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.
Author:Sevil Duvarci, Eleanor H. Simpson, Gaby SchneiderGND, Eric R. Kandel, Jochen RoeperORCiD, Torfi Sigurdsson
Pubmed Id:
Parent Title (English):Nature Communications
Publisher:Nature Publishing Group UK
Place of publication:[London]
Document Type:Article
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
Issue:1, Art. 2822
Page Number:13
First Page:1
Last Page:13
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Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 4.0