyright © 2016 Elsevier Inc. All rights reserved.

REM-3D Reference Datasets: Reconciling large and diverse compilations of travel-time observations

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Moulik, P.; Lekic, V.; Romanowicz, B. A.

2017-12-01

A three-dimensional Reference Earth model (REM-3D) should ideally represent the consensus view of long-wavelength heterogeneity in the Earth's mantle through the joint modeling of large and diverse seismological datasets. This requires reconciliation of datasets obtained using various methodologies and identification of consistent features. The goal of REM-3D datasets is to provide a quality-controlled and comprehensive set of seismic observations that would not only enable construction of REM-3D, but also allow identification of outliers and assist in more detailed studies of heterogeneity. The community response to data solicitation has been enthusiastic with several groups across the world contributing recent measurements of normal modes, (fundamental mode and overtone) surface waves, and body waves. We present results from ongoing work with body and surface wave datasets analyzed in consultation with a Reference Dataset Working Group. We have formulated procedures for reconciling travel-time datasets that include: (1) quality control for salvaging missing metadata; (2) identification of and reasons for discrepant measurements; (3) homogenization of coverage through the construction of summary rays; and (4) inversions of structure at various wavelengths to evaluate inter-dataset consistency. In consultation with the Reference Dataset Working Group, we retrieved the station and earthquake metadata in several legacy compilations and codified several guidelines that would facilitate easy storage and reproducibility. We find strong agreement between the dispersion measurements of fundamental-mode Rayleigh waves, particularly when made using supervised techniques. The agreement deteriorates substantially in surface-wave overtones, for which discrepancies vary with frequency and overtone number. A half-cycle band of discrepancies is attributed to reversed instrument polarities at a limited number of stations, which are not reflected in the instrument response history

Neural correlates of dream lucidity obtained from contrasting lucid versus non-lucid REM sleep: a combined EEG/fMRI case study.

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Dresler, Martin; Wehrle, Renate; Spoormaker, Victor I; Koch, Stefan P; Holsboer, Florian; Steiger, Axel; Obrig, Hellmuth; Sämann, Philipp G; Czisch, Michael

2012-07-01

To investigate the neural correlates of lucid dreaming. Parallel EEG/fMRI recordings of night sleep. Sleep laboratory and fMRI facilities. Four experienced lucid dreamers. N/A. Out of 4 participants, one subject had 2 episodes of verified lucid REM sleep of sufficient length to be analyzed by fMRI. During lucid dreaming the bilateral precuneus, cuneus, parietal lobules, and prefrontal and occipito-temporal cortices activated strongly as compared with non-lucid REM sleep. In line with recent EEG data, lucid dreaming was associated with a reactivation of areas which are normally deactivated during REM sleep. This pattern of activity can explain the recovery of reflective cognitive capabilities that are the hallmark of lucid dreaming.

Involvement of dopaminergic and cholinergic pathways in the induction of yawning and genital grooming by the aqueous extract of Saccharum officinarum L. (sugarcane) in rats.

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Gamberini, Maria T; Gamberini, Maria C; Nasello, Antonia G

2015-01-01

Yawning, associated with genital grooming, is a physiological response that may be used for elucidating the mechanism of action of drugs. Preliminary analysis showed that aqueous extract (AE) of Saccharum induced yawns in rats. So, we aimed to quantify these behavioral responses and investigate the pharmacological mechanisms involved in these actions. During 120 min, after AE administration, the yawns and the genital grooming were quantified at 10 min intervals. Since dopaminergic and cholinergic pathways are implied in these responses, AE were evaluated in the presence of haloperidol 0.5 mg/kg and atropine 2 mg/kg. AE 0.5 g/kg increased the yawns, effect that was blocked both by haloperidol and atropine. Genital grooming could only be stimulated by AE 0.5 g/kg when dopaminergic receptors were blocked by haloperidol. However, it was inhibited when atropine was previously administered. So, we demonstrated a central action of Saccharum and it was postulated that neural circuits with the participation of dopaminergic and cholinergic pathways are involved. The fact that AE is comprised of innumerous compounds could justify the extract's distinct responses. Also, we cannot disregard the presence of different neural circuits that count on the participation of dopaminergic and cholinergic pathways and could be activated by the same induction agent. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Fear Extinction Memory Consolidation Requires Potentiation of Pontine-Wave Activity during REM Sleep

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Datta, Subimal; O'Malley, Matthew W .

2013-01-01

Sleep plays an important role in memory consolidation within multiple memory systems including contextual fear extinction memory, but little is known about the mechanisms that underlie this process. Here, we show that fear extinction training in rats, which extinguished conditioned fear, increased both slow-wave sleep and rapid-eye movement (REM) sleep. Surprisingly, 24 h later, during memory testing, only 57% of the fear-extinguished animals retained fear extinction memory. We found that these animals exhibited an increase in phasic pontine-wave (P-wave) activity during post-training REM sleep, which was absent in the 43% of animals that failed to retain fear extinction memory. The results of this study provide evidence that brainstem activation, specifically potentiation of phasic P-wave activity, during post-training REM sleep is critical for consolidation of fear extinction memory. The results of this study also suggest that, contrary to the popular hypothesis of sleep and memory, increased sleep after training alone does not guarantee consolidation and/or retention of fear extinction memory. Rather, the potentiation of specific sleep-dependent physiological events may be a more accurate predictor for successful consolidation of fear extinction memory. Identification of this unique mechanism will significantly improve our present understanding of the cellular and molecular mechanisms that underlie the sleep-dependent regulation of emotional memory. Additionally, this discovery may also initiate development of a new, more targeted treatment method for clinical disorders of fear and anxiety in humans that is more efficacious than existing methods such as exposure therapy that incorporate only fear extinction. PMID:23467372

Approaching disturbed sleep in late Parkinson's Disease: first step toward a proposal for a revised UPDRS.

Science.gov (United States)

Askenasy, J J

2001-10-01

nigrostriatal degeneration and the increased sensitivity of the terminals which alter the normal modulator mechanisms of motor centers in LPD patients. Among the many neurotransmitters of the nigro-striatal pathway one can distinguish two with a major influence on REM and non-REM sleep. REM sleep corresponds to an increased cholinergic receptor activity and a decreased dopaminergic activity. This is the reason why REM sleep deprivation by suppressing cholinergic receptor activity ameliorates LPD motor symptoms. L-Dopa and its agonists by suppressing cholinergic receptors suppress REM sleep. L-Dopa has also an arousal effect on Non-REM sleep, repeatedly awakening the patient and enhancing the fragmentation due to the involuntary movements. (c) Socio-physical assistance. (3) The specific therapy consists of: LFS-Sinemet CR, Tolcapone, Intranasal Desmopressin, Domperidon, Cisapride and neurosurgery; SRBD-CPAP, UPPP, nasal interventions, losing weight; RLS-PLM-Benzodiazepine (Clonazepam), Opioid, Apomorphine infusion; RBD-Clonazepam and dopaminergic agonists; SRH-Clozapine, Risperidone; SRPD-Nortriptyline, Clozapine, Olanzepine; SA-adjustment; EDS-arousing drugs. Each therapeutic approach must be tailored to the individual LPD patient.

Effect of Estradiol on Neurotrophin Receptors in Basal Forebrain Cholinergic Neurons: Relevance for Alzheimer's Disease.

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Kwakowsky, Andrea; Milne, Michael R; Waldvogel, Henry J; Faull, Richard L

2016-12-17

The basal forebrain is home to the largest population of cholinergic neurons in the brain. These neurons are involved in a number of cognitive functions including attention, learning and memory. Basal forebrain cholinergic neurons (BFCNs) are particularly vulnerable in a number of neurological diseases with the most notable being Alzheimer's disease, with evidence for a link between decreasing cholinergic markers and the degree of cognitive impairment. The neurotrophin growth factor system is present on these BFCNs and has been shown to promote survival and differentiation on these neurons. Clinical and animal model studies have demonstrated the neuroprotective effects of 17β-estradiol (E2) on neurodegeneration in BFCNs. It is believed that E2 interacts with neurotrophin signaling on cholinergic neurons to mediate these beneficial effects. Evidence presented in our recent study confirms that altering the levels of circulating E2 levels via ovariectomy and E2 replacement significantly affects the expression of the neurotrophin receptors on BFCN. However, we also showed that E2 differentially regulates neurotrophin receptor expression on BFCNs with effects depending on neurotrophin receptor type and neuroanatomical location. In this review, we aim to survey the current literature to understand the influence of E2 on the neurotrophin system, and the receptors and signaling pathways it mediates on BFCN. In addition, we summarize the physiological and pathophysiological significance of E2 actions on the neurotrophin system in BFCN, especially focusing on changes related to Alzheimer's disease.

Hippocampal P3-Like Auditory Event-Related Potentials are Disrupted in a Rat Model of Cholinergic Degeneration in Alzheimer's Disease: Reversal by Donepezil Treatment

DEFF Research Database (Denmark)

Laursen, Bettina; Mørk, Arne; Kristiansen, Uffe

2014-01-01

P300 (P3) event-related potentials (ERPs) have been suggested to be an endogenous marker of cognitive function and auditory oddball paradigms are frequently used to evaluate P3 ERPs in clinical settings. Deficits in P3 amplitude and latency reflect some of the neurological dysfunctions related...... cholinergic degeneration induced by SAP. SAP-lesioned rats may constitute a suitable model to test the efficacy of pro-cognitive substances in an applied experimental setup....

The role of the intrinsic cholinergic system of the striatum: What have we learned from TAN recordings in behaving animals?

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Apicella, Paul

2017-09-30

Cholinergic interneurons provide rich local innervation of the striatum and play an important role in controlling behavior, as evidenced by the variety of movement and psychiatric disorders linked to disrupted striatal cholinergic transmission. Much progress has been made in recent years regarding our understanding of how these interneurons contribute to the processing of information in the striatum. In particular, investigation of the activity of presumed striatal cholinergic interneurons, identified as tonically active neurons or TANs in behaving animals, has pointed to their role in the signaling and learning of the motivational relevance of environmental stimuli. Although the bulk of this work has been conducted in monkeys, several studies have also been carried out in behaving rats, but information remains rather disparate across studies and it is still questionable whether rodent TANs correspond to TANs described in monkeys. Consequently, our current understanding of the function of cholinergic transmission in the striatum is challenged by the rapidly growing, but often confusing literature on the relationship between TAN activity and specific behaviors. As regards the precise nature of the information conveyed by the cholinergic TANs, a recent influential view emphasized that these local circuit neurons may play a special role in the processing of contextual information that is important for reinforcement learning and selection of appropriate actions. This review provides a summary of recent progress in TAN physiology from which it is proposed that striatal cholinergic interneurons are crucial elements for flexible switching of behaviors under changing environmental conditions. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

Effects of acute exposure to chlorpyrifos on cholinergic and non-cholinergic targets in normal and high-fat fed male C57BL/6J mice.

Science.gov (United States)

Kondakala, Sandeep; Lee, Jung Hwa; Ross, Matthew K; Howell, George E

2017-12-15

The prevalence of obesity is increasing at an alarming rate in the United States with 36.5% of adults being classified as obese. Compared to normal individuals, obese individuals have noted pathophysiological alterations which may alter the toxicokinetics of xenobiotics and therefore alter their toxicities. However, the effects of obesity on the toxicity of many widely utilized pesticides has not been established. Therefore, the present study was designed to determine if the obese phenotype altered the toxicity of the most widely used organophosphate (OP) insecticide, chlorpyrifos (CPS). Male C57BL/6J mice were fed normal or high-fat diet for 4weeks and administered a single dose of vehicle or CPS (2.0mg/kg; oral gavage) to assess cholinergic (acetylcholinesterase activities) and non-cholinergic (carboxylesterase and endocannabinoid hydrolysis) endpoints. Exposure to CPS significantly decreased red blood cell acetylcholinesterase (AChE) activity, but not brain AChE activity, in both diet groups. Further, CPS exposure decreased hepatic carboxylesterase activity and hepatic hydrolysis of a major endocannabinoid, anandamide, in a diet-dependent manner with high-fat diet fed animals being more sensitive to CPS-mediated inhibition. These in vivo studies were corroborated by in vitro studies using rat primary hepatocytes, which demonstrated that fatty acid amide hydrolase and CES activities were more sensitive to CPS-mediated inhibition than 2-arachidonoylglycerol hydrolase activity. These data demonstrate hepatic CES and FAAH activities in high-fat diet fed mice were more potently inhibited than those in normal diet fed mice following CPS exposure, which suggests that the obese phenotype may exacerbate some of the non-cholinergic effects of CPS exposure. Copyright © 2017 Elsevier Inc. All rights reserved.

Cypermethrin Poisoning and Anti-cholinergic Medication- A Case Report

Directory of Open Access Journals (Sweden)

Dr Sudip Parajuli

2006-07-01

Full Text Available A 30 years old male was brought to emergency department of Manipal Teaching Hospital, Pokhara, Nepal with alleged history of consumption of pyrethroid compound ‘cypermethrin’. It was found to be newer insecticide poisoning reported in Nepal. We reported this case to show effectiveness of anti-cholinergic like hyosciane and chlorpheniramine maleate in the treatment of cypermethrin poisoning.

Brain cholinergic involvement during the rapid development of tolerance to morphine

Science.gov (United States)

Wahba, Z. Z.; Oriaku, E. T.; Soliman, S. F. A.

1987-01-01

The effect of repeated administration of morphine on the activities of the cholinergic enzymes, choline acetyltransferase (ChAT) and acetylcholinesterase (AChE), in specific brain regions were studied in rats treated with 10 mg/kg morphine for one or two days. Repeated administration of morphine was associated with a decline in the degree of analgesia produced and with a significant increase of AChE activity of the medulla oblongata. A single injection of morphine resulted in a significant decline in ChAT activity in the hypothalamus, cerebellum, and medulla oblongata regions. After two consecutive injections, no decline in ChAT was observed in these regions, while in the cerebral cortex the second administration elicited a significant decline. The results suggest that the development of tolerance to morphine may be mediated through changes in ChAT activity and lend support to the involvement of the central cholinergic system in narcotic tolerance.

Neuropharmacology of memory consolidation and reconsolidation: Insights on central cholinergic mechanisms.

Science.gov (United States)

Blake, M G; Krawczyk, M C; Baratti, C M; Boccia, M M

2014-01-01

Central cholinergic system is critically involved in all known memory processes. Endogenous acetylcholine release by cholinergic neurons is necessary for modulation of acquisition, encoding, consolidation, reconsolidation, extinction, retrieval and expression. Experiments from our laboratory are mainly focused on elucidating the mechanisms by which acetylcholine modulates memory processes. Blockade of hippocampal alpha-7-nicotinic receptors (α7-nAChRs) with the antagonist methyllycaconitine impairs memory reconsolidation. However, the administration of a α7-nAChR agonist (choline) produce a paradoxical modulation, causing memory enhancement in mice trained with a weak footshock, but memory impairment in animals trained with a strong footshock. All these effects are long-lasting, and depend on the age of the memory trace. This review summarizes and discusses some of our recent findings, particularly regarding the involvement of α7-nAChRs on memory reconsolidation. Copyright © 2014 Elsevier Ltd. All rights reserved.

Regulatory changes in presynaptic cholinergic function assessed in rapid autopsy material from patients with Alzheimer disease: Implications for etiology and therapy

International Nuclear Information System (INIS)

Slotkin, T.A.; Seidler, F.J.; Crain, B.J.; Bell, J.M.; Bissette, G.; Nemeroff, C.B.

1990-01-01

Brain regions from patients with or without Alzheimer disease (AD) were obtained within 2 hr of death and examined for indices of presynaptic cholinergic function. Consistent with loss of cholinergic projections, cerebral cortical areas involved in AD exhibited decreased choline acetyltransferase activity. However, remaining nerve terminals in these regions displayed marked up-regulation of synaptosomal high affinity [ 3 H]choline uptake, a result indicative of relative cholinergic hyperactivity. As choline uptake is also rate-limiting in acetylcholine biosynthesis, these findings have implications for both therapy and identification of causes contributing to neuronal death in AD

Beta-amyloid-induced cholinergic denervation correlates with enhanced nitric oxide synthase activity in rat cerebral cortex: Reversal by NMDA receptor blockade : Reversal by NMDA receptor blockade

NARCIS (Netherlands)

O’Mahony, S.; Harkany, T.; Ábrahám, I.; Jong, G.I. de; Varga, J.L.; Zarándi, M.; Penke, B.; Nyakas, C.; Luiten, P.G.M.; Leonard, B.E.

1998-01-01

Ample experimental evidence indicates that acute beta-amyloid infusion into the nucleus basalis of rats elicits abrupt degeneration of the magnocellular cholinergic neurons projecting to the cerebral cortex, In fact, involvement of a permanent Ca2+ overload, partially via N-methyl-D-aspartate (NMDA)

Loss of MeCP2 in cholinergic neurons causes part of RTT-like phenotypes via α7 receptor in hippocampus.

Science.gov (United States)

Zhang, Ying; Cao, Shu-Xia; Sun, Peng; He, Hai-Yang; Yang, Ci-Hang; Chen, Xiao-Juan; Shen, Chen-Jie; Wang, Xiao-Dong; Chen, Zhong; Berg, Darwin K; Duan, Shumin; Li, Xiao-Ming

2016-06-01

Mutations in the X-linked MECP2 gene cause Rett syndrome (RTT), an autism spectrum disorder characterized by impaired social interactions, motor abnormalities, cognitive defects and a high risk of epilepsy. Here, we showed that conditional deletion of Mecp2 in cholinergic neurons caused part of RTT-like phenotypes, which could be rescued by re-expressing Mecp2 in the basal forebrain (BF) cholinergic neurons rather than in the caudate putamen of conditional knockout (Chat-Mecp2(-/y)) mice. We found that choline acetyltransferase expression was decreased in the BF and that α7 nicotine acetylcholine receptor signaling was strongly impaired in the hippocampus of Chat-Mecp2(-/y) mice, which is sufficient to produce neuronal hyperexcitation and increase seizure susceptibility. Application of PNU282987 or nicotine in the hippocampus rescued these phenotypes in Chat-Mecp2(-/y) mice. Taken together, our findings suggest that MeCP2 is critical for normal function of cholinergic neurons and dysfunction of cholinergic neurons can contribute to numerous neuropsychiatric phenotypes.

Cholinergic modulation of epithelial integrity in the proximal colon of pigs.

Science.gov (United States)

Lesko, Szilvia; Wessler, Ignaz; Gäbel, Gotthold; Petto, Carola; Pfannkuche, Helga

2013-01-01

Within the gut, acetylcholine (ACh) is synthesised by enteric neurons, as well as by 'non-neuronal' epithelial cells. In studies of non-intestinal epithelia, ACh was involved in the generation of an intact epithelial barrier. In the present study, primary cultured porcine colonocytes were used to determine whether treatment with exogenous ACh or expression of endogenous epithelium-derived ACh may modulate epithelial tightness in the gastrointestinal tract. Piglet colonocytes were cultured on filter membranes for 8 days. The tightness of the growing epithelial cell layer was evaluated by measuring transepithelial electrical resistance (TEER). To determine whether ACh modulates the tightness of the cell layer, cells were treated with cholinergic, muscarinic and/or nicotinic agonists and antagonists. Choline acetyltransferase (ChAT), cholinergic receptors and ACh were determined by immunohistochemistry, RT-PCR and HPLC, respectively. Application of the cholinergic agonist carbachol (10 µm) and the muscarinic agonist oxotremorine (10 µM) resulted in significantly higher TEER values compared to controls. The effect was completely inhibited by the muscarinic antagonist atropine. Application of atropine alone (without any agonist) led to significantly lower TEER values compared to controls. Synthesis of ACh by epithelial cells was proven by detection of muscarinic and nicotinic receptor mRNAs, immunohistochemical detection of ChAT and detection of ACh by HPLC. ACh is strongly involved in the regulation of epithelial tightness in the proximal colon of pigs via muscarinic pathways. Non-neuronal ACh seems to be of particular importance for epithelial cells forming a tight barrier. Copyright © 2013 S. Karger AG, Basel.

Cholinergic Degeneration and Alterations in the TrkA and p75NTR Balance as a Result of Pro-NGF Injection into Aged Rats

Directory of Open Access Journals (Sweden)

Ashley M. Fortress

2011-01-01

Full Text Available Learning and memory impairments occurring with Alzheimer's disease (AD are associated with degeneration of the basal forebrain cholinergic neurons (BFCNs. BFCNs extend their axons to the hippocampus where they bind nerve growth factor (NGF which is retrogradely transported to the cell body. While NGF is necessary for BFCN survival and function via binding to the high-affinity receptor TrkA, its uncleaved precursor, pro-NGF has been proposed to induce neurodegeneration via binding to the p75NTR and its coreceptor sortilin. Basal forebrain TrkA and NGF are downregulated with aging while pro-NGF is increased. Given these data, the focus of this paper was to determine a mechanism for how pro-NGF accumulation may induce BFCN degeneration. Twenty-four hours after a single injection of pro-NGF into hippocampus, we found increased hippocampal p75NTR levels, decreased hippocampal TrkA levels, and cholinergic degeneration. The data suggest that the increase in p75NTR with AD may be mediated by elevated pro-NGF levels as a result of decreased cleavage, and that pro-NGF may be partially responsible for age-related degenerative changes observed in the basal forebrain. This paper is the first in vivo evidence that pro-NGF can affect BFCNs and may do so by regulating expression of p75NTR neurotrophin receptors.

Why Does Rem Sleep Occur? A Wake-Up Hypothesis 1

OpenAIRE

Klemm, W. R.

2011-01-01

Brain activity differs in the various sleep stages and in conscious wakefulness. Awakening from sleep requires restoration of the complex nerve impulse patterns in neuronal network assemblies necessary to re-create and sustain conscious wakefulness. Herein I propose that the brain uses rapid eye movement (REM) to help wake itself up after it has had a sufficient amount of sleep. Evidence suggesting this hypothesis includes the facts that, (1) when first going to sleep, the brain plunges into ...

Effects of Pyridostigmine in Flinders Line Rats Differing in Cholinergic Sensitivity (AIBS GWI 0055)

National Research Council Canada - National Science Library

Overstreet, David

1999-01-01

.... The second aim was to determine whether pyridostigmine had prophylactic effects against the organophosphates chlorpyrifos and diisopropylfluorophosphate regardless of innate cholinergic sensitivity...

The modulatory role of M2 muscarinic receptor on apomorphine-induced yawning and genital grooming.

Science.gov (United States)

Gamberini, Maria Thereza; Bolognesi, Maria Laura; Nasello, Antonia Gladys

2012-12-07

The interaction between dopaminergic and cholinergic pathways in the induction of behavioral responses has been previously established. In the brain, M2 receptors are found predominantly in presynaptic cholinergic neurons as autoreceptors, and in dopaminergic neurons as heteroceptors, suggesting a control role of acetylcholine and dopamine release, respectively. Our aim was to investigate the role of M2 receptors on the yawning and genital grooming of rats induced by apomorphine, a dopaminergic receptor agonist, focusing on the interaction between cholinergic and dopaminergic pathways. Initially, the effect of atropine, a non-selective muscarinic antagonist, on yawning and genital grooming induced by apomorphine (100 μg/kg s.c.) was analyzed. Atropine doses of 0.5, 1 and 2 mg/kg i.p. were administered to Wistar rats 30 min before induction of the behavioral responses by apomorphine. Number of yawns and time spent genital grooming were quantified over a 60 min period. Apomorphine-induced yawning was increased by low dose (0.5 mg/kg i.p.) but not by high doses (1 and 2 mg/kg, i.p.) of atropine. Genital grooming was antagonized by 2 mg/kg i.p. of atropine and showed no changes at the other doses tested. Tripitramine, a selective M2 cholinergic antagonist, was used as a tool for distinguishing between M2 and all other muscarinic receptor subtypes in yawning and genital grooming. Tripitramine doses of 0.01, 0.02 and 0.04 μmol/kg i.p. were administered to Wistar rats 30 min before apomorphine (100 μg/kg s.c.). Number of yawns and time spent genital grooming were also quantified over a 60 min period. Tripitramine 0.01 μmol/kg increased all parameters. Higher doses, which possibly block all subtypes of muscarinic receptor, did not modify the response of apomorphine, suggesting a non-selective effect of tripitramine at these doses. Given that low doses of tripitramine increased the behavioral responses induced by apomorphine and that the main distribution of the M2

Cholinergic anti-inflammatory pathway in the non-obese diabetic mouse model

NARCIS (Netherlands)

Koopman, F. A.; Vosters, J. L.; Roescher, N.; Broekstra, N.; Tak, P. P.; Vervoordeldonk, M. J.

2015-01-01

Activation of the cholinergic anti-inflammatory pathway (CAP) has been shown to reduce inflammation in animal models, while abrogation of the pathway increases inflammation. We investigated whether modulation of CAP influences inflammation in the non-obese diabetic (NOD) mouse model for Sjögren's

Normal Morning MCH Levels and No Association with REM or NREM Sleep Parameters in Narcolepsy Type 1 and Type 2

DEFF Research Database (Denmark)

Schrölkamp, Maren; Jennum, Poul J; Gammeltoft, Steen

2017-01-01

in rapid eye movement (REM) and nonrapid eye movement (NREM) sleep regulation. Hypocretin neurons reciprocally interact with MCH neurons. We hypothesized that altered MCH secretion contributes to the symptoms and sleep abnormalities of narcolepsy and that this is reflected in morning cerebrospinal fluid...... MCH levels. CONCLUSION: Our study shows that MCH levels in CSF collected in the morning are normal in narcolepsy and not associated with the clinical symptoms, REM sleep abnormalities, nor number of muscle movements during REM or NREM sleep of the patients. We conclude that morning lumbar CSF MCH......STUDY OBJECTIVES: Other than hypocretin-1 (HCRT-1) deficiency in narcolepsy type 1 (NT1), the neurochemical imbalance of NT1 and narcolepsy type 2 (NT2) with normal HCRT-1 levels is largely unknown. The neuropeptide melanin-concentrating hormone (MCH) is mainly secreted during sleep and is involved...

[3H]cytisine binding to nicotinic cholinergic receptors in brain

International Nuclear Information System (INIS)

Pabreza, L.A.; Dhawan, S.; Kellar, K.J.

1991-01-01

Cytisine, a ganglionic agonist, competes with high affinity for brain nicotinic cholinergic receptors labeled by any of several nicotinic 3 H-agonist ligands. Here we have examined the binding of [ 3 H]cytisine in rat brain homogenates. [ 3 H]Cytisine binds with high affinity (Kd less than 1 nM), and specific binding represented 60-90% of total binding at all concentrations examined up to 15 nM. The nicotinic cholinergic agonists nicotine, acetylcholine, and carbachol compete with high affinity for [ 3 H]cytisine binding sites, whereas among nicotinic receptor antagonists only dihydro-beta-erythroidine competes with high affinity (in the nanomolar range). Comparison of binding in several brain regions showed that [ 3 H]cytisine binding is higher in the thalamus, striatum, and cortex than in the hippocampus, cerebellum, or hypothalamus. The pharmacology and brain regional distribution of [ 3 H]cytisine binding sites are those predicted for neuronal nicotinic receptor agonist recognition sites. The high affinity and low nonspecific binding of [ 3 H]cytisine should make it a very useful ligand for studying neuronal nicotinic receptors

Sociality Affects REM Sleep Episode Duration Under Controlled Laboratory Conditions in the Rock Hyrax, Procavia capensis

Directory of Open Access Journals (Sweden)

Nadine Gravett

2017-11-01

Full Text Available The rock hyrax, Procavia capensis, is a highly social, diurnal mammal. In the current study several physiologically measurable parameters of sleep, as well as the accompanying behavior, were recorded continuously from five rock hyraxes, for 72 h under solitary (experimental animal alone in the recording chamber, and social conditions (experimental animal with 1 or 2 additional, non-implanted animals in the recording chamber. The results revealed no significant differences between solitary and social conditions for total sleep times, number of episodes, episode duration or slow wave activity (SWA for all states examined. The only significant difference observed between social and solitary conditions was the average duration of rapid eye movement (REM sleep episodes. REM sleep episode duration was on average 20 s and 40 s longer under social conditions daily and during the dark period, respectively. It is hypothesized that the increase in REM sleep episode duration under social conditions could possibly be attributed to improved thermoregulation strategies, however considering the limited sample size and design of the current study further investigations are needed to confirm this finding. Whether the conclusions and the observations made in this study can be generalized to all naturally socially sleeping mammals remains an open question.

REM Sleep Behavior and Motor Findings in Parkinson's Disease: A Cross-sectional Analysis

Directory of Open Access Journals (Sweden)

Abhimanyu Mahajan

2014-06-01

Full Text Available Background: Parkinson's disease (PD represents a major public health challenge that will only grow in our aging population. Understanding the connection between PD and associated prodromal conditions, such as rapid eye movement sleep behavioral disorder (RBD, is critical to identifying prevention strategies. However, the relationship between RBD and severity of motor findings in early PD is unknown. This study aims to examine this relationship. Methods: The study population consisted of 418 PD patients who completed the Movement Disorders Society‐United Parkinson's Disease Rating Scale (MDS‐UPDRS and rapid eye movement sleep (REM disorder questionnaires at the baseline visit of the Michael J. Fox's Parkinson's Progression Markers Initiative (PPMI. Cross‐sectional analysis was carried out to assess the association between REM Sleep Behavior Screening Questionnaire score and MDS UPDRS‐3 (motor score categories. Correlation with a higher score category was described as “worse motor findings”. A score of 5 on the REM disorder questionnaire was defined as predictive of RBD.Results: Out of the 418 PD patients, 113 (27.0% had RBD. With univariate logistic regression analysis, individuals with scores predictive of RBD were 1.66 times more likely to have worse motor findings (p = 0.028. Even with age, gender, and Geriatric Depression Scale scores taken into account, individuals with scores predictive of RBD were 1.69 times more likely to have worse motor findings (p = 0.025.Discussion: PD patients with RBD symptoms had worse motor findings than those unlikely to have RBD. This association provides further evidence for the relationship between RBD and PD.

Characteristic comparison of triglyceride-rich remnant lipoprotein measurement between a new homogenous assay (RemL-C and a conventional immunoseparation method (RLP-C

Directory of Open Access Journals (Sweden)

Saikawa Shinichi

2008-05-01

Full Text Available Abstract Background Increased serum remnant lipoproteins are supposed to predict cardiovascular disease in addition to increased LDL. A new homogenous assay for remnant lipoprotein-cholesterol (RemL-C has been developed as an alternative to remnant-like particle-cholesterol (RLP-C, an immunoseparation assay, widely used for the measurement of remnant lipoprotein cholesterol. Methods We evaluated the correlations and data validation between the 2 assays in 83 subjects (49 men and 34 women without diabetes, hypertension and medications for hyperlipidemia, diabetes, and hypertension, and investigated the characteristics of remnant lipoproteins obtained by the two methods (RLP-C and RemL-C and their relationships with IDL-cholesterol determined by our developed HPLC method. Results A positive correlation was significantly found between the two methods (r = 0.853, 95%CI 0.781–0.903, p RLP-C level. RemL-C (r = 0.339, 95%CI 0.152–0.903; p = 0.0005 significantly correlated with IDL-cholesterol, but not RLP-C (r = 0.17, 95%CI -0.047–0.372; p = 0.1237 in all the samples (n = 83. Conclusion These results suggest that there is generally a significant correlation between RemL-C and RLP-C. However, RemL-C assay is likely to reflect IDL more closely than RLP-C.

Rem Koolhaas. Utopie ve sférách globálního trhu

Czech Academy of Sciences Publication Activity Database

Hnídková, Vendula

-, Č. 19-20 (2006), s. 212-214 ISSN 1210-6887 Institutional research plan: CEZ:AV0Z80330511 Keywords : Rem Koolhaas * contemporary architecture * utopia of architectural production Subject RIV: AL - Art, Architecture, Cultural Heritage

Organization of the sleep-related neural systems in the brain of the harbour porpoise (Phocoena phocoena).

Science.gov (United States)

Dell, Leigh-Anne; Patzke, Nina; Spocter, Muhammad A; Siegel, Jerome M; Manger, Paul R

2016-07-01

The present study provides the first systematic immunohistochemical neuroanatomical investigation of the systems involved in the control and regulation of sleep in an odontocete cetacean, the harbor porpoise (Phocoena phocoena). The odontocete cetaceans show an unusual form of mammalian sleep, with unihemispheric slow waves, suppressed REM sleep, and continuous bodily movement. All the neural elements involved in sleep regulation and control found in bihemispheric sleeping mammals were present in the harbor porpoise, with no specific nuclei being absent, and no novel nuclei being present. This qualitative similarity of nuclear organization relates to the cholinergic, noradrenergic, serotonergic, and orexinergic systems and is extended to the γ-aminobutyric acid (GABA)ergic elements involved with these nuclei. Quantitative analysis of the cholinergic and noradrenergic nuclei of the pontine region revealed that in comparison with other mammals, the numbers of pontine cholinergic (126,776) and noradrenergic (122,878) neurons are markedly higher than in other large-brained bihemispheric sleeping mammals. The diminutive telencephalic commissures (anterior commissure, corpus callosum, and hippocampal commissure) along with an enlarged posterior commissure and supernumerary pontine cholinergic and noradrenergic neurons indicate that the control of unihemispheric slow-wave sleep is likely to be a function of interpontine competition, facilitated through the posterior commissure, in response to unilateral telencephalic input related to the drive for sleep. In addition, an expanded peripheral division of the dorsal raphe nuclear complex appears likely to play a role in the suppression of REM sleep in odontocete cetaceans. Thus, the current study provides several clues to the understanding of the neural control of the unusual sleep phenomenology present in odontocete cetaceans. J. Comp. Neurol. 524:1999-2017, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals

Shutdown radiation level and man-rem control for water cooled reactors

International Nuclear Information System (INIS)

Cripps, S.J.; Regan, J.D.

1978-01-01

The importance of controlling the formation and subsequent deposition of active corrosion products (crud) is highlighted as a method of reducing occupational exposure. A semi-empirical model is described and used to predict the effectiveness of various methods of crud control. The relative merits of reactor coolant clean-up techniques including ion-exchange and electromagnetic filtration are assessed in terms of man-rem savings and associated cost penalties. (author)

FDG PET, Dopamine Transporter SPECT, and Olfaction: Combining Biomarkers in REM Sleep Behavior Disorder

NARCIS (Netherlands)

Meles, Sanne K.; Vadasz, David; Renken, Remco J.; Sittig-Wiegand, Elisabeth; Mayer, Geert; Depboylu, Candan; Reetz, Kathrin; Overeem, Sebastiaan; Pijpers, Angelique; Reesink, Fransje E.; van Laar, Teus; Heinen, Lisette; Teune, Laura K.; Höffken, Helmut; Luster, Marcus; Kesper, Karl; Adriaanse, Sofie M.; Booij, Jan; Leenders, Klaus L.; Oertel, Wolfgang H.

2017-01-01

Background: Idiopathic REM sleep behavior disorder is a prodromal stage of Parkinson's disease and dementia with Lewy bodies. Hyposmia, reduced dopamine transporter binding, and expression of the brain metabolic PD-related pattern were each associated with increased risk of conversion to PD. The

Effect of Estradiol on Neurotrophin Receptors in Basal Forebrain Cholinergic Neurons: Relevance for Alzheimer’s Disease

Science.gov (United States)

Kwakowsky, Andrea; Milne, Michael R.; Waldvogel, Henry J.; Faull, Richard L.

2016-01-01

The basal forebrain is home to the largest population of cholinergic neurons in the brain. These neurons are involved in a number of cognitive functions including attention, learning and memory. Basal forebrain cholinergic neurons (BFCNs) are particularly vulnerable in a number of neurological diseases with the most notable being Alzheimer’s disease, with evidence for a link between decreasing cholinergic markers and the degree of cognitive impairment. The neurotrophin growth factor system is present on these BFCNs and has been shown to promote survival and differentiation on these neurons. Clinical and animal model studies have demonstrated the neuroprotective effects of 17β-estradiol (E2) on neurodegeneration in BFCNs. It is believed that E2 interacts with neurotrophin signaling on cholinergic neurons to mediate these beneficial effects. Evidence presented in our recent study confirms that altering the levels of circulating E2 levels via ovariectomy and E2 replacement significantly affects the expression of the neurotrophin receptors on BFCN. However, we also showed that E2 differentially regulates neurotrophin receptor expression on BFCNs with effects depending on neurotrophin receptor type and neuroanatomical location. In this review, we aim to survey the current literature to understand the influence of E2 on the neurotrophin system, and the receptors and signaling pathways it mediates on BFCN. In addition, we summarize the physiological and pathophysiological significance of E2 actions on the neurotrophin system in BFCN, especially focusing on changes related to Alzheimer’s disease. PMID:27999310

Effect of Estradiol on Neurotrophin Receptors in Basal Forebrain Cholinergic Neurons: Relevance for Alzheimer’s Disease

Directory of Open Access Journals (Sweden)

Andrea Kwakowsky

2016-12-01

Full Text Available The basal forebrain is home to the largest population of cholinergic neurons in the brain. These neurons are involved in a number of cognitive functions including attention, learning and memory. Basal forebrain cholinergic neurons (BFCNs are particularly vulnerable in a number of neurological diseases with the most notable being Alzheimer’s disease, with evidence for a link between decreasing cholinergic markers and the degree of cognitive impairment. The neurotrophin growth factor system is present on these BFCNs and has been shown to promote survival and differentiation on these neurons. Clinical and animal model studies have demonstrated the neuroprotective effects of 17β-estradiol (E2 on neurodegeneration in BFCNs. It is believed that E2 interacts with neurotrophin signaling on cholinergic neurons to mediate these beneficial effects. Evidence presented in our recent study confirms that altering the levels of circulating E2 levels via ovariectomy and E2 replacement significantly affects the expression of the neurotrophin receptors on BFCN. However, we also showed that E2 differentially regulates neurotrophin receptor expression on BFCNs with effects depending on neurotrophin receptor type and neuroanatomical location. In this review, we aim to survey the current literature to understand the influence of E2 on the neurotrophin system, and the receptors and signaling pathways it mediates on BFCN. In addition, we summarize the physiological and pathophysiological significance of E2 actions on the neurotrophin system in BFCN, especially focusing on changes related to Alzheimer’s disease.

Increased dopamine D1 receptor binding in the human mesocortical system following central cholinergic activation

International Nuclear Information System (INIS)

Fedi, M.; Berkovic, S.F.; Tochon-Danguy, H.J.; Reutens, D.C.

2002-01-01

Full text: The interaction between the cholinergic and dopaminergic system has been implicated in many pathological processes including, Alzheimer's disease, schizophrenia and drug addiction. Little is known about the control of dopamine (DA) release following central cholinergic activation in humans, but experimental studies suggest that endogenously released Acetylcholine (ACh) achieved by the administration of cholinesterase inhibitors, can increase dopamine efflux in different regions of the brain. This leads to the activation of different types of post-synaptic dopaminergic receptors which belong to the family of G-protein coupled receptors (GPCRs). A common paradigm of the GPCRs desensitization is that agonist-induced receptor signaling is rapidly attenuated by receptor internalisation. Several experiments have shown that the activation of Dl receptors in acute conditions leads, within minutes, to translocation of the receptor from the surface of the neurons to the endosomal compartment in the cytoplasm and increased receptor turnover. To assess changes in Dl receptor density following an intravenous infusion of the selective cholinesterase inhibitor physostigmine salicylate (PHY), we studied eleven normal subjects (10 male and 1 female, mean age 36.1 and 61617; 9.9) using [11C]-SCH23390 and PET The binding potential (BP) for SCH23390 was significantly (p 0.05). There was no statistically significant difference between baseline and physostigmine Kl ratio (p>0.05) suggesting that BP changes observed were not secondary to regional blood flow changes or to an order effect of the scans. Copyright (2002) The Australian and New Zealand Society of Nuclear Medicine Inc

An accurate and portable solid state neutron rem meter

Energy Technology Data Exchange (ETDEWEB)

Oakes, T.M. [Nuclear Science and Engineering Institute, University of Missouri, Columbia, MO (United States); Bellinger, S.L. [Department of Mechanical and Nuclear Engineering, Kansas State University, Manhattan, KS (United States); Miller, W.H. [Nuclear Science and Engineering Institute, University of Missouri, Columbia, MO (United States); Missouri University Research Reactor, Columbia, MO (United States); Myers, E.R. [Department of Physics, University of Missouri, Kansas City, MO (United States); Fronk, R.G.; Cooper, B.W [Department of Mechanical and Nuclear Engineering, Kansas State University, Manhattan, KS (United States); Sobering, T.J. [Electronics Design Laboratory, Kansas State University, KS (United States); Scott, P.R. [Department of Physics, University of Missouri, Kansas City, MO (United States); Ugorowski, P.; McGregor, D.S; Shultis, J.K. [Department of Mechanical and Nuclear Engineering, Kansas State University, Manhattan, KS (United States); Caruso, A.N., E-mail: carusoan@umkc.edu [Department of Physics, University of Missouri, Kansas City, MO (United States)

2013-08-11

Accurately resolving the ambient neutron dose equivalent spanning the thermal to 15 MeV energy range with a single configuration and lightweight instrument is desirable. This paper presents the design of a portable, high intrinsic efficiency, and accurate neutron rem meter whose energy-dependent response is electronically adjusted to a chosen neutron dose equivalent standard. The instrument may be classified as a moderating type neutron spectrometer, based on an adaptation to the classical Bonner sphere and position sensitive long counter, which, simultaneously counts thermalized neutrons by high thermal efficiency solid state neutron detectors. The use of multiple detectors and moderator arranged along an axis of symmetry (e.g., long axis of a cylinder) with known neutron-slowing properties allows for the construction of a linear combination of responses that approximate the ambient neutron dose equivalent. Variations on the detector configuration are investigated via Monte Carlo N-Particle simulations to minimize the total instrument mass while maintaining acceptable response accuracy—a dose error less than 15% for bare {sup 252}Cf, bare AmBe, an epi-thermal and mixed monoenergetic sources is found at less than 4.5 kg moderator mass in all studied cases. A comparison of the energy dependent dose equivalent response and resultant energy dependent dose equivalent error of the present dosimeter to commercially-available portable rem meters and the prior art are presented. Finally, the present design is assessed by comparison of the simulated output resulting from applications of several known neutron sources and dose rates.

Methyl-CpG binding-protein 2 function in cholinergic neurons mediates cardiac arrhythmogenesis.

Science.gov (United States)

Herrera, José A; Ward, Christopher S; Wehrens, Xander H T; Neul, Jeffrey L

2016-11-15

Sudden unexpected death occurs in one quarter of deaths in Rett Syndrome (RTT), a neurodevelopmental disorder caused by mutations in Methyl-CpG-binding protein 2 (MECP2). People with RTT show a variety of autonomic nervous system (ANS) abnormalities and mouse models show similar problems including QTc interval prolongation and hypothermia. To explore the role of cardiac problems in sudden death in RTT, we characterized cardiac rhythm in mice lacking Mecp2 function. Male and female mutant mice exhibited spontaneous cardiac rhythm abnormalities including bradycardic events, sinus pauses, atrioventricular block, premature ventricular contractions, non-sustained ventricular arrhythmias, and increased heart rate variability. Death was associated with spontaneous cardiac arrhythmias and complete conduction block. Atropine treatment reduced cardiac arrhythmias in mutant mice, implicating overactive parasympathetic tone. To explore the role of MeCP2 within the parasympathetic neurons, we selectively removed MeCP2 function from cholinergic neurons (MeCP2 ChAT KO), which recapitulated the cardiac rhythm abnormalities, hypothermia, and early death seen in RTT male mice. Conversely, restoring MeCP2 only in cholinergic neurons rescued these phenotypes. Thus, MeCP2 in cholinergic neurons is necessary and sufficient for autonomic cardiac control, thermoregulation, and survival, and targeting the overactive parasympathetic system may be a useful therapeutic strategy to prevent sudden unexpected death in RTT.

Decreased sleep spindle density in patients with idiopathic REM sleep behavior disorder and patients with Parkinson’s disease

DEFF Research Database (Denmark)

Christensen, Julie Anja Engelhard; Kempfner, Jacob; Zoetmulder, Marielle

2014-01-01

ObjectiveTo determine whether sleep spindles (SS) are potentially a biomarker for Parkinson’s disease (PD). MethodsFifteen PD patients with REM sleep behavior disorder (PD+RBD), 15 PD patients without RBD (PD−RBD), 15 idiopathic RBD (iRBD) patients and 15 age-matched controls underwent...... polysomnography (PSG). SS were scored in an extract of data from control subjects. An automatic SS detector using a Matching Pursuit (MP) algorithm and a Support Vector Machine (SVM) was developed and applied to the PSG recordings. The SS densities in N1, N2, N3, all NREM combined and REM sleep were obtained...

Characterization of cholinergic muscarinic receptor-stimulated phosphoinositide metabolism in brain from immature rats

International Nuclear Information System (INIS)

Balduini, W.; Murphy, S.D.; Costa, L.G.

1990-01-01

Hydrolysis of phosphoinositides elicited by stimulation of cholinergic muscarinic receptors has been studied in brain from neonatal (7-day-old) rats in order to determine: (1) whether the neonatal rat could provide a good model system to study this signal-transduction pathway; and (2) whether potential differences with adult nerve tissue would explain the differential, age-related effects of cholinergic agonists. Accumulation of [3H] inositol phosphates in [3H]inositol prelabeled slices from neonatal and adult rats was measured as an index of phosphoinositide metabolism. Full (acetylcholine, methacholine, carbachol) and partial (oxotremorine, bethanechol) agonists had qualitatively similar, albeit quantitatively different, effects in neonatal and adult rats. Atropine and pirenzepine effectively blocked the carbachol-induced response with inhibition constants of 1.2 and 20.7 nM, respectively. In all brain areas, response to all agonists was higher in neonatal than adult rats, and in hippocampus and cerebral cortex the response was higher than in cerebellum or brainstem. The relative intrinsic activity of partial agonists was higher in the latter two areas (0.6-0.7) than in the former two (0.3-0.4). Carbachol-stimulated phosphoinositide metabolism in brain areas correlated well with the binding of [3H]QNB (r2 = 0.627) and, particularly, with [3H]pirenzepine (r2 = 0.911). In cerebral cortex the effect of carbachol was additive to that of norepinephrine and glutamate. The presence of calcium (250-500 microM) was necessary for maximal response to carbachol to be elicited; the EC50 value for Ca2+ was 65.4 microM. Addition of EDTA completely abolished the response. Removal of sodium ions from the incubation medium reduced the response to carbachol by 50%

Curcumin attenuates surgery-induced cognitive dysfunction in aged mice.

Science.gov (United States)

Wu, Xiang; Chen, Huixin; Huang, Chunhui; Gu, Xinmei; Wang, Jialing; Xu, Dilin; Yu, Xin; Shuai, Chu; Chen, Liping; Li, Shun; Xu, Yiguo; Gao, Tao; Ye, Mingrui; Su, Wei; Liu, Haixiong; Zhang, Jinrong; Wang, Chuang; Chen, Junping; Wang, Qinwen; Cui, Wei

2017-06-01

Post-operative cognitive dysfunction (POCD) is associated with elderly patients undergoing surgery. However, pharmacological treatments for POCD are limited. In this study, we found that curcumin, an active compound derived from Curcuma longa, ameliorated the cognitive dysfunction following abdominal surgery in aged mice. Further, curcumin prevented surgery-induced anti-oxidant enzyme activity. Curcumin also increased brain-derived neurotrophic factor (BDNF)-positive area and expression of pAkt in the brain, suggesting that curcumin activated BDNF signaling in aged mice. Furthermore, curcumin neutralized cholinergic dysfunction involving choline acetyltransferase expression induced by surgery. These results strongly suggested that curcumin prevented cognitive impairments via multiple targets, possibly by increasing the activity of anti-oxidant enzymes, activation of BDNF signaling, and neutralization of cholinergic dysfunction, concurrently. Based on these novel findings, curcumin might be a potential agent in POCD prophylaxis and treatment.

The REM route to more syncrude

Energy Technology Data Exchange (ETDEWEB)

Law, C

1980-09-03

Norcen will become the first industry major to support a feasibility study of REM, an acronym for Resource and Energy Management. The prospective joint project involving Norcen Energy Resources and the Federal Department of Energy, Mines and Resources will consider coal utilization in the recovery and upgrading of heavy crude from Western Canadian deposits. The project will facilitate smaller projects at Cold Lake and will also be relevant to large scale plants, whether in-situ or surface-mined tar sands or heavy oil applications. The innovation: gasifying coal (rather than burning natural gas or liquids) to raise steam and electric power in a synergistic combined cycle system, and electrolyzing water to win essential hydrogen and oxygen for the upgrading process. The bonuses: the generation of hydrogen and oxygen without the consumption of premium light hydrocarbons in a clean, energy efficient process. The objective: higher yield of light oil at lower unit cost, better sulfur control and modular design for small or large scale plants.

Age-dependent loss of cholinergic neurons in learning and memory-related brain regions and impaired learning in SAMP8 mice with trigeminal nerve damage

Institute of Scientific and Technical Information of China (English)

Yifan He; Jihong Zhu; Fang Huang; Liu Qin; Wenguo Fan; Hongwen He

2014-01-01

The tooth belongs to the trigeminal sensory pathway. Dental damage has been associated with impairments in the central nervous system that may be mediated by injury to the trigeminal nerve. In the present study, we investigated the effects of damage to the inferior alveolar nerve, an important peripheral nerve in the trigeminal sensory pathway, on learning and memory be-haviors and structural changes in related brain regions, in a mouse model of Alzheimer’s disease. Inferior alveolar nerve transection or sham surgery was performed in middle-aged (4-month-old) or elderly (7-month-old) senescence-accelerated mouse prone 8 (SAMP8) mice. When the middle-aged mice reached 8 months (middle-aged group 1) or 11 months (middle-aged group 2), and the elderly group reached 11 months, step-down passive avoidance and Y-maze tests of learn-ing and memory were performed, and the cholinergic system was examined in the hippocampus (Nissl staining and acetylcholinesterase histochemistry) and basal forebrain (choline acetyltrans-ferase immunohistochemistry). In the elderly group, animals that underwent nerve transection had fewer pyramidal neurons in the hippocampal CA1 and CA3 regions, fewer cholinergic ifbers in the CA1 and dentate gyrus, and fewer cholinergic neurons in the medial septal nucleus and vertical limb of the diagonal band, compared with sham-operated animals, as well as showing impairments in learning and memory. Conversely, no signiifcant differences in histology or be-havior were observed between middle-aged group 1 or group 2 transected mice and age-matched sham-operated mice. The present ifndings suggest that trigeminal nerve damage in old age, but not middle age, can induce degeneration of the septal-hippocampal cholinergic system and loss of hippocampal pyramidal neurons, and ultimately impair learning ability. Our results highlight the importance of active treatment of trigeminal nerve damage in elderly patients and those with Alzheimer’s disease, and

Circadian variation of EEG power spectra in NREM and REM sleep in humans: dissociation from body temperature

Science.gov (United States)

Dijk, D. J.

1999-01-01

In humans, EEG power spectra in REM and NREM sleep, as well as characteristics of sleep spindles such as their duration, amplitude, frequency and incidence, vary with circadian phase. Recently it has been hypothesized that circadian variations in EEG spectra in humans are caused by variations in brain or body temperature and may not represent phenomena relevant to sleep regulatory processes. To test this directly, a further analysis of EEG power spectra - collected in a forced desynchrony protocol in which sleep episodes were scheduled to a 28-h period while the rhythms of body temperature and plasma melatonin were oscillating at their near 24-h period - was carried out. EEG power spectra were computed for NREM and REM sleep occurring between 90-120 and 270-300 degrees of the circadian melatonin rhythm, i.e. just after the clearance of melatonin from plasma in the 'morning' and just after the 'evening' increase in melatonin secretion. Average body temperatures during scheduled sleep at these two circadian phases were identical (36.72 degrees C). Despite identical body temperatures, the power spectra in NREM sleep were very different at these two circadian phases. EEG activity in the low frequency spindle range was significantly and markedly enhanced after the evening increase in plasma melatonin as compared to the morning phase. For REM sleep, significant differences in power spectra during these two circadian phases, in particular in the alpha range, were also observed. The results confirm that EEG power spectra in NREM and REM sleep vary with circadian phase, suggesting that the direct contribution of temperature to the circadian variation in EEG power spectra is absent or only minor, and are at variance with the hypothesis that circadian variations in EEG power spectra are caused by variations in temperature.

REM sleep behavior disorder in Parkinson disease: association with abnormal ocular motor findings.

Science.gov (United States)

Kim, Young Eun; Yang, Hui June; Yun, Ji Young; Kim, Han-Joon; Lee, Jee-Young; Jeon, Beom S

2014-04-01

The anatomical substrates associated with generalized muscle atonia during REM sleep are located on the pontine tegmentum and medial medulla oblongata. We examined whether patients with REM sleep behavior disorder (RBD) have abnormal ocular movements suggesting brainstem or cerebellar dysfunction in Parkinson's disease (PD). Cross-sectional survey for the existence of RBD and abnormal ocular movements. Ocular movements were examined by video-oculography (VOG). A total of 202 patients were included in this study. One hundred and sixteen (57.4%) of the 202 patients have clinically probable RBD, and 28 (24.1%) of the 116 with clinically probable RBD patients had abnormal VOG findings suggesting brainstem or cerebellar dysfunction; whereas 86 of the 202 patients did not have clinically probable RBD, and only 7 (8.1%) of the 86 patients had abnormal VOG findings suggesting brainstem or cerebellar dysfunction (P=0.001). This study suggests that the presence of RBD is associated with more severe or extensive brainstem pathology or different distribution of pathology in PD. Copyright © 2013 Elsevier Ltd. All rights reserved.

Neutron measurement in 12,13C+ 27Al system using CR-39 detectors and neutron rem meter

International Nuclear Information System (INIS)

Sahoo, G.S.; Tripathy, S.P.; Shanbhag, A.A.; Sunil, C.; Joshi, D.S.; Sarkar, P.K.

2011-01-01

In this work, neutron measurements carried out for the interaction of 60 and 67.5 MeV 12 C, 57.3 and 65 MeV 13 C ions with thick aluminium target by using CR-39 detectors and neutron rem meter is reported. Both the detector systems were irradiated at different angles viz. 0 deg, 30 deg, 60 deg, 90 deg with respect to the beam direction. The normalized track density measurements (tracks/cm 2 /projectile at 1m) in CR-39 detectors were correlated with the normalized dose equivalent values (μSv/projectile at 1m) obtained using the neutron rem meter. The track density was found to be more in case of 13 C than 12 C. However in all the cases, the track density per incident projectile was found to decrease as the angle with respect to beam direction increases, indicating non-isotropic nature of neutron emission. The ratio between measured dose equivalent in rem meter to the measured track densities in CR-39 detectors was found to be 2.8±0.2, which remains constant irrespective of the change in angle from beam direction as well as neutron spectrum, indicating a flat dose response of CR-39 detectors. (author)

Design and development of wide energy neutron REM equivalent spectrometer-dosimeters based on polycarbonates and Cr-39

International Nuclear Information System (INIS)

Faermann, S.

1985-03-01

This work describes a system composed of a Rem response personnel neutron dosemeter, based on boron radiators and a polycarbonate track detector, for monitoring dose equivalents in the energy range 1 eV to 14 MeV, an electrochemical etching system for revealing damage sites in solid state track etch detectors, a reader for magnifying the etched pits and a microprocessor for evaluating the dose equivalents and their uncertainties. The performance and directional dependence of the dosemeter when exposed to monoenergetic and polyenergetic neutron fields in the epithermal and fast energy regions are discussed. Saturation effects in polycarbonate foils are presented and a comparison is made between the response of polycarbonate and CR-39 foils, used as passive detectors in the dosemeter. A new passive miniature fast neutron spectrometer-dosimeter is also described. The device is based on the detection of proton tracks by electrochemical etching of CR-39 foils covered with thin polyethylene layers of different thicknesses. By means of this device it is possible to assess the fast neutron energy spectrum in 10 energy intervals in the energy range 0.5-15 MeV. Dose equivalents can be determined in the dose equivalent range 20 mRem to 8 Rem, approximately (author)

Cholinergic pairing with visual activation results in long-term enhancement of visual evoked potentials.

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Jun Il Kang

Full Text Available Acetylcholine (ACh contributes to learning processes by modulating cortical plasticity in terms of intensity of neuronal activity and selectivity properties of cortical neurons. However, it is not known if ACh induces long term effects within the primary visual cortex (V1 that could sustain visual learning mechanisms. In the present study we analyzed visual evoked potentials (VEPs in V1 of rats during a 4-8 h period after coupling visual stimulation to an intracortical injection of ACh analog carbachol or stimulation of basal forebrain. To clarify the action of ACh on VEP activity in V1, we individually pre-injected muscarinic (scopolamine, nicotinic (mecamylamine, alpha7 (methyllycaconitine, and NMDA (CPP receptor antagonists before carbachol infusion. Stimulation of the cholinergic system paired with visual stimulation significantly increased VEP amplitude (56% during a 6 h period. Pre-treatment with scopolamine, mecamylamine and CPP completely abolished this long-term enhancement, while alpha7 inhibition induced an instant increase of VEP amplitude. This suggests a role of ACh in facilitating visual stimuli responsiveness through mechanisms comparable to LTP which involve nicotinic and muscarinic receptors with an interaction of NMDA transmission in the visual cortex.

Cognitive impairment as a central cholinergic deficit in patients with Myasthenia Gravis

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Antonia Kaltsatou

2015-06-01

Conclusions: VCmax and ACmax are governed mainly by the action of the Parasympathetic Nervous System, through acetylcholine. The results of this study demonstrate that the CNS may be affected in MG and support the hypothesis that MG has central cholinergic effects manifested by cognitive dysfunction.

Acute Treatment with T-Type Calcium Channel Enhancer SAK3 Reduces Cognitive Impairments Caused by Methimazole-Induced Hypothyroidism Via Activation of Cholinergic Signaling.

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Husain, Noreen; Yabuki, Yasushi; Shinoda, Yasuharu; Fukunaga, Kohji

2018-01-01

Hypothyroidism is a common disorder that is associated with psychological disturbances such as dementia, depression, and psychomotor disorders. We recently found that chronic treatment with the T-type calcium channel enhancer SAK3 prevents the cholinergic neurodegeneration induced by a single intraperitoneal (i.p.) injection of methimazole (MMI; 75 mg/kg), thereby improving cognition. Here, we evaluated the acute effect of SAK3 on cognitive impairments and its mechanism of action following the induction of hypothyroidism. Hypothyroidism was induced by 2 injections of MMI (75 mg/kg, i.p.) administered once per week. Four weeks after the final MMI treatment, MMI-treated mice showed reduced serum thyroxine (T4) levels and cognitive impairments without depression-like behaviors. Although acute SAK3 (1.0 mg/kg, p.o.) administration failed to ameliorate the decreased T4 levels and histochemical destruction of the glomerular structure, acute SAK3 (1.0 mg/kg, p.o.) administration significantly reduced cognitive impairments in MMI-treated mice. Importantly, the α7 nicotinic acetylcholine receptor (nAChR)-selective inhibitor methyllycaconitine (MLA; 12 mg/kg, i.p.) and T-type calcium channel-specific blocker NNC 55-0396 (25 mg/kg, i.p.) antagonized the acute effect of SAK3 on memory deficits in MMI-treated mice. We also confirmed that acute SAK3 administration does not rescue reduced olfactory marker protein or choline acetyltransferase immunoreactivity levels in the olfactory bulb or medial septum. Taken together, these results suggest that SAK3 has the ability to improve the cognitive decline caused by hypothyroidism directly through activation of nAChR signaling and T-type calcium channels. © 2018 S. Karger AG, Basel.

Ameliorating Effects of Ethanol Extract of Fructus mume on Scopolamine-Induced Memory Impairment in Mice

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Min-Soo Kim

2015-01-01

Full Text Available We previously reported that Fructus mume (F. mume extract shows protective effects on memory impairments and anti-inflammatory effects induced by chronic cerebral hypoperfusion. Neurodegeneration of basal cholinergic neurons is also observed in the brain with chronic cerebral hypoperfusion. Therefore, the present study was conducted to examine whether F. mume extracts enhance cognitive function via the action of cholinergic neuron using a scopolamine-induced animal model of memory impairments. F. mume (50, 100, or 200 mg/kg was administered to C57BL/6 mice for 14 days (days 1–14 and memory impairment was induced by scopolamine (1 mg/kg, a muscarinic receptor antagonist for 7 days (days 8–14. Spatial memory was assessed using Morris water maze and hippocampal level of acetylcholinesterase (AChE and choline acetyltransferase (ChAT was examined by ELISA and immunoblotting. Mice that received scopolamine alone showed impairments in acquisition and retention in Morris water maze task and increased activity of AChE in the hippocampus. Mice that received F. mume and scopolamine showed no scopolamine-induced memory impairment and increased activity of AChE. In addition, treatments of F. mume increased ChAT expression in the hippocampus. These results indicated that F. mume might enhance cognitive function via action of cholinergic neurons.

Chronic REM-sleep deprivation of rats elevates metabolic rate and increases UCP1 gene expression in brown adipose tissue.

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Koban, Michael; Swinson, Kevin L

2005-07-01

A cluster of unique pathologies progressively develops during chronic total- or rapid eye movement-sleep deprivation (REM-SD) of rats. Two prominent and readily observed symptoms are hyperphagia and decline in body weight. For body weight to be lost despite a severalfold increase in food consumption suggests that SD elevates metabolism as the subject enters a state of negative energy balance. To test the hypothesis that mediation of this hypermetabolism involves increased gene expression of uncoupling protein-1 (UCP1), which dissipates the thermodynamic energy of the mitochondrial proton-motive force as heat instead of ATP formation in brown adipose tissue (BAT), we 1) established the time course and magnitude of change in metabolism by measuring oxygen consumption, 2) estimated change in UCP1 gene expression in BAT by RT-PCR and Western blot, and 3) assayed serum leptin because of its role in regulating energy balance and food intake. REM-SD of male Sprague-Dawley rats was enforced for 20 days with the platform (flowerpot) method, wherein muscle atonia during REM sleep causes contact with surrounding water and awakens it. By day 20, rats more than doubled food consumption while losing approximately 11% of body weight; metabolism rose to 166% of baseline with substantial increases in UCP1 mRNA and immunoreactive UCP1 over controls; serum leptin decreased and remained suppressed. The decline in leptin is consistent with the hyperphagic response, and we conclude that one of the mediators of elevated metabolism during prolonged REM-SD is increased gene expression of UCP1 in BAT.

The effect of heat treatment on recrystallized microstructure, precipitation and ductility of hot-rolled Fe–Cr–Al–REM ferritic stainless steel sheets

International Nuclear Information System (INIS)

Qu, H.P.; Lang, Y.P.; Yao, C.F.; Chen, H.T.; Yang, C.Q.

2013-01-01

This study presents research works about the effects of heat treatment on recrystallized equiaxed grain size, precipitation, room temperature (RT) toughness and ductile to brittle transition temperature (DBTT) of Fe–Cr–Al–REM ferritic stainless steel (FSS) hot-rolled sheet. Results showed that the recrystallization of hot-rolled Fe–Cr–Al–REM FSS sheet could be completed after annealing treatment at 750 °C for 15 min with the equiaxed grain diameter of approximately 50 μm. Inappropriate annealing treatment would inevitably leads to the unexpected grain coarsening. On the other hand, a great deal of needle-like or spot-like fine aluminum–lanthanum compound Al 11 La 3 precipitates were observed in the ferrite matrix after 1 h aging treatment at 750 °C. The microstructure observation results associated with the impact test definitely illustrated that the Al 11 La 3 precipitates was the reason for the brittle crack in the as-casted ingot and as-forged slab. The real DBTT of the annealed Fe–Cr–Al–REM FSS sheet with average grain size of about 50 μm was −4 °C. Meanwhile, the DBTT of the hot-rolled Fe–Cr–Al–REM stainless steel sheet was evidently increased as the recrystallized grain size increased.

The effect of heat treatment on recrystallized microstructure, precipitation and ductility of hot-rolled Fe-Cr-Al-REM ferritic stainless steel sheets

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