scholarly journals Molecular and anatomical organization of the dorsal raphe nucleus

2019 ◽  
Author(s):  
Kee Wui Huang ◽  
Nicole E. Ochandarena ◽  
Adrienne C. Philson ◽  
Minsuk Hyun ◽  
Jaclyn E. Birnbaum ◽  
...  

ABSTRACTThe dorsal raphe nucleus (DRN) is an important source of neuromodulators in the brain and has been implicated in a wide variety of behavioral and neurological disorders. Although mostly studied as a source of serotonin, the DRN is comprised of multiple cell types that are subdivided into distinct anatomical subregions. However, the complex and incompletely characterized cellular organization of the DRN has impeded efforts to investigate the distinct circuit and behavioral functions of its subdomains. Here we used high-throughput single-cell RNA sequencing within situhybridization and viral tracing to develop a map of transcriptional and spatial profiles of cells in and around the mouse DRN. Our studies reveal the molecular and spatial organization of multiple neuron subtypes that are the cellular bases of functionally and anatomically distinct serotonergic subsystems, and provide a resource for the design of strategies for further dissection of these subsystems and their diverse functions.

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Kee Wui Huang ◽  
Nicole E Ochandarena ◽  
Adrienne C Philson ◽  
Minsuk Hyun ◽  
Jaclyn E Birnbaum ◽  
...  

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 39,411 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.


2021 ◽  
Vol 15 ◽  
Author(s):  
Romeo Rebusi ◽  
Joshua Phillipe Olorocisimo ◽  
Jeric Briones ◽  
Yasumi Ohta ◽  
Makito Haruta ◽  
...  

Fluorescence imaging devices have been indispensable in elucidating the workings of the brain in living animals, including unrestrained, active ones. Various devices are available, each with their own strengths and weaknesses in terms of many factors. We have developed CMOS-based needle-type imaging devices that are small and lightweight enough to be doubly implanted in freely moving mice. The design also allowed angled implantations to avoid critical areas. We demonstrated the utility of the devices by using them on GCaMP6 mice in a formalin test experiment. Simultaneous implantations to the capsular-lateral central amygdala (CeLC) and dorsal raphe nucleus (DRN) were proven to be safe and did not hinder the execution of the study. Analysis of the collected calcium signaling data, supported by behavior data, showed increased activity in both regions as a result of pain stimulation. Thus, we have successfully demonstrated the various advantages of the device in its application in the pain experiment.


2016 ◽  
Vol 113 (19) ◽  
pp. 5429-5434 ◽  
Author(s):  
Sean D. Geddes ◽  
Saleha Assadzada ◽  
David Lemelin ◽  
Alexandra Sokolovski ◽  
Richard Bergeron ◽  
...  

Serotonin (5-HT) neurons located in the raphe nuclei modulate a wide range of behaviors by means of an expansive innervation pattern. In turn, the raphe receives a vast array of synaptic inputs, and a remaining challenge lies in understanding how these individual inputs are organized, processed, and modulated in this nucleus to contribute ultimately to the core coding features of 5-HT neurons. The details of the long-range, top-down control exerted by the medial prefrontal cortex (mPFC) in the dorsal raphe nucleus (DRN) are of particular interest, in part, because of its purported role in stress processing and mood regulation. Here, we found that the mPFC provides a direct monosynaptic, glutamatergic drive to both DRN 5-HT and GABA neurons and that this architecture was conducive to a robust feed-forward inhibition. Remarkably, activation of cannabinoid (CB) receptors differentially modulated the mPFC inputs onto these cell types in the DRN, in effect regulating the synaptic excitatory/inhibitory balance governing the excitability of 5-HT neurons. Thus, the CB system dynamically reconfigures the processing features of the DRN, a mood-related circuit believed to provide a concerted and distributed regulation of the excitability of large ensembles of brain networks.


1990 ◽  
Vol 258 (6) ◽  
pp. R1464-R1471 ◽  
Author(s):  
J. Mattila ◽  
R. D. Bunag

Pressor, tachycardic, and sympathoexcitatory responses to intracerebroventricularly (icv) infused thyrotropin-releasing hormone (TRH) were recorded in urethan-anesthetized rats to identify where centrally administered TRH acts in the brain. None of these responses was altered either by electrolytic lesions in the medial preoptic, posterior, or paraventricular hypothalamus or by chemical lesions produced by destroying catecholaminergic neurons with icv infused 6-hydroxydopamine. By contrast, when serotonergic neurons were similarly destroyed with 5,7-dihydroxytryptamine, TRH-induced tachycardia was inhibited. Attendant pressor responses were also inhibited by electrolytic lesions of the dorsal, but not of the median, raphe nucleus. Pressor and sympathoexcitatory responses elicited by infusing TRH directly into the dorsal raphe nucleus resembled those produced by icv infusion, and their magnitude diminished after pentolinium-induced ganglioplegia. These results are compatible with the interpretation that icv infused TRH may produce its cardiovascular and sympathetic effects by acting, at least in part, on serotonergic mechanisms located in the dorsal raphe nucleus.


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