Bases and implications of learning in the cerebellum — adaptive control and internal model mechanism

Abstract

The cerebellum has a fine compartment structure, which represents various discrete functions. Evolutionarily old, medial parts of the cerebellum are involved in the adaptive control of vairous brainstem and spinal cord functions, and long-term depression (LTD) plays a key role in this adaptive control. To extend these views to evolutionarily newer, lateral parts of the cerebellum involved in cerebral cortical functions such as voluntary movement, perception and language, the internal model hypothesis is instrumental. This hypothesis explains not only the characteristic cerebellar symptom, dysmetria, but also a number of otherwise unexplainable phenomena displayed in movements and mental actions.

Introduction

Investigations of the cerebellum have been greatly advanced during the past century, and several lines of basic knowledge accumulated thus, to provide the basis for understanding the neuronal mechanisms and functional roles of the cerebellum. First, the neuroanatomical studies revealed that the cerebellum has a unique geometrical architecture represented by the checkered board map shown in Fig. 1. It is divided into the middle longitudinal area, vermis, and the intermediate and lateral parts of the hemisphere, which are further subdivided into 13 major longitudinal zones (A in the middle and B, C1, C2, C3, D1 and D2 on the right and left sides) (Groenewegen et al., 1979). At the vermis, grooves running along the right–left axis divide the cerebellum into ten lobules I–X, which continue to the hemisphere as lobules HII–HX (Larsell and Yansen, 1972). While certain divisions are missing in the posterior part of the B, C1 and C3 zones, and there are additional zones such as x in the anterior vermis (Fig. 1), the cerebellum contains more than one hundred divisions.

Second, the cerebellar divisions have uniformly structured neuronal circuits and hence are presumed to operate by the same local circuit principles. The elaborate network structures of the cerebellar cortex composed of the Purkinje, basket, stellate, Golgi and granule cells, and mossy and climbing fiber afferents have been analyzed extensively. More recently, Lugaro cells (see Lane and Axelrod, 2002), unipolar brush cells (see Dino et al., 1999) and serotonergic, noradrenergic, dopaminergic and acetylcholinergic afferents (see Schweighofer et al., 2004) have also been recognized as unique elements of the network. While various types of synaptic plasticity have been located in the network as possible memory elements (Hansel et al., 2001), the long-term depression (LTD) is unique being induced by the convergence of signals from both granule cell axons and climbing fibers to a Purkinje cell. The signal transduction underlying LTD has recently been analyzed extensively (see Ito, 2001, 2002). Earlier, the author proposed a cerebellar corticonuclear microcomplex (hereafter referred to as ‘microcomplex’) as a functional unit capable of learning with LTD as a major memory process (Ito, 1984). A microcomplex is composed of a microzone of the cerebellar cortex interconnected to a small group of cerebellar nuclear neurons (or vestibular nuclear neurons) and a small group of inferior olive neurons that project climbing fiber afferents. A microcomplex modifies the relationship between the input from mossy fiber afferents and the output from nuclear neurons in response to error signals conveyed by the climbing fibers.

Third, these microcomplexes are connected to different extracerebellar structures, and hence are involved in diverse functions. Since a microcomplex has an area of 10 mm² in the cerebellar cortex, and since the entire cortex has an area of 50,000 mm², a human cerebellum may contain 5000 microcomplexes (Ito, 1984). A prototype of a cerebellar control has been developed from the manner in which the vermis, including the A and B zones, and the intermediate part of the hemisphere including the C1–C3 zones are connected to the spinal cord and the brainstem. Figure 2 illustrates the involvement of the flocculus in the two-degrees-of-freedom control of the eye movements in response to the head movements and optokinetic stimulation. A relatively small number of specific functions have so far been localized in the cerebellar surface, as illustrated in Fig. 1. Locomotion is represented in the vermis of lobule V (Yanagihara and Udo, 1994) and the C1 and C3 zones of the rostral paramedian lobule (Apps and Lee, 1999), and the saccadic eye movements in the oculomotor vermis covering lobules VI–VIII (Noda and Fujikado, 1987; Barash et al., 1999). A major site involved in the eye-blink conditioning is the C1 and C3 zones of lobule HVI (Attwell et al., 2001). The scheme of adaptive control applies well to the evolutionarily old, medial part of the cerebellum connected to the brainstem and the spinal cord (Ito, 1984; Barlow, 2002). In particular, the vestibuloocular reflex adaptation (Nagao and Ito, 1991; De Zeeuw et al., 1998), eyeblink conditioning (Bao et al., 1998) and locomotion (Ichise et al., 2000) are now widely used as model systems for testing the cerebellar learning function under various pharmacological and genetic manipulations of the cerebellar neuronal circuits.

Fourth, during the course of evolution in vertebrates beyond birds toward humans, the cerebellar hemisphere expanded markedly in association with the development of the cerebral cortex. The cerebellar hemisphere is thus involved in voluntary movements such as pointing with a hand (Kitazawa et al., 1998), visuomotor tracking with a computer mouse (Imamizu et al., 2000) and the hand-grip control (Kawato et al., 2003) (Fig. 1). Furthermore, the posterolateral part of the hemisphere represents language (Petersen et al., 1989; Fiez et al., 1992; Gebhart et al., 2002). In this chapter, the author presents the effort to expand the adaptive control system concepts thus far developed in studies of the evolutionarily old, medial parts of the cerebellum involved in the brainstem and spinal cord functions to the evolutionarily newer, lateral parts of the cerebellum involved in the cerebral cortical functions. To this effort, the internal model mechanism is instrumental. It is still largely hypothetical, but it receives increasing support from neuroanatomy and imaging analyses of human brains and computational studies in robotics. The internal model mechanism explains a number of seemingly unexplainable observations in movements as well as mental actions, covering a broad range of central nervous system functions, and its verification will be a major target for future cerebellar research.