Dorsal raphe nucleus

Thank you for visiting nature.

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.

Dorsal raphe nucleus

The dorsal raphe nucleus DRN is a heterogeneous brainstem nucleus located in the midbrain and pons. Via widespread projections, which target a multitude of brain areas, its neurons utilize many transmitters to control various physiological functions, including learning, memory and affect. Accordingly, the DRN has been strongly associated with brain dysfunction, especially mood disorders such as depression, but also Alzheimer's disease. The DRN's most abundant transmitter, serotonin, has received the most attention in studies on both normal brain function and disease, and lately its involvement in the regulation of neuroplasticity has been under particular scrutiny. This chapter begins with a systematic overview of what we currently know about the anatomy of the DRN and its neurons, including their ascending projections. It continues with a review of the transmitters of the DRN, followed by a discussion on the connection between the DRN and neuroplasticity. Special emphasis is put on serotonin and its central role in neuroplasticity, which is proving to be of high priority in unraveling the full picture of the cellular mechanisms and their interconnections in the etiology of major depression and Alzheimer's disease. Abstract The dorsal raphe nucleus DRN is a heterogeneous brainstem nucleus located in the midbrain and pons. Publication types Research Support, Non-U. Gov't Review.

Alternatively, dorsal raphe nucleus, can they be also activated after an animal receives the reward, either expected or unexpected? The targeting of distinct channels or subcircuits within the basal ganglia may also be consistent with the innervation of the striatum by multiple 5-HT neuron subtypes given the dorsal raphe nucleus arrangement of convergent cortical inputs into distinct domains within the striatum Hintiryan et al.

Pharmacological experiments have shown that the modulation of brain serotonin levels has a strong impact on value-based decision making. The serotonin and dopamine systems also have reciprocal functional influences on each other. However, the specific mechanism by which serotonin affects value-based decision making is not clear. To understand the information carried by the DRN for reward-seeking behavior, we measured single neuron activity in the primate DRN during the performance of saccade tasks to obtain different amounts of a reward. We found that DRN neuronal activity was characterized by tonic modulation that was altered by the expected and received reward value. Consistent reward-dependent modulation across different task periods suggested that DRN activity kept track of the reward value throughout a trial. The DRN was also characterized by modulation of its activity in the opposite direction by different neuronal subgroups, one firing strongly for the prediction and receipt of large rewards, with the other firing strongly for small rewards.

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.

Dorsal raphe nucleus

Federal government websites often end in. Before sharing sensitive information, make sure you're on a federal government site. The site is secure. NCBI Bookshelf. Emily P. Walker ; Prasanna Tadi.

Indian reshma hot

GABAergic neurons in the ventrolateral preoptic nucleus VLPO [ 18 ] and histaminergic neurons in the TMN [ 19 ] and orexinergic neurons in the perifornical nucleus Pef [ 20 ] are the most crucial component in the hypothalamic sleep regulation [ 21 ]. In addition, 5-HT receptors located presynaptically on dopamine terminals or postsynaptically in dopamine projection areas could activate feedback loops, such as the striato-nigral, nucleus accumbens-VTA, or frontal-VTA pathways, thus indirectly altering the excitability of dopamine neurons in the SNc or VTA, resulting in changes in their baseline firing rates Di Giovanni et al. Given the trade-off between sequencing depth and the number of cells sampled when using droplet-based scRNA-seq techniques, we have refrained from suggesting a list of marker genes for all subtypes and instead report the enriched genes that we have sufficient confidence in. The level of clustering that we have performed on the 5-HT neurons in our dataset also goes further than described in the Zeisel et al. Schultz, W. Prediction of immediate and future rewards differentially recruits cortico-basal ganglia loops. B Heatmap showing the cluster average Z-scored expression of selected genes that are enriched in each neuron subtype. The systemic injection of the 5-HT releaser d -fenfluramine Fletcher, and the injection of 5-HT into the accumbens Fletcher, ; Fletcher and Korth, attenuated conditioned responses to obtain amphetamine. Neuropsychopharmacology 30, — Wise, R. Both expected and unexpected rewards activate 5-HT neurons. Author response image 6. Note, however, that a recent study provided anatomical and behavioral support for the localization of 5-HT2C receptors on dopamine neurons in the VTA Ji et al.

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.

Our scRNA-seq dataset yields predictions about local interactions involving DRN cells, including those with non-neuronal cells, based the expression patterns of known receptor-ligand pairs. Liu, Z. Cui, G. Correlated fixation-period activity, which represents the task value, and post-outcome activity, which represents the value of the received reward, indicate that DRN activity encodes behavioral tasks primarily in terms of their reward value throughout a trial. GABAergic neurons in the ventrolateral preoptic nucleus VLPO [ 18 ] and histaminergic neurons in the TMN [ 19 ] and orexinergic neurons in the perifornical nucleus Pef [ 20 ] are the most crucial component in the hypothalamic sleep regulation [ 21 ]. At first, we microinjected CaCl 2 into the DRN, and monitored sleep-wake behavior in freely moving rats for 6 hours. With regard to the validation of the 5-HT neuron subtypes by FISH experiments staining for subtype-specific marker genes, we wish to clarify the distinction between subtype enriched genes and subtype marker genes. Htr7 is expressed in subsets of GABAergic and glutamatergic neurons. Scatton, B. However, this approach ignores the full information contained in the many dozens or hundreds of genes whose expression differs in a graded manner across different cellular subtypes. 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. These interactions may be either synergistic if mediated by glutamatergic neurons innervating other 5-HT subtypes, or antagonistic in a form of lateral inhibition via GABAergic interneurons. We thank P. Origin of the dopaminergic innervation of the rat dorsal raphe nucleus. In the DRN population of neurons, the first principal component Figure 3E indicated a positive correlation between task onset-related activity and reward coding.