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Anja K E Horn - One of the best experts on this subject based on the ideXlab platform.
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the Reticular Formation and the neuromodulatory systems
2020Co-Authors: Anja K E Horn, Hendrik Jan Ten Donkelaar, Veronika Němcova, Sebastiaan OvereemAbstract:Almost a century ago, Constantin von Economo observed that in patients with encephalitis lethargica lesions in the upper brain stem and posterior hypothalamus impaired consciousness. From lesion studies in cats and anatomical data, the idea arose that the brain stem Reticular Formation is the origin of the ascending Reticular activating system (ARAS) that would operate through the intralaminar nuclei and activate widespread regions of the cerebral cortex. This view of the Reticular Formation has been extensively modified, and nowadays the Reticular Formation is viewed as a series of highly specific cell groups, which closely surround the individual motor and sensory nuclei of the brain stem (► Sects. 5.2 and 5.4). The diffuse system, driving arousal and consciousness, is now attributed to the neuromodulatory system, including the serotonergic raphe nuclei, the locus coeruleus and other noradrenergic or adrenergic cell groups and cholinergic cell groups, all close to the Reticular Formation (► Sects. 5.3 and 5.5). The English terms of the Terminologia Neuroanatomica are used throughout.
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a central mesencephalic Reticular Formation projection to the edinger westphal nuclei
Brain Structure & Function, 2016Co-Authors: Susan Warren, Martin O Bohlen, Miriam Barnerssoi, Anja K E HornAbstract:The central mesencephalic Reticular Formation, a region associated with horizontal gaze control, has recently been shown to project to the supraoculomotor area in primates. The Edinger–Westphal nucleus is found within the supraoculomotor area. It has two functionally and anatomically distinct divisions: (1) the preganglionic division, which contains motoneurons that control both the actions of the ciliary muscle, which focuses the lens, and the sphincter pupillae muscle, which constricts the iris, and (2) the centrally projecting division, which contains peptidergic neurons that play a role in food and fluid intake, and in stress responses. In this study, we used neuroanatomical tracers in conjunction with immunohistochemistry in Macaca fascicularis monkeys to examine whether either of these Edinger–Westphal divisions receives synaptic input from the central mesencephalic Reticular Formation. Anterogradely labeled Reticular axons were observed making numerous boutonal associations with the cholinergic, preganglionic motoneurons of the Edinger–Westphal nucleus. These associations were confirmed to be synaptic contacts through the use of confocal and electron microscopic analysis. The latter indicated that these terminals generally contained pleomorphic vesicles and displayed symmetric, synaptic densities. Examination of urocortin-1-positive cells in the same cases revealed fewer examples of unambiguous synaptic relationships, suggesting the centrally projecting Edinger–Westphal nucleus is not the primary target of the projection from the central mesencephalic Reticular Formation. We conclude from these data that the central mesencephalic Reticular Formation must play a here-to-for unexpected role in control of the near triad (vergence, lens accommodation and pupillary constriction), which is used to examine objects in near space.
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A central mesencephalic Reticular Formation projection to the Edinger–Westphal nuclei
Brain Structure & Function, 2015Co-Authors: Susan Warren, Martin O Bohlen, Miriam Barnerssoi, Anja K E HornAbstract:The central mesencephalic Reticular Formation, a region associated with horizontal gaze control, has recently been shown to project to the supraoculomotor area in primates. The Edinger–Westphal nucleus is found within the supraoculomotor area. It has two functionally and anatomically distinct divisions: (1) the preganglionic division, which contains motoneurons that control both the actions of the ciliary muscle, which focuses the lens, and the sphincter pupillae muscle, which constricts the iris, and (2) the centrally projecting division, which contains peptidergic neurons that play a role in food and fluid intake, and in stress responses. In this study, we used neuroanatomical tracers in conjunction with immunohistochemistry in Macaca fascicularis monkeys to examine whether either of these Edinger–Westphal divisions receives synaptic input from the central mesencephalic Reticular Formation. Anterogradely labeled Reticular axons were observed making numerous boutonal associations with the cholinergic, preganglionic motoneurons of the Edinger–Westphal nucleus. These associations were confirmed to be synaptic contacts through the use of confocal and electron microscopic analysis. The latter indicated that these terminals generally contained pleomorphic vesicles and displayed symmetric, synaptic densities. Examination of urocortin-1-positive cells in the same cases revealed fewer examples of unambiguous synaptic relationships, suggesting the centrally projecting Edinger–Westphal nucleus is not the primary target of the projection from the central mesencephalic Reticular Formation. We conclude from these data that the central mesencephalic Reticular Formation must play a here-to-for unexpected role in control of the near triad (vergence, lens accommodation and pupillary constriction), which is used to examine objects in near space.
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Reticular Formation eye movements gaze and blinks
The Human Nervous System (Second Edition), 2012Co-Authors: Anja K E Horn, Christopher AdamczykAbstract:This chapter describes the locations, connections, and histochemistry of functional cell groups in the Reticular Formation that are important for the control of eye, head, and lid movements. Whereas the mescencephalic Reticular Formation is involved in the control of vertical eye and lid movements, the paramedian pontine Reticular Formation is involved in horizontal gaze and the medullary Reticular Formation in head movements, blinks, and gaze holding. A short overview of the cortical areas that control these Reticular cell groups is included.
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the Reticular Formation
Progress in Brain Research, 2006Co-Authors: Anja K E HornAbstract:Abstract The Reticular Formation of the brainstem contains functional cell groups that are important for the control of eye, head, or lid movements. The mesencephalic Reticular Formation is primarily involved in the control of vertical gaze, the paramedian pontine Reticular Formation in horizontal gaze, and the medullary pontine Reticular Formation in head movements and gaze holding. In this chapter, the locations, connections, and histochemical properties of the functional cell groups are reviewed and correlated with specific subdivisions of the Reticular Formation.
Helen A Baghdoyan - One of the best experts on this subject based on the ideXlab platform.
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adenosine a1 receptors in mouse pontine Reticular Formation modulate nociception only in the presence of systemic leptin
Neuroscience, 2014Co-Authors: Sarah L Watson, Helen A Baghdoyan, Chris J Watson, Ralph LydicAbstract:Human obesity is associated with increased leptin levels and pain, but the specific brain regions and neurochemical mechanisms underlying this association remain poorly understood. This study used adult male C57BL/6J (B6, n = 14) mice and leptin-deficient, obese B6.Cg-Lepob/J (obese, n = 10) mice to evaluate the hypothesis that nociception is altered by systemic leptin levels and by adenosine A1 receptors in the pontine Reticular Formation. Nociception was quantified as paw withdrawal latency (PWL) in s after onset of a thermal stimulus. PWL was converted to percent maximum possible effect (%MPE). After obtaining baseline PWL measures, the pontine Reticular Formation was microinjected with saline (control), three concentrations of the adenosine A1 receptor agonist N6-p-sulfophenyladenosine (SPA), or super-active mouse leptin receptor antagonist (SMLA) followed by SPA 15 min later, and PWL was again quantified. In obese, leptin-deficient mice, nociception was quantified before and during leptin replacement via subcutaneous osmotic pumps. SPA was administered into the pontine Reticular Formation of leptin-replaced mice and PWL testing was repeated. During baseline (before vehicle or SPA administration), PWL was significantly (p = 0.0013) lower in leptin-replaced obese mice than in B6 mice. Microinjecting SPA into the pontine Reticular Formation of B6 mice caused a significant (p = 0.0003) concentration-dependent increase in %MPE. SPA also significantly (p < 0.05) increased %MPE in B6 mice and in leptin-replaced obese mice, but not in leptin-deficient obese mice. Microinjection of the mouse super-active leptin antagonist (SMLA) into the pontine Reticular Formation before SPA did not alter PWL. The results show for the first time that pontine Reticular Formation administration of the adenosine A1 receptor agonist SPA produced antinociception only in the presence of systemic leptin. The concentration-response data support the interpretation that adenosine A1 receptors localized to the pontine Reticular Formation significantly alter nociception.
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extrasynaptic gabaa receptors in rat pontine Reticular Formation increase wakefulness
Sleep, 2013Co-Authors: Giancarlo Vanini, Helen A BaghdoyanAbstract:STUDY OBJECTIVES: Gamma-aminobutyric acid (GABA) causes phasic inhibition via synaptic GABAA receptors and tonic inhibition via extrasynaptic GABAA receptors. GABA levels in the extracellular space regulate arousal state and cognition by volume transmission via extrasynaptic GABAA receptors. GABAergic transmission in the pontine Reticular Formation promotes wakefulness. No previous studies have determined whether an agonist at extrasynaptic GABAA receptors administered into the pontine Reticular Formation alters sleep and wakefulness. Therefore, this study used gaboxadol (THIP; agonist at extrasynaptic GABAA receptors that contain a δ subunit) to test the hypothesis that extrasynaptic GABAA receptors within the pontine Reticular Formation modulate sleep and wakefulness. DESIGN: Within/between subjects. SETTING: University of Michigan. PATIENTS OR PARTICIPANTS: Adult male Crl:CD*(SD) (Sprague-Dawley) rats (n = 10). INTERVENTIONS: Microinjection of gaboxadol, the nonsubtype selective GABAA receptor agonist muscimol (positive control), and saline (negative control) into the rostral pontine Reticular Formation. MEASUREMENTS AND RESULTS: Gaboxadol significantly increased wakefulness and decreased both nonrapid eye movement sleep and rapid eye movement sleep in a concentration-dependent manner. Relative to saline, gaboxadol did not alter electroencephalogram power. Microinjection of muscimol into the pontine Reticular Formation of the same rats that received gaboxadol increased wakefulness and decreased sleep. CONCLUSION: Tonic inhibition via extrasynaptic GABAA receptors that contain a δ subunit may be one mechanism by which the extracellular pool of endogenous GABA in the rostral pontine Reticular Formation promotes wakefulness. CITATION: Vanini G; Baghdoyan HA. Extrasynaptic GABAA receptors in rat pontine Reticular Formation increase wakefulness. SLEEP 2013;36(3):337-343.
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γ aminobutyric acid mediated neurotransmission in the pontine Reticular Formation modulates hypnosis immobility and breathing during isoflurane anesthesia
Anesthesiology, 2008Co-Authors: Giancarlo Vanini, Ralph Lydic, Chris J Watson, Helen A BaghdoyanAbstract:BACKGROUND: Many general anesthetics are thought to produce a loss of wakefulness, in part, by enhancing gamma-aminobutyric acid (GABA) neurotransmission. However, GABAergic neurotransmission in the pontine Reticular Formation promotes wakefulness. This study tested the hypotheses that (1) relative to wakefulness, isoflurane decreases GABA levels in the pontine Reticular Formation; and (2) pontine Reticular Formation administration of drugs that increase or decrease GABA levels increases or decreases, respectively, isoflurane induction time. METHODS: To test hypothesis 1, cats (n = 5) received a craniotomy and permanent electrodes for recording the electroencephalogram and electromyogram. Dialysis samples were collected from the pontine Reticular Formation during isoflurane anesthesia and wakefulness. GABA levels were quantified using high-performance liquid chromatography. For hypothesis 2, rats (n = 10) were implanted with a guide cannula aimed for the pontine Reticular Formation. Each rat received microinjections of Ringer's (vehicle control), the GABA uptake inhibitor nipecotic acid, and the GABA synthesis inhibitor 3-mercaptopropionic acid. Rats were then anesthetized with isoflurane, and induction time was quantified as loss of righting reflex. Breathing rate was also measured. RESULTS: Relative to wakefulness, GABA levels were significantly decreased by isoflurane. Increased power in the electroencephalogram and decreased activity in the electromyogram caused by isoflurane covaried with pontine Reticular Formation GABA levels. Nipecotic acid and 3-mercaptopropionic acid significantly increased and decreased, respectively, isoflurane induction time. Nipecotic acid also increased breathing rate. CONCLUSION: Decreasing pontine Reticular Formation GABA levels comprises one mechanism by which isoflurane causes loss of consciousness, altered cortical excitability, muscular hypotonia, and decreased respiratory rate.
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m2 muscarinic receptors in pontine Reticular Formation of c57bl 6j mouse contribute to rapid eye movement sleep generation
Neuroscience, 2004Co-Authors: C G Coleman, Ralph Lydic, Helen A BaghdoyanAbstract:Microinjecting the acetylcholinesterase inhibitor neostigmine into the pontine Reticular Formation of C57BL/6J (B6) mouse causes a rapid eye movement (REM) sleep-like state. This finding is consistent with similar studies in cat and both sets of data indicate that the REM sleep-like state is caused by increasing levels of endogenous acetylcholine (ACh). Muscarinic cholinergic receptors have been localized to the pontine Reticular Formation of B6 mouse but no previous studies have examined which of the five muscarinic receptor subtypes participate in cholinergic REM sleep enhancement. This study examined the hypothesis that M2 receptors in pontine Reticular Formation of B6 mouse contribute to the REM sleep-like state caused by pontine Reticular Formation administration of neostigmine. B6 mice (n=13) were implanted with electrodes for recording states of sleep and wakefulness and with microinjection cannulae aimed for the pontine Reticular Formation. States of sleep and wakefulness were recorded for 4 h following pontine Reticular Formation injection of saline (control) or neostigmine. Experiments designed to gain insight into the muscarinic receptor subtypes mediating REM sleep enhancement involved pontine Reticular Formation administration of neostigmine after pertussis toxin, neostigmine after methoctramine, and neostigmine after pirenzepine. Pertussis toxin was used to block effects mediated by M2 and M4 receptors. Methoctramine was used to block M2 and M4 receptors, and pirenzepine was used to block M1 and M4 receptors. Pertussis toxin and methoctramine significantly decreased the neostigmine-induced REM sleep-like state. In contrast, pretreatment with pirenzepine did not significantly decrease the REM sleep-like state caused by neostigmine. These results support the interpretation that M2 receptors in the pontine Reticular Formation of B6 mouse contribute to the generation of REM sleep.
Susan Warren - One of the best experts on this subject based on the ideXlab platform.
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a central mesencephalic Reticular Formation projection to the supraoculomotor area in macaque monkeys
Brain Structure & Function, 2016Co-Authors: Martin O Bohlen, Susan WarrenAbstract:The central mesencephalic Reticular Formation is physiologically implicated in oculomotor function and anatomically interwoven with many parts of the oculomotor system’s premotor circuitry. This study in Macaca fascicularis monkeys investigates the pattern of central mesencephalic Reticular Formation projections to the area in and around the extraocular motor nuclei, with special emphasis on the supraoculomotor area. It also examines the location of the cells responsible for this projection. Injections of biotinylated dextran amine were stereotaxically placed within the central mesencephalic Reticular Formation to anterogradely label axons and terminals. These revealed bilateral terminal fields in the supraoculomotor area. In addition, dense terminations were found in both the preganglionic Edinger–Westphal nuclei. The dense terminations just dorsal to the oculomotor nucleus overlap with the location of the C-group medial rectus motoneurons projecting to multiply innervated muscle fibers suggesting they may be targeted. Minor terminal fields were observed bilaterally within the borders of the oculomotor and abducens nuclei. Injections including the supraoculomotor area and oculomotor nucleus retrogradely labeled a tight band of neurons crossing the central third of the central mesencephalic Reticular Formation at all rostrocaudal levels, indicating a subregion of the nucleus provides this projection. Thus, these experiments reveal that a subregion of the central mesencephalic Reticular Formation may directly project to motoneurons in the oculomotor and abducens nuclei, as well as to preganglionic neurons controlling the tone of intraocular muscles. This pattern of projections suggests an as yet undetermined role in regulating the near triad.
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a central mesencephalic Reticular Formation projection to the edinger westphal nuclei
Brain Structure & Function, 2016Co-Authors: Susan Warren, Martin O Bohlen, Miriam Barnerssoi, Anja K E HornAbstract:The central mesencephalic Reticular Formation, a region associated with horizontal gaze control, has recently been shown to project to the supraoculomotor area in primates. The Edinger–Westphal nucleus is found within the supraoculomotor area. It has two functionally and anatomically distinct divisions: (1) the preganglionic division, which contains motoneurons that control both the actions of the ciliary muscle, which focuses the lens, and the sphincter pupillae muscle, which constricts the iris, and (2) the centrally projecting division, which contains peptidergic neurons that play a role in food and fluid intake, and in stress responses. In this study, we used neuroanatomical tracers in conjunction with immunohistochemistry in Macaca fascicularis monkeys to examine whether either of these Edinger–Westphal divisions receives synaptic input from the central mesencephalic Reticular Formation. Anterogradely labeled Reticular axons were observed making numerous boutonal associations with the cholinergic, preganglionic motoneurons of the Edinger–Westphal nucleus. These associations were confirmed to be synaptic contacts through the use of confocal and electron microscopic analysis. The latter indicated that these terminals generally contained pleomorphic vesicles and displayed symmetric, synaptic densities. Examination of urocortin-1-positive cells in the same cases revealed fewer examples of unambiguous synaptic relationships, suggesting the centrally projecting Edinger–Westphal nucleus is not the primary target of the projection from the central mesencephalic Reticular Formation. We conclude from these data that the central mesencephalic Reticular Formation must play a here-to-for unexpected role in control of the near triad (vergence, lens accommodation and pupillary constriction), which is used to examine objects in near space.
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A central mesencephalic Reticular Formation projection to the Edinger–Westphal nuclei
Brain Structure & Function, 2015Co-Authors: Susan Warren, Martin O Bohlen, Miriam Barnerssoi, Anja K E HornAbstract:The central mesencephalic Reticular Formation, a region associated with horizontal gaze control, has recently been shown to project to the supraoculomotor area in primates. The Edinger–Westphal nucleus is found within the supraoculomotor area. It has two functionally and anatomically distinct divisions: (1) the preganglionic division, which contains motoneurons that control both the actions of the ciliary muscle, which focuses the lens, and the sphincter pupillae muscle, which constricts the iris, and (2) the centrally projecting division, which contains peptidergic neurons that play a role in food and fluid intake, and in stress responses. In this study, we used neuroanatomical tracers in conjunction with immunohistochemistry in Macaca fascicularis monkeys to examine whether either of these Edinger–Westphal divisions receives synaptic input from the central mesencephalic Reticular Formation. Anterogradely labeled Reticular axons were observed making numerous boutonal associations with the cholinergic, preganglionic motoneurons of the Edinger–Westphal nucleus. These associations were confirmed to be synaptic contacts through the use of confocal and electron microscopic analysis. The latter indicated that these terminals generally contained pleomorphic vesicles and displayed symmetric, synaptic densities. Examination of urocortin-1-positive cells in the same cases revealed fewer examples of unambiguous synaptic relationships, suggesting the centrally projecting Edinger–Westphal nucleus is not the primary target of the projection from the central mesencephalic Reticular Formation. We conclude from these data that the central mesencephalic Reticular Formation must play a here-to-for unexpected role in control of the near triad (vergence, lens accommodation and pupillary constriction), which is used to examine objects in near space.
Martin O Bohlen - One of the best experts on this subject based on the ideXlab platform.
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a central mesencephalic Reticular Formation projection to the supraoculomotor area in macaque monkeys
Brain Structure & Function, 2016Co-Authors: Martin O Bohlen, Susan WarrenAbstract:The central mesencephalic Reticular Formation is physiologically implicated in oculomotor function and anatomically interwoven with many parts of the oculomotor system’s premotor circuitry. This study in Macaca fascicularis monkeys investigates the pattern of central mesencephalic Reticular Formation projections to the area in and around the extraocular motor nuclei, with special emphasis on the supraoculomotor area. It also examines the location of the cells responsible for this projection. Injections of biotinylated dextran amine were stereotaxically placed within the central mesencephalic Reticular Formation to anterogradely label axons and terminals. These revealed bilateral terminal fields in the supraoculomotor area. In addition, dense terminations were found in both the preganglionic Edinger–Westphal nuclei. The dense terminations just dorsal to the oculomotor nucleus overlap with the location of the C-group medial rectus motoneurons projecting to multiply innervated muscle fibers suggesting they may be targeted. Minor terminal fields were observed bilaterally within the borders of the oculomotor and abducens nuclei. Injections including the supraoculomotor area and oculomotor nucleus retrogradely labeled a tight band of neurons crossing the central third of the central mesencephalic Reticular Formation at all rostrocaudal levels, indicating a subregion of the nucleus provides this projection. Thus, these experiments reveal that a subregion of the central mesencephalic Reticular Formation may directly project to motoneurons in the oculomotor and abducens nuclei, as well as to preganglionic neurons controlling the tone of intraocular muscles. This pattern of projections suggests an as yet undetermined role in regulating the near triad.
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a central mesencephalic Reticular Formation projection to the edinger westphal nuclei
Brain Structure & Function, 2016Co-Authors: Susan Warren, Martin O Bohlen, Miriam Barnerssoi, Anja K E HornAbstract:The central mesencephalic Reticular Formation, a region associated with horizontal gaze control, has recently been shown to project to the supraoculomotor area in primates. The Edinger–Westphal nucleus is found within the supraoculomotor area. It has two functionally and anatomically distinct divisions: (1) the preganglionic division, which contains motoneurons that control both the actions of the ciliary muscle, which focuses the lens, and the sphincter pupillae muscle, which constricts the iris, and (2) the centrally projecting division, which contains peptidergic neurons that play a role in food and fluid intake, and in stress responses. In this study, we used neuroanatomical tracers in conjunction with immunohistochemistry in Macaca fascicularis monkeys to examine whether either of these Edinger–Westphal divisions receives synaptic input from the central mesencephalic Reticular Formation. Anterogradely labeled Reticular axons were observed making numerous boutonal associations with the cholinergic, preganglionic motoneurons of the Edinger–Westphal nucleus. These associations were confirmed to be synaptic contacts through the use of confocal and electron microscopic analysis. The latter indicated that these terminals generally contained pleomorphic vesicles and displayed symmetric, synaptic densities. Examination of urocortin-1-positive cells in the same cases revealed fewer examples of unambiguous synaptic relationships, suggesting the centrally projecting Edinger–Westphal nucleus is not the primary target of the projection from the central mesencephalic Reticular Formation. We conclude from these data that the central mesencephalic Reticular Formation must play a here-to-for unexpected role in control of the near triad (vergence, lens accommodation and pupillary constriction), which is used to examine objects in near space.
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A central mesencephalic Reticular Formation projection to the Edinger–Westphal nuclei
Brain Structure & Function, 2015Co-Authors: Susan Warren, Martin O Bohlen, Miriam Barnerssoi, Anja K E HornAbstract:The central mesencephalic Reticular Formation, a region associated with horizontal gaze control, has recently been shown to project to the supraoculomotor area in primates. The Edinger–Westphal nucleus is found within the supraoculomotor area. It has two functionally and anatomically distinct divisions: (1) the preganglionic division, which contains motoneurons that control both the actions of the ciliary muscle, which focuses the lens, and the sphincter pupillae muscle, which constricts the iris, and (2) the centrally projecting division, which contains peptidergic neurons that play a role in food and fluid intake, and in stress responses. In this study, we used neuroanatomical tracers in conjunction with immunohistochemistry in Macaca fascicularis monkeys to examine whether either of these Edinger–Westphal divisions receives synaptic input from the central mesencephalic Reticular Formation. Anterogradely labeled Reticular axons were observed making numerous boutonal associations with the cholinergic, preganglionic motoneurons of the Edinger–Westphal nucleus. These associations were confirmed to be synaptic contacts through the use of confocal and electron microscopic analysis. The latter indicated that these terminals generally contained pleomorphic vesicles and displayed symmetric, synaptic densities. Examination of urocortin-1-positive cells in the same cases revealed fewer examples of unambiguous synaptic relationships, suggesting the centrally projecting Edinger–Westphal nucleus is not the primary target of the projection from the central mesencephalic Reticular Formation. We conclude from these data that the central mesencephalic Reticular Formation must play a here-to-for unexpected role in control of the near triad (vergence, lens accommodation and pupillary constriction), which is used to examine objects in near space.
Barbara E Jones - One of the best experts on this subject based on the ideXlab platform.
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immunohistochemical study of choline acetyltransferase immunoreactive processes and cells innervating the pontomedullary Reticular Formation in the rat
The Journal of Comparative Neurology, 1990Co-Authors: Barbara E JonesAbstract:The present study was undertaken to examine the cholinergic innervation of the brainstem Reticular Formation in an effort to understand the potential role of cholinergic neurons in processes of sensory-motor modulation and state control. The cholinergic cells and processes within the pontomedullary Reticular Formation were studied in the rat by application of peroxidase-antiperoxidase immunohistochemistry with silver intensification for cholineacetyltransferase (ChAT). ChAT-immunoreactive cells were located in the pontomesencephalic tegmentum within the laterodorsal and pedunculopontine tegmental (LDT and PPT) nuclei, where they numbered approximately 3,000 on each side and were scattered in the midline, medial, and lateral medullary Reticular Formation, where they numbered approximately 10,000 in total on each side. The cholinergic neurons within the Reticular Formation were commonly medium in size and gave rise to multiple dendrites that extended for considerable distances within the periventricular gray or the Reticular Formation, as is typical of other isodendritic Reticular neurons. A prominent innervation of the entire pontomedullary Reticular Formation was evident by varicose ChAT-immunoreactive fibers that often surrounded large noncholinergic Reticular neurons in a typical perisomatic pattern of termination, suggesting a potent influence of the cholinergic innervation on pontomedullary Reticular neurons. The contribution of the pontomesencephalic cholinergic neurons to the innervation of the medial medullary and lateral pontine Reticular Formation was studied by retrograde transport of horseradish peroxidase conjugated wheat germ agglutinin (WGA-HRP) in combination with ChAT immunohistochemistry. A proportion of the cholinergic neurons within the laterodorsal tegmental nucleus (pars alpha) and the pedunculopontine tegmental nucleus were retrogradely labelled on the ipsilateral (10–15%) and contralateral (5–10%) sides from the medial medullary Reticular Formation, indicating a significant contribution to the cholinergic innervation of this region, which, however, also appeared to derive in part from intrinsic medullary cholinergic neurons. The major fiber system by which the medial medullary Reticular Formation was reached by the pontomesencephalic cholinergic neurons appeared to correspond to the lateral tegmentoReticular tract. Fibers passed from these cholinergic cells ventrally through the lateral pontine tegmentum, in the region of the subcoeruleus, where they also appeared to innervate by fibres en passage the noncholinergic neurons of the region. A significant proportion of the pontomesencephalic cholinergic neurons were retrogradely labelled from the lateral pontine tegmentum. The prominent innervation of the pontomedullary Reticular Formation by the pontomesencephalic cholinergic neurons provides a potential neuroanatomical substrate for the hypothesized role of cholinergic neurons in sensory-motor modulation and state control, particularly the state of paradoxical sleep.
