Lateralized nigrostriatal dopamine pathway activation promotes early reversal learning

Area of Science:

• Neuroscience
• Behavioral Neuroscience
• Computational Neuroscience

Background:

• The dorsomedial striatum (DMS) integrates diverse inputs to support action-outcome learning.
• Dopamine signaling within the DMS is implicated in reinforcement learning and shows lateralized patterns.
• Previous research suggests the DMS plays a role in associating actions with their outcomes.

Purpose of the Study:

• To investigate how dopamine axon activity dynamics in the DMS change during reversal learning.
• To determine the role of lateralized dopamine signaling in the DMS during shifting action-outcome contingencies.
• To explore the causal contribution of nigrostriatal dopamine to reversal learning.

Main Methods:

• Recorded dopamine axon Ca2+ activity in the DMS of mice using a miniaturized fluorescence microscope.
• Utilized a lateralized reversal learning task to manipulate action-outcome contingencies.
• Employed unilateral optogenetic inhibition of the nigrostriatal dopamine pathway.

Main Results:

• Dopamine axon activation in the DMS exhibited a lateral bias for choices and rewards early in reversal learning, favoring contralateral actions.
• This lateral bias diminished over successive sessions as mice adapted to the new contingency.
• Optogenetic inhibition of dopamine during the initial reversal session transiently impaired contralateral reversal performance, specifically reducing "win-stay" behavior.

Conclusions:

• Lateralized dopamine signaling in the DMS transiently facilitates the exploration of new actions following a contingency switch.
• This effect is most pronounced when the new action and outcome are contralateral to the recording hemisphere.
• Findings elucidate the DMS's role in adaptive action-outcome learning and behavioral flexibility.