title: A Central Amygdala CRF Circuit Facilitates Learning about Weak Threats.
abstract: Fear is a graded central motive state ranging from mild to intense. As threat intensity increases, fear transitions from discriminative to generalized. The circuit mechanisms that process threats of different intensity are not well resolved. Here, we isolate a unique population of locally projecting neurons in the central nucleus of the amygdala (CeA) that produce the neuropeptide corticotropin-releasing factor (CRF). CRF-producing neurons and CRF in the CeA are required for discriminative fear, but both are dispensable for generalized fear at high US intensities. Consistent with a role in discriminative fear, CRF neurons undergo plasticity following threat conditioning and selectively respond to threat-predictive cues. We further show that excitability of genetically isolated CRF-receptive (CRFR1) neurons in the CeA is potently enhanced by CRF and that CRFR1 signaling in the CeA is critical for discriminative fear. These findings demonstrate a novel CRF gain-control circuit and show separable pathways for graded fear processing.
authors.affiliation: Department of Pharmacology, University of Washington, Seattle, WA 98105, USA.
authors.forename: Christina A
authors.initials: CA
authors.lastname: Sanford
authors.affiliation: Department of Pharmacology, University of Washington, Seattle, WA 98105, USA.
authors.forename: Marta E
authors.initials: ME
authors.lastname: Soden
authors.affiliation: Department of Pharmacology, University of Washington, Seattle, WA 98105, USA.
authors.forename: Madison A
authors.initials: MA
authors.lastname: Baird
authors.affiliation: Department of Pharmacology, University of Washington, Seattle, WA 98105, USA.
authors.forename: Samara M
authors.initials: SM
authors.lastname: Miller
authors.affiliation: Department of Physiology and Biophysics, Georgetown University, Washington, DC 20057, USA; Department of Neuroscience, Georgetown University, Washington, DC 20057, USA; Department of Obstetrics and Gynecology, University of Washington, Seattle, WA 98105, USA.
authors.forename: Jay
authors.initials: J
authors.lastname: Schulkin
authors.affiliation: Department of Biochemistry, University of Washington, Seattle, WA 98105, USA.
authors.forename: Richard D
authors.initials: RD
authors.lastname: Palmiter
authors.affiliation: Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA 98105, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Clark
authors.affiliation: Department of Pharmacology, University of Washington, Seattle, WA 98105, USA; Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA 98105, USA. Electronic address: larryz@uw.edu.
authors.forename: Larry S
authors.initials: LS
authors.lastname: Zweifel
mesh_terms: D000679:Amygdala / Q000502:physiology; D000818:Animals; D066274:Central Amygdaloid Nucleus / Q000378:metabolism* / Q000502:physiology; D003346:Corticotropin-Releasing Hormone / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D005239:Fear / Q000502:physiology*; D007858:Learning / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism* / Q000502:physiology; D018019:Receptors, Corticotropin-Releasing Hormone / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D009435:Synaptic Transmission; D000099052:CRF Receptor, Type 1
chemical_list: D018019:Receptors, Corticotropin-Releasing Hormone; D000099052:CRF Receptor, Type 1; D003346:Corticotropin-Releasing Hormone
keywords: CRF; GABA; LTP; central amygdala; circuits; differential fear conditioning; fear; plasticity; threat