The paraventricular thalamus controls a central amygdala fear circuit

Penzo, M. A., Robert, V., Tucciarone, J., De Bundel, D., Wang, M., Van Aelst, L., Darvas, M., Parada, L. F., Palmiter, R. D., He, M., Huang, Z. J., Li, B. (March 2015) The paraventricular thalamus controls a central amygdala fear circuit. Nature, 519 (7544). pp. 455-459. ISSN 0028-0836

URL: http://www.ncbi.nlm.nih.gov/pubmed/25600269
DOI: 10.1038/nature13978

Abstract

Appropriate responses to an imminent threat brace us for adversities. The ability to sense and predict threatening or stressful events is essential for such adaptive behaviour. In the mammalian brain, one putative stress sensor is the paraventricular nucleus of the thalamus (PVT), an area that is readily activated by both physical and psychological stressors. However, the role of the PVT in the establishment of adaptive behavioural responses remains unclear. Here we show in mice that the PVT regulates fear processing in the lateral division of the central amygdala (CeL), a structure that orchestrates fear learning and expression. Selective inactivation of CeL-projecting PVT neurons prevented fear conditioning, an effect that can be accounted for by an impairment in fear-conditioning-induced synaptic potentiation onto somatostatin-expressing (SOM+) CeL neurons, which has previously been shown to store fear memory. Consistently, we found that PVT neurons preferentially innervate SOM+ neurons in the CeL, and stimulation of PVT afferents facilitated SOM+ neuron activity and promoted intra-CeL inhibition, two processes that are critical for fear learning and expression. Notably, PVT modulation of SOM+ CeL neurons was mediated by activation of the brain-derived neurotrophic factor (BDNF) receptor tropomysin-related kinase B (TrkB). As a result, selective deletion of either Bdnf in the PVT or Trkb in SOM+ CeL neurons impaired fear conditioning, while infusion of BDNF into the CeL enhanced fear learning and elicited unconditioned fear responses. Our results demonstrate that the PVT-CeL pathway constitutes a novel circuit essential for both the establishment of fear memory and the expression of fear responses, and uncover mechanisms linking stress detection in PVT with the emergence of adaptive behaviour.

Item Type: Paper
Subjects: organism description > animal behavior
organism description > animal behavior > fear
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 > tissues types and functions > thalamus
CSHL Authors:
Communities: CSHL labs > Huang lab
CSHL labs > Li lab
CSHL labs > Van Aelst lab
Stanley Institute for Cognitive Genomics
Depositing User: Matt Covey
Date: 26 March 2015
Date Deposited: 30 Jan 2015 20:12
Last Modified: 06 Nov 2015 20:50
PMCID: PMC4376633
Related URLs:
URI: https://repository.cshl.edu/id/eprint/31163

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