Dopamine modulation of spatial navigation memory in Parkinson's disease

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• 作者：Franka Thurm^a ; ^{franka.thurm@tu-dresden.de" class="auth_mail" title="E-mail the corresponding author} ; Nicolas W. Schuck^b ; Mareike Fauser^c ; Christian F. Doeller^d ; Yuliya Stankevich^e ; Ricarda Evens^e ; Oliver Riedel^e ; ² ; Alexander Storch^c ; ^f ; ³ ; Ulrike Lueken^e ; ⁴ ; ¹ ; Shu-Chen Li^a ; ^g ; ¹ ; ^{shu-chen.li@tu-dresden.de" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Spatial navigation ; Striatum ; Hippocampus ; Parkinson's disease ; Dopamine ; Aging
• 刊名：Neurobiology of Aging
• 出版年：2016
• 出版时间：February 2016
• 年：2016
• 卷：38
• 期：Complete
• 页码：93-103
• 全文大小：1118 K

文摘

Striatal dopamine depletion is a key pathophysiological feature of Parkinson's disease (PD) causing motor and nonmotor symptoms. Research on nonmotor symptoms has mainly focused on frontostriatal functions. However, dopamine pathways ascending from the ventral tegmental area also innervate hippocampal structures and modulate hippocampal-dependent functions, such as spatial memory. Using a virtual spatial navigation task, we investigated dopaminergic modulation of spatial memory in PD patients in a crossover medication ON/OFF design. We examined medication effects on striatal- and hippocampal-dependent spatial memory by either replacing a location cue in the environment or enlarging its spatial boundary. Key results indicate that in contrast to prior evidence for younger adults, PD patients, like their age-matched controls, rely more on striatal cue-based than hippocampal spatial learning. Medication facilitated striatal-dependent cue-location learning, whereas medication benefit in hippocampal boundary-related spatial memory depended on prior experience with the task. Medication effects on spatial memory were comparable to and independent of benefits on motor symptoms. These findings shed new light on dopaminergic modulation of hippocampal-striatal functions in PD.