Dorsal raphe nucleus

Molecular Brain volume 9Article number: 71 Cite this article. Metrics details. Serotonergic neurons in the dorsal raphe nucleus DRN are involved in the control of sleep-wake states, dorsal raphe nucleus. Application of CaCl 2 25 or 50 nmol in the DRN significantly increased serotonin in the DRN and hypothalamus, and noradrenaline in the locus coeruleus and hypothalamus.

Federal government websites often end in. The site is secure. Harvard Dataverse. Molecular and anatomical organization of the dorsal raphe nucleus. The dorsal raphe nucleus DRN is an important source of neuromodulators and has been implicated in a wide variety of behavioral and neurological disorders.

Dorsal raphe nucleus

The dorsal raphe nucleus DRN is an important source of neuromodulators and has been implicated in a wide variety of behavioral and neurological disorders. The DRN is subdivided into distinct anatomical subregions comprised of multiple cell types, and its complex cellular organization has impeded efforts to investigate the distinct circuit and behavioral functions of its subdomains. Here we used single-cell RNA sequencing, in situ hybridization, anatomical tracing, and spatial correlation analysis to map the transcriptional and spatial profiles of cells from the mouse DRN. Our analysis of 39, single-cell transcriptomes revealed at least 18 distinct neuron subtypes and 5 serotonergic neuron subtypes with distinct molecular and anatomical properties, including a serotonergic neuron subtype that preferentially innervates the basal ganglia. Our study lays out the molecular organization of distinct serotonergic and non-serotonergic subsystems, and will facilitate the design of strategies for further dissection of the DRN and its diverse functions. The dorsal raphe nucleus DRN is a major source of neuromodulators in the central nervous system, and is the largest of the serotonergic nuclei, containing approximately a third of all serotonergic neurons 5-HT neurons in the brain Hornung, DRN 5-HT neurons send highly divergent projections that target many functionally distinct brain regions Azmitia and Segal, ; Muzerelle et al. Concordantly, diverse and at times conflicting functions have been proposed for DRN 5-HT neurons, including arousal Monti, , motor facilitation Jacobs and Fornal, , behavioral inhibition Miyazaki et al. Serotonergic signaling pathways are also targets of widely-used therapeutic drugs, such as selective serotonin reuptake inhibitors SSRIs and atypical antipsychotics Meltzer and Massey, ; Vaswani et al. However many of these drugs can acutely induce adverse side effects including anxiety and increased risk of suicidal behaviors Ferguson, ; Gartlehner et al.

Two separate infrared photodiodes detected nose poking through the reward port and licking behaviour. A Textbook of Neuroanatomy 2nd ed. Stress increases aversive prediction error dorsal raphe nucleus in the ventral striatum.

Thank you for visiting nature. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser or turn off compatibility mode in Internet Explorer. In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. 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. 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.

Federal government websites often end in. The site is secure. 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.

Dorsal raphe nucleus

The dorsal raphe nucleus DRN is an important source of neuromodulators and has been implicated in a wide variety of behavioral and neurological disorders. The DRN is subdivided into distinct anatomical subregions comprised of multiple cell types, and its complex cellular organization has impeded efforts to investigate the distinct circuit and behavioral functions of its subdomains. Here we used single-cell RNA sequencing, in situ hybridization, anatomical tracing, and spatial correlation analysis to map the transcriptional and spatial profiles of cells from the mouse DRN. Our analysis of 39, single-cell transcriptomes revealed at least 18 distinct neuron subtypes and 5 serotonergic neuron subtypes with distinct molecular and anatomical properties, including a serotonergic neuron subtype that preferentially innervates the basal ganglia. Our study lays out the molecular organization of distinct serotonergic and non-serotonergic subsystems, and will facilitate the design of strategies for further dissection of the DRN and its diverse functions. Keywords: dorsal raphe nucleus; mouse; neuromodulation; neuroscience; serotonin; single cell RNAseq. Abstract The dorsal raphe nucleus DRN is an important source of neuromodulators and has been implicated in a wide variety of behavioral and neurological disorders.

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Facilitation of a dendritic calcium conductance by 5-hydroxytryptamine in the substantia nigra. Tissue chunks were then mechanically triturated using fine-tip plastic micropipette tips of progressively decreasing size. Most GABA neurons reduced spike firing when a mouse sought sucrose in the reward zone. Finally, I will discuss the possible mechanisms by which 5-HT modulates value-based decision making, together with dopamine and other brain structures, such as the lateral habenula, amygdala, frontal cortex, and basal ganglia. A mouse completed 40—80 trials in a single session. Hale MW Lowry CA Functional topography of midbrain and pontine serotonergic systems: implications for synaptic regulation of serotonergic circuits Psychopharmacology — Wright, D. Its principle neurons project widely over the brain and strongly interconnect with several reward-related brain areas 5 , 6 , 7 , 8. Sakai, K. Similar results were obtained when using CCA-based dataset alignment techniques that are available in the Seurat package Author response image 9. Further studies incurring a trade-off on cell count and the number of cell types captured for higher sequencing depth may also resolve additional transcriptional heterogeneity between subtypes within specific populations.

The dorsal raphe nucleus is one of the raphe nuclei. It is situated in the brainstem at the midline.

For example, for the neuron shown in Figure 2A , the pre-reward activity increased compared with the baseline in both the large- and small-reward trials. Among several receptor types, 5-HT2A receptors are particularly dense in the prefrontal and anterior cingulate cortices Pazos et al. Concordantly, diverse and at times conflicting functions have been proposed for DRN 5-HT neurons, including arousal Monti, , motor facilitation Jacobs and Fornal, , behavioral inhibition Miyazaki et al. Tissue chunks were then mechanically triturated using fine-tip plastic micropipette tips of progressively decreasing size. Consistent with this hypothesis, our results suggest that many of the physiological and anatomical differences between 5-HT neuron subtypes are a result of molecular differences specified by expression of overlapping but distinct transcriptional networks. During the delay period, three out of the seven test mice started licking during the waiting period before sucrose delivery, whereas the other four mice licked only after sucrose delivery Supplementary Fig. Samuels ER, Szabadi E. Miyazaki, K. Cui, SY. To characterize the activity patterns of neurons during all task phases in an unbiased manner, we applied principal component analysis Richmond and Optican, ; Paz et al. See " Single-cell transcriptomes and whole-brain projections of serotonin neurons in the mouse dorsal and median raphe nuclei " in volume 8, e Distributions of each projection-defined subpopulation are represented as probability maps magenta overlaid on the averaged Tph2 expression. Nevertheless, further analysis indicated that only the first two principal components explained significantly more variance in activity than would be expected under the null hypothesis that there were no systematic patterns in the data using shuffled datasets Bromberg-Martin et al. Effects of CaCl 2 microinjection in the DRN on neuronal activity in sleep-wake regulating nucleus raw data.