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Activity in the Dorsomedial Striatum Underlies Serial Reversal Learning Performance Under Probabilistic Uncertainty.
Madison K Young1, Kyna-Anne Conn1, Joyosmita Das1
1Queensland Brain Institute, The University of Queensland, Brisbane, Queensland, Australia.
Biological Psychiatry Global Open Science
|October 26, 2023
Summary
Altered dorsomedial striatum (DMS) activity impairs reversal learning, particularly under uncertainty. This suggests elevated dopamine in the DMS may underlie decision-making deficits in psychosis.
Area of Science:
- Neuroscience
- Computational Psychiatry
- Behavioral Neuroscience
Background:
- Corticostriatal circuits, including the dorsomedial striatum (DMS) and lateral orbitofrontal cortex, are vital for reversal learning under probabilistic uncertainty.
- Impairments in these circuits and reversal learning are observed in psychosis, suggesting shared neurobiological underpinnings.
- This study investigates the role of corticostriatal activity in psychosis-related reversal learning deficits.
Purpose of the Study:
- To examine the causal role of dorsomedial striatum (DMS) activity in reversal learning.
- To investigate how psychostimulant-induced psychosis-relevant neurobiology affects corticostriatal circuits during reversal learning.
- To determine the impact of DMS activation on reversal learning under varying probabilistic contingencies.
Main Methods:
- Utilized amphetamine treatment in male mice to model psychosis-relevant neurobiology during reversal learning.
- Employed chemogenetics to specifically activate midbrain inputs to the DMS, assessing causal roles in reversal learning.
- Examined pathway-specific corticostriatal activation and its dependence on probabilistic contingencies.
Main Results:
- Amphetamine-treated mice exhibited impaired punishment learning, reduced shifting after losses, and increased perseverative errors during reversal learning.
- Increased activity in the lateral orbitofrontal cortex to DMS circuits and the DMS itself modulated reversal learning performance and strategies.
- Direct activation of midbrain to DMS circuits impaired shifting after losses and overall reversal learning, contingent on probabilistic uncertainty.
Conclusions:
- The dorsomedial striatum (DMS) plays a complex role in reversal learning, with increased activity impairing processes dependent on uncertainty.
- DMS activity is crucial for maintaining and selecting cortical inputs during reversal learning.
- Elevated dopamine levels in the DMS may contribute to the decision-making impairments observed in individuals with psychosis.
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