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Publication : Dissociable control of unconditioned responses and associative fear learning by parabrachial CGRP neurons.

First Author  Bowen AJ Year  2020
Journal  Elife Volume  9
PubMed ID  32856589 Mgi Jnum  J:298642
Mgi Id  MGI:6477040 Doi  10.7554/eLife.59799
Citation  Bowen AJ, et al. (2020) Dissociable control of unconditioned responses and associative fear learning by parabrachial CGRP neurons. Elife 9:e59799
abstractText  Parabrachial CGRP neurons receive diverse threat-related signals and contribute to multiple phases of adaptive threat responses in mice, with their inactivation attenuating both unconditioned behavioral responses to somatic pain and fear-memory formation. Because CGRP(PBN) neurons respond broadly to multi-modal threats, it remains unknown how these distinct adaptive processes are individually engaged. We show that while three partially separable subsets of CGRP(PBN) neurons broadly collateralize to their respective downstream partners, individual projections accomplish distinct functions: hypothalamic and extended amygdalar projections elicit assorted unconditioned threat responses including autonomic arousal, anxiety, and freezing behavior, while thalamic and basal forebrain projections generate freezing behavior and, unexpectedly, contribute to associative fear learning. Moreover, the unconditioned responses generated by individual projections are complementary, with simultaneous activation of multiple sites driving profound freezing behavior and bradycardia that are not elicited by any individual projection. This semi-parallel, scalable connectivity schema likely contributes to flexible control of threat responses in unpredictable environments.
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