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Hector Jantos - One of the best experts on this subject based on the ideXlab platform.
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effects of the 5 ht1a receptor ligands flesinoxan and way 100635 given systemically or microinjected into the Laterodorsal Tegmental Nucleus on rem sleep in the rat
Behavioural Brain Research, 2004Co-Authors: Jaime M Monti, Hector JantosAbstract:Abstract The effects of flesinoxan, a selective 5-HT1A receptor agonist, and of WAY 100635, a selective high affinity 5-HT1A receptor antagonist, on spontaneous sleep were studied in adult rats implanted for chronic sleep recordings. Systemic administration of flesinoxan (0.03 and/or 0.06 μmol/kg, s.c.) increased waking (W) and sleep latencies and reduced REM sleep (REMS) and the number of REM periods during the first and/or second 2-h period after treatment. Systemic injection of WAY 100635 (0.46 and/or 0.92 μmol/kg, s.c.) augmented W and REMS latency and reduced REMS and the number of REM periods during the 6-h recording period. Microinjection of flesinoxan (0.03, 0.06 and/or 0.12 nmol) into the Laterodorsal Tegmental Nucleus (LDT) reduced REMS and the number of REM periods, and augmented REMS latency during the first, second, and/or third 2-h recording period. Direct infusion of WAY 100635 (0.06 and/or 0.12 nmol) into the LDT increased REMS and the number of REM periods during the first and/or second 2 h of recording. It is proposed that the activation by flesinoxan of postsynaptic 5-HT1A receptors located in the LDT could be responsible for the REMS suppression. The increase in REMS after the blockade of postsynaptic 5-HT1A receptors in the LDT by WAY 100635 further supports our proposal. The effects of systemic flesinoxan on sleep variables may depend mainly on the activation of postsynaptic 5-HT1A receptors, whereas the effects corresponding to systemic WAY 100635 may be predominantly related to the blockade of presynaptic somatodendritic 5-HT1A autoreceptors.
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differential effects of the 5 ht1a receptor agonist flesinoxan given locally or systemically on rem sleep in the rat
European Journal of Pharmacology, 2003Co-Authors: Jaime M Monti, Hector JantosAbstract:The effects of flesinoxan, a selective 5-HT1A receptor agonist on spontaneous sleep, were studied in adult rats implanted for chronic sleep recordings. Flesinoxan was administered systemically or infused directly into the dorsal raphe Nucleus, the left Laterodorsal Tegmental Nucleus or the medial pontine reticular formation. Systemic administration of flesinoxan (0.03 and/or 0.06 micromol/kg) significantly increased wakefulness and sleep latencies, and reduced rapid eye movement (REM) sleep and the number of REM periods, during the first and/or second 2-h period after treatment. Direct infusion of the 5-HT1A receptor agonist (0.06 and/or 0.12 nmol) into the dorsal raphe Nucleus induced a significant increment of REM sleep and augmented the number of REM periods during the second and/or third 2-h period of recording. Microinjection of flesinoxan (0.03, 0.06 and/or 0.12 nmol) into the Laterodorsal Tegmental Nucleus reduced REM sleep and the number of REM periods, and augmented REM sleep latency during the first, second and/or third 2-h recording period. Finally, direct infusion of flesinoxan (0.48 nmol) into the medial pontine reticular formation decreased REM sleep and the number of REM periods, and increased REM sleep latency during the first and second 2 h of recording. Our results indicate that the 5-HT1A receptor is involved in the inhibitory effect of serotonin on brainstem structures that act to promote and to induce REM sleep.
Katsuyuki Kaneda - One of the best experts on this subject based on the ideXlab platform.
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chronic cocaine exposure induces noradrenergic modulation of inhibitory synaptic transmission to cholinergic neurons of the Laterodorsal Tegmental Nucleus
European Journal of Neuroscience, 2016Co-Authors: Naofumi Taoka, Masabumi Minami, Katsuyuki Kaneda, Ryota Kamiizawa, Shintaro WadaAbstract:The Laterodorsal Tegmental Nucleus (LDT), which sends cholinergic efferent connections to dopaminergic (DA) neurons in the ventral Tegmental area (VTA), plays a critical role in the development of addictive behavior and the reinstatement of cocaine-seeking behavior. Although repeated cocaine exposure elicits plastic changes in excitatory synaptic transmission and intrinsic membrane excitability in LDT cholinergic neurons, it remains unclear whether inhibitory synaptic transmission is modulated by cocaine exposure. The LDT receives fibers containing noradrenaline (NA), a neurotransmitter whose extracellular levels increase with cocaine exposure. Therefore, it is hypothesized that repeated cocaine exposure induces plastic changes in LDT cholinergic neurons via NA. Ex vivo electrophysiological recordings in LDT cholinergic neurons were obtained from rats repeatedly exposed to cocaine. Bath-application of NA induced similar levels of hyperpolarization in both saline- and cocaine-treated neurons. However, NA attenuated the amplitude of inhibitory postsynaptic currents (IPSCs) in cocaine- but not saline-treated neurons through α2 adrenoceptors. This NA-induced IPSC attenuation was observed in the presence of strychnine, but not gabazine, indicating that NA modulated GABAergic but not glycinergic neurotransmission. NA increased the paired-pulse ratios of evoked IPSCs and decreased the frequencies of miniature IPSCs (mIPSCs) without affecting their amplitudes, suggesting a presynaptic mechanism. These findings suggest that repeated cocaine exposure induces neuroplasticity in GABAergic synaptic transmission onto LDT cholinergic neurons by probably modulating presynaptic α2 adrenoceptors. This potentially increases the activity of LDT cholinergic neurons, which might contribute to the development of addictive behavior by enhancing VTA DA neuronal activity.
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intrinsic membrane plasticity via increased persistent sodium conductance of cholinergic neurons in the rat Laterodorsal Tegmental Nucleus contributes to cocaine induced addictive behavior
European Journal of Neuroscience, 2015Co-Authors: Hironori Kamii, Fumiya Shinohara, Masabumi Minami, Ryo Kurosawa, Naofumi Taoka, Katsuyuki KanedaAbstract:: The Laterodorsal Tegmental Nucleus (LDT) is a brainstem Nucleus implicated in reward processing and is one of the main sources of cholinergic afferents to the ventral Tegmental area (VTA). Neuroplasticity in this structure may affect the excitability of VTA dopamine neurons and mesocorticolimbic circuitry. Here, we provide evidence that cocaine-induced intrinsic membrane plasticity in LDT cholinergic neurons is involved in addictive behaviors. After repeated experimenter-delivered cocaine exposure, ex vivo whole-cell recordings obtained from LDT cholinergic neurons revealed an induction of intrinsic membrane plasticity in regular- but not burst-type neurons, resulting in increased firing activity. Pharmacological examinations showed that increased riluzole-sensitive persistent sodium currents, but not changes in Ca(2+) -activated BK, SK or voltage-dependent A-type potassium conductance, mediated this plasticity. In addition, bilateral microinjection of riluzole into the LDT immediately before the test session in a cocaine-induced conditioned place preference (CPP) paradigm inhibited the expression of cocaine-induced CPP. These findings suggest that intrinsic membrane plasticity in LDT cholinergic neurons is causally involved in the development of cocaine-induced addictive behaviors.
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critical role of cholinergic transmission from the Laterodorsal Tegmental Nucleus to the ventral Tegmental area in cocaine induced place preference
Neuropharmacology, 2014Co-Authors: Fumiya Shinohara, Yukari Kihara, Soichiro Ide, Masabumi Minami, Katsuyuki KanedaAbstract:Conditioned place preference (CPP) is widely used to investigate the rewarding properties of cocaine. Various brain regions and neurotransmitters are involved in developing cocaine CPP. However, the contribution of cholinergic transmission in the ventral Tegmental area (VTA) to cocaine CPP remains largely unexplored. Here, we examined the role of cholinergic input arising from the Laterodorsal Tegmental Nucleus (LDT) to the VTA in the acquisition and expression of cocaine CPP in rats. Intra-LDT injection of carbachol, which hyperpolarizes LDT neurons, and of NMDA and AMPA receptor antagonists before cocaine conditioning blocked and attenuated cocaine CPP, respectively, indicating the necessity of LDT activity for acquiring the CPP. Additionally, intra-VTA injection of scopolamine or mecamylamine before cocaine conditioning also attenuated cocaine CPP, demonstrating the contribution of cholinergic transmission via muscarinic and nicotinic acetylcholine receptors in CPP acquisition. Furthermore, intra-VTA injection of scopolamine or mecamylamine immediately before the test attenuated cocaine CPP, indicating that cholinergic signaling is also associated with the expression of CPP. These results suggest that cholinergic transmission from the LDT to the VTA is critically involved in both acquiring and retrieving cocaine-associated memories in cocaine CPP.
Robert W. Mccarley - One of the best experts on this subject based on the ideXlab platform.
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role of adenosine in behavioral state modulation a microdialysis study in the freely moving cat
Neuroscience, 1997Co-Authors: C M Portas, Mahesh M Thakkar, Donald G Rainnie, Robert W Greene, Robert W. MccarleyAbstract:Abstract There is considerable evidence to suggest that the activity of forebrain and mesopontine cholinergic neurons is intimately involved in electroencephalographic arousal. Furthermore, our previous in vitro investigation suggested that both cholinergic systems are under a powerful tonic inhibitory control by endogenous adenosine. We thus examined the in vivo effect, on electrographically defined behavioral states, of microdialysis perfusion of adenosine into the cholinergic zones of the substantia innominata of the basal forebrain and the Laterodorsal Tegmental Nucleus of freely moving cats. Localized perfusion of adenosine into either the basal forebrain or the Laterodorsal Tegmental Nucleus caused a marked alteration in sleep–wake architecture. Adenosine (300 μ M) perfused into either the basal forebrain or Laterodorsal Tegmental Nucleus produced a dramatic decrease in waking, to about 50% of the basal level. Perfusion into the basal forebrain resulted in a significant increase in rapid eye movement sleep, while slow wave sleep was unchanged. In contrast, adenosine perfusion into the Laterodorsal Tegmental Nucleus produced an increase of both slow wave sleep and rapid eye movement sleep, the magnitude of which were proportional to the decrease in waking. Electroencephalographic power spectral analysis showed that adenosine perfusion into the basal forebrain increased the relative power in the delta frequency band, whereas higher frequency bands (theta, alpha, beta and gamma) showed a decrease. These data strongly support the hypothesis that adenosine might play a key role as an endogenous modulator of wakefulness and sleep. The decrease in wakefulness may be directly related to the inhibition of cholinergic neurons of the basal forebrain and the Laterodorsal tegmentum. The increase in rapid eye movement sleep is a novel but robust effect whose origin, at present, is uncertain. The observation that local perfusion of adenosine into either the basal forebrain or the Laterodorsal Tegmental Nucleus dramatically decreases wakefulness suggests that these areas might represent a major site of action of the xanthine stimulants (adenosine antagonists) found in coffee and tea.
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Electrical stimulation of the cholinergic Laterodorsal Tegmental Nucleus elicits scopolamine-sensitive excitatory postsynaptic potentials in medial pontine reticular formation neurons
Neuroscience, 1996Co-Authors: H. Imon, Keihachiro Ito, L. Dauphin, Robert W. MccarleyAbstract:Abstract A large and consistent body of data implicates mesopontine cholinergic neurons in the production of rapid eye movement sleep, and indicates that many rapid eye movement sleep events are mediated by activation of pontine reticular formation neurons. There is anatomical evidence for projections from the mesopontine cholinergic nuclei to the pontine reticular formation, but no study has shown that stimulation of this cholinergic zone produces excitatory postsynaptic potentials in pontine reticular formation neurons. In the present study, intracellular recordings were made from 168 pontine reticular formation neurons, identified by antidromic activation from the bulbar reticular formation and by neurobiotin intracellular labeling, in acutely anesthetized cats. The effects of single-pulse electrical stimulation of the laterordorsal Tegmental Nucleus portion of the ipsilateral mesopontine cholinergic zone were evaluated in these neurons. Under urethane anesthesia this stimulation produced, in 21 of 22 recorded neurons, long-latency excitatory postsynaptic potentials (mean = 3 ms), consistent with the conduction velocity of unmyelinated cholinergic fibers (measured conduction velocity was 2 m/s). This excitatory postsynaptic potential was virtually abolished by intravenous administration of the muscarinic cholinergic receptor blocker scopolamine ( n = 40 neurons), and by acute cuts separating the Laterodorsal Tegmental Nucleus and the recorded neurons ( n = 40). In contrast, a short-latency excitatory postsynaptic potential (0.7–1.5 ms) was not reduced in amplitude by scopolamine and could still be elicited following acute transverse cuts. Unlike the longer-latency excitatory postsynaptic potential, its amplitude was not reduced by barbiturate anesthesia. These data, suggesting the presence of an excitatory, cholinergic Laterodorsal Tegmental Nucleus projection to the pontine reticular formation, provide further support to other lines of evidence implicating mesopontine cholinergic neurons in the production of rapid eye movement sleep, and are compatible with a model of rapid eye movement sleep generation in which a key element is mesopontine cholinergic input depolarizing and increasing the excitability of reticular core neurons.
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Serotonin hyperpolarizes cholinergic low-threshold burst neurons in the rat Laterodorsal Tegmental Nucleus in vitro.
Proceedings of the National Academy of Sciences of the United States of America, 1992Co-Authors: Jennifer I. Luebke, Robert W. Mccarley, Robert W Greene, K Semba, A. Kamondi, Peter B ReinerAbstract:Serotonergic suppression of cholinergic neuronal activity implicated in the regulation of rapid eye movement sleep and its associated phenomenon, pontogeniculooccipital waves, has long been postulated, but no direct proof has been available. In this study, intracellular and whole-cell patch-clamp recording techniques were combined with enzyme histochemistry to examine the intrinsic electrophysiological properties and response to serotonin (5-HT) of identified cholinergic rat Laterodorsal Tegmental Nucleus neurons in vitro. Sixty-five percent of the recorded neurons demonstrated a prominent low-threshold burst, and of these, 83% were cholinergic. In current-clamp recordings 64% of the bursting cholinergic neurons tested responded to the application of 5-HT with a membrane hyperpolarization and decrease in input resistance. This effect was mimicked by application of the selective 5-HT type 1 receptor agonist carboxamidotryptamine maleate. Whole-cell patch-clamp recordings revealed that the hyperpolarizing response was mediated by an inwardly rectifying K+ current. Application of 5-HT decreased excitability and markedly modulated the discharge pattern of cholinergic bursting neurons: during a 5-HT-induced hyperpolarization these neurons exhibited no rebound burst after hyperpolarizing current input and a burst in response to depolarizing current input. In the absence of 5-HT, the relatively depolarized cholinergic bursting neurons responded to an identical hyperpolarizing current input with a burst and did not produce a burst after depolarizing current input. These data provide a cellular and molecular basis for the hypothesis that 5-HT modulates rapid eye movement sleep phenomenology by altering the firing pattern of bursting cholinergic neurons.
Kazue Semba - One of the best experts on this subject based on the ideXlab platform.
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discriminable excitotoxic effects of ibotenic acid ampa nmda and quinolinic acid in the rat Laterodorsal Tegmental Nucleus
Brain Research, 1997Co-Authors: Wendy L Inglis, Kazue SembaAbstract:Abstract Excitotoxins are valuable tools in neuroscience research as they can help us to discover the extent to which certain neurones are necessary for different types of behaviour. They have distinctive neurotoxic effects depending on where they are infused, and this study was conducted to delineate the neurotoxic profiles of excitotoxins in the Laterodorsal Tegmental Nucleus (LDTg). Two 0.1 ml infusions of 0.1 M ibotenate, 0.1 M quinolinate, 0.04–0.1 M NMDA, or 0.05–0.015 M AMPA, were made unilaterally into the LDTg under either pentobarbitone or Avertin anaesthesia. The injection needle was oriented at an angle of 24° from vertical in the mediolateral plane. After 23–27 days, sections through the mesopontine tegmentum were processed using standard histological procedures for NADPH-diaphorase histochemistry, tyrosine hydroxylase or 5-hydroxytryptamine immunohistochemistry, and Cresyl violet. Lesions were assessed in terms of the size of the damaged area (identified by reactive gliosis), the extent of cholinergic cell loss in the mesopontine tegmentum (by counting NADPH-diaphorase-positive neurones), and neuronal loss induced in the locus coeruleus and dorsal raphe Nucleus. Ibotenate induced compact lesions in the LDTg (more than 80% cholinergic loss) and did little damage to the locus coeruleus and dorsal raphe Nucleus. Quinolinate and low doses of AMPA and NMDA made very small lesions with less than 35% cholinergic loss, while at higher doses, AMPA and NMDA induced large areas of reactive gliosis but killed only a proportion of the cholinergic neurones. AMPA appeared to have a particular affinity for noradrenergic neurones in the locus coeruleus, with the 0.015 M dose injected into the LDTg typically destroying the majority of these neurones. The results are discussed in the context of what is known about the mechanisms of excitotoxins and the glutamate receptor profile of mesopontine neurones.
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Serotonergic synaptic input to cholinergic neurons in the rat mesopontine tegmentum
Brain research, 1994Co-Authors: Takashi Honda, Kazue SembaAbstract:Serotonergic synaptic inputs to cholinergic neurons in the Laterodorsal and pedunculopontine Tegmental nuclei were examined with pre-embedding dual-label immunoelectron microscopy. Numerous serotonin-immunoreactive axon terminals visualized with a silver-enhanced immunogold method were present in both of these Tegmental nuclei. Serotonergic terminals occasionally made synaptic contacts with the soma and proximal dendrites of cholinergic Tegmental neurons labelled with a choline acetyltransferase-immunoreactive peroxidase-anti-peroxidase diaminobenzidine reaction product. In the rostralmost region of the Laterodorsal Tegmental Nucleus, a few serotonergic neurons of the dorsal raphe Nucleus were interspersed among cholinergic neurons. Some dendrites of these serotonergic neurons appeared to contain synaptic vesicles. Both myelinated and unmyelinated serotonergic axons were present in the mesopontine tegmentum. The presence of serotonergic synapses onto Tegmental cholinergic neurons is consistent with previous behavioral and electrophysiological findings suggesting an inhibitory role of serotonin in the induction of rapid eye movement sleep and its phenomenology through an action on cholinergic neurons in the mesopontine tegmentum.
Jaime M Monti - One of the best experts on this subject based on the ideXlab platform.
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effects of the 5 ht1a receptor ligands flesinoxan and way 100635 given systemically or microinjected into the Laterodorsal Tegmental Nucleus on rem sleep in the rat
Behavioural Brain Research, 2004Co-Authors: Jaime M Monti, Hector JantosAbstract:Abstract The effects of flesinoxan, a selective 5-HT1A receptor agonist, and of WAY 100635, a selective high affinity 5-HT1A receptor antagonist, on spontaneous sleep were studied in adult rats implanted for chronic sleep recordings. Systemic administration of flesinoxan (0.03 and/or 0.06 μmol/kg, s.c.) increased waking (W) and sleep latencies and reduced REM sleep (REMS) and the number of REM periods during the first and/or second 2-h period after treatment. Systemic injection of WAY 100635 (0.46 and/or 0.92 μmol/kg, s.c.) augmented W and REMS latency and reduced REMS and the number of REM periods during the 6-h recording period. Microinjection of flesinoxan (0.03, 0.06 and/or 0.12 nmol) into the Laterodorsal Tegmental Nucleus (LDT) reduced REMS and the number of REM periods, and augmented REMS latency during the first, second, and/or third 2-h recording period. Direct infusion of WAY 100635 (0.06 and/or 0.12 nmol) into the LDT increased REMS and the number of REM periods during the first and/or second 2 h of recording. It is proposed that the activation by flesinoxan of postsynaptic 5-HT1A receptors located in the LDT could be responsible for the REMS suppression. The increase in REMS after the blockade of postsynaptic 5-HT1A receptors in the LDT by WAY 100635 further supports our proposal. The effects of systemic flesinoxan on sleep variables may depend mainly on the activation of postsynaptic 5-HT1A receptors, whereas the effects corresponding to systemic WAY 100635 may be predominantly related to the blockade of presynaptic somatodendritic 5-HT1A autoreceptors.
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differential effects of the 5 ht1a receptor agonist flesinoxan given locally or systemically on rem sleep in the rat
European Journal of Pharmacology, 2003Co-Authors: Jaime M Monti, Hector JantosAbstract:The effects of flesinoxan, a selective 5-HT1A receptor agonist on spontaneous sleep, were studied in adult rats implanted for chronic sleep recordings. Flesinoxan was administered systemically or infused directly into the dorsal raphe Nucleus, the left Laterodorsal Tegmental Nucleus or the medial pontine reticular formation. Systemic administration of flesinoxan (0.03 and/or 0.06 micromol/kg) significantly increased wakefulness and sleep latencies, and reduced rapid eye movement (REM) sleep and the number of REM periods, during the first and/or second 2-h period after treatment. Direct infusion of the 5-HT1A receptor agonist (0.06 and/or 0.12 nmol) into the dorsal raphe Nucleus induced a significant increment of REM sleep and augmented the number of REM periods during the second and/or third 2-h period of recording. Microinjection of flesinoxan (0.03, 0.06 and/or 0.12 nmol) into the Laterodorsal Tegmental Nucleus reduced REM sleep and the number of REM periods, and augmented REM sleep latency during the first, second and/or third 2-h recording period. Finally, direct infusion of flesinoxan (0.48 nmol) into the medial pontine reticular formation decreased REM sleep and the number of REM periods, and increased REM sleep latency during the first and second 2 h of recording. Our results indicate that the 5-HT1A receptor is involved in the inhibitory effect of serotonin on brainstem structures that act to promote and to induce REM sleep.
