Project description:Single-neuron transcriptome profiles of Dorsal Raphe neurons marked by a history of expression of Drd2::Cre and Pet1::Flpe (GFP+), as well as Dorsal Raphe neurons marked by a history of Pet1::Flpe expression only (mCherry+).
Project description:Here we use high-throughput and DR subdomain-targeted single-cell transcriptomics and intersectional genetic tools to map molecular and anatomical diversity of DR-Pet1 neurons. We describe up to fourteen neuron subtypes, many showing biased cell body distributions across the DR.
Project description:Hunger, driven by negative energy balance, elicits the search for and consumption of food. In mammals, this is orchestrated principally through the activity of neurons in the hypothalamus, direct manipulation of which can potently drive food intake. However, the neural circuits outside of the hypothalamus that control feeding are poorly understood. Here, we identify two functionally opponent cell types within the dorsal raphe nucleus (DRN), marked by the vesicular transporters for GABA (Vgat) or glutamate (VGLUT3), that project to many known feeding centers and rapidly control feeding. We find that DRNVgat neurons drive, while DRNVGLUT3 neurons suppress, food intake. Furthermore, through the development and application of cell type-specific molecular profiling technologies, we identify many differentially expressed transmembrane receptors, which may represent unique druggable targets. Local application of agonists for these receptors potently modulates feeding, recapitulating the effects of cell-specific manipulations. Together, these data establish a key role for the DRN in controlling food intake and add an important anatomic site that controls energy balance.
Project description:We identified 271 transcripts as differentially regulated in the dorsal raphe and/or the amygdala of high-responder and low-responder rats
Project description:We report 33 microRNAs are differentially expressed in the dorsal raphe and/or amygdala of rats selectively bred for high and low locomotor response to novelty (high responder and low responder rats)
Project description:Small blocks of the midbrain containing the dorsal raphe nucleus was obtained from ovariectomized monkeys treated with placebo, estrogen, progesterone or estrogen plus progesterone for one month. The RNA was extracted and hybridized to the human U95A Affymetrix chip. Each chip represents one monkey. N=3 monkeys per treatment.
Project description:A small block of the midbrain containing the dorsal raphe nucleus was obtained from ovariectomized monkeys treated with placebo, estrogen, progesterone or estrogen plus progesterone for one month. The RNA was extracted and hybridized to the Rhesus Affymetrix chip. The results were analyzed with GCOS 1.0 Each chip represents one monkey. N=3 monkeys per treatment.
Project description:We have used large-scale single-cell RNA sequencing (RNA-seq) to classify sensory neurons in the mouse dorsal horn, with the purpose of identifying neuronal subclasses, in particular making a systematic and comprehensive molecular classification of spinal cord sensory neurons, providing the neuronal basis for somatic sensation.
Project description: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 the DRN and its diverse functions.