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Kazue Semba - One of the best experts on this subject based on the ideXlab platform.
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substance p in the descending cholinergic projection to rem Sleep Induction regions of the rat pontine reticular formation anatomical and electrophysiological analyses
European Journal of Neuroscience, 2002Co-Authors: Kristi A Kohlmeier, Joan Burns, Peter B Reiner, Kazue SembaAbstract:Release of acetylcholine within the pontine reticular formation (PRF) from the axon terminals of mesopontine cholinergic neurons has long been hypothesized to play an important role in rapid eye movement (REM) Sleep generation. As some of these cholinergic neurons are known to contain substance P (SP), we used anatomical, electrophysiological and pharmacological techniques to characterize this projection in the rat. Double immunofluorescence demonstrated that 16% of all cholinergic neurons within the mesopontine tegmentum contained SP; this percentage increased to 27% in its caudal regions. When double immunofluorescence was combined with retrograde tracing techniques, it was observed that up to 11% of all SP-containing cholinergic neurons project to the PRF. Whole-cell patch-clamp recordings from in vitro brainstem slices revealed that SP administration depolarized or evoked an inward current in a dose-dependent manner in all PRF neurons examined, and that these effects were antagonized by a SP antagonist. The amplitude of the SP-induced inward current varied with changes in the Na + concentration, did not reverse at the calculated K + or Cl - equilibrium potentials, and was not attenuated in the presence of tetrodotoxin, low Ca 2 + concentration or caesium ions. These data suggest that activation of a tetrodotoxin-insensitive cation channel(s) permeable to Na + is responsible for a SP-induced inward current at resting membrane potentials. The depolarizing actions of SP appeared to be primarily due to activation of the adenylate cyclase pathway, and were additive with cholinergic receptor activation even at maximal concentrations. These data indicate that SP is colocalized in a subpopulation of mesopontine tegmental cholinergic neurons projecting to REM Sleep-Induction regions of the PRF, and that actions of these two neuroactive substances on PRF neurons are additive. If SP is coreleased with acetylcholine, the additive actions of the two neurotransmitters might heighten the excitability of postsynaptic PRF neurons and ensure the initiation and maintenance of REM Sleep.
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aminergic and cholinergic afferents to rem Sleep Induction regions of the pontine reticular formation in the rat
The Journal of Comparative Neurology, 1993Co-Authors: Kazue SembaAbstract:Microinjection of cholinergic agonists in a dorsolateral part of the mesopontine tegmentum has been shown to induce a rapid eye movement (REM) Sleep-like state. Physiological evidence indicates that not only acetylcholine but also various amine transmitters, including those implicated in behavioral state regulation, affect neuronal activity in this region of the pontine reticular formation. In the present study, sources of select aminergic and cholinergic inputs to this REM Sleep Induction zone were identified and quantitatively analyzed by using fluorescence retrograde tracing combined with immunofluorescence in the rat. In addition to previously demonstrated cholinergic projections from the pedunculopontine and laterodorsal tegmental nuclei, the REM Sleep Induction zone received various aminergic inputs that originated in widely distributed regions of the brainstem and hypothalamus. Serotoninergic afferents represented a mean of 44% of all aminergic/cholinergic source neurons projecting to the REM Sleep Induction zone, which was comparable to the mean percentage of 39% represented by cholinergic afferent neurons. The serotoninergic afferents originated from the raphe nuclei at all brainstem levels, with heavier projections from the pontine than from the medullary raphe nuclei. Unexpectedly, an additional major serotoninergic input was provided by serotoninergic neurons in the nucleus prosupralemniscus (B9). Noradrenergic afferent neurons represented a mean of 14% of all aminergic/cholinergic source neurons, which was only about one-third of the mean percentage of either cholinergic or serotoninergic source neurons. These noradrenergic projection neurons were located not only in the locus ceruleus (8%) but also in the lateral tegmentum, including the A5 (4%) and A7 (2%) cell groups. Histaminergic neurons in the tuberomammillary hypothalamic nucleus represented a minor group of afferent neurons (3%), and a still smaller input came from adrenegic C1 neurons. The pattern of these transmitter-specific afferent connections appeared to be similar regardless of the longitudinal level within the REM Sleep Induction zone. The present results are consistent with previous behavioral and physiological evidence for a role of the pontine REM Sleep Induction zone in triggering REM Sleep. The regulation of REM Sleep Induction would be best understood in terms of a state-dependent interplay of cholinergic, serotoninergic, and other inputs all acting convergently upon neurons in the REM Sleep-inducing region of the pontine reticular formation.
Fernando Reinososuarez - One of the best experts on this subject based on the ideXlab platform.
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gabaergic mechanisms in the ventral oral pontine tegmentum the rem Sleep Induction site in the modulation of Sleep wake states
2010Co-Authors: Fernando Reinososuarez, Margarita L Rodrigoangulo, Isabel De Andrés, Carmen De La Roza, Angel Nunez, Miguel GarzonAbstract:The ventral part of the oral pontine reticular nucleus (vRPO) is a nodal link in the neuronal network responsible for the generation and maintenance of rapid eye movement (REM) Sleep and is reciprocally connected with structures involved in the control of wakefulness and non-REM (NREM) Sleep. Shifting from one Sleep state to another depends on the balance between excitation and inhibition in the reciprocal connections between these structures. Gamma-aminobutyric acid (GABA) occupies an outstanding place in these processes. In this review, we report the important role of GABA in vRPO function, specifying and discussing its location, origin, and role in this nucleus. Results from our laboratory revealed a few small GABA-immunoreactive cell bodies in vRPO; but we estimated that 30% of all vRPO synaptic terminals are actually immunoreactive to GABA. These inhibitory GABAergic terminals directly target somata and the different segments of the vRPO dendritic tree neurons. GABAergic terminals innervate serotonergic, GABAergic, and no-immunoreactive dendrites and terminals in the vRPO. Functionally, GABA elicits long-lasting hyperpolarizations of vRPO neurons in intracellular recording experiments in vitro. Small-volume microinjections of the GABAA receptor agonist muscimol in vRPO produce a statistically significant decrease of REM Sleep proportions in freely moving cats. GABAergic axon terminals mainly originate in neurons located in diencephalic structures related with NREM Sleep (such as the reticular thalamic nucleus) and wakefulness (such as the lateralposterior hypothalamus). These terminals would inhibit the vRPO REM “on” neurons either directly through postsynaptic mechanisms and/or indirectly through presynaptic inhibition of the excitatory terminals that form synapses with these neurons. Non-GABAergic and nonserotonergic terminals making asymmetric synapses (putatively excitatory) would indirectly inhibit REM “on” neurons through excitation of both serotonergic and GABAergic neurons, and terminals in the vRPO. Inhibition of GABAergic transmission in the vRPO contributes to the generation and maintenance of REM Sleep.
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a quantitative study of the brainstem cholinergic projections to the ventral part of the oral pontine reticular nucleus rem Sleep Induction site in the cat
Experimental Brain Research, 2005Co-Authors: Margarita L Rodrigoangulo, Elisia Rodriguezveiga, Fernando ReinososuarezAbstract:The ventral part of the cat oral pontine reticular nucleus (vRPO) is the site in which microinjections of small dose and volume of cholinergic agonists produce long-lasting rapid eye movement Sleep with short latency. The present study determined the precise location and proportions of the cholinergic brainstem neuronal population that projects to the vRPO using a double-labeling method that combines the neuronal tracer horseradish peroxidase–wheat germ agglutinin with choline acetyltransferase immunocytochemistry in cats. Our results show that 88.9% of the double-labeled neurons in the brainstem were located, noticeably bilaterally, in the cholinergic structures of the pontine tegmentum. These neurons occupied not only the pedunculopontine and laterodorsal tegmental nuclei, which have been described to project to other pontine tegmentum structures, but also the locus ceruleus complex principally the locus ceruleus α and peri-α, and the parabrachial nuclei. Most double-labeled neurons were found in the pedunculopontine tegmental nucleus and locus ceruleus complex and, much less abundantly, in the laterodorsal tegmental nucleus and the parabrachial nuclei. The proportions of these neurons among all choline acetyltransferase positive neurons within each structure were highest in the locus ceruleus complex, followed in descending order by the pedunculopontine and laterodorsal tegmental nuclei and then, the parabrachial nuclei. The remaining 11.1% of double-labeled neurons were found bilaterally in other cholinergic brainstem structures: around the oculomotor, facial and masticatory nuclei, the caudal pontine tegmentum and the praepositus hypoglossi nucleus. The disperse origins of the cholinergic neurons projecting to the vRPO, in addition to the abundant noncholinergic afferents to this nucleus may indicate that cholinergic stimulation is not the only or even the most decisive event in the generation of REM Sleep.
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location and anatomical connections of a paradoxical Sleep Induction site in the cat ventral pontine tegmentum
European Journal of Neuroscience, 1994Co-Authors: Fernando Reinososuarez, Margarita L Rodrigoangulo, Isabel De Andrés, Elisia RodriguezveigaAbstract:: The brainstem mechanisms for the generation of paradoxical Sleep are under considerable debate. Previous experiments in cats have demonstrated that injections of the cholinergic agonist carbachol into the oral pontine tegmentum elicit paradoxical Sleep behaviour and its polygraphic correlates. The different results on the pontine structures that mediate this effect do not agree. We report here that limited microinjections of a carbachol solution into the ventral part of the oral pontine reticular nucleus in the cat induce, with a short latency, a dramatic, long-lasting increase in paradoxical Sleep. Moreover, neuronal tracing experiments show that this pontine site is connected with brain structures responsible for the different bioelectric events of paradoxical Sleep. These two facts suggest that the ventral part of the oral pontine reticular nucleus is a nodal link in the neuronal network underlying paradoxical Sleep mechanisms.
Samuel G Speciale - One of the best experts on this subject based on the ideXlab platform.
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adenosine a1 receptors mediate inhibition of camp formation in vitro in the pontine rem Sleep Induction zone
Brain Research, 2005Co-Authors: Gerald A. Marks, C G Birabil, Samuel G SpecialeAbstract:Abstract Microinjection of adenosine A1 receptor agonist or an inhibitor of adenylyl cyclase into the caudal, oral pontine reticular formation (PnOc) of the rat induces a long-lasting increase in REM Sleep. Here, we report significant inhibition of forskolin-stimulated cAMP in dissected pontine tissue slices containing the PnOc incubated with the A1 receptor agonist, cyclohexaladenosine (10 −8 M). These data are consistent with adenosine A1 receptor agonist actions on REM Sleep mediated through inhibition of cAMP.
Gerald A. Marks - One of the best experts on this subject based on the ideXlab platform.
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inhibitory and excitatory amino acid neurotransmitters are utilized by the projection from the dorsal deep mesencephalic nucleus to the sublaterodorsal nucleus rem Sleep Induction zone
Brain Research, 2014Co-Authors: Chang Lin Liang, Tin Quang Nguyen, Gerald A. MarksAbstract:The sublaterodorsal nucleus (SLD) in the pons of the rat is a locus supporting short-latency Induction of a REM Sleep-like state following local application of a GABAA receptor antagonist or kainate, glutamate receptor agonist. One putatively relevant source of these neurotransmitters is from the region of the deep mesencephalic nucleus (DpMe) just ventrolateral to the periaquiductal gray, termed the dorsal DpMe (dDpMe). Here, the amino acid neurotransmitter innervation of SLD from dDpMe was studied utilizing anterograde tract-tracing with biotinylated dextranamine (BDA) and fluorescence immunohistochemistry visualized with laser scanning confocal microscopy. Both markers for inhibitory and excitatory amino acid neurotransmitters were found in varicose axon fibers in SLD originating from dDpMe. Vesicular glutamate transporter2 (VGLUT2) represented the largest number of anterogradely labeled varicosities followed by vesicular GABA transporter (VGAT). Numerous VGAT and VGLUT2 labeled varicosities were observed apposed to dDpMe-labeled axon fibers indicating both excitatory and inhibitory presynaptic, local modulation within the SLD. Some double-labeled BDA/VGAT varicosities were seen apposed to small somata labeled for glutamate consistent with being presynaptic to the phenotype of REM Sleep-active SLD neurons. Results found support the current theoretical framework of the interaction of dDpMe and SLD in control of REM Sleep, while also indicating operation of mechanisms with a greater level of complexity.
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adenosine a1 receptors mediate inhibition of camp formation in vitro in the pontine rem Sleep Induction zone
Brain Research, 2005Co-Authors: Gerald A. Marks, C G Birabil, Samuel G SpecialeAbstract:Abstract Microinjection of adenosine A1 receptor agonist or an inhibitor of adenylyl cyclase into the caudal, oral pontine reticular formation (PnOc) of the rat induces a long-lasting increase in REM Sleep. Here, we report significant inhibition of forskolin-stimulated cAMP in dissected pontine tissue slices containing the PnOc incubated with the A1 receptor agonist, cyclohexaladenosine (10 −8 M). These data are consistent with adenosine A1 receptor agonist actions on REM Sleep mediated through inhibition of cAMP.
Margarita L Rodrigoangulo - One of the best experts on this subject based on the ideXlab platform.
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gabaergic mechanisms in the ventral oral pontine tegmentum the rem Sleep Induction site in the modulation of Sleep wake states
2010Co-Authors: Fernando Reinososuarez, Margarita L Rodrigoangulo, Isabel De Andrés, Carmen De La Roza, Angel Nunez, Miguel GarzonAbstract:The ventral part of the oral pontine reticular nucleus (vRPO) is a nodal link in the neuronal network responsible for the generation and maintenance of rapid eye movement (REM) Sleep and is reciprocally connected with structures involved in the control of wakefulness and non-REM (NREM) Sleep. Shifting from one Sleep state to another depends on the balance between excitation and inhibition in the reciprocal connections between these structures. Gamma-aminobutyric acid (GABA) occupies an outstanding place in these processes. In this review, we report the important role of GABA in vRPO function, specifying and discussing its location, origin, and role in this nucleus. Results from our laboratory revealed a few small GABA-immunoreactive cell bodies in vRPO; but we estimated that 30% of all vRPO synaptic terminals are actually immunoreactive to GABA. These inhibitory GABAergic terminals directly target somata and the different segments of the vRPO dendritic tree neurons. GABAergic terminals innervate serotonergic, GABAergic, and no-immunoreactive dendrites and terminals in the vRPO. Functionally, GABA elicits long-lasting hyperpolarizations of vRPO neurons in intracellular recording experiments in vitro. Small-volume microinjections of the GABAA receptor agonist muscimol in vRPO produce a statistically significant decrease of REM Sleep proportions in freely moving cats. GABAergic axon terminals mainly originate in neurons located in diencephalic structures related with NREM Sleep (such as the reticular thalamic nucleus) and wakefulness (such as the lateralposterior hypothalamus). These terminals would inhibit the vRPO REM “on” neurons either directly through postsynaptic mechanisms and/or indirectly through presynaptic inhibition of the excitatory terminals that form synapses with these neurons. Non-GABAergic and nonserotonergic terminals making asymmetric synapses (putatively excitatory) would indirectly inhibit REM “on” neurons through excitation of both serotonergic and GABAergic neurons, and terminals in the vRPO. Inhibition of GABAergic transmission in the vRPO contributes to the generation and maintenance of REM Sleep.
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a quantitative study of the brainstem cholinergic projections to the ventral part of the oral pontine reticular nucleus rem Sleep Induction site in the cat
Experimental Brain Research, 2005Co-Authors: Margarita L Rodrigoangulo, Elisia Rodriguezveiga, Fernando ReinososuarezAbstract:The ventral part of the cat oral pontine reticular nucleus (vRPO) is the site in which microinjections of small dose and volume of cholinergic agonists produce long-lasting rapid eye movement Sleep with short latency. The present study determined the precise location and proportions of the cholinergic brainstem neuronal population that projects to the vRPO using a double-labeling method that combines the neuronal tracer horseradish peroxidase–wheat germ agglutinin with choline acetyltransferase immunocytochemistry in cats. Our results show that 88.9% of the double-labeled neurons in the brainstem were located, noticeably bilaterally, in the cholinergic structures of the pontine tegmentum. These neurons occupied not only the pedunculopontine and laterodorsal tegmental nuclei, which have been described to project to other pontine tegmentum structures, but also the locus ceruleus complex principally the locus ceruleus α and peri-α, and the parabrachial nuclei. Most double-labeled neurons were found in the pedunculopontine tegmental nucleus and locus ceruleus complex and, much less abundantly, in the laterodorsal tegmental nucleus and the parabrachial nuclei. The proportions of these neurons among all choline acetyltransferase positive neurons within each structure were highest in the locus ceruleus complex, followed in descending order by the pedunculopontine and laterodorsal tegmental nuclei and then, the parabrachial nuclei. The remaining 11.1% of double-labeled neurons were found bilaterally in other cholinergic brainstem structures: around the oculomotor, facial and masticatory nuclei, the caudal pontine tegmentum and the praepositus hypoglossi nucleus. The disperse origins of the cholinergic neurons projecting to the vRPO, in addition to the abundant noncholinergic afferents to this nucleus may indicate that cholinergic stimulation is not the only or even the most decisive event in the generation of REM Sleep.
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location and anatomical connections of a paradoxical Sleep Induction site in the cat ventral pontine tegmentum
European Journal of Neuroscience, 1994Co-Authors: Fernando Reinososuarez, Margarita L Rodrigoangulo, Isabel De Andrés, Elisia RodriguezveigaAbstract:: The brainstem mechanisms for the generation of paradoxical Sleep are under considerable debate. Previous experiments in cats have demonstrated that injections of the cholinergic agonist carbachol into the oral pontine tegmentum elicit paradoxical Sleep behaviour and its polygraphic correlates. The different results on the pontine structures that mediate this effect do not agree. We report here that limited microinjections of a carbachol solution into the ventral part of the oral pontine reticular nucleus in the cat induce, with a short latency, a dramatic, long-lasting increase in paradoxical Sleep. Moreover, neuronal tracing experiments show that this pontine site is connected with brain structures responsible for the different bioelectric events of paradoxical Sleep. These two facts suggest that the ventral part of the oral pontine reticular nucleus is a nodal link in the neuronal network underlying paradoxical Sleep mechanisms.
