June 24, 2021 / Dept of Neurobiology

Midbrain dopaminergic inputs gate amygdala intercalated cell clusters by distinct and cooperative mechanisms in male mice. Aksoy-Aksel et al, (2021) Elife

Dopaminergic signaling in the brain plays important roles in learning, but the mechanisms are incompletely understood. We found that dopaminergic inputs to amygdala intercalated cells, which are important for fear and extinction learning, control these neurons by co-release of two transmitters, GABA and dopamine. Their action is modulated by extinction learning, and could thus shape the activity of intercalated cells to support low fear behavior.

 

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.

Aksoy-Aksel A, Gall A, Seewald A, Ferraguti F, Ehrlich I. (2021) Midbrain dopaminergic inputs gate amygdala intercalated cell clusters by distinct and cooperative mechanisms in male mice.Elife. 2021 May 24;10:e63708. doi: 10.7554/eLife.63708.

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