Dorsal raphe nucleus

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Molecular Brain volume 9 , Article number: 71 Cite this article. Metrics details. Serotonergic neurons in the dorsal raphe nucleus DRN are involved in the control of sleep-wake states. 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. Immunohistochemistry study indicated that application of CaCl 2 25 or 50 nmol in the DRN significantly increased c-Fos expression ratio in wake-promoting neurons including serotonergic neurons in the DRN, noradrenergic neurons in the locus coeruleus, and orxinergic neurons in the perifornical nucleus, but decreased c-Fos expression ratio of GABAergic sleep-promoting neurons in the ventrolateral preoptic nucleus. Dorsal raphe nucleus DRN provides the majority of serotonin 5-HT throughout the central nervous system, including the cerebral cortex, hypothalamus and brain stem [ 1 ].

Dorsal raphe nucleus

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. Conversely, putative dopamine neurons showed positive phasic responses to reward-indicating cues and the receipt of an unexpected reward amount, which supports the reward prediction error signal hypothesis of dopamine. I suggest that the tonic reward monitoring signal of the DRN, possibly together with its interaction with the dopamine system, reports a continuous level of motivation throughout the performance of a task. Serotonin 5-hydroxytryptamine, 5-HT is present in almost all organisms from plants to vertebrates. In mammals, 5-HT has been found in all organs, such as the brain, gut, lung, liver, kidney, and skin, as well as platelets.

The relative differences in the expression of highly expressed genes that the reviewers pointed to from Figure 3 are seen more easily with the centered Z-scored expression when making comparisons within the 5-HT neuron group Figure 4rather than across the full neuronal population Figure 3. Spatial information from in situ hybridization imaging datasets allowed us to infer the anatomical distribution of these DRN 5-HT neuron subtypes within dorsal raphe nucleus DRN, dorsal raphe nucleus. Supplementary file 2: Genes for spatial correlation analysis.

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.

Federal government websites often end in. The site is secure. Serotonin 5-HT is a neurotransmitter critically involved in a broad range of brain functions and implicated in the pathophysiology of neuropsychiatric illnesses including major depression, anxiety and sleep disorders. Despite being widely distributed throughout the brain, there is limited knowledge on the contribution of 5-HT to intrinsic brain activity. The dorsal raphe DR and median raphe MR nuclei are the source of most serotonergic neurons projecting throughout the brain and thus provide a compelling target for a seed-based probe of resting-state activity related to 5-HT. Here we implemented a novel multimodal neuroimaging approach for investigating resting-state functional connectivity FC between DR and MR and cortical, subcortical and cerebellar target areas. The DR and MR seeds produced largely similar FC maps: significant positive FC with brain regions involved in cognitive and emotion processing including anterior cingulate, amygdala, insula, hippocampus, thalamus, basal ganglia and cerebellum. Our results provide evidence for a resting-state network related to DR and MR and comprising regions receiving serotonergic innervation and centrally involved in 5-HT related behaviors including emotion, cognition and reward processing. These findings provide a novel advance in estimating resting-state FC related to 5-HT signaling, which can benefit our understanding of its role in behavior and neuropsychiatric illnesses. The serotonin 5-hydroxytryptamine, 5-HT neurotransmitter system is a critical component in the healthy functioning of the human brain and is involved in many functions such as sleep-wake cycle Portas et al.

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.

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Curves represent the normalized firing rate of the principal component during the fixation period black and after the onset of the rewarded red and unrewarded blue target, separately for the contralateral-rewarded block dark colors and ipsilateral-rewarded block light colors. Within the cortical-projecting group, frontal- and prefrontal-projecting subpopulations were differentially distributed along the anterior-posterior axis of the DRN — M1-projecting neurons were relatively confined to the anterior half of the DRN, whereas mPFC-projecting neurons were found in both anterior and posterior halves. If, however, the observed number of clusters is smaller focus on serotonergic cells; Figure 4A , than the small expression differences suddenly appear huge for these two genes. European Journal of Pharmacology. Ultrastructure and synaptic targets of the raphe-nigral projection in the rat. Distribution of serotonin-immunoreactivity in the central nervous system of the rat-cell bodies and terminals. This suggests these drugs affect multiple 5-HT pathways with distinct and contrasting effects on behavior and highlights the need for new approaches to target specific 5-HT neurons and their outputs Marcinkiewcz et al. The grey line in the lower panel indicates lick rates. 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. J Neurochem. Bromberg-Martin for helpful comments. Cortical areas projecting to the DRN include the medial prefrontal Arnsten and Goldman-Rakic, , lateral and medial orbital, cingulate, infralimbic, and insular cortices Arnsten and Goldman-Rakic, ; Sesack et al.

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All cells in our dataset were combined into one simulated pool since our dataset consisted of only R1-derived DRN neurons. These plots have been included in new supplements to both Figure 3 Figure 3—figure supplement 1 and Figure 4 now Figure 4—figure supplement 1. Reward encoding in the monkey anterior cingulate cortex. Mice were individually housed for at least 1 week to recover. It should also be clarified whether the regulation of the reward circuit by 5-HT is always dopamine-dependent, like the proposed scheme, or it can act independently and directly. Serotonin 5-hydroxytryptamine, 5-HT is present in almost all organisms from plants to vertebrates. 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. J Affect Disord. The test male often initiated mating behaviour following the introduction of a sexually receptive female Fig. Differential effects of 5-HT2C receptor activation by WAY on nicotine-induced place conditioning and locomotor activity in rats. Wikimedia Commons. Subsequently, correlation coefficients between the normalized expression scores for DE genes for each of these voxels and each 5-HT neuron subtype cluster were calculated Figure 5—figure supplement 1D , Figure 5—figure supplement 2. The activity of a neuron during the fixation period was strongly positively correlated with its degree of reward discrimination during the post-target and post-reward periods Figure 3D.