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The cerebellum, a gateway to modern neuroscience
Brain Research Bulletin, Vol. 50, Nos. 5/6, p. 331, 1999 Copyright © 1999 Elsevier Science Inc. Printed in the USA. All rights reserved 0361-9230/99/$–see front matter
PII S0361-9230(99)00147-1
The cerebellum, a gateway to modern neuroscience Masao Ito* Brain Science Institute, RIKEN, Wako, Saitama, Japan [Received 4 May 1999; Accepted 8 May 1999] as recently summarized in the special cerebellum issues in three journals, Learning & Memory (1997), Trends in Neurosciences (1998), and Trends in Cognitive Sciences (1998). The unique compartmental, modular structure of the cerebellum was uncovered [10], and complex signal transduction processes in cerebellar neurons were revealed [2]. Transgenic technology [3] and cell/ tissue transplantation [8] have achieved a unprecedented success. At the same time, involvement of the cerebellum in cognitive and language functions has been implicated both experimentally and theoretically [9]. The study of neuronal circuits in the cerebellum thus has been, and will continue to be, the forefront of modern neuroscience which aims at clarifying how neuronal circuits operate to generate diverse brain functions including our mental activities.
The 1960s was an exciting period of time in my life. The study of electrophysiology of nerve cells, which began with Eccles’ discovery of inhibitory postsynaptic potentials in 1951, had covered simple neuronal circuits in the spinal cord, and interest had begun to be directed toward higher levels of the brain. The cerebellum was the next obvious target because of its relatively simple, regularly organized neuronal circuit. When I returned to Tokyo in 1962 from Canberra, where I had spent 3 years with John Eccles, I was not aware that the professor was gearing to investigate neuronal circuits in the cerebellar cortex with his new colleagues. In Tokyo, shortly after I had set up a laboratory with several colleagues, we discovered the inhibitory action of cerebellar Purkinje cells, which prompted us to investigate the entire cerebellar output circuits to deep nuclei, vestibular nuclei, the red nucleus and the thalamus. The results of these works were integrated in the book “The Cerebellum as a Neuronal Machine” written by Eccles, Ito, and Szenta´gothai [4]. The beautiful demonstration of neuronal circuits in the cerebellum evoked in us a great dream of soon being able to uncover the structural and functional principles of the cerebellum. However, when we attempted to explain how the cerebellum contributes to motor skills or how cerebellar lesions produce unique symptoms such as dysmetria, it appeared to be simply impossible. Obviously, something of essential importance was missing in our knowledge. Meetings were then held to invite mathematicians, computer scientists and bioengineers to look into every detail of the neuronal circuit diagram of the cerebellum in order to elucidate its meaning. Eventually, Marr [7], Albus [1], and some other theorists proposed models of the cerebellum as a learning machine under the assumption that the cerebellar neuronal circuits contain synaptic plasticity as a memory element. This was the beginning of a decade-long debate on the existence of such plasticity, which lasted until Sakurai, Tongroach and myself [6] obtained the first direct evidence for it. Experimental and theoretical approaches thus merged to yield the basic concept that the cerebellum is a learning machine subserving diverse forms of neural control, as I have clarified in my monograph “The Cerebellum and Neuroal Control” [5]. Studies of the cerebellum then branched in various directions,
REFERENCES 1. Albus, J. S. A theory of cerebellar function. Math. Biosci. 10:25– 61; 1971. 2. Daniel, H.; Levenes, C.; Cre´pel, F. Cellular mechanisms of cerebellar LTD. Trends Neurosci. 21:401– 407; 1998. 3. De Zeeuw, C. I.; Hansel, C.; Bian, F.; Koekkoek, S. K.; van Alphen, A. M.; Linden, D. J.; Oberdick, J. Expression of a protein kinase C inhibitor in Purkinje cells blocks cerebellar LTD and adaptation of the vestibulo-ocular reflex. Neuron 20:495–508; 1998. 4. Eccles, J. C.; Ito, M.; Szenta´gothai, J. The cerebellum as a neuronal machine. Berlin: Springer-Verlag; 1967. 5. Ito, M. The cerebellum and neural control. New York: Raven Press; 1982. 6. Ito, M.; Sakurai, M.; Tongroach, P. Climbing fibre induced depression of both mossy fibre responsiveness and glutamate sensitivity of cerebellar Purkinje cells. J. Physiol. (Lond.) 324:113–134; 1982. 7. Marr, D. A theory of cerebellar cortex. J. Physiol. (Lond.) 202:437– 470; 1969. 8. Sotelo, C.; Alvarado-Mallart, R. M. The reconstruction of cerebellar circuits. Trends Neurosci. 14:350 –355; 1991. 9. Schmahmann, J. D., ed. The cerebellum and cognition. International Review of Neurobiololgy, New York: Academic Press; 1997: 1– 665. 10. Voogd, J.; Glickstein, M. The anatomy of the cerebellum. Trends Neurosci. 21:370 –375; 1998.
* Address for correspondence: Prof. Masao Ito, Brain Science Institute, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan. Fax: ⫹81-48467-9683; E-mail: [email protected]
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PII S0361-9230(99)00147-1
The cerebellum, a gateway to modern neuroscience Masao Ito* Brain Science Institute, RIKEN, Wako, Saitama, Japan [Received 4 May 1999; Accepted 8 May 1999] as recently summarized in the special cerebellum issues in three journals, Learning & Memory (1997), Trends in Neurosciences (1998), and Trends in Cognitive Sciences (1998). The unique compartmental, modular structure of the cerebellum was uncovered [10], and complex signal transduction processes in cerebellar neurons were revealed [2]. Transgenic technology [3] and cell/ tissue transplantation [8] have achieved a unprecedented success. At the same time, involvement of the cerebellum in cognitive and language functions has been implicated both experimentally and theoretically [9]. The study of neuronal circuits in the cerebellum thus has been, and will continue to be, the forefront of modern neuroscience which aims at clarifying how neuronal circuits operate to generate diverse brain functions including our mental activities.
The 1960s was an exciting period of time in my life. The study of electrophysiology of nerve cells, which began with Eccles’ discovery of inhibitory postsynaptic potentials in 1951, had covered simple neuronal circuits in the spinal cord, and interest had begun to be directed toward higher levels of the brain. The cerebellum was the next obvious target because of its relatively simple, regularly organized neuronal circuit. When I returned to Tokyo in 1962 from Canberra, where I had spent 3 years with John Eccles, I was not aware that the professor was gearing to investigate neuronal circuits in the cerebellar cortex with his new colleagues. In Tokyo, shortly after I had set up a laboratory with several colleagues, we discovered the inhibitory action of cerebellar Purkinje cells, which prompted us to investigate the entire cerebellar output circuits to deep nuclei, vestibular nuclei, the red nucleus and the thalamus. The results of these works were integrated in the book “The Cerebellum as a Neuronal Machine” written by Eccles, Ito, and Szenta´gothai [4]. The beautiful demonstration of neuronal circuits in the cerebellum evoked in us a great dream of soon being able to uncover the structural and functional principles of the cerebellum. However, when we attempted to explain how the cerebellum contributes to motor skills or how cerebellar lesions produce unique symptoms such as dysmetria, it appeared to be simply impossible. Obviously, something of essential importance was missing in our knowledge. Meetings were then held to invite mathematicians, computer scientists and bioengineers to look into every detail of the neuronal circuit diagram of the cerebellum in order to elucidate its meaning. Eventually, Marr [7], Albus [1], and some other theorists proposed models of the cerebellum as a learning machine under the assumption that the cerebellar neuronal circuits contain synaptic plasticity as a memory element. This was the beginning of a decade-long debate on the existence of such plasticity, which lasted until Sakurai, Tongroach and myself [6] obtained the first direct evidence for it. Experimental and theoretical approaches thus merged to yield the basic concept that the cerebellum is a learning machine subserving diverse forms of neural control, as I have clarified in my monograph “The Cerebellum and Neuroal Control” [5]. Studies of the cerebellum then branched in various directions,
REFERENCES 1. Albus, J. S. A theory of cerebellar function. Math. Biosci. 10:25– 61; 1971. 2. Daniel, H.; Levenes, C.; Cre´pel, F. Cellular mechanisms of cerebellar LTD. Trends Neurosci. 21:401– 407; 1998. 3. De Zeeuw, C. I.; Hansel, C.; Bian, F.; Koekkoek, S. K.; van Alphen, A. M.; Linden, D. J.; Oberdick, J. Expression of a protein kinase C inhibitor in Purkinje cells blocks cerebellar LTD and adaptation of the vestibulo-ocular reflex. Neuron 20:495–508; 1998. 4. Eccles, J. C.; Ito, M.; Szenta´gothai, J. The cerebellum as a neuronal machine. Berlin: Springer-Verlag; 1967. 5. Ito, M. The cerebellum and neural control. New York: Raven Press; 1982. 6. Ito, M.; Sakurai, M.; Tongroach, P. Climbing fibre induced depression of both mossy fibre responsiveness and glutamate sensitivity of cerebellar Purkinje cells. J. Physiol. (Lond.) 324:113–134; 1982. 7. Marr, D. A theory of cerebellar cortex. J. Physiol. (Lond.) 202:437– 470; 1969. 8. Sotelo, C.; Alvarado-Mallart, R. M. The reconstruction of cerebellar circuits. Trends Neurosci. 14:350 –355; 1991. 9. Schmahmann, J. D., ed. The cerebellum and cognition. International Review of Neurobiololgy, New York: Academic Press; 1997: 1– 665. 10. Voogd, J.; Glickstein, M. The anatomy of the cerebellum. Trends Neurosci. 21:370 –375; 1998.
* Address for correspondence: Prof. Masao Ito, Brain Science Institute, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan. Fax: ⫹81-48467-9683; E-mail: [email protected]
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