Grid cells: the missing link in understanding Parkinson's disease?

Front Neurosci. 2024 Feb 8:18:1276714. doi: 10.3389/fnins.2024.1276714. eCollection 2024.

Abstract

The mechanisms underlying Parkinson's disease (PD) are complex and not fully understood, and the box-and-arrow model among other current models present significant challenges. This paper explores the potential role of the allocentric brain and especially its grid cells in several PD motor symptoms, including bradykinesia, kinesia paradoxa, freezing of gait, the bottleneck phenomenon, and their dependency on cueing. It is argued that central hubs, like the locus coeruleus and the pedunculopontine nucleus, often narrowly interpreted in the context of PD, play an equally important role in governing the allocentric brain as the basal ganglia. Consequently, the motor and secondary motor (e.g., spatially related) symptoms of PD linked with dopamine depletion may be more closely tied to erroneous computation by grid cells than to the basal ganglia alone. Because grid cells and their associated central hubs introduce both spatial and temporal information to the brain influencing velocity perception they may cause bradykinesia or hyperkinesia as well. In summary, PD motor symptoms may primarily be an allocentric disturbance resulting from virtual faulty computation by grid cells revealed by dopamine depletion in PD.

Keywords: Parkinson ‘s disease; allocentric; dopamine; grid cell; medial entorhinal cortex; striato-HF/EC loop; striatum.

Grants and funding

The author declares that no financial support was received for the research, authorship, and/or publication of this article.