title: The paraventricular thalamus controls a central amygdala fear circuit.
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.
authors.affiliation: Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA.
authors.forename: Mario A
authors.initials: MA
authors.lastname: Penzo
authors.affiliation: 1] Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA [2] Ecole Normale Supérieure de Cachan, 94230 Cachan, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Robert
authors.affiliation: 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.
authors.forename: Jason
authors.initials: J
authors.lastname: Tucciarone
authors.affiliation: CNRS, UMR-5203, INSERM U661, Institut de Génomique Fonctionnelle, 34090 Montpellier, France.
authors.forename: Dimitri
authors.initials: D
authors.lastname: De Bundel
authors.affiliation: Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA.
authors.forename: Minghui
authors.initials: M
authors.lastname: Wang
authors.affiliation: Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA.
authors.forename: Linda
authors.initials: L
authors.lastname: Van Aelst
authors.affiliation: Department of Pathology, University of Washington, Seattle, Washington 98104, USA.
authors.forename: Martin
authors.initials: M
authors.lastname: Darvas
authors.affiliation: Department of Developmental Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
authors.forename: Luis F
authors.initials: LF
authors.lastname: Parada
authors.affiliation: Howard Hughes Medical Institute; Department of Biochemistry, University of Washington, Seattle, Washington 98195, USA.
authors.forename: Richard D
authors.initials: RD
authors.lastname: Palmiter
authors.affiliation: Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200032, China.
authors.forename: Miao
authors.initials: M
authors.lastname: He
authors.affiliation: Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA.
authors.forename: Z Josh
authors.initials: ZJ
authors.lastname: Huang
authors.affiliation: Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA.
authors.forename: Bo
authors.initials: B
authors.lastname: Li
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D066274:Central Amygdaloid Nucleus / Q000166:cytology / Q000502:physiology*; D003213:Conditioning, Psychological / Q000502:physiology; D005239:Fear / Q000502:physiology* / Q000523:psychology; D005260:Female; D008297:Male; D008568:Memory / Q000502:physiology; D051379:Mice; D009434:Neural Pathways / Q000166:cytology / Q000502:physiology*; D009473:Neuronal Plasticity; D009474:Neurons / Q000378:metabolism; D020813:Receptor, trkB / Q000378:metabolism; D013004:Somatostatin / Q000378:metabolism; D013788:Thalamus / Q000166:cytology / Q000502:physiology*; D013997:Time Factors
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D013004:Somatostatin; D020813:Receptor, trkB