Better explicating the strengths and shortcomings of these models will help refine projections and improve transparency in the years ahead.
Image credit: Witsawat.S.
Edited by Marcus E. Raichle, Washington University in St. Louis, St. Louis, MO, and approved May 24, 2016 (received for review April 20, 2016)
Significance
Cognitive functioning depends in part on dopamine neurotransmission in the brain. Research implicates the dopamine D1 receptor family in cognitive functions linked to the prefrontal cortex, such as working memory. The dopamine D2 receptor family has also been linked to cognition, but it remains unclear to which cognitive functions it is specifically related. We examined the relation of D2 receptors to episodic memory, working memory, and speed of processing. D2 receptors in the caudate and hippocampus were related to episodic memory and modulated caudate–hippocampal functional connections. These findings link the dopamine D2 system to hippocampus-based cognitive functions.
Abstract
D1 and D2 dopamine receptors (D1DRs and D2DRs) may contribute differently to various aspects of memory and cognition. The D1DR system has been linked to functions supported by the prefrontal cortex. By contrast, the role of the D2DR system is less clear, although it has been hypothesized that D2DRs make a specific contribution to hippocampus-based cognitive functions. Here we present results from 181 healthy adults between 64 and 68 y of age who underwent comprehensive assessment of episodic memory, working memory, and processing speed, along with MRI and D2DR assessment with [11C]raclopride and PET. Caudate D2DR availability was positively associated with episodic memory but not with working memory or speed. Whole-brain analyses further revealed a relation between hippocampal D2DR availability and episodic memory. Hippocampal and caudate D2DR availability were interrelated, and functional MRI-based resting-state functional connectivity between the ventral caudate and medial temporal cortex increased as a function of caudate D2DR availability. Collectively, these findings indicate that D2DRs make a specific contribution to hippocampus-based cognition by influencing striatal and hippocampal regions, and their interactions.
Footnotes
- ↵1To whom correspondence should be addressed. Email: lars.nyberg{at}umu.se.
Author contributions: L.N., K.R., M.L., U.L., and L.B. designed research; N. Karalija performed research; N. Karalija, A.S., M.A., A.W., N. Kaboovand, Y.K., J.A., A.R., G.P., and D.D.G. analyzed data; and L.N. and L.B. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
Freely available online through the PNAS open access option.
Dopamine D2, hippocampus, and episodic memory
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