Ventral tegmental area dopamine neural activity switches simultaneously with rule representations in the prefrontal cortex and hippocampus

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Publicado en:bioRxiv (Feb 11, 2025)
Autor principal: Ding, Mingxin
Otros Autores: Tomsick, Porter L, Young, Ryan A, Jadhav, Shantanu P
Publicado:
Cold Spring Harbor Laboratory Press
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Acceso en línea:Citation/Abstract
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Resumen:Multiple brain regions need to coordinate activity to support cognitive flexibility and behavioral adaptation. Neural activity in both the hippocampus (HPC) and prefrontal cortex (PFC) is known to represent spatial context and is sensitive to reward and rule alterations. Midbrain dopamine (DA) activity is key in reward seeking behavior and learning. There is abundant evidence that midbrain DA modulates HPC and PFC activity. However, it remains underexplored how these networks engage dynamically and coordinate temporally when animals must adjust their behavior according to changing reward contingencies. In particular, is there any relationship between DA reward prediction change during rule switching, and rule representation changes in PFC and CA1? We addressed these questions using simultaneous recording of neuronal population activity from the hippocampal area CA1, PFC and ventral tegmental area (VTA) in male TH-Cre rats performing two spatial working memory tasks with frequent rule switches in blocks of trials. CA1 and PFC ensembles showed rule-specific activity both during maze running and at reward locations, with PFC rule coding more consistent across animals compared to CA1. Optogenetically tagged VTA DA neuron firing activity responded to and predicted reward outcome. We found that the correct prediction in DA emerged gradually over trials after rule-switching in coordination with transitions in PFC and CA1 ensemble representations of the current rule after a rule switch, followed by behavioral adaptation to the correct rule sequence. Therefore, our study demonstrates a crucial temporal coordination between the rule representation in PFC/CA1, the dopamine reward signal and behavioral strategy.Competing Interest StatementThe authors have declared no competing interest.Footnotes* Figure 3 and 5 revised to provide further details of and comparisons between neural rule decoding probability, behavior transition timing and dopamine reward signal. Methods, results and discussion sections updated to reflect added analyses and their implications.
ISSN:2692-8205
DOI:10.1101/2024.09.09.611811
Fuente:Biological Science Database