Elsevier

Progress in Neurobiology

Volume 78, Issues 3–5, February–April 2006, Pages 272-303
Progress in Neurobiology

Cerebellar circuitry as a neuronal machine

https://doi.org/10.1016/j.pneurobio.2006.02.006Get rights and content

Abstract

Shortly after John Eccles completed his studies of synaptic inhibition in the spinal cord, for which he was awarded the 1963 Nobel Prize in physiology/medicine, he opened another chapter of neuroscience with his work on the cerebellum. From 1963 to 1967, Eccles and his colleagues in Canberra successfully dissected the complex neuronal circuitry in the cerebellar cortex. In the 1967 monograph, “The Cerebellum as a Neuronal Machine”, he, in collaboration with Masao Ito and Janos Szentágothai, presented blue-print-like wiring diagrams of the cerebellar neuronal circuitry. These stimulated worldwide discussions and experimentation on the potential operational mechanisms of the circuitry and spurred theoreticians to develop relevant network models of the machinelike function of the cerebellum. In following decades, the neuronal machine concept of the cerebellum was strengthened by additional knowledge of the modular organization of its structure and memory mechanism, the latter in the form of synaptic plasticity, in particular, long-term depression. Moreover, several types of motor control were established as model systems representing learning mechanisms of the cerebellum. More recently, both the quantitative preciseness of cerebellar analyses and overall knowledge about the cerebellum have advanced considerably at the cellular and molecular levels of analysis. Cerebellar circuitry now includes Lugaro cells and unipolar brush cells as additional unique elements. Other new revelations include the operation of the complex glomerulus structure, intricate signal transduction for synaptic plasticity, silent synapses, irregularity of spike discharges, temporal fidelity of synaptic activation, rhythm generators, a Golgi cell clock circuit, and sensory or motor representation by mossy fibers and climbing fibers. Furthermore, it has become evident that the cerebellum has cognitive functions, and probably also emotion, as well as better-known motor and autonomic functions. Further cerebellar research is required for full understanding of the cerebellum as a broad learning machine for neural control of these functions.

Section snippets

Introduction: John Eccles and the cerebellum

Characteristic features of neuronal circuitry vary from area to area within the brain. The outstanding feature of the cerebellum's circuitry is the precision and geometric beauty of its arrangement. For these reasons, it has been a target of intensive investigation these past four decades. In this article, I review four aspects of the progress of neuroscience as it pertains to the cerebellum. (1) How Sir John Eccles (1903–1997) advanced the analysis of cerebellar neuronal circuitry so

Functional implications of the neuronal machine concept

Our 1967 concept of the cerebellum as a neuronal machine was certainly a stimulus for inviting the development of meaningful wiring diagrams of the brain. These diagrams had gaps, however, particularly from the viewpoint of their functional implications. As a result, it was difficult to offer a self-consistent explanation about how the machine actually operates. It remained for efforts in the 1970s and 1980s to fill the gaps by work on the modular organization and learning/memory mechanisms of

An update on the structure and operation of the cerebellar neuronal machine

Following the above-mentioned development of a self-consistent design of the cerebellar neuronal machine in the 1970s and 1980s, work on this issue has continued. In particular, Lugaro cells and unipolar brush cells were identified as additional unique elements of cerebellar neuronal circuitry by use of improved techniques for cell morphology and physiology. Our knowledge increased more substantially, however, about cerebellar synapses and signal transduction. This was due to remarkable

Future possibilities for the neuronal machine concept

Despite remarkable advances throughout six decades, knowledge of the cerebellum is still incomplete for formulating the full functional design of the cerebellar neuronal machine. Further research is clearly required. To emphasize this point, five particular issues are addressed below.

Concluding comments

Four decades have passed since Sir John Eccles pioneered a modern neuroscientific approach to the cerebellum. The neuronal machine concept of the cerebellum was developed into a self-consistent form, and its further refinement is still underway. Currently, knowledge in neuroscience is advancing rapidly at the molecular/cellular level on one hand and the behavioral/cognitive level on the other. To understand mechanisms underlying the generation of brain functions, however, it is essential to

Acknowledgements

Writing this article reminded me of the time when I had the extraordinary good fortune to co-author the 1967 monograph “The Cerebellum as a Neuronal Machine” with two great scholars, Sir John Eccles and Janos Szentágothai. I owed this honor to my then-colleagues in my University of Tokyo laboratory. They included Nakaakira Tsukahara (1933–1985), Kyoji Maekawa (1929–1990), Masao Udo (1938–1993) and Mitsuo Yoshida (1933–1998). I am also greatly indebted to the RIKEN Brain Science Institute, which

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