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.

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.

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.

Neuropsychopharmacology 35, —

The dorsal raphe nucleus is one of the raphe nuclei. It is situated in the brainstem at the midline. It has rostral and caudal subdivisions:. The DRN issues serotonergic efferents to the hippocampal formation, limbic lobe, and amygdala these efferents are involved in regulation of memory processing. The dorsal raphe is the largest serotonergic nucleus and provides a substantial proportion of the serotonin innervation to the forebrain. Serotonergic neurons are found throughout the dorsal raphe nucleus and tend to be larger than other cells. A substantial population of cells synthesizing substance P are found in the rostral aspects, many of these co-express serotonin and substance P.

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

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.

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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 topographical arrangement of convergent cortical inputs into distinct domains within the striatum Hintiryan et al. Topography of serotonin neurons in the dorsal raphe nucleus that send axon collaterals to the rat prefrontal cortex and nucleus accumbens. Together, these results provide a molecular foundation of the heterogenous serotonin neuronal phenotypes. One possibility is that this tonic modulation of activity encodes sustained aspects of motivated behavior, such as the state of expectation of future rewards for each moment. ISH for each of these subtype-enriched genes was performed on separate sets of RbV-labeled cells Figure 7. Altogether, 5-HT2C receptors tonically regulate, mainly by inhibition, dopamine release from the terminal regions of the nigrostriatal and mesolimbic pathways Di Giovanni et al. A spatial expression matrix for the differentially expressed DE genes was constructed using in situ hybridization images from the Allen Brain Atlas. Synapse 15, 90— J Physiol. However, neither Str-projecting nor M1-projecting subpopulations were fully contained within the distribution of a single 5-HT neuron subtype. The first three major principle components were then used to calculate Euclidean distance metric. Confocal images were first processed in Fiji. Evers, E.

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Haj-Dahmane, S. Although the DRN has many shared functions with the basal ganglia, DRN neurons are also involved in modulation of sensory pathways, limbic and neuroendocrine systems, and brainstem motor nuclei, and it has been proposed that anatomically segregated subsets of DRN 5-HT neurons form separate efferent pathways to perform these different functions Hale and Lowry, ; Lowry, ; Muzerelle et al. I will review the results of single unit recordings from the DRN, including our recent experiments in monkeys. Muscat, R. Additionally, the close spatial proximity of these two subtypes also presents a plausible mechanism for competitive inhibition between these separate subsystems via 5-HT1A receptors and local 5-HT release, which may be relevant to selective sensory modulation by movement or changes in behavioral state Hall et al. The 5-HT signalling system regulates feeding and social behaviours 12 , 13 , See " Single-cell transcriptomes and whole-brain projections of serotonin neurons in the mouse dorsal and median raphe nuclei " in volume 8, e The transcriptomic information we obtained on DRN 5-HT neuron subtypes allowed us to access a specific 5-HT subsystem that innervates circuits of the basal ganglia. Liu, Z. Social interaction.