Striatal low-threshold spiking interneurons locally gate dopamine

Area of Science:

• Neuroscience
• Cellular Neuroscience
• Systems Neuroscience

Background:

• The dorsomedial striatum (DMS) is crucial for goal-directed learning and motor control.
• Local inhibitory GABAergic networks within the striatum play a significant role in modulating its output and behavior.
• Sparse low-threshold spiking interneurons (LTSI) are known regulators of early goal-directed learning.

Purpose of the Study:

• To investigate the hypothesis that LTSIs provide a novel GABAergic mechanism for local striatal dopaminergic regulation.
• To explore the role of LTSIs in shaping early goal-directed learning through dopamine modulation.

Main Methods:

• Anatomical analysis to assess the proximity of LTSI terminals and dopaminergic processes.
• In vitro fast scan cyclic voltammetry to measure dopamine release.
• In vivo GRAB_DA dopamine sensor imaging during operant learning.
• Pharmacological manipulation of dopamine levels using aripiprazole.

Main Results:

• Anatomical evidence shows close apposition between LTSI terminals and dopaminergic axons.
• LTSIs were found to directly attenuate dopamine release via GABA_B receptor signaling.
• LTSI activity significantly modulated striatal dopamine dynamics during operant learning.
• Stabilizing dopamine levels suppressed the impact of LTSI inhibition on learning.

Conclusions:

• LTSIs play an unexpected role in gating striatal dopamine release.
• This LTSI-mediated dopaminergic regulation is essential for facilitating goal-directed learning.
• The findings reveal a novel circuit mechanism by which local interneurons control neuromodulatory systems to shape behavior.