OPEN ACCESS ARTICLE – Physiological and Morphological Principles Underpinning Recruitment of the Cerebellar Reserve

Journal Name: CNS & Neurological Disorders – Drug Targets

Author(s): Shinji Kakei*, Takahiro Ishikawa, Jongho Lee, Takeru Honda, Donna S. Hoffman.



Graphical Abstract:



Background: In order to optimize outcomes of novel therapies for cerebellar ataxias (CAs), it is desirable to start these therapies while declined functions are restorable: i.e. while the so-called cerebellar reserve remains.

Objective: In this mini-review, we tried to define and discuss the cerebellar reserve from physiological and morphological points of view.

Method: The cerebellar neuron circuitry is designed to generate spatiotemporally organized outputs, regardless of the region. Therefore, the cerebellar reserve may be defined as a mechanism to restore its proper input-output organization of the cerebellar neuron circuitry, when it is damaged. Then, the following four components are essential for recruitment of the cerebellar reserve: operational local neuron circuitry; proper combination of mossy fiber inputs to be integrated; climbing fiber inputs to instruct favorable reorganization of the integration; deep cerebellar nuclei to generate reorganized outputs.

Results: We discussed three topics related to these resources, 1) principles of generating organized cerebellar outputs, 2) redundant mossy fiber inputs to the cerebellum, 3) plasticity of the cerebellar neuron circuitry.

Conclusion: To make most of the cerebellar reserve, it is desirable to start any intervention as early as possible when the cerebellar cell loss is minimal or even negligible. Therefore, an ideal future therapy for degenerative cerebellar diseases should start before consuming the cerebellar reserve at all. In the meantime, our real challenge is to establish a reliable method to identify the decrease in the cerebellar reserve as early as possible.


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Author: Bentham Science Publishers

A major STM journal publisher of more than 100 online and print journals and related print/online book series, Bentham Science answers the information needs of scientists in the fields of pharmaceutical, biomedical, medical, engineering, technology, computer and social sciences.

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