Levodopa suppresses grid-like activity and impairs spatial learning in novel environments in healthy young adults

Accumulated evidence from animal studies suggests a role for the neuromodulator dopamine in memory processes, particularly under conditions of novelty or reward. Our understanding of how dopaminergic modulation impacts spatial representations and spatial memory in humans remains limited. Recent evidence suggests age-specific regulation effects of dopamine pharmacology on activity in the medial temporal lobe, a key region for spatial memory. To which degree this modulation affects spatially patterned medial temporal representations remains unclear. We reanalyzed recent data from a pharmacological dopamine challenge during functional brain imaging combined with a virtual object-location memory paradigm to assess the effect of Levodopa, a dopamine precursor, on grid-like activity in the entorhinal cortex. We found that Levodopa impaired grid cell-like representations in a sample of young adults (n = 55, age = 26-35 years) in a novel environment, accompanied by reduced spatial memory performance. We observed no such impairment when Levodopa was delivered to participants who had prior experience with the task. These results are consistent with a role of dopamine in modulating the encoding of novel spatial experiences. Our results suggest that dopamine signaling may play a larger role in shaping ongoing spatial representations than previously thought.

Automated summary

Accumulated evidence from animal studies suggests that dopamine plays a role in memory processes, especially in situations involving novelty or rewards. However, our understanding of how dopamine affects spatial representations and spatial memory in humans is limited. Recent research indicates that dopamine pharmacology has age-specific regulation effects on the medial temporal lobe, a region crucial for spatial memory. The extent to which this modulation affects spatially patterned medial temporal representations is still unclear. By reanalyzing recent data, this study found that Levodopa, a dopamine precursor, impaired grid cell-like representations in a sample of young adults in a novel environment, along with reduced spatial memory performance. Interestingly, no impairment was observed when Levodopa was given to participants with prior experience of the task. These findings suggest that dopamine signaling may have a larger impact on shaping ongoing spatial representations than previously believed.