Ventral tegmental area dopamine neural activity switches simultaneously with rule representations in the prefrontal cortex and hippocampus.
| Title: | Ventral tegmental area dopamine neural activity switches simultaneously with rule representations in the prefrontal cortex and hippocampus. |
|---|---|
| Authors: | Ding M; Graduate Program in Neuroscience, Brandeis University, Waltham, MA 02453, USA.; Tomsick PL; Undergraduate Program in Neuroscience, Brandeis University, Waltham, MA 02453, USA.; Department of Neuroscience, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA.; Young RA; Department of Psychology, Brandeis University, Waltham, MA, 02453, USA.; Jadhav SP; Graduate Program in Neuroscience, Brandeis University, Waltham, MA 02453, USA.; Department of Psychology, Brandeis University, Waltham, MA, 02453, USA.; Volen National Center for Complex Systems, Brandeis University, Waltham, MA, 02453, USA. |
| Source: | BioRxiv : the preprint server for biology [bioRxiv] 2025 Feb 11. Date of Electronic Publication: 2025 Feb 11. |
| Publication Type: | Journal Article; Preprint |
| Language: | English |
| Journal Info: | Country of Publication: United States NLM ID: 101680187 Publication Model: Electronic Cited Medium: Internet ISSN: 2692-8205 (Electronic) Linking ISSN: 26928205 NLM ISO Abbreviation: bioRxiv Subsets: PubMed not MEDLINE |
| Abstract: | 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 Interests: | Conflicts of Interest: Authors report no conflict of interest. |
| Comments: | Update in: J Neurosci. 2025 Sep 10;45(37):e1670242025. doi: 10.1523/JNEUROSCI.1670-24.2025.. (PMID: 40097186) |
| Grant Information: | R01 MH112661 United States MH NIMH NIH HHS; R90 DA033463 United States DA NIDA NIH HHS |
| Entry Date(s): | Date Created: 20240924 Latest Revision: 20260511 |
| Update Code: | 20260511 |
| PubMed Central ID: | PMC11419070 |
| DOI: | 10.1101/2024.09.09.611811 |
| PMID: | 39314328 |
| Database: | MEDLINE |
Journal Article; Preprint