The Experts below are selected from a list of 297 Experts worldwide ranked by ideXlab platform
Christopher A Lowry - One of the best experts on this subject based on the ideXlab platform.
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Stress-related Serotonergic Systems: Implications for Symptomatology of Anxiety and Affective Disorders
Cellular and Molecular Neurobiology, 2012Co-Authors: Matthew W Hale, Anantha Shekhar, Christopher A LowryAbstract:Previous studies have suggested that Serotonergic neurons in the midbrain raphe complex have a functional topographic organization. Recent studies suggest that stimulation of a bed nucleus of the stria terminalis-dorsal raphe nucleus pathway by stress- and anxiety-related stimuli modulates a subpopulation of Serotonergic neurons in the dorsal part of the dorsal raphe nucleus (DRD) and caudal part of the dorsal raphe nucleus (DRC) that participates in facilitation of anxiety-like responses. In contrast, recent studies suggest that activation of a spinoparabrachial pathway by peripheral thermal or immune stimuli excites subpopulations of Serotonergic neurons in the ventrolateral part of the dorsal raphe nucleus/ventrolateral periaqueducal gray (DRVL/VLPAG) region and interfascicular part of the dorsal raphe nucleus (DRI). Studies support a role for Serotonergic neurons in the DRVL/VLPAG in inhibition of panic-like responses, and Serotonergic neurons in the DRI in antidepressant-like effects. Thus, data suggest that while some subpopulations of Serotonergic neurons in the dorsal raphe nucleus play a role in facilitation of anxiety-like responses, others play a role in inhibition of anxiety- or panic-like responses, while others play a role in antidepressant-like effects. Understanding the anatomical and functional properties of these distinct Serotonergic systems may lead to novel therapeutic strategies for the prevention and/or treatment of affective and anxiety disorders. In this review, we describe the anatomical and functional properties of subpopulations of Serotonergic neurons in the dorsal raphe nucleus, with a focus on those implicated in symptoms of anxiety and affective disorders, the DRD/DRC, DRVL/VLPAG, and DRI.
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Functional topography of midbrain and pontine Serotonergic systems: implications for synaptic regulation of Serotonergic circuits
Psychopharmacology, 2011Co-Authors: Matthew W Hale, Christopher A LowryAbstract:Rationale Dysfunction of Serotonergic systems is thought to play an important role in a number of neurological and psychiatric disorders. Recent studies suggest that there is anatomical and functional diversity among Serotonergic systems innervating forebrain systems involved in the control of physiologic and behavioral responses, including the control of emotional states. Objective Here, we highlight the methods that have been used to investigate the heterogeneity of Serotonergic systems and review the evidence for the unique anatomical, hodological, and functional properties of topographically organized subpopulations of Serotonergic neurons in the midbrain and pontine raphe complex. Conclusion The emerging understanding of the topographically organized synaptic regulation of brainstem Serotonergic systems, the topography of the efferent projections of these systems, and their functional properties, should enable identification of novel therapeutic approaches to treatment of neurological and psychiatric conditions that are associated with dysregulation of Serotonergic systems.
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evidence for in vivo thermosensitivity of Serotonergic neurons in the rat dorsal raphe nucleus and raphe pallidus nucleus implicated in thermoregulatory cooling
Experimental Neurology, 2011Co-Authors: Matthew W Hale, Christopher A Lowry, Andrew K Evans, Kathleen F DadyAbstract:The ability to sense and respond appropriately to increases in ambient and body temperatures is critical for the survival of all animals. Although evidence suggests that brain Serotonergic systems play a role in thermoregulation, including thermoregulatory cooling, evidence for activation of brainstem Serotonergic neurons in vivo, in unanesthetized animals, during heat exposure is lacking. In this experiment we tested the hypothesis that populations of Serotonergic neurons in the midbrain and medullary raphe complex are activated following exposure to warm ambient temperature. Rats were exposed to an incubation chamber at either warm ambient temperature (37°C) or room temperature (RT; 23°C) for 105 min. Brains then were removed and processed for immunohistochemical detection of the protein product of the immediate-early gene c-fos (as a marker of neuronal activation) and tryptophan hydroxylase (as a marker of Serotonergic neurons). Exposure to warm ambient temperature increased body temperature and c-Fos expression in topographically organized populations of Serotonergic neurons in the dorsal raphe nucleus. Activation of the dorsal raphe nucleus Serotonergic system was positively correlated with body temperature following exposure to the incubation chamber. In the medulla, exposure to warm ambient temperature, compared with exposure to RT, decreased c-Fos expression in Serotonergic neurons in the raphe pallidus nucleus and in non-Serotonergic cells in the rostral ventrolateral medulla. Together, these results provide evidence for multiple but anatomically discrete thermosensitive Serotonergic systems that may have implications for the regulation of body temperature, as well as, via projections to forebrain targets, cognitive and affective functions.
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Functional topography of midbrain and pontine Serotonergic systems: implications for synaptic regulation of Serotonergic circuits.
Psychopharmacology, 2010Co-Authors: Matthew W Hale, Christopher A LowryAbstract:Dysfunction of Serotonergic systems is thought to play an important role in a number of neurological and psychiatric disorders. Recent studies suggest that there is anatomical and functional diversity among Serotonergic systems innervating forebrain systems involved in the control of physiologic and behavioral responses, including the control of emotional states. Here, we highlight the methods that have been used to investigate the heterogeneity of Serotonergic systems and review the evidence for the unique anatomical, hodological, and functional properties of topographically organized subpopulations of Serotonergic neurons in the midbrain and pontine raphe complex. The emerging understanding of the topographically organized synaptic regulation of brainstem Serotonergic systems, the topography of the efferent projections of these systems, and their functional properties, should enable identification of novel therapeutic approaches to treatment of neurological and psychiatric conditions that are associated with dysregulation of Serotonergic systems.
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topographic organization and chemoarchitecture of the dorsal raphe nucleus and the median raphe nucleus
2008Co-Authors: Christopher A Lowry, Andrew K Evans, Paul J Gasser, Matthew W Hale, Daniel R Staub, Anantha ShekharAbstract:The role of Serotonergic systems in regulation of behavioral arousal and sleep-wake cycles is complex and may depend on both the receptor subtype and brain region involved. Increasing evidence points toward the existence of multiple topographically organized subpopulations of Serotonergic neurons that receive unique afferent connections, give rise to unique patterns of projections to forebrain systems, and have unique functional properties. A better understanding of the properties of these subpopulations of Serotonergic neurons may aid in the understanding of the role of Serotonergic systems in regulation of behavioral arousal, sleep-wake cycles and other physiological and behavioral responses attributed to serotonin. In this chapter, we outline evidence for multiple Serotonergic systems within the midbrain and pontine raphe complex that can be defined based on cytoarchitectonic and hodological properties. In addition, we describe how these topographically organized groups of Serotonergic neurons correspond to the six major ascending Serotonergic tracts innervating the forebrain.
Matthew W Hale - One of the best experts on this subject based on the ideXlab platform.
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Stress-related Serotonergic Systems: Implications for Symptomatology of Anxiety and Affective Disorders
Cellular and Molecular Neurobiology, 2012Co-Authors: Matthew W Hale, Anantha Shekhar, Christopher A LowryAbstract:Previous studies have suggested that Serotonergic neurons in the midbrain raphe complex have a functional topographic organization. Recent studies suggest that stimulation of a bed nucleus of the stria terminalis-dorsal raphe nucleus pathway by stress- and anxiety-related stimuli modulates a subpopulation of Serotonergic neurons in the dorsal part of the dorsal raphe nucleus (DRD) and caudal part of the dorsal raphe nucleus (DRC) that participates in facilitation of anxiety-like responses. In contrast, recent studies suggest that activation of a spinoparabrachial pathway by peripheral thermal or immune stimuli excites subpopulations of Serotonergic neurons in the ventrolateral part of the dorsal raphe nucleus/ventrolateral periaqueducal gray (DRVL/VLPAG) region and interfascicular part of the dorsal raphe nucleus (DRI). Studies support a role for Serotonergic neurons in the DRVL/VLPAG in inhibition of panic-like responses, and Serotonergic neurons in the DRI in antidepressant-like effects. Thus, data suggest that while some subpopulations of Serotonergic neurons in the dorsal raphe nucleus play a role in facilitation of anxiety-like responses, others play a role in inhibition of anxiety- or panic-like responses, while others play a role in antidepressant-like effects. Understanding the anatomical and functional properties of these distinct Serotonergic systems may lead to novel therapeutic strategies for the prevention and/or treatment of affective and anxiety disorders. In this review, we describe the anatomical and functional properties of subpopulations of Serotonergic neurons in the dorsal raphe nucleus, with a focus on those implicated in symptoms of anxiety and affective disorders, the DRD/DRC, DRVL/VLPAG, and DRI.
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Functional topography of midbrain and pontine Serotonergic systems: implications for synaptic regulation of Serotonergic circuits
Psychopharmacology, 2011Co-Authors: Matthew W Hale, Christopher A LowryAbstract:Rationale Dysfunction of Serotonergic systems is thought to play an important role in a number of neurological and psychiatric disorders. Recent studies suggest that there is anatomical and functional diversity among Serotonergic systems innervating forebrain systems involved in the control of physiologic and behavioral responses, including the control of emotional states. Objective Here, we highlight the methods that have been used to investigate the heterogeneity of Serotonergic systems and review the evidence for the unique anatomical, hodological, and functional properties of topographically organized subpopulations of Serotonergic neurons in the midbrain and pontine raphe complex. Conclusion The emerging understanding of the topographically organized synaptic regulation of brainstem Serotonergic systems, the topography of the efferent projections of these systems, and their functional properties, should enable identification of novel therapeutic approaches to treatment of neurological and psychiatric conditions that are associated with dysregulation of Serotonergic systems.
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evidence for in vivo thermosensitivity of Serotonergic neurons in the rat dorsal raphe nucleus and raphe pallidus nucleus implicated in thermoregulatory cooling
Experimental Neurology, 2011Co-Authors: Matthew W Hale, Christopher A Lowry, Andrew K Evans, Kathleen F DadyAbstract:The ability to sense and respond appropriately to increases in ambient and body temperatures is critical for the survival of all animals. Although evidence suggests that brain Serotonergic systems play a role in thermoregulation, including thermoregulatory cooling, evidence for activation of brainstem Serotonergic neurons in vivo, in unanesthetized animals, during heat exposure is lacking. In this experiment we tested the hypothesis that populations of Serotonergic neurons in the midbrain and medullary raphe complex are activated following exposure to warm ambient temperature. Rats were exposed to an incubation chamber at either warm ambient temperature (37°C) or room temperature (RT; 23°C) for 105 min. Brains then were removed and processed for immunohistochemical detection of the protein product of the immediate-early gene c-fos (as a marker of neuronal activation) and tryptophan hydroxylase (as a marker of Serotonergic neurons). Exposure to warm ambient temperature increased body temperature and c-Fos expression in topographically organized populations of Serotonergic neurons in the dorsal raphe nucleus. Activation of the dorsal raphe nucleus Serotonergic system was positively correlated with body temperature following exposure to the incubation chamber. In the medulla, exposure to warm ambient temperature, compared with exposure to RT, decreased c-Fos expression in Serotonergic neurons in the raphe pallidus nucleus and in non-Serotonergic cells in the rostral ventrolateral medulla. Together, these results provide evidence for multiple but anatomically discrete thermosensitive Serotonergic systems that may have implications for the regulation of body temperature, as well as, via projections to forebrain targets, cognitive and affective functions.
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Functional topography of midbrain and pontine Serotonergic systems: implications for synaptic regulation of Serotonergic circuits.
Psychopharmacology, 2010Co-Authors: Matthew W Hale, Christopher A LowryAbstract:Dysfunction of Serotonergic systems is thought to play an important role in a number of neurological and psychiatric disorders. Recent studies suggest that there is anatomical and functional diversity among Serotonergic systems innervating forebrain systems involved in the control of physiologic and behavioral responses, including the control of emotional states. Here, we highlight the methods that have been used to investigate the heterogeneity of Serotonergic systems and review the evidence for the unique anatomical, hodological, and functional properties of topographically organized subpopulations of Serotonergic neurons in the midbrain and pontine raphe complex. The emerging understanding of the topographically organized synaptic regulation of brainstem Serotonergic systems, the topography of the efferent projections of these systems, and their functional properties, should enable identification of novel therapeutic approaches to treatment of neurological and psychiatric conditions that are associated with dysregulation of Serotonergic systems.
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topographic organization and chemoarchitecture of the dorsal raphe nucleus and the median raphe nucleus
2008Co-Authors: Christopher A Lowry, Andrew K Evans, Paul J Gasser, Matthew W Hale, Daniel R Staub, Anantha ShekharAbstract:The role of Serotonergic systems in regulation of behavioral arousal and sleep-wake cycles is complex and may depend on both the receptor subtype and brain region involved. Increasing evidence points toward the existence of multiple topographically organized subpopulations of Serotonergic neurons that receive unique afferent connections, give rise to unique patterns of projections to forebrain systems, and have unique functional properties. A better understanding of the properties of these subpopulations of Serotonergic neurons may aid in the understanding of the role of Serotonergic systems in regulation of behavioral arousal, sleep-wake cycles and other physiological and behavioral responses attributed to serotonin. In this chapter, we outline evidence for multiple Serotonergic systems within the midbrain and pontine raphe complex that can be defined based on cytoarchitectonic and hodological properties. In addition, we describe how these topographically organized groups of Serotonergic neurons correspond to the six major ascending Serotonergic tracts innervating the forebrain.
Padma Gulur - One of the best experts on this subject based on the ideXlab platform.
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Incidence of Serotonin Syndrome in Patients Treated with Fentanyl on Serotonergic Agents
Pain Physician, 2015Co-Authors: Padma GulurAbstract:Background: There has been a recent surge in the literature highlighting the association of fentanyl as precipitating serotonin syndrome in patients on a Serotonergic agent. Objective: The purpose of our study was to understand the incidence of serotonin syndrome in patients who receive fentanyl while on Serotonergic agents. Study Design: This retrospective analysis was conducted from 2012 to 2013 after approval from the Institutional Review Board. We searched for all patients that had received a Serotonergic agent and were admitted to the hospital during the study period. Next, we split these patients into 2 groups by placing all patients who had received fentanyl and a Serotonergic agent into one group. We then searched for any of the Hunter Serotonin Toxicity Criteria in the records of patients that had received both fentanyl and a Serotonergic agent. Further, we searched for all patients with serotonin syndrome mentioned in their records. Setting: This study was conducted at a 900 bed tertiary care academic center. Results: Over the 2 year study period, 112,045 patients were on a Serotonergic agent, and 4,538 of these patients were treated with both fentanyl and a Serotonergic agent. A search for Hunter’s Criteria through the records of the patients receiving both fentanyl and a Serotonergic agent revealed 23 patients had been documented with some of these symptoms. On detailed chart review, only 4 [95% CI 1 – 10] of these patients truly met Hunter’s Criteria for serotonin syndrome. We then searched all admissions for a diagnosis code of serotonin syndrome during the study period. Five additional cases of serotonin syndrome were found, but none of these patients were treated with fentanyl. Limitations: Some of the limitations of our study include that it represents a single institution, although it is a large academic center. An inherent limitation may be the under diagnosis of serotonin syndrome. Conclusion: The incidence of serotonin syndrome in patients who receive both fentanyl and a Serotonergic agent is low. Key words: Fentanyl, serotonin syndrome, Serotonergic drugs, opioids, SSRI, antidepressant
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incidence of serotonin syndrome in patients treated with fentanyl on Serotonergic agents
Pain Physician, 2015Co-Authors: Katharine Koury, Becky Tsui, Padma GulurAbstract:BACKGROUND There has been a recent surge in the literature highlighting the association of fentanyl as precipitating serotonin syndrome in patients on a Serotonergic agent. OBJECTIVE The purpose of our study was to understand the incidence of serotonin syndrome in patients who receive fentanyl while on Serotonergic agents. STUDY DESIGN This retrospective analysis was conducted from 2012 to 2013 after approval from the Institutional Review Board. We searched for all patients that had received a Serotonergic agent and were admitted to the hospital during the study period. Next, we split these patients into 2 groups by placing all patients who had received fentanyl and a Serotonergic agent into one group. We then searched for any of the Hunter Serotonin Toxicity Criteria in the records of patients that had received both fentanyl and a Serotonergic agent. Further, we searched for all patients with serotonin syndrome mentioned in their records. SETTING This study was conducted at a 900 bed tertiary care academic center. RESULTS Over the 2 year study period, 112,045 patients were on a Serotonergic agent, and 4,538 of these patients were treated with both fentanyl and a Serotonergic agent. A search for Hunter's Criteria through the records of the patients receiving both fentanyl and a Serotonergic agent revealed 23 patients had been documented with some of these symptoms. On detailed chart review, only 4 [95% CI 1 - 10] of these patients truly met Hunter's Criteria for serotonin syndrome. We then searched all admissions for a diagnosis code of serotonin syndrome during the study period. Five additional cases of serotonin syndrome were found, but none of these patients were treated with fentanyl. LIMITATIONS Some of the limitations of our study include that it represents a single institution, although it is a large academic center. An inherent limitation may be the under diagnosis of serotonin syndrome. CONCLUSION The incidence of serotonin syndrome in patients who receive both fentanyl and a Serotonergic agent is low.
Carey D. Balaban - One of the best experts on this subject based on the ideXlab platform.
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selective anterograde tracing of the individual Serotonergic and nonSerotonergic components of the dorsal raphe nucleus projection to the vestibular nuclei
Neuroscience, 2007Co-Authors: Adam L Halberstadt, Carey D. BalabanAbstract:Abstract It is well known that the dorsal raphe nucleus (DRN) sends Serotonergic and nonSerotonergic projections to target regions in the brain stem and forebrain, including the vestibular nuclei. Although retrograde tracing studies have reported consistently that there are differences in the relative innervation of different target regions by Serotonergic and nonSerotonergic DRN neurons, the relative termination patterns of these two projections have not been compared using anterograde tracing methods. The object of the present investigation was to trace anterogradely the individual Serotonergic and nonSerotonergic components of the projection from DRN to the vestibular nuclei in rats. To trace nonSerotonergic DRN projections, animals were pretreated with the Serotonergic neurotoxin 5,7-dihydroxytryptamine (5,7-DHT), and then, after 7 days, the anterograde tracer biotinylated dextran amine (BDA) was iontophoretically injected into the DRN. In animals treated with 5,7-DHT, nonSerotonergic BDA-labeled fibers were found to descend exclusively within the ventricular plexus and to terminate predominantly within the periventricular aspect of the vestibular nuclei. Serotonergic DRN projections were traced by injecting 5,7-DHT directly into DRN, and amino–cupric–silver staining was used to visualize the resulting pattern of terminal degeneration. Eighteen hours after microinjection of 5,7-DHT into the DRN, fine-caliber degenerating Serotonergic terminals were found within the region of the medial vestibular nucleus (MVN) that borders the fourth ventricle, and a mixture of fine- and heavier-caliber degenerating Serotonergic terminals was located further laterally within the vestibular nuclear complex. These findings indicate that fine-caliber projections from Serotonergic and nonSerotonergic DRN neurons primarily innervate the periventricular regions of MVN, whereas heavier-caliber projections from Serotonergic DRN neurons innervate terminal fields located in more lateral regions of the vestibular nuclei. Thus, Serotonergic and nonSerotonergic DRN axons target distinct but partially overlapping terminal fields within the vestibular nuclear complex, raising the possibility that these two DRN projection systems are organized in a manner that permits regionally-specialized regulation of processing within the vestibular nuclei.
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selective anterograde tracing of the individual Serotonergic and nonSerotonergic components of the dorsal raphe nucleus projection to the vestibular nuclei
Neuroscience, 2007Co-Authors: Adam L Halberstadt, Carey D. BalabanAbstract:Abstract It is well known that the dorsal raphe nucleus (DRN) sends Serotonergic and nonSerotonergic projections to target regions in the brain stem and forebrain, including the vestibular nuclei. Although retrograde tracing studies have reported consistently that there are differences in the relative innervation of different target regions by Serotonergic and nonSerotonergic DRN neurons, the relative termination patterns of these two projections have not been compared using anterograde tracing methods. The object of the present investigation was to trace anterogradely the individual Serotonergic and nonSerotonergic components of the projection from DRN to the vestibular nuclei in rats. To trace nonSerotonergic DRN projections, animals were pretreated with the Serotonergic neurotoxin 5,7-dihydroxytryptamine (5,7-DHT), and then, after 7 days, the anterograde tracer biotinylated dextran amine (BDA) was iontophoretically injected into the DRN. In animals treated with 5,7-DHT, nonSerotonergic BDA-labeled fibers were found to descend exclusively within the ventricular plexus and to terminate predominantly within the periventricular aspect of the vestibular nuclei. Serotonergic DRN projections were traced by injecting 5,7-DHT directly into DRN, and amino–cupric–silver staining was used to visualize the resulting pattern of terminal degeneration. Eighteen hours after microinjection of 5,7-DHT into the DRN, fine-caliber degenerating Serotonergic terminals were found within the region of the medial vestibular nucleus (MVN) that borders the fourth ventricle, and a mixture of fine- and heavier-caliber degenerating Serotonergic terminals was located further laterally within the vestibular nuclear complex. These findings indicate that fine-caliber projections from Serotonergic and nonSerotonergic DRN neurons primarily innervate the periventricular regions of MVN, whereas heavier-caliber projections from Serotonergic DRN neurons innervate terminal fields located in more lateral regions of the vestibular nuclei. Thus, Serotonergic and nonSerotonergic DRN axons target distinct but partially overlapping terminal fields within the vestibular nuclear complex, raising the possibility that these two DRN projection systems are organized in a manner that permits regionally-specialized regulation of processing within the vestibular nuclei.
Florence M. Bareyre - One of the best experts on this subject based on the ideXlab platform.
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Semaphorin 7A restricts Serotonergic innervation and ensures recovery after spinal cord injury
Cellular and Molecular Life Sciences, 2020Co-Authors: Kristina Loy, Julie Fourneau, Ning Meng, Carmen Denecke, Giuseppe Locatelli, Florence M. BareyreAbstract:Descending Serotonergic (5-HT) projections originating from the raphe nuclei form an important input to the spinal cord that control basic locomotion. The molecular signals that control this projection pattern are currently unknown. Here, we identify Semaphorin7A (Sema7A) as a critical cue that restricts Serotonergic innervation in the spinal cord. Sema7A deficient mice show a marked increase in Serotonergic fiber density in all layers of the spinal cord while the density of neurons expressing the corresponding 5-HTR2α receptor remains unchanged. These alterations appear to be successfully compensated as no obvious changes in rhythmic locomotion and skilled stepping are observed in adult mice. When the system is challenged with a spinal lesion, Serotonergic innervation patterns in both Sema7A-deficient and -competent mice evolve over time with excessive innervation becoming most pronounced in the dorsal horn of Sema7A-deficient mice. These altered Serotonergic innervation patterns correlate with diminished functional recovery that predominantly affects rhythmic locomotion. Our findings identify Sema7A as a critical regulator of Serotonergic circuit formation in the injured spinal cord.
