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| Status |
Public on May 31, 2018 |
| Title |
A central extended amygdala circuit that modulates anxiety |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Other
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| Summary |
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.
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| Overall design |
Analysis of differential expression between 10 IP (SOM+ neurons) & 4 input replicates from CeL tissue in 8-12 pooled mice for each replicate
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| Contributor(s) |
Li B, Tollkuhn J |
| Citation(s) |
29844022 |
| |
| Submission date |
May 02, 2018 |
| Last update date |
Mar 25, 2019 |
| Contact name |
Jessica Tollkuhn |
| E-mail(s) |
tollkuhn@cshl.edu
|
| Organization name |
Cold Spring Harbor Laboratory
|
| Street address |
1 Bungtown Rd
|
| City |
Cold Spring Harbor |
| ZIP/Postal code |
11724 |
| Country |
USA |
| |
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| Platforms (2) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (14)
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| Relations |
| BioProject |
PRJNA454720 |
| SRA |
SRP144385 |
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