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Christopher A Lowry - One of the best experts on this subject based on the ideXlab platform.
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Two models of inescapable stress increase tph2 mRNA expression in the anxiety-related dorsomedial part of the dorsal Raphe Nucleus
Elsevier, 2018Co-Authors: Nina C Donner, Steven F Maier, Kenneth H Kubala, James E Hassell, Margaret W Lieb, Kadi T Nguyen, Jared D Heinze, Robert C Drugan, Christopher A LowryAbstract:Expression of TPH2, the rate-limiting enzyme for brain serotonin synthesis, is elevated in the dorsal Raphe Nucleus (DR) of depressed suicide victims. One hypothesis is that this increase in TPH2 expression is stress-induced. Here, we used an established animal model to address whether exposure to an acute stressor, inescapable tail shock (IS), increases tph2 mRNA and Tph2 protein expression, and if IS sensitizes the DR to a subsequent, heterotypic stressor. In Experiment 1, we measured tph2 mRNA expression 4 h after IS or home cage (HC) control conditions in male rats, using in situ hybridization histochemistry. In Experiment 2, we measured Tph2 protein expression 12 h or 24 h after IS using western blot. In Experiment 3, we measured tph2 mRNA expression following IS on Day 1, and cold swim stress (10 min, 15 °C) on Day 2. Inescapable tail shock was sufficient to increase tph2 mRNA expression 4 h and 28 h later, selectively in the dorsomedial DR (caudal aspect of the dorsal DR, cDRD; an area just rostral to the caudal DR, DRC) and increased Tph2 protein expression in the DRD (rostral and caudal aspects of the dorsal DR combined) 24 h later. Cold swim increased tph2 mRNA expression in the dorsomedial DR (cDRD) 4 h later. These effects were associated with increased immobility during cold swim, elevated plasma corticosterone, and a proinflammatory plasma cytokine milieu (increased interleukin (IL)-6, decreased IL-10). Our data demonstrate that two models of inescapable stress, IS and cold swim, increase tph2 mRNA expression selectively in the anxiety-related dorsomedial DR (cDRD). Keywords: Anxiety, Dorsal Raphe Nucleus, Inescapable stress, Inflammation, Tryptophan hydroxylas
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repeated social defeat increases reactive emotional coping behavior and alters functional responses in serotonergic neurons in the rat dorsal Raphe Nucleus
Physiology & Behavior, 2011Co-Authors: Evan D Paul, Christopher A Lowry, Matthew W Hale, Jodi L Lukkes, Mckenzie J Valentine, Derek M SarchetAbstract:Chronic stress is a vulnerability factor for a number of psychiatric disorders, including anxiety and affective disorders. Social defeat in rats has proven to be a useful paradigm to investigate the neural mechanisms underlying physiologic and behavioral adaptation to acute and chronic stress. Previous studies suggest that serotonergic systems may contribute to the physiologic and behavioral adaptation to chronic stress, including social defeat in rodent models. In order to test the hypothesis that repeated social defeat alters the emotional behavior and the excitability of brainstem serotonergic systems implicated in control of emotional behavior, we exposed adult male rats either to home cage control conditions, acute social defeat, or social defeat followed 24 h later by a second social defeat encounter. We then assessed behavioral responses during social defeat as well as the excitability of serotonergic neurons within the dorsal Raphe Nucleus using immunohistochemical staining of tryptophan hydroxylase, a marker of serotonergic neurons, and the protein product of the immediate-early gene, c-fos. Repeated social defeat resulted in a shift away from proactive emotional coping behaviors, such as rearing (explorative escape behavior), and toward reactive emotional coping behaviors such as freezing. Both acute and repeated defeat led to widespread increases in c-Fos expression in serotonergic neurons in the dorsal Raphe Nucleus. Changes in behavior following a second exposure to social defeat, relative to acute defeat, were associated with decreased c-Fos expression in serotonergic neurons within the dorsal and ventral parts of the mid-rostrocaudal dorsal Raphe Nucleus, regions that have been implicated in 1) serotonergic modulation of fear- and anxiety-related behavior and 2) defensive behavior in conspecific aggressive encounters, respectively. These data support the hypothesis that serotonergic systems play a role in physiologic and behavioral responses to both acute and repeated social defeat.
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serotonergic systems anxiety and affective disorder focus on the dorsomedial part of the dorsal Raphe Nucleus
Annals of the New York Academy of Sciences, 2008Co-Authors: Christopher A Lowry, Matthew W Hale, Andrew K Evans, Jasper Heerkens, Daniel R Staub, Paul J Gasser, Anantha ShekharAbstract:Depressed suicide patients have elevated expression of neuronal tryptophan hydroxylase 2 (TPH2) mRNA and protein in midbrain serotonergic neurons, as well as increases in brain serotonin turnover. The mechanisms underlying these changes are uncertain, but increased TPH2 expression and serotonin turnover could result from genetic influences, adverse early life experiences, or acute stressful life events, all of which can alter serotonergic neurotransmission and have been implicated in determining vulnerability to major depression. Emerging evidence suggests that there are several different stress-related subsets of serotonergic neurons, each with a unique role in the integrated stress response. Here we review our current understanding of how genetic and environmental factors may influence TPH2 mRNA expression and serotonergic neurotransmission, focusing in particular on the dorsomedial part of the dorsal Raphe Nucleus. This subdivision of the dorsal Raphe Nucleus is selectively innervated by key forebrain structures implicated in regulation of anxiety states, it gives rise to projections to a distributed neural system mediating anxiety states, and serotonergic neurons within this subdivision are selectively activated by a number of stress- and anxiety-related stimuli. A better understanding of the anatomical and functional properties of specific stress- or anxiety-related serotonergic systems should aid our understanding of the neural mechanisms underlying the etiology of anxiety and affective disorders.
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corticotropin releasing factor in the dorsal Raphe Nucleus increases medial prefrontal cortical serotonin via type 2 receptors and median Raphe Nucleus activity
European Journal of Neuroscience, 2008Co-Authors: Gina L. Forster, R B Pringle, Nicholas J Mouw, Shawn M Vuong, Michael J Watt, Andrew R Burke, Christopher A Lowry, Cliff H. Summers, Kenneth J RennerAbstract:: Interactions between central corticotropin-releasing factor (CRF) and serotonergic systems are believed to be important for mediating fear and anxiety behaviors. Recently we demonstrated that infusions of CRF into the rat dorsal Raphe Nucleus result in a delayed increase in serotonin release within the medial prefrontal cortex that coincided with a reduction in fear behavior. The current studies were designed to study the CRF receptor mechanisms and pathways involved in this serotonergic response. Infusions of CRF (0.5 microg/0.5 microL) were made into the dorsal Raphe Nucleus of urethane-anesthetized rats following either inactivation of the median Raphe Nucleus by muscimol (25 ng/0.25 microL) or antagonism of CRF receptor type 1 or CRF receptor type 2 in the dorsal Raphe Nucleus with antalarmin (25-50 ng/0.5 microL) or antisauvagine-30 (2 microg/0.5 microL), respectively. Medial prefrontal cortex serotonin levels were measured using in-vivo microdialysis and high-performance liquid chromatography with electrochemical detection. Increased medial prefrontal cortex serotonin release elicited by CRF infusion into the dorsal Raphe Nucleus was abolished by inactivation of the median Raphe Nucleus. Furthermore, antagonism of CRF receptor type 2 but not CRF receptor type 1 in the dorsal Raphe Nucleus abolished CRF-induced increases in medial prefrontal cortex serotonin. Follow-up studies involved electrical stimulation of the central Nucleus of the amygdala, a source of CRF afferents to the dorsal Raphe Nucleus. Activation of the central Nucleus increased medial prefrontal cortex serotonin release. This response was blocked by CRF receptor type 2 antagonism in the dorsal Raphe. Overall, these results highlight complex CRF modulation of medial prefrontal cortex serotonergic activity at the level of the Raphe nuclei.
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anatomic and functional topography of the dorsal Raphe Nucleus
Annals of the New York Academy of Sciences, 2004Co-Authors: Jolane K Abrams, Philip L Johnson, Jacob Harvey Hollis, Christopher A LowryAbstract:: Serotonergic systems play an important and generalized role in regulation of sleep-wake states and behavioral arousal. Recent in vivo electrophysiologic recording studies in animals suggest that several different subtypes of serotonergic neurons with unique behavioral correlates exist within the brainstem Raphe nuclei, raising the possibility that topographically organized subpopulations of serotonergic neurons may have unique behavioral or physiologic correlates and unique functional properties. We have shown that the stress-related and anxiogenic neuropeptide corticotropin-releasing factor can stimulate the in vitro neuronal firing rates of topographically organized subpopulations of serotonergic neurons within the dorsal Raphe Nucleus (DR). These findings are consistent with a wealth of behavioral studies suggesting that serotonergic systems within the DR are involved in the modulation of ongoing anxiety-related behavior and in behavioral sensitization, a process whereby anxiety- and fear-related behavioral responses are sensitized for a period of up to 24 to 48 h. The dorsomedial subdivision of the DR, particularly its middle and caudal aspects, has attracted considerable attention as a region that may play a critical role in the regulation of acute and chronic anxiety states. Future studies aimed at characterization of the molecular and cellular properties of topographically organized subpopulations of serotonergic neurons are likely to lead to major advances in our understanding of the role of serotonergic systems in stress-related physiology and behavior.
Bernat Kocsis - One of the best experts on this subject based on the ideXlab platform.
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gabaergic control of the ascending input from the median Raphe Nucleus to the limbic system
Journal of Neurophysiology, 2005Co-Authors: Shaomin Li, Viktor Sebestyen Varga, Bernat KocsisAbstract:The median Raphe Nucleus (MRN) is the primary source of serotonergic afferents to the limbic system that are generally considered to suppress hippocampal theta oscillations. GABA receptors are expr...
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discharge properties of neurons of the median Raphe Nucleus during hippocampal theta rhythm in the rat
Experimental Brain Research, 2002Co-Authors: Zimbul Albo, Gonzalo Viana Di Prisco, Bernat KocsisAbstract:The serotonin (5-HT)-containing median Raphe Nucleus has been shown to be critically involved in the control of desynchronized (non theta) states of the hippocampal electroencephalogram (EEG). We examined the activity of 181 cells of the median Raphe Nucleus in the urethane-anesthetized rat and found that approximately 80% (145/181) of them showed changes in activity associated with changes in the hippocampal EEG. These cells were subdivided into theta-on (68%) and theta-off (32%) based on increased or decreased rates of activity with theta, respectively. They were further classified as slow-firing (~1 Hz), moderate-firing (5–11 Hz), or fast-firing (>12 Hz) theta-on or theta-off cells. The slow-firing cells as well as a subset of moderate-firing theta-off cells displayed characteristics of “classic” serotonin-containing Raphe neurons. All fast-firing neurons were theta-on cells and showed either tonic or phasic (rhythmical) increases in activity with theta. We propose that: (1) the slow-firing cells (on and off) as well as a subset of moderate-firing theta-off cells are serotonergic neurons; (2) the phasic and tonic fast-firing theta-on cells are GABAergic cells; and (3) these populations of cells mutually interact in the modulation of the hippocampal EEG. An activation of local serotonergic and GABAergic theta-on cells would inhibit 5-HT slow- or moderate-firing theta-off projection cells to release or generate theta, whereas the suppression of serotonergic- or GABAergic theta-on cells would disinhibit 5-HT theta-off cells, resulting in a blockade of theta or a desynchronization of the hippocampal EEG. A role for the median Raphe Nucleus in memory-associated functions of the hippocampus is discussed.
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gabab receptors in the median Raphe Nucleus distribution and role in the serotonergic control of hippocampal activity
Neuroscience, 2002Co-Authors: Viktor Sebestyen Varga, T F Freund, Bernat KocsisAbstract:Abstract Previous studies have shown that serotonergic neurons of the median Raphe Nucleus have a suppressive effect on theta synchronization in the hippocampus. Median Raphe lesion, suppression of 5-HT neuronal activity by administration of GABA A receptor antagonist or by glutamate blockade or depletion produced long-lasting non-interrupted hippocampal theta in freely behaving rats independent of behavior and in rats anesthetized with urethane. Serotonergic neurons show a characteristic sleep–wake pattern of activity and there is evidence that GABAergic mechanisms play an important role in their regulation. In this study we analyzed the distribution and subcellular localization of GABA B receptors in the midbrain Raphe complex using combined 5-HT/GABA B receptor immunohistochemistry at the light and electron microscopic levels and studied the effects of their pharmacological manipulation on hippocampal electroencephalographic activity in urethane-anesthetized rats. We found that sustained infusion of the GABA B receptor agonist baclofen into the median Raphe Nucleus, using the microdialysis technique, elicited lasting theta activity in the hippocampus. The effect was antagonized by selective GABA B receptor antagonists. The predominant localization of GABA B receptors in the median, as well as in dorsal Raphe was found on serotonergic neurons which strongly indicates that the increase in theta occurrence after baclofen injection resulted from suppression of the serotonergic output originating from the median Raphe. On the electron microscopic level, we found GABA B receptors located extrasynaptically indicating that these receptors are preferentially activated by strong inputs, i.e. when GABA released from the synaptic terminals is sufficient to spill over from the synaptic cleft. Such conditions might be satisfied during rapid eye movement sleep when GABAergic neurons in the Raphe are firing at their highest rate and in rhythmic synchronized bursts. Our data indicate that midbrain Raphe GABA B mechanisms play an important role in behavioral state control and in hippocampal activity, in particular.
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reduction of the extracellular level of glutamate in the median Raphe Nucleus associated with hippocampal theta activity in the anaesthetized rat
Neuroscience, 1998Co-Authors: Viktor Sebestyen Varga, A Kekesi, Gábor Juhász, Bernat KocsisAbstract:Abstract The relationship between hippocampal activity and the extracellular level of excitatory amino acids in the median Raphe Nucleus has been studied in urethane anaesthetized rats, using the in vivo microdialysis technique. Dialysates were collected from the median Raphe Nucleus during two to eight sampling periods of equal length (20 min) and hippocampal electroencephalogram was continuously monitored. For each observation period, the average glutamate level in the median Raphe Nucleus was determined and the percentage of theta and non-theta segments in the hippocampal recordings was calculated. Theta synchronization, in these experiments, either developed spontaneously or it was elicited by injection of anticholinesterase (Physostigmine or Sintostigmine, i.p.) or by a series of short tail pinches. The relationship between hippocampal activity and glutamate release in the median Raphe Nucleus was characterized by comparison of the direction of changes in these two parameters in consecutive sampling periods. We found that as long as theta/non-theta ratio changed spontaneously or under the effect of anticholinesterase ( n =7), the extracellular level of glutamate in the median Raphe Nucleus was elevated during periods dominated by desynchronized hippocampal activity as compared with those mostly containing long and/or frequently occurring theta segments. Such relationship was not observed in the adjacent reticular formation ( n =4) and in the median Raphe Nucleus during sensory stimulation ( n =2). The present data complete those found earlier indicating that the desynchronizing serotonergic influence originating from the brainstem is maintained by a tonic excitatory input to the median Raphe Nucleus. Since the majority of glutamatergic afferents to the median Raphe Nucleus originates from the lateral habenula and the interpeduncular Nucleus, known to connect limbic forebrain to the brainstem, theta associated changes in median Raphe Nucleus glutamate levels might reflect descending forebrain influences, suggesting therefore a feedback regulation of the hippocampal activity involving brainstem structures.
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Pharmacological suppression of the median Raphe Nucleus with serotonin1a agonists, 8-OH-DPAT and buspirone, produces hippocampal theta rhythm in the rat
Neuroscience, 1994Co-Authors: Gene G Kinney, Bernat Kocsis, W.j. FortinAbstract:Abstract The effects on the hippocampal electroencephalogram of microinjections of procaine hydrochloride and the serotonin 1a agonists, 8-OH-DPAT and buspirone, into the median Raphe Nucleus were examined in the urethane anesthetized rat. Injections of procaine, 8-OH-DPAT or buspirone into the median Raphe Nucleus produced a change in the hippocampal electroencephalogram from a spontaneous desynchronized pattern to a synchronized pattern (theta rhythm) within short latencies and for long durations post-injection. Procaine was shown to elicit theta at a mean latency of 52 s and for a mean duration of 21.75 min; buspirone at a mean latency of 2 min and for a mean duration of 34.5 min. A dose dependent relationship was observed between 8-OH-DPAT injections and latencies but not durations. Small doses (0.5μg) of 8-OH-DPAT produced theta at a mean latency of 1.33 min and large doses (3.0μg) at a mean latency of 1.17 min. 8-OH-DPAT injections generated theta for a mean duration of 62 min. Injections of each of these substances into structures dorsal, lateral or rostrocaudal to the median Raphe (dorsal Raphe Nucleus, pontine reticular formation, caudal linear Nucleus or Raphe pontis, respectively) failed to generate theta or in a few cases produced theta at very long latencies (> 24 min). Saline injections in the median Raphe Nucleus or control structures were without effect. The demonstration that agents injected into the median Raphe Nucleus that inhibit its activity (procaine and serotonin 1a agonists) produce theta indicate that serotonin-containing median Raphe neurons normally suppress theta or are involved in the control of hippocampal desynchronization. The present findings are consistent with previous work showing that median Raphe Nucleus stimulation desynchronizes the hippocampal electroencephalogram and that median Raphe Nucleus lesions produce constant theta, but are at odds with the proposal that serotonergic mechanisms may play a role in the generation of the theta rhythm.
Minmin Luo - One of the best experts on this subject based on the ideXlab platform.
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serotonin neurons in the dorsal Raphe Nucleus encode reward signals
Nature Communications, 2016Co-Authors: Weixin Zhong, Daqing Wang, Qiru Feng, Zhixiang Liu, Jingfeng Zhou, Chunying Jia, Jiawei Zeng, Qingchun Guo, Minmin LuoAbstract:The dorsal Raphe Nucleus (DRN) is involved in organizing reward-related behaviours; however, it remains unclear how genetically defined neurons in the DRN of a freely behaving animal respond to various natural rewards. Here we addressed this question using fibre photometry and single-unit recording from serotonin (5-HT) neurons and GABA neurons in the DRN of behaving mice. Rewards including sucrose, food, sex and social interaction rapidly activate 5-HT neurons, but aversive stimuli including quinine and footshock do not. Both expected and unexpected rewards activate 5-HT neurons. After mice learn to wait for sucrose delivery, most 5-HT neurons fire tonically during waiting and then phasically on reward acquisition. Finally, GABA neurons are activated by aversive stimuli but inhibited when mice seek rewards. Thus, DRN 5-HT neurons positively encode a wide range of reward signals during anticipatory and consummatory phases of reward responses. Moreover, GABA neurons play a complementary role in reward processing.
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reward processing by the dorsal Raphe Nucleus 5 ht and beyond
Learning & Memory, 2015Co-Authors: Minmin Luo, Jingfeng Zhou, Zhixiang LiuAbstract:The dorsal Raphe Nucleus (DRN) represents one of the most sensitive reward sites in the brain. However, the exact relationship between DRN neuronal activity and reward signaling has been elusive. In this review, we will summarize anatomical, pharmacological, optogenetics, and electrophysiological studies on the functions and circuit mechanisms of DRN neurons in reward processing. The DRN is commonly associated with serotonin (5-hydroxytryptamine; 5-HT), but this Nucleus also contains neurons of the neurotransmitter phenotypes of glutamate, GABA and dopamine. Pharmacological studies indicate that 5-HT might be involved in modulating reward- or punishment-related behaviors. Recent optogenetic stimulations demonstrate that transient activation of DRN neurons produces strong reinforcement signals that are carried out primarily by glutamate. Moreover, activation of DRN 5-HT neurons enhances reward waiting. Electrophysiological recordings reveal that the activity of DRN neurons exhibits diverse behavioral correlates in reward-related tasks. Studies so far thus demonstrate the strong power of DRN neurons in reward signaling and at the same time invite additional efforts to dissect the roles and mechanisms of different DRN neuron types in various processes of reward-related behaviors.
Viktor Sebestyen Varga - One of the best experts on this subject based on the ideXlab platform.
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gabaergic control of the ascending input from the median Raphe Nucleus to the limbic system
Journal of Neurophysiology, 2005Co-Authors: Shaomin Li, Viktor Sebestyen Varga, Bernat KocsisAbstract:The median Raphe Nucleus (MRN) is the primary source of serotonergic afferents to the limbic system that are generally considered to suppress hippocampal theta oscillations. GABA receptors are expr...
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gabab receptors in the median Raphe Nucleus distribution and role in the serotonergic control of hippocampal activity
Neuroscience, 2002Co-Authors: Viktor Sebestyen Varga, T F Freund, Bernat KocsisAbstract:Abstract Previous studies have shown that serotonergic neurons of the median Raphe Nucleus have a suppressive effect on theta synchronization in the hippocampus. Median Raphe lesion, suppression of 5-HT neuronal activity by administration of GABA A receptor antagonist or by glutamate blockade or depletion produced long-lasting non-interrupted hippocampal theta in freely behaving rats independent of behavior and in rats anesthetized with urethane. Serotonergic neurons show a characteristic sleep–wake pattern of activity and there is evidence that GABAergic mechanisms play an important role in their regulation. In this study we analyzed the distribution and subcellular localization of GABA B receptors in the midbrain Raphe complex using combined 5-HT/GABA B receptor immunohistochemistry at the light and electron microscopic levels and studied the effects of their pharmacological manipulation on hippocampal electroencephalographic activity in urethane-anesthetized rats. We found that sustained infusion of the GABA B receptor agonist baclofen into the median Raphe Nucleus, using the microdialysis technique, elicited lasting theta activity in the hippocampus. The effect was antagonized by selective GABA B receptor antagonists. The predominant localization of GABA B receptors in the median, as well as in dorsal Raphe was found on serotonergic neurons which strongly indicates that the increase in theta occurrence after baclofen injection resulted from suppression of the serotonergic output originating from the median Raphe. On the electron microscopic level, we found GABA B receptors located extrasynaptically indicating that these receptors are preferentially activated by strong inputs, i.e. when GABA released from the synaptic terminals is sufficient to spill over from the synaptic cleft. Such conditions might be satisfied during rapid eye movement sleep when GABAergic neurons in the Raphe are firing at their highest rate and in rhythmic synchronized bursts. Our data indicate that midbrain Raphe GABA B mechanisms play an important role in behavioral state control and in hippocampal activity, in particular.
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reduction of the extracellular level of glutamate in the median Raphe Nucleus associated with hippocampal theta activity in the anaesthetized rat
Neuroscience, 1998Co-Authors: Viktor Sebestyen Varga, A Kekesi, Gábor Juhász, Bernat KocsisAbstract:Abstract The relationship between hippocampal activity and the extracellular level of excitatory amino acids in the median Raphe Nucleus has been studied in urethane anaesthetized rats, using the in vivo microdialysis technique. Dialysates were collected from the median Raphe Nucleus during two to eight sampling periods of equal length (20 min) and hippocampal electroencephalogram was continuously monitored. For each observation period, the average glutamate level in the median Raphe Nucleus was determined and the percentage of theta and non-theta segments in the hippocampal recordings was calculated. Theta synchronization, in these experiments, either developed spontaneously or it was elicited by injection of anticholinesterase (Physostigmine or Sintostigmine, i.p.) or by a series of short tail pinches. The relationship between hippocampal activity and glutamate release in the median Raphe Nucleus was characterized by comparison of the direction of changes in these two parameters in consecutive sampling periods. We found that as long as theta/non-theta ratio changed spontaneously or under the effect of anticholinesterase ( n =7), the extracellular level of glutamate in the median Raphe Nucleus was elevated during periods dominated by desynchronized hippocampal activity as compared with those mostly containing long and/or frequently occurring theta segments. Such relationship was not observed in the adjacent reticular formation ( n =4) and in the median Raphe Nucleus during sensory stimulation ( n =2). The present data complete those found earlier indicating that the desynchronizing serotonergic influence originating from the brainstem is maintained by a tonic excitatory input to the median Raphe Nucleus. Since the majority of glutamatergic afferents to the median Raphe Nucleus originates from the lateral habenula and the interpeduncular Nucleus, known to connect limbic forebrain to the brainstem, theta associated changes in median Raphe Nucleus glutamate levels might reflect descending forebrain influences, suggesting therefore a feedback regulation of the hippocampal activity involving brainstem structures.
Pierre-hervé Luppi - One of the best experts on this subject based on the ideXlab platform.
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FOREBRAIN AFFERENTS TO THE RAT DORSAL Raphe Nucleus DEMONSTRATED BY RETROGRADE AND ANTEROGRADE TRACING METHODS
Neuroscience, 1998Co-Authors: Christelle Peyron, Jean-marie Petit, Claire Rampon, Michel Jouvet, Pierre-hervé LuppiAbstract:Abstract The dorsal Raphe Nucleus through its extensive efferents has been implicated in a great variety of physiological and behavioural functions. However, little is know about its afferents. Therefore, to identify the systems likely to influence the activity of serotonergic neurons of the dorsal Raphe Nucleus, we re-examined the forebrain afferents to the dorsal Raphe Nucleus using cholera toxin b subunit and Phaseolus vulgaris-leucoagglutinin as retrograde or anterograde tracers. With small cholera toxin b subunit injection sites, we further determined the specific afferents to the ventral and dorsal parts of the central dorsal Raphe Nucleus, the rostral dorsal Raphe Nucleus and the lateral wings. In agreement with previous studies, we observed a large number of retrogradely-labelled cells in the lateral habenula following injections in all subdivisions of the dorsal Raphe Nucleus. In addition, depending on the subdivision of the dorsal Raphe Nucleus injected, we observed a small to large number of retrogradely-labelled cells in the orbital, cingulate, infralimbic, dorsal peduncular, and insular cortice, a moderate or substantial number in the ventral pallidum and a small to substantial number in the claustrum. In addition, we observed a substantial to large number of cells in the medial and lateral preoptic areas and the medial preoptic Nucleus after cholera toxin b subunit injections in the dorsal Raphe Nucleus excepting for those located in the ventral part of the central dorsal Raphe Nucleus, after which we found a moderate number of retrogradely-labelled cells. Following cholera toxin b subunit injections in the dorsal part of the central dorsal Raphe Nucleus, a large number of retrogradely-labelled cells was seen in the lateral, ventral and medial parts of the bed Nucleus of the stria terminalis whereas only a small to moderate number was visualized after injections in the other dorsal Raphe Nucleus subdivisions. In addition, respectively, a substantial and a moderate number of retrogradely-labelled cells was distributed in the zona incerta and the subincertal Nucleus following all tracer injections in the dorsal Raphe Nucleus. A large number of retrogradely-labelled cells was also visualized in the lateral, dorsal and posterior hypothalamic areas and the perifornical Nucleus after cholera toxin b subunit injections in the dorsal part of the central Raphe Nucleus and to a lesser extent following injections in the other subdivisions. We further observed a substantial to large number of retrogradely-labelled cells in the tuber cinereum and the medial tuberal Nucleus following cholera toxin b subunit injections in the dorsal part of the central Raphe Nucleus or the lateral wings and a small to moderate number after injections in the two other dorsal Raphe Nucleus subdivisions. A moderate or substantial number of labelled cells was also seen in the ventromedial hypothalamic area and the arcuate Nucleus following cholera toxin injections in the dorsal part of the central dorsal Raphe Nucleus and the lateral wings and an occasional or small number with injection sites located in the other subdivisions. Finally, we observed, respectively, a moderate and a substantial number of retrogradely-labelled cells in the central Nucleus of the amygdala following tracer injections in the ventral or dorsal parts of the central dorsal Raphe Nucleus and a small number after injections in the other subnuclei. In agreement with these retrograde data, we visualized anterogradely-labelled fibres heterogeneously distributed in the dorsal Raphe Nucleus following Phaseolus vulgaris-leucoagglutinin injections in the lateral orbital or infralimbic cortice, the lateral preoptic area, the perifornical Nucleus, the lateral or posterior hypothalamic areas, the zona incerta, the subincertal Nucleus or the medial tuberal Nucleus. Altogether our retrograde and anterograde results clearly indicate, in contrast to previous studies, that each dorsal Raphe Nucleus subdivision receives a differential distribution of afferents from numerous forebrain structures.
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forebrain afferents to the rat dorsal Raphe Nucleus demonstrated by retrograde and anterograde tracing methods
Neuroscience, 1997Co-Authors: Christelle Peyron, Jean-marie Petit, Claire Rampon, Michel Jouvet, Pierre-hervé LuppiAbstract:The dorsal Raphe Nucleus through its extensive efferents has been implicated in a great variety of physiological and behavioural functions. However, little is know about its afferents. Therefore, to identify the systems likely to influence the activity of serotonergic neurons of the dorsal Raphe Nucleus, we re-examined the forebrain afferents to the dorsal Raphe Nucleus using cholera toxin b subunit and Phaseolus vulgaris-leucoagglutinin as retrograde or anterograde tracers. With small cholera toxin b subunit injection sites, we further determined the specific afferents to the ventral and dorsal parts of the central dorsal Raphe Nucleus, the rostral dorsal Raphe Nucleus and the lateral wings. In agreement with previous studies, we observed a large number of retrogradely-labelled cells in the lateral habenula following injections in all subdivisions of the dorsal Raphe Nucleus. In addition, depending on the subdivision of the dorsal Raphe Nucleus injected, we observed a small to large number of retrogradely-labelled cells in the orbital, cingulate, infralimbic, dorsal peduncular, and insular cortice, a moderate or substantial number in the ventral pallidum and a small to substantial number in the claustrum. In addition, we observed a substantial to large number of cells in the medial and lateral preoptic areas and the medial preoptic Nucleus after cholera toxin b subunit injections in the dorsal Raphe Nucleus excepting for those located in the ventral part of the central dorsal Raphe Nucleus, after which we found a moderate number of retrogradely-labelled cells. Following cholera toxin b subunit injections in the dorsal part of the central dorsal Raphe Nucleus, a large number of retrogradely-labelled cells was seen in the lateral, ventral and medial parts of the bed Nucleus of the stria terminalis whereas only a small to moderate number was visualized after injections in the other dorsal Raphe Nucleus subdivisions. In addition, respectively, a substantial and a moderate number of retrogradely-labelled cells was distributed in the zona incerta and the subincertal Nucleus following all tracer injections in the dorsal Raphe Nucleus. A large number of retrogradely-labelled cells was also visualized in the lateral, dorsal and posterior hypothalamic areas and the perifornical Nucleus after cholera toxin b subunit injections in the dorsal part of the central Raphe Nucleus and to a lesser extent following injections in the other subdivisions. We further observed a substantial to large number of retrogradely-labelled cells in the tuber cinereum and the medial tuberal Nucleus following cholera toxin b subunit injections in the dorsal part of the central dorsal Raphe Nucleus or the lateral wings and a small to moderate number after injections in the two other dorsal Raphe Nucleus subdivisions. A moderate or substantial number of labelled cells was also seen in the ventromedial hypothalamic area and the arcuate Nucleus following cholera toxin injections in the dorsal part of the central dorsal Raphe Nucleus and the lateral wings and an occasional or small number with injection sites located in the other subdivisions. Finally, we observed, respectively, a moderate and a substantial number of retrogradely-labelled cells in the central Nucleus of the amygdala following tracer injections in the ventral or dorsal parts of the central dorsal Raphe Nucleus and a small number after injections in the other subnuclei. In agreement with these retrograde data, we visualized anterogradely-labelled fibres heterogeneously distributed in the dorsal Raphe Nucleus following Phaseolus vulgaris-leucoagglutinin injections in the lateral orbital or infralimbic cortice, the lateral preoptic area, the perifornical Nucleus, the lateral or posterior hypothalamic areas, the zona incerta, the subincertal Nucleus or the medial tuberal Nucleus. (ABSTRACT TRUNCATED)