Ayla Aksoy-Aksel,1,2,3 Andrea Gall,1,2,3 Anna Seewald,4 Francesco Ferraguti,4 and Ingrid Ehrlich1,2,3
1Hertie Institute for Clinical Brain Research, Tübingen, Germany
2Centre for Integrative Neuroscience, Tübingen, Germany
3Department of Neurobiology, Institute of Biomaterials and Biomolecular Systems, University of Stuttgart, Stuttgart, Germany
4Department of Pharmacology, Medical University of Innsbruck, Innsbruck, Austria
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.
Optical stimulation was achieved by triggering a light-emitting diode (LED; 470 nm, KSL70; Rapp Opto-Electronics, Hamburg, Germany or CoolLED pE, CoolLED, Andover, UK) coupled to the upright microscope objective (Olympus Germany; 60x/1.0 NA).
Product Associated Features
The pE-100 series is a family of single-wavelength fluorescence LED Illumination Systems, and in this case the pE-100 (470 nm) provides highly controllable and precise pulsing for optogenetic stimulation.
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