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

eLife

Francesco Ferraguti¹  Anna Seewald¹  Andrea Gall²  Ayla Aksoy-Aksel²  Ingrid Ehrlich² 

[1] Department of Pharmacology, Medical University of Innsbruck, Innsbruck, Austria;Hertie Institute for Clinical Brain Research, Tübingen, Germany;Centre for Integrative Neuroscience, Tübingen, Germany;Department of Neurobiology, Institute of Biomaterials and Biomolecular Systems, University of Stuttgart, Stuttgart, Germany;

关键词: dopamine;    amygdala;    extinction;    intercalated neurons;    GABA;    corelease;    Mouse;   

DOI  :  10.7554/eLife.63708

来源: eLife Sciences Publications, Ltd

【 摘 要 】

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.

【 授权许可】

CC BY