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Midbrain dopaminergic inputs gate amygdala intercalated cell clusters by distinct and cooperative mechanisms in male mice

Authors :
Ayla Aksoy-Aksel
Andrea Gall
Anna Seewald
Francesco Ferraguti
Ingrid Ehrlich
Source :
eLife, Vol 10 (2021)
Publication Year :
2021
Publisher :
eLife Sciences Publications Ltd, 2021.

Abstract

Dopaminergic signaling plays an important role in associative learning, including fear and extinction learning. Dopaminergic midbrain neurons encode prediction error-like signals when threats differ from expectations. Within the amygdala, GABAergic intercalated cell (ITC) clusters receive one of the densest dopaminergic projections, but their physiological consequences are incompletely understood. ITCs are important for fear extinction, a function thought to be supported by activation of ventromedial ITCs that inhibit central amygdala fear output. In mice, we reveal two distinct novel mechanisms by which mesencephalic dopaminergic afferents control ITCs. Firstly, they co-release GABA to mediate rapid, direct inhibition. Secondly, dopamine suppresses inhibitory interactions between distinct ITC clusters via presynaptic D1 receptors. Early extinction training augments both GABA co-release onto dorsomedial ITCs and dopamine-mediated suppression of dorso- to ventromedial inhibition between ITC clusters. These findings provide novel insights into dopaminergic mechanisms shaping the activity balance between distinct ITC clusters that could support their opposing roles in fear behavior.

Details

Language :
English
ISSN :
2050084X
Volume :
10
Database :
Directory of Open Access Journals
Journal :
eLife
Publication Type :
Academic Journal
Accession number :
edsdoj.4d4e5946a2074400a39ab19c777f2b7a
Document Type :
article
Full Text :
https://doi.org/10.7554/eLife.63708