Project description:We performed single-nuclei RNAseq of Sprague Dawley rat area postrema and nucleus tractus solitarius brain samples to identify cellular subtypes.
Project description:We performed single-nuclei RNAseq of Sprague Dawley rat area postrema and nucleus tractus solitarius brain samples from animals treated with GDF-15 to identify cellular subtype specific changes in the neural transcriptome.
Project description:We performed single-nuclei RNAseq of Sprague Dawley rat area postrema and nucleus tractus solitarius brain samples from animals treated with cisplatin to identify cellular subtype specific changes in the neural transcriptome.
Project description:Nausea, the unpleasant sensation of visceral malaise, remains a mysterious process. The area postrema is implicated in some nausea responses, and contains poorly understood brain-resident sensory neurons that are anatomically privileged to detect bloodborne signals. To investigate nausea mechanisms, we built an area postrema cell atlas through single-nucleus RNA sequencing, revealing a few neuron types. Using mouse genetic tools for cell-specific manipulation, we discovered excitatory neurons that induce nausea-related behaviors, with one neuron type mediating aversion imposed by multiple poisons. Nausea-associated responses were observed to agonists of identified area postrema receptors, and suppressed by targeted cell ablation and/or gene knockout. Anatomical mapping revealed a distributed network of long-range excitatory but not inhibitory projections with subtype-specific patterning. These studies reveal the basic organization of area postrema nausea circuitry, and provide a framework towards understanding and therapeutically controlling nausea.
Project description:Medial nucleus tractus solitarius (mNTS) neurons express leptin receptors (LepRs), and intra-mNTS delivery of leptin reduces food intake and body weight. Here, the contribution of endogenous LepR signaling in mNTS neurons to energy balance control was examined. Knockdown of LepR in mNTS and area postrema (AP) neurons of rats (LepRKD) via adeno-associated virus short hairpin RNA-interference (AAV-shRNAi) resulted in significant hyperphagia for chow, high-fat, and sucrose diets, yielding increased body weight and adiposity. The chronic hyperphagia of mNTS/AP LepRKD rats is likely mediated by a reduction in leptin potentiation of gastrointestinal satiation signaling, as LepRKD rats showed decreased sensitivity to the intake-reducing effects of cholecystokinin. LepRKD rats showed increased basal AMP-kinase activity in mNTS/AP micropunches, and pharmacological data suggest that this increase provides a likely mechanism for their chronic hyperphagia. Overall these findings demonstrate that LepRs in mNTS and AP neurons are required for normal energy balance control.
Project description:To identify LPS activated cell types in the NTS and AP we region we used single-nuclei RNA seq comparing baseline cell types and cell types labeled using the TRAP2 mouse line crossed to the INTACT mouse line after labeling during LPS treatment.