Ventral Tegmental Area Dopamine Neural Activity Switches Simultaneously with Rule Representations in the Medial Prefrontal Cortex and Hippocampus.
| Title: | Ventral Tegmental Area Dopamine Neural Activity Switches Simultaneously with Rule Representations in the Medial Prefrontal Cortex and Hippocampus. |
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| Authors: | Ding M; Graduate Program in Neuroscience, Brandeis University, Waltham, Massachusetts 02453.; Tomsick PL; Undergraduate Program in Neuroscience, Brandeis University, Waltham, Massachusetts 02453.; Department of Neuroscience, Virginia Polytechnic Institute and State University, Blacksburg, Virginia 24061.; Young RA; Department of Psychology, Brandeis University, Waltham, Massachusetts 02453.; Jadhav SP; Graduate Program in Neuroscience, Brandeis University, Waltham, Massachusetts 02453 shantanu@brandeis.edu.; Department of Psychology, Brandeis University, Waltham, Massachusetts 02453.; Volen National Center for Complex Systems, Brandeis University, Waltham, Massachusetts 02453. |
| Source: | The Journal of neuroscience : the official journal of the Society for Neuroscience [J Neurosci] 2025 Sep 10; Vol. 45 (37). Date of Electronic Publication: 2025 Sep 10. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Society for Neuroscience Country of Publication: United States NLM ID: 8102140 Publication Model: Electronic Cited Medium: Internet ISSN: 1529-2401 (Electronic) Linking ISSN: 02706474 NLM ISO Abbreviation: J Neurosci Subsets: MEDLINE |
| Imprint Name(s): | Publication: Washington, DC : Society for Neuroscience; Original Publication: [Baltimore, Md.] : The Society, c1981- |
| MeSH Terms: | Ventral Tegmental Area*/physiology ; Ventral Tegmental Area*/cytology ; Prefrontal Cortex*/physiology ; Dopaminergic Neurons*/physiology ; Hippocampus*/physiology ; Dopamine*/metabolism; Memory, Short-Term/physiology ; Action Potentials/physiology ; Maze Learning/physiology ; CA1 Region, Hippocampal/physiology ; Animals ; Male ; Rats ; Reward ; Rats, Long-Evans |
| Abstract: | Multiple brain regions need to coordinate activity to support cognitive flexibility and behavioral adaptation. Neural activity in both the hippocampus (HPC) and medial prefrontal cortex (mPFC) is known to represent the spatial context and is sensitive to reward and rule alterations. Midbrain dopamine (DA) activity is key to 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 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 mPFC and CA1? We addressed these questions using simultaneous recordings of neuronal population activity from the hippocampal area CA1, mPFC, 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 mPFC ensembles showed rule-specific activity both during maze running and at reward locations, with mPFC rule coding more consistent across animals compared with 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 mPFC 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 mPFC/CA1, the dopamine reward signal, and behavioral strategy.; (Copyright © 2025 Ding et al.) |
| Competing Interests: | The authors declare no competing financial interests. |
| Comments: | Update of: bioRxiv. 2025 Feb 11:2024.09.09.611811. doi: 10.1101/2024.09.09.611811.. (PMID: 39314328) |
| Grant Information: | R01 MH112661 United States MH NIMH NIH HHS; R90 DA033463 United States DA NIDA NIH HHS |
| Contributed Indexing: | Keywords: VTA; dopamine; hippocampal CA1; medial prefrontal cortex; rule switching |
| Substance Nomenclature: | VTD58H1Z2X (Dopamine) |
| Entry Date(s): | Date Created: 20250317 Date Completed: 20260511 Latest Revision: 20260511 |
| Update Code: | 20260511 |
| PubMed Central ID: | PMC12424963 |
| DOI: | 10.1523/JNEUROSCI.1670-24.2025 |
| PMID: | 40097186 |
| Database: | MEDLINE |
Journal Article