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Impaired recruitment of dopamine neurons during working memory in mice with striatal D2 receptor overexpression
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Impaired recruitment of dopamine neurons during working memory in mice with striatal D2 receptor overexpression
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Impaired recruitment of dopamine neurons during working memory in mice with striatal D2 receptor overexpression
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Journal Article
Impaired recruitment of dopamine neurons during working memory in mice with striatal D2 receptor overexpression
2018
Overview
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.
Disrupted dopamine neuron firing is thought to contribute to cognitive dysfunction in psychiatric disorders. Here the authors show that mice overexpressing D2R in the striatum, commonly seen in schizophrenia, are also impaired in recruitment of dopamine neurons during working memory performance.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 64
/ 64/60
/ 9/30
/ Action Potentials - physiology
/ Animals
/ Brain
/ Cognitive Dysfunction - genetics
/ Cognitive Dysfunction - metabolism
/ Cognitive Dysfunction - physiopathology
/ Corpus Striatum - metabolism
/ Corpus Striatum - physiopathology
/ Dopamine
/ Dopaminergic Neurons - metabolism
/ Dopaminergic Neurons - pathology
/ Humanities and Social Sciences
/ Male
/ Mice
/ Neural Pathways - metabolism
/ Neural Pathways - physiopathology
/ Neurons
/ Prefrontal Cortex - metabolism
/ Prefrontal Cortex - physiopathology
/ Receptors, Dopamine D2 - genetics
/ Receptors, Dopamine D2 - metabolism
/ Science
/ Ventral Tegmental Area - metabolism
