Impaired recruitment of dopamine neurons during working memory in mice with striatal D2 receptor overexpression
- The dopamine (DA) system plays a major role in cognitive functions through its interactions with several brain regions including the prefrontal cortex (PFC). Conversely, disturbances in the DA system contribute to cognitive deficits in psychiatric diseases, yet exactly how they do so remains poorly understood. Here we show, using mice with disease-relevant alterations in DA signaling (D2R-OE mice), that deficits in working memory (WM) are associated with impairments in the WM-dependent firing patterns of DA neurons in the ventral tegmental area (VTA). The WM-dependent phase-locking of DA neurons to 4 Hz VTA-PFC oscillations is absent in D2R-OE mice and VTA-PFC synchrony deficits scale with their WM impairments. We also find reduced 4 Hz synchrony between VTA DA neurons and selective impairments in their representation of WM demand. These results identify how altered DA neuron activity—at the level of long-range network activity and task-related firing patterns—may underlie cognitive impairments.
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| Author: | Sevil Duvarci, Eleanor H. Simpson, Gaby SchneiderGND, Eric R. Kandel, Jochen RoeperORCiD, Torfi SigurdssonORCiD |
|---|---|
| URN: | urn:nbn:de:hebis:30:3-471707 |
| DOI: | https://doi.org/10.1038/s41467-018-05214-4 |
| ISSN: | 2041-1723 |
| Pubmed Id: | https://pubmed.ncbi.nlm.nih.gov/30026489 |
| Parent Title (English): | Nature Communications |
| Publisher: | Nature Publishing Group UK |
| Place of publication: | [London] |
| Document Type: | Article |
| Language: | English |
| Year of Completion: | 2018 |
| Date of first Publication: | 2018/07/19 |
| Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
| Release Date: | 2018/09/06 |
| Tag: | Neural circuits; Schizophrenia; Working memory |
| Volume: | 9 |
| Issue: | 1, Art. 2822 |
| Page Number: | 13 |
| First Page: | 1 |
| Last Page: | 13 |
| Note: | Rights and permissions: Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
| HeBIS-PPN: | 437748499 |
| Institutes: | Medizin / Medizin |
| Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
| Sammlungen: | Universitätspublikationen |
| Licence (German): |  Creative Commons - Namensnennung 4.0 |
