| Autor: |
R K, van der Merwe, J A, Nadel, D, Copes-Finke, S, Pawelko, J S, Scott, M, Ghanem, M, Fox, C, Morehouse, R, McLaughlin, C, Maddox, R, Albert-Lyons, G, Malaki, V, Groce, A, Turocy, N, Aggadi, X, Jin, C D, Howard |
| Rok vydání: |
2022 |
| Zdroj: |
The European journal of neuroscience. |
| ISSN: |
1460-9568 |
| Popis: |
Behavioral flexibility is key to survival in a dynamic environment. While flexible, goal-directed behaviors are initially dependent on dorsomedial striatum, they become dependent on lateral striatum as behaviors become inflexible. Similarly, lesions of dopamine terminals in lateral striatum disrupt the development of inflexible habits. This work suggests that dopamine release in lateral striatum may drive inflexible behaviors, though few studies have investigated a causative role of subpopulations of striatal dopamine terminals in reversal learning, a measure of flexibility. Here, we performed two optogenetic experiments to activate dopamine terminals in dorsal medial (DMS), dorsal lateral (DLS), or ventral (NAc) striatum in DAT-Cre mice that expressed channelrhodopsin-2 via viral injection (Experiment I) or through transgenic breeding with an Ai32 reporter line (Experiment II) to determine how specific dopamine subpopulations impact reversal learning. Mice performed a reversal task in which they self-stimulated DMS, DLS, or NAc dopamine terminals by pressing one of two levers before action-outcome lever contingencies were reversed. Largely consistent with presumed ventromedial/lateral striatal function, we found that mice self-stimulating medial dopamine terminals reversed lever preference following contingency reversal, while mice self-stimulating NAc showed parial flexibility, and DLS self-stimulation resulted in impaired reversal. Impairments in DLS mice were characterized by more regressive errors and reliance on lose-stay strategies following reversal, as well as reduced within-session learning, suggesting reward insensitivity and overreliance on previously learned actions. This study supports a model of striatal function in which dorsomedial and ventral dopamine facilitate goal-directed responding, and dorsolateral dopamine supports more inflexible responding. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
|
Plný text