Dopamine D2 receptor availability is linked to hippocampal-caudate functional connectivity and episodic memory

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 [(11)C]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.

Keywords: dopamine; hippocampus; memory.

Fig. 1.

Mean caudate (A) and hippocampal (B) D2DR BP_ND correlated with episodic-memory performance, and (C) caudate D2DR BP_ND was related to hippocampal D2DR BP_ND.

Fig. 2.

(A) Horizontal, sagittal, and coronal slices showing that the functional connectivity pattern of the inferior ventral caudate included the bilateral hippocampus (P < 0.05, familywise error-corrected). (B) The degree of functional connectivity between the VCi and MTL was positively associated with caudate D2DR BP_ND. (C) Path analysis showing that the link between caudate D2DR BP_ND and episodic memory was mediated through functional connectivity between the VCi and MTL. c, coefficient. Both the total and indirect effects were significant (P < 0.05), whereas the direct effect (dashed line) was not.