Regulation of learned fear expression through the MgN-amygdala pathway. Neurobiol Learn Mem 2021 Nov;185:107526
Date
09/26/2021Pubmed ID
34562619DOI
10.1016/j.nlm.2021.107526Scopus ID
2-s2.0-85115785081 (requires institutional sign-in at Scopus site) 3 CitationsAbstract
Heightened fear responding is characteristic of fear- and anxiety-related disorders, including post-traumatic stress disorder. Neural plasticity in the amygdala is essential for both initial fear learning and fear expression, and strengthening of synaptic connections between the medial geniculate nucleus (MgN) and amygdala is critical for auditory fear learning. However, very little is known about what happens in the MgN-amygdala pathway during fear recall and extinction, in which conditional fear decreases with repeated presentations of the auditory stimulus alone. In the present study, we found that optogenetic inhibition of activity in the MgN-amygdala pathway during fear retrieval and extinction reduced expression of conditional fear. While this effect persisted for at least two weeks following pathway inhibition, it was specific to the context in which optogenetic inhibition occurred, linking MgN-BLA inhibition to facilitation of extinction-like processes. Reduced fear expression through inhibition of the MgN-amygdala pathway was further characterized by similar synaptic expression of GluA1 and GluA2 AMPA receptor subunits compared to what was seen in controls. Inhibition also decreased CREB phosphorylation in the amygdala, similar to what has been reported following auditory fear extinction. We then demonstrated that this effect was reduced by inhibition of GluN2B-containing NMDA receptors. These results demonstrate a new and important role for the MgN-amygdala pathway in extinction-like processes, and show that suppressing activity in this pathway results in a persistent decrease in fear behavior.
Author List
Ferrara NC, Trask S, Pullins SE, Helmstetter FJAuthor
Fred Helmstetter PhD Professor in the Psychology / Neuroscience department at University of Wisconsin - MilwaukeeMESH terms used to index this publication - Major topics in bold
Acoustic StimulationAmygdala
Animals
Conditioning, Classical
Extinction, Psychological
Fear
Fluorescent Antibody Technique
Geniculate Bodies
Hylobatidae
Male
Neural Pathways
Optogenetics
Piperidines
Rats
Rats, Long-Evans
Receptors, N-Methyl-D-Aspartate
