The molecular organization of cerebellar long-term depression.
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Animals↗
Biomedical subjects
Masao Ito
Publications and source records attributed to Masao Ito.
Hopes for cerebellar research in the 21st century.
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Animals↗
Historical review of the significance of the cerebellum and the role of Purkinje cells in motor learning.
Classic studies of the cerebellum before the middle of the twentieth century established the structural entity of the cerebellum and characterized its function as enabling animals and humans to carry out smooth and accurate movements, even at a high speed and without visual feedback. In the 1960s, neuronal circuit structures of the cerebellum were analyzed in detail, which promoted computational approaches toward the study of neuronal network principles of the cerebellum. In the 1970s and 1980s, vestibulo-ocular reflex adaptation, adaptive locomotion, eye blink conditioning, and learning in hand/arm movement were established as effective experimental paradigms for investigating neural mechanisms of cerebellar functions. In the 1980s, long-term depression (LTD) was discovered and considered as a memory process in the cerebellum; in the 1990s, complex signal transduction processes underlying LTD were revealed. It was also in the 1980s that computational approaches were advanced for modeling control system functions of the cerebellum. Currently, there are two alternative models proposed for VOR adaptation. In this decade, we envisage new developments toward the fusion of knowledge of the cerebellum at molecular and cellular levels and those in systems and computation. Studies of LTD will play a key role in pursuing this direction.
Animals↗
Controller-regulator model of the central nervous system.
In the central nervous system, activities of numerous neurons are integrated to constitute a number of major functional blocks, each characterized by unique structural and functional features. Five controller systems are centers of reflexes, compound movements and innate behaviors in the brainstem and spinal cord and those of the sensory/motor and executive/cognitive functions in the cerebral neocortex. Four regulator systems are the sleep-wakefulness centers in the brainstem, cerebellum, basal ganglia and limbic system. This article describes characteristic features of these nine systems based on current knowledge of neuroscience, and attempts to account for several important aspects of the central nervous system (hierarchy, top-down operation, internal model and will) by compounding these component functions.
Animals↗
[Roles of brain science in psychiatry].
At the opportunity of celebrating the 100th Anniversary of the Japanese Society of Psychiatry and Neurology, I am filled with deep emotion when I recall the time only a few decades ago, when mental disorders were believed to be an illness of the mind without any disorder in the brain. It has now become apparent that a mental disease emerges from the malfunction of the brain's unique biological mechanisms, so that any mental disease can be cured or prevented if the cause of the malfunction is clarified. Analyses of intercellular as well as intracellular signal transduction and the mechanisms underlying gene regulation in brain cells have recently advanced markedly and have brought a marked improvement in the methods and technology for investigating pathogenesis of neurological and psychiatric diseases. These impressive results have been derived in the search for the cause of Parkinson's disease, Alzheimer's disease and spinocerebellar degeneration. Certain minor changes in the molecular structure of sodium channels have been found to cause epilepsy. It has also been revealed that ten particular sites in chromosomes harbor the remote cause of schizophrenia and depression. These sites are probably responsible for production of certain synaptic transmitters and modulators. Another major challenge in the field of psychiatry is to understand the unique symptoms exhibited by patients with psychiatric disorders, which requires research to head in a direction different from molecular and cellular brain science. It is a challenge similar to the very fundamental challenge of determining how our brain, which is composed of numerous brain cells, yields our mind (or, should I say, supports our mind). To understand the brain as a complex system is more difficult than researching its molecular and cellular machinery, and accordingly, the progress of research in this field has been slow. However, it is gradually gaining speed thanks to the improvement in non-invasive methods for measuring activities in conscious human brains as well as that to the establishment of computational models. For example, it is a major mystery why a schizophrenic patient experiences auditory hallucinations, but an interesting hypothesis is derived by considering activities of the thinking brain as a neural system. Under this hypothesis, we gather information from the outside world by using our sensory systems and establish its internal model in our brain. Thus, manipulation of the internal model to run a simulation is an important part of our thinking activities. When an internal model behaves abnormally, abnormal information is generated, which makes the patient mistake it for sound from the outside, thus causing auditory hallucinations. It is highly expected that substantial progress will be made in psychiatry through proposals of new hypothetical models such as this one as well as verification of them through non-invasive measurement of brain activities. In the near future, patients with mental disorders will most likely benefit from the results of this two-directional research in psychiatry. The expectation is high for the strong leadership of the Japanese Society of Psychiatry and Neurology to promote research in Japan. Effective research effort requires efficient collection of human materials and systematic survey of patients, which will inevitably increase the involvement of patients in basic research. Improvement of research environments such as by developing a method for assessing research ethics and upgrading brain banks is urgently needed.
Alzheimer Disease↗
Cerebellar circuitry as a neuronal machine.
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.
Action Potentials↗