The organization of divergent axonal projections from the midbrain raphe nuclei in the rat

Imai, Hisamasa; Steindler, Dennis A.; Kitai, S.T.

doi:10.1002/cne.902430307

Cited by 347 publications

(225 citation statements)

References 53 publications

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“…Nor is there any data regarding distributions of projections from the shell (as opposed to core) dorsomedial DRN. Available data suggests that the dorsomedial DRN near the region in question projects heavily to bed nucleus stria terminalis, central and basolateral nuclei of the amygdala, lateral septum, nucleus acumbens, as well as several cortical regions (Imai et al, 1986, Vertes, 1991, Van Bockstaele et al, 1993. Possible involvement of the bed nucleus stria terminalis is intriguing, as this region has been implicated in recognition of unconditioned aversive environments (Walker and Davis, 1997, Walker et al, 2003, and has been found essential for the development of the animal model of depression referred to as learned helplessness .…”

Section: Serotonergic Gene Expression Following Chronic Crf Receptor mentioning

confidence: 99%

“…In any case, mid-rostral ventromedial DRN is well positioned to alter anxiety behavior. Its projection targets include frontal cortex (including medial prefrontal cortex), central nucleus of the amygdala, caudal locus coeruleus, and ventral hippocampus (Imai et al, 1986, Peyron et al, 1998, Lee et al, 2003, Kim et al, 2004. All of these structures have been implicated in modulating behavior in the open field (Velley et al, 1991, Burns et al, 1996, Daenen et al, 2002, making it possible that alterations in serotonergic function in the mid-rostral ventromedial DRN could underlie the changes in exploratory behavior observed.…”

Section: Serotonergic Gene Expression Following Chronic Crf Receptor mentioning

confidence: 99%

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Chronic low dose ovine corticotropin releasing factor or urocortin II into the rostral dorsal raphe alters exploratory behavior and serotonergic gene expression in specific subregions of the dorsal raphe

et al. 2007

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Corticotropin releasing factor (CRF) family peptides play key roles in integrating neural responses to stress. Both major CRF receptors have been pharmacologically identified in the dorsal raphe nucleus (DRN), a stress sensitive and internally heterogeneous nucleus supplying many forebrain regions with serotonergic input. Despite the involvement of chronic stress and serotonergic dysfunction in human mood and anxiety disorders, little is known about the effects of chronic CRF receptor activation on the DRN. We infused ovine CRF (1ng/hr), urocortin II (UCNII, 1ng/hr), or vehicle alone into rat DRN over 6 days. During infusion, animals were allowed to freely explore an open field for 15 minutes on each of two days, with the addition of a novel object on the second day. Following behavioral testing, 5-HT 1A , 5-HT 1B , serotonin transporter (SERT), and tryptophan hydroxylase-2 (Tph2) expression were examined through the DRN by in situ hybridization. Ovine CRF infusion resulted in significantly decreased novel object touches, climbs, as well as increased latency to first novel object contact. UCNII had a similar but less dramatic effect, decreasing only climbing behavior. Both ovine CRF and UCNII blunted the decrease in corner time expected on reexposure to the open field. Both peptides also produced regionally specific changes in gene expression: 5-HT 1A expression was increased 30% in the mid-rostral ventromedial DRN, while SERT was decreased by 30% in the mid-caudal shell dorsomedial DRN. There also appeared to be a shift in the relative level of Tph2 expression between the ventromedial and core dorsomedial DRN at the mid-rostral level. Changes in 5-HT 1A , SERT, and relative Tph2 mRNA abundance were correlated with novel object exploration. These findings suggest chronic intra-DRN administration of CRF agonists decreases exploratory behavior, while producing subregionally limited changes in serotonergic gene expression. These studies may be relevant to mechanisms underlying behavioral changes after chronic stress. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptDepression and anxiety disorders are among the leading causes of morbidity, mortality, and disability in the United States (Greenberg et al., 2003). They are often comorbid, and both are highly associated with chronic exposure to stress. Multiple lines of evidence suggest that chronic and inescapable stress produce long lasting effects on brain function and behavior that play a prominent role in the development, maintenance, and recurrence of both depression and a variety of anxiety disorders (Gulley and Nemeroff, 1993, Arborelius et al., 1999, Ressler and Nemeroff, 2000.Altered serotonin neurotransmission appears to be a central mechanism inducing both depressive (Maes and Meltzer, 1995) and anxiety disorders (Ressler and Nemeroff, 2000). The majority of serotonergic fibers to forebrain regions thought to be involved in mood and anxiety regulation arise from the dorsal raphe nucleus (DRN) and median raphe nucleus (MRN) ...

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Section: Serotonergic Gene Expression Following Chronic Crf Receptor mentioning

confidence: 99%

Section: Serotonergic Gene Expression Following Chronic Crf Receptor mentioning

confidence: 99%

Chronic low dose ovine corticotropin releasing factor or urocortin II into the rostral dorsal raphe alters exploratory behavior and serotonergic gene expression in specific subregions of the dorsal raphe

et al. 2007

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“…Proceeding rostrally, CRF innervation shifts medially and ventrally (Kirby et al, 2000;Valentino et al, 2001). The relevance of this pattern lies in the topographical organization of efferent projections arising from the DR. Anatomical studies have provided evidence for an encephalotopy within the DR, such that different brain regions are targeted by distinct cell groups within the DR (Kohler and Steinbusch, 1982;O'Hearn and Molliver, 1984;Imai et al, 1986;Vertes, 1991). In this regard, the amygdala and lateral septum, two regions in which swim stress decreases 5-HT release, receive a 5-HT innervation from the dorsolateral ).…”

Section: Relevance Of the Topography Of C-fos Expression In The Drmentioning

confidence: 99%

Circuitry Underlying Regulation of the Serotonergic System by Swim Stress

et al. 2003

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The dorsal raphe nucleus (DR)-serotonin (5-HT) system has been implicated in depression and is dramatically affected by swim stress, an animal model with predictive value for antidepressants. Accumulating evidence implicates the stress-related neuropeptide corticotropin-releasing factor (CRF) in the effect of swim stress on this system. This study investigated neural circuits within the DR that are activated by swim stress as revealed by neuronal expression of the immediate early gene, c-fos. Swim stress increased c-fos expression in the dorsolateral subregion of the DR. The majority of c-fos-expressing neurons were doubly labeled for GABA (85 Ϯ 5%), whereas relatively few were immunolabeled for 5-HT (4 Ϯ 1%), glutamate (0.5 Ϯ 0.3%) or calbindin (1.5 Ϯ 0.3%). Dual immunohistochemical labeling revealed that c-fos-expressing neurons in the dorsolateral DR were enveloped by dense clusters of CRF-immunoreactive fibers and also contained immunolabeling for CRF receptor, suggesting that c-fos-expressing neurons in the DR were specifically targeted by CRF. Consistent with this, the CRF receptor 1 antagonist, antalarmin, prevented swim-stress-elicited c-fos expression in the dorsolateral DR. Together with previous findings that both swim stress and CRF decrease 5-HT release in certain forebrain regions, these results suggest that swim stress engages CRF inputs to GABA neurons in the dorsolateral DR that function to inhibit 5-HT neurons and 5-HT release in the forebrain. This circuitry may underlie some of the acute behavioral responses to swim stress as well as the neuronal plasticity involved in long-term behavioral changes produced by this stress.

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“…This is reasonable given the role of 5-HT in depression and anxiety (Graeff et al, 1996;Kent et al, 1998;Anderson and Mortimore, 1999;Blier and de Montigny, 1999;Ninan, 1999;Blier, 2001b). Furthermore, the DRN is a primary source of 5-HT projections to regions implicated in affective and behavioral responses (Imai et al, 1986;Ma et al, 1991;Vertes, 1991;Kazakov et al, 1993). Attenuation of the activity of 5-HT neurons in the DRN during exposure to uncontrollable stress is sufficient to prevent LH.…”

Section: Introductionmentioning

confidence: 99%

Freewheel Running Prevents Learned Helplessness/Behavioral Depression: Role of Dorsal Raphe Serotonergic Neurons

Foley²,

et al. 2003

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The organization of divergent axonal projections from the midbrain raphe nuclei in the rat

Cited by 347 publications

References 53 publications

Chronic low dose ovine corticotropin releasing factor or urocortin II into the rostral dorsal raphe alters exploratory behavior and serotonergic gene expression in specific subregions of the dorsal raphe

Chronic low dose ovine corticotropin releasing factor or urocortin II into the rostral dorsal raphe alters exploratory behavior and serotonergic gene expression in specific subregions of the dorsal raphe

Circuitry Underlying Regulation of the Serotonergic System by Swim Stress

Freewheel Running Prevents Learned Helplessness/Behavioral Depression: Role of Dorsal Raphe Serotonergic Neurons

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