Project description:TRAP translational profiling is a method that allows investigators to genetically characterize specific cell types in complex tissues such as mouse brain. Using this technique we obtained RNA-Seq data from actively translating transcripts present in medium spiny neurons in the whole striatum of adult Drd2-EGFP/Rpl10a (CP101) mice that were administered either saline or cocaine.
Project description:TRAP translational profiling is a method that allows investigators to genetically characterize specific cell types in complex tissues such as mouse brain. Using this technique we obtained RNA-Seq data from actively translating transcripts present in medium spiny neurons in the accumbens nucleus of adult Drd2-EGFP/Rpl10a (CP101) mice that were administered either saline or cocaine under long access conditions
Project description:TRAP translational profiling is a method that allows investigators to genetically characterize specific cell types in complex tissues such as mouse brain. Using this technique we obtained RNA-Seq data from actively translating transcripts present in medium spiny neurons in the dorsal striatum of adult Drd2-EGFP/Rpl10a (CP101) mice that were administered either saline or cocaine under long access conditions
Project description:The amygdala or amygdala-like structure in the brain are found in all vertebrates, and plays a critical role for emotional processing. But the cellular architecture of amygdala and how they evolved are still elusive. Here, we generated single-nucleus RNA-sequencing data for more than 200,000 cells in human, macaque, mouse and chicken amygdala. Abundant neuronal cell types derived from different subnuclei of amygdala were identified in all datasets. Cross-species analyses revealed GABAergic neurons and GABAergic neuron-enriched subnuclei of amygdala were well-conserved in cellular composition and marker gene expression, whereas glutamatergic neuron-enriched subnuclei were relatively divergent. Furthermore, we discovered that LAMP5+ interneurons were much more numerous in primates, while DRD2+ GABAergic neurons, LAMP5+ and SATB2+ glutamatergic neurons were predominant in the human central amygdalar nucleus (CEA) and basolateral amygdala complex (BLA), respectively. In addition, we also identified GABAergic neuron-enriched subnuclei of amygdala in the chicken. Altogether, our study highlight extremely cell-type diversity in the amygdala across species and their species-specifc adaptations.
Project description:Inhibitory neurons are the predominant type of neuron in the mouse central amygdala. Here, we examined diversity in this cell type using single-cell RNA-seq.
Project description:Both the amygdala and the bed nucleus of the stria terminalis (BNST) have been implicated in maladaptive anxiety characteristic of anxiety disorders. However, the underlying circuit and cellular mechanisms have remained elusive. Here we show that mice with Erbb4 gene deficiency in somatostatin-expressing (SOM+) neurons exhibit heightened anxiety as measured in the elevated plus maze test and the open field test, two assays commonly used to assess anxiety-related behaviors in rodents. Using a combination of electrophysiological, molecular, genetic and pharmacological techniques we demonstrate that the abnormal anxiety in the mutant mice is caused by enhanced excitatory synaptic inputs onto SOM+ neurons in the central amygdala (CeA), and the resulting reduction in inhibition onto downstream SOM+ neurons in the BNST. Notably, our results indicate that an increase in dynorphin signaling in SOM+ CeA neurons mediates the paradoxical reduction in inhibition onto SOM+ BNST neurons, and that the consequent enhanced activity of SOM+ BNST neurons is both necessary for and sufficient to drive the elevated anxiety. Finally, we show that the elevated anxiety and the associated synaptic dysfunctions and increased dynorphin signaling in the CeA-BNST circuit of the Erbb4 mutant mice can be recapitulated by stress in wild-type mice. Together, our results unravel previously unknown circuit and cellular processes in the central extended amygdala that can cause maladaptive anxiety.