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Dopamine and glutamate regulate striatal acetylcholine in decision-making.
Lynne Chantranupong1, Celia C Beron1, Joshua A Zimmer1
1Department of Neurobiology, Howard Hughes Medical Institute, Harvard Medical School, Boston, USA.
Nature
|August 9, 2023
Summary
Dopamine and acetylcholine signaling in the striatum are crucial for decision-making. This study reveals dopamine inhibits acetylcholine release via D2 receptors, a mechanism vital for effective choices.
Area of Science:
- Neuroscience
- Neurobiology
- Behavioral Science
Background:
- Striatal dopamine and acetylcholine are critical for motor control and decision-making.
- In vitro studies suggest a circuit where acetylcholine drives dopamine release, and dopamine inhibits cholinergic interneurons (CINs) via D2 receptors.
Purpose of the Study:
- To investigate the in vivo function of the dopamine-acetylcholine intrastriatal circuit during decision-making.
- To elucidate the dynamic interplay between dopamine and acetylcholine in the striatum.
Main Methods:
- Monitoring of acetylcholine and dopamine signals in the mouse ventrolateral striatum during a reward-based decision-making task.
- Assessment of dopamine D2 receptor (D2R) dependence and the role of cortical and thalamic inputs.
Main Results:
- Dopamine and acetylcholine exhibit multiphasic, anticorrelated signaling patterns influenced by decision history and reward.
- Dopamine's reward encoding is independent of acetylcholine release from CINs.
- Dopamine inhibits acetylcholine transients in a D2R-dependent manner, and its absence impairs decision-making.
- Cortical and thalamic glutamate release is necessary for acetylcholine release.
Conclusions:
- A dynamic, D2R-dependent inhibitory relationship exists between dopamine and acetylcholine during decision-making.
- Multiple regulatory mechanisms control cholinergic interneuron activity.
- These findings enhance understanding of the neurochemical underpinnings of decision-making and behavior.
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