Nitrergic neurons of the dorsal raphe nucleus encode information about stress duration

Nichols, India; Jones, M I; Okere, Chuma O.; Ananaba, Godwin A.; Bush, Brittany J; Gray, Cloe L; Brager, Allison J.; Ehlen, J. Christopher; Paul, Ketema N.

doi:10.1371/journal.pone.0187071

Cited by 5 publications

(3 citation statements)

References 24 publications

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“…Electrophysiological studies have shown DR 5‐HT neurons can alter the release probability of glutamate and GABA from presynaptic terminals in the DR using endocannabinoids (eCBs) and nitric oxide (NO) as retrograde messengers (Haj‐Dahmane, Beique, & Shen, ; Kim et al., ; Wang et al., ). eCBs have been directly implicated in glucocorticoid‐induced reductions of sEPSC frequency in DR 5‐HT neurons (Wang et al., ) and restraint stress as well as capsaicin injection increase NO production in 5‐HT neurons within specific subregions of the nucleus (Nichols et al., ; Okere & Waterhouse, , ). Our previous finding that a significantly greater proportion of DR 5‐HT neurons projecting to mPFC versus LGN (60% vs. 22%) have the capacity to synthesize NO also supports the possibility of target‐specific differences in retrograde signaling (Prouty et al., ).…”

Section: Discussionmentioning

confidence: 99%

Selective vulnerability of dorsal raphe‐medial prefrontal cortex projection neurons to corticosterone‐induced hypofunction

Prouty

Chandler

Gao

et al. 2019

Eur J of Neuroscience

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Glucocorticoid hormones and serotonin (5‐HT) are strongly associated with the development and treatment of depression, respectively. Glucocorticoids regulate the function of serotonergic neurons in the dorsal raphe nucleus (DR), which are the major source of 5‐HT to the forebrain. DR 5‐HT neurons are electrophysiologically heterogeneous, though whether this phenotypic variation aligns with specific brain functions or neuropsychiatric disease states is largely unknown. The goal of this work was to determine if chronic exogenous glucocorticoid administration differentially affects the electrophysiological profile of DR neurons implicated in the regulation of emotion versus visual sensation by comparing properties of cells projecting to medial prefrontal cortex (mPFC) versus lateral geniculate nucleus (LGN). Following retrograde tracer injection into mPFC or LGN, male Sprague‐Dawley rats received daily injections of corticosterone (CORT) for 21 days, after which whole‐cell patch clamp recordings were made from retrogradely labeled DR neurons. CORT‐treatment significantly increased the action potential half‐width of LGN‐projecting DR neurons, but did not significantly affect the firing frequency or excitatory postsynaptic currents of these cells. CORT‐treatment significantly reduced the input resistance, evoked firing frequency, and spontaneous excitatory postsynaptic current frequency of mPFC‐projecting DR neurons, indicating a concurrent reduction of both intrinsic excitability and excitatory drive. Our results suggest that the serotonergic regulation of cognitive and emotional networks in the mPFC may be more sensitive to the effects of glucocorticoid excess than visual sensory circuits in the LGN and that reduced 5‐HT transmission in the mPFC may underlie the association between glucocorticoid excess and depression.

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Section: Discussionmentioning

confidence: 99%

Selective vulnerability of dorsal raphe‐medial prefrontal cortex projection neurons to corticosterone‐induced hypofunction

Prouty

Chandler

Gao

et al. 2019

Eur J of Neuroscience

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“…The dorsal raphe nucleus (DRN), which contains 5-HT neurons distributed widely, is involved in the inhibition of pain through engagement with the descending pain modulation system 32 , 33 . Our findings showed that the expression levels of 5-HT in the DRN were increased in the BLM group compared to those of the other groups.…”

Section: Discussionmentioning

confidence: 99%

Evidence for chronic headaches induced by pathological changes of myodural bridge complex

Song,

Yu,

Yuan

et al. 2024

Sci Rep

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Clinical studies have shown that there may be a certain relationship between pathological changes of the myodural bridge complex (MDBC) and chronic headaches of unknown cause. But there is still a lack of experimental evidence to explain the possible mechanism. This study aims to further confirm this relationship between MDBC and chronic headaches and explore its potential occurrence mechanism in rats. Bleomycin (BLM) or phosphate-buffered saline (PBS) was injected into the myodural bridge fibers of rats to establish the hyperplastic model of MDBC. After 4 weeks, the occurrence of headaches in rats was evaluated through behavioral scores. The immunohistochemistry staining method was applied to observe the expression levels of headache-related neurotransmitters in the brain. Masson trichrome staining results showed that the number of collagen fibers of MDBC was increased in the BLM group compared to those of the other two groups. It revealed hyperplastic changes of MDBC. The behavioral scores of the BLM group were significantly higher than those of the PBS group and the blank control group. Meanwhile, expression levels of CGRP and 5-HT in the headache-related nuclei of the brain were increased in the BLM group. The current study further confirms the view that there is a relationship between pathological changes of MDBC and chronic headaches of unknown cause. This study may provide anatomical and physiological explanations for the pathogenesis of some chronic headaches of unknown cause.

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“…The dorsal raphe nucleus (DR) is an integral component of the serotonin (5-HT) system in the central nervous system. The DR responds potently to external stress, such as motion restraints and early maternal separation (Grahn et al, 1999;Hardaway, Crowley, Bulik, & Kash, 2015;Nichols et al, 2017;Pollano, Trujillo, & Suarez, 2018).Furthermore, a recent study using optogenetic tools revealed a causal relationship between activation of the serotonergic neurons in DR and active coping under inescapable stress in rats and mice (Nishitani et al, 2019). Anatomically, GABAergic interneurons (GABA-IN) in DR receive inputs from Layer 5 pyramidal neurons in the medial prefrontal cortex (mPFC) (Jankowski & Sesack, 2004).…”

Section: Introductionmentioning

confidence: 99%

Feedback inhibition by GABAergic interneurons that are driven by dorsal raphe-projecting pyramidal neurons of the medial prefrontal cortex suppress feeding of adolescent female mice undergoing activity-based anorexia

Du¹,

Santiago²,

Akiz³

et al. 2021

Preprint

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Anorexia Nervosa (AN) is characterized by voluntary food restriction, excessive exercise and mortality rate surpassing that of major depression. Activity-based anorexia (ABA) is an animal model that captures these characteristics of AN, thus having the potential to reveal the neurobiology underlying individual differences in AN vulnerability. Dorsal raphe (DR) is known to regulate feeding but its role in ABA remains unexplored. Through chemogenetic activation, we investigated the role of mPFC pyramidal neurons projecting to DR (mPFC→DR) in an animal’s decision to eat or exercise following ABA induction. Although the DREADD ligand C21 could activate 44% of the mPFC→DR neurons, this did not generate significant group mean difference in the amount of food intake, compared to control ABA mice without chemogenetic activation. However, further analysis of individual animals’ responses to C21 revealed a significant, positive correlation between food intake and mPFC→ DR neurons that co-express cFos, a marker for neuronal activity. cFos expression by GABAergic interneurons (GABA-IN) in mPFC was significantly greater than that for the control ABA mice, indicating recruitment of GABA-IN by mPFC→DR neurons. Electron microscopic immunohistochemistry (EM-ICC) revealed that GABAergic innervation is 60% greater for the PFC→DR neurons than the Layer 5 pyramidal neurons without projections to DR. Moreover, individual differences in this innervation correlated negatively with food intake specifically on the day of C21 administration. We propose that C21 activates two antagonistic pathways: 1) PFC→DR pyramidal neurons that promote food intake; and 2) GABA-IN in the mPFC that dampen food intake through feedback inhibition of mPFC→DR neurons.

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Nitrergic neurons of the dorsal raphe nucleus encode information about stress duration

Cited by 5 publications

References 24 publications

Selective vulnerability of dorsal raphe‐medial prefrontal cortex projection neurons to corticosterone‐induced hypofunction

Selective vulnerability of dorsal raphe‐medial prefrontal cortex projection neurons to corticosterone‐induced hypofunction

Evidence for chronic headaches induced by pathological changes of myodural bridge complex

Feedback inhibition by GABAergic interneurons that are driven by dorsal raphe-projecting pyramidal neurons of the medial prefrontal cortex suppress feeding of adolescent female mice undergoing activity-based anorexia

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