A central extended amygdala circuit that modulates anxiety

Ahrens, S., Wu, M., Furlan, A., Hwang, G. R., Paik, R., Li, H., Penzo, M. A., Tollkuhn, J., Li, B. (May 2018) A central extended amygdala circuit that modulates anxiety. J Neurosci, 38 (24). pp. 5567-5583. ISSN 0270-6474

Abstract

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.SIGNIFICANCE STATEMENTThe central extended amygdala has been implicated in anxiety-related behaviors, but the underlying mechanisms are unclear. Here we found that somatostatin-expressing (SOM(+)) neurons in the central amygdala (CeA) controls anxiety through modulation of the stria terminalis (BNST), a process that is mediated by an increase in dynorphin signaling in the CeA. Our results reveal circuit and cellular dysfunctions that may account for maladaptive anxiety.

Item Type:	Paper
Subjects:	organs, tissues, organelles, cell types and functions > tissues types and functions > amygdala organism description > animal organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions organism description > animal > mammal organism description > animal > mammal > rodent > mouse organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neurons > neuronal circuits organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neurons > neuronal circuits organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neurons > neuronal circuits organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neurons organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neurons organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neurons organs, tissues, organelles, cell types and functions organism description > animal > mammal > rodent
CSHL Authors:	Ahrens, Sandra Wu, Melody Furlan, Alessandro Paik, Raehum Li, Haohong Penzo, Mario Tollkuhn, Jessica Li, Bo Hwang, Ga-Ram
Communities:	CSHL labs > Li lab CSHL labs > Tollkuhn lab
Depositing User:	Matt Covey
Date:	29 May 2018
Date Deposited:	01 Jun 2018 19:46
Last Modified:	06 Feb 2024 20:36
PMCID:	PMC6001032
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/36704

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