PMID- 25600269 OWN - NLM STAT- MEDLINE DCOM- 20150618 LR - 20191210 IS - 1476-4687 (Electronic) IS - 0028-0836 (Print) IS - 0028-0836 (Linking) VI - 519 IP - 7544 DP - 2015 Mar 26 TI - The paraventricular thalamus controls a central amygdala fear circuit. PG - 455-9 LID - 10.1038/nature13978 [doi] AB - 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. FAU - Penzo, Mario A AU - Penzo MA AD - Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA. FAU - Robert, Vincent AU - Robert V AD - 1] Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA [2] Ecole Normale Superieure de Cachan, 94230 Cachan, France. FAU - Tucciarone, Jason AU - Tucciarone J AD - 1] Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA [2] Medical Scientist Training Program &Program in Neuroscience, Stony Brook University, Stony Brook, New York 11790, USA. FAU - De Bundel, Dimitri AU - De Bundel D AD - CNRS, UMR-5203, INSERM U661, Institut de Genomique Fonctionnelle, 34090 Montpellier, France. FAU - Wang, Minghui AU - Wang M AD - Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA. FAU - Van Aelst, Linda AU - Van Aelst L AD - Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA. FAU - Darvas, Martin AU - Darvas M AD - Department of Pathology, University of Washington, Seattle, Washington 98104, USA. FAU - Parada, Luis F AU - Parada LF AD - Department of Developmental Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA. FAU - Palmiter, Richard D AU - Palmiter RD AD - Howard Hughes Medical Institute; Department of Biochemistry, University of Washington, Seattle, Washington 98195, USA. FAU - He, Miao AU - He M AD - Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200032, China. FAU - Huang, Z Josh AU - Huang ZJ AD - Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA. FAU - Li, Bo AU - Li B AD - Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA. LA - eng GR - R01 MH094705/MH/NIMH NIH HHS/United States GR - R01 MH101214/MH/NIMH NIH HHS/United States GR - P50 NS062684/NS/NINDS NIH HHS/United States GR - Howard Hughes Medical Institute/United States GR - R01 NS082266/NS/NINDS NIH HHS/United States GR - R01 MH082808/MH/NIMH NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20150119 PL - England TA - Nature JT - Nature JID - 0410462 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 51110-01-1 (Somatostatin) RN - EC 2.7.10.1 (Receptor, trkB) SB - IM CIN - Nat Rev Neurosci. 2015 Mar;16(3):121. PMID: 25697151 MH - Animals MH - Brain-Derived Neurotrophic Factor/metabolism MH - Central Amygdaloid Nucleus/cytology/*physiology MH - Conditioning, Psychological/physiology MH - Fear/*physiology/psychology MH - Female MH - Male MH - Memory/physiology MH - Mice MH - Neural Pathways/cytology/*physiology MH - Neuronal Plasticity MH - Neurons/metabolism MH - Receptor, trkB/metabolism MH - Somatostatin/metabolism MH - Thalamus/cytology/*physiology MH - Time Factors PMC - PMC4376633 MID - NIHMS636237 EDAT- 2015/01/21 06:00 MHDA- 2015/06/19 06:00 PMCR- 2015/09/26 CRDT- 2015/01/21 06:00 PHST- 2014/02/09 00:00 [received] PHST- 2014/10/16 00:00 [accepted] PHST- 2015/01/21 06:00 [entrez] PHST- 2015/01/21 06:00 [pubmed] PHST- 2015/06/19 06:00 [medline] PHST- 2015/09/26 00:00 [pmc-release] AID - nature13978 [pii] AID - 10.1038/nature13978 [doi] PST - ppublish SO - Nature. 2015 Mar 26;519(7544):455-9. doi: 10.1038/nature13978. Epub 2015 Jan 19.