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.
journal_name
Neuronjournal_title
Neuronauthors
Sanford CA,Soden ME,Baird MA,Miller SM,Schulkin J,Palmiter RD,Clark M,Zweifel LSdoi
10.1016/j.neuron.2016.11.034subject
Has Abstractpub_date
2017-01-04 00:00:00pages
164-178issue
1eissn
0896-6273issn
1097-4199pii
S0896-6273(16)30902-3journal_volume
93pub_type
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