Carta Acesso aberto Revisado por pares

Climbing fibres ‐ a key to cerebellar function

1999; Wiley; Volume: 516; Issue: 3 Linguagem: Inglês

10.1111/j.1469-7793.1999.0629u.x

ISSN

1469-7793

Autores

C.‐F. Ekerot,

Tópico(s)

Hearing, Cochlea, Tinnitus, Genetics

Resumo

Due to the unique features of cerebellar climbing fibres, their extremely powerful synapses on the Purkinje cells and the lack of convergence there has been much speculation about their function. As early as 1970 Miller and Oscarsson suggested that climbing fibres carried information about differences between intended and actual movements (Ito, 1984). This was based on the convergence between ascending spinal cord pathways and descending cerebral cortical inputs in the inferior olive, the origin of climbing fibres. This idea had a strong influence on several theories of cerebellar function advanced in the seventies (for references see Ito, 1984), in which mossy fibres were assumed to carry information used for the immediate control of movements whereas climbing fibres carried information about errors in motor performance. Climbing fibre activity was assumed to induce plastic changes of parallel fibre synapses thereby, in an adaptive manner, eliminating errors in motor performance as shown schematically in Fig. 1A. Although not undisputed, these theories have gained substantial experimental support. The predicted long term depression (LTD) of parallel synapses active in conjunction with climbing fibres was first demonstrated by Ito and colleagues in 1982 (see Ito, 1984) and has been investigated both at a cellular and at a molecular level (Ito, 1989). A, model of cerebellar learning. IO, inferior olive. For explanation see text. B, examples of climbing fibre receptive fields on the forelimb recorded in the C3 zone of the cat. Black areas indicate central and hatched areas peripheral parts of the receptive fields. The cerebellar cortex is subdivided into a number of parasagittal zones. These were identified from the organization of cerebellar anatomy, of the information carried by climbing fibre pathways, their termination in the cortex, the cerebellar myeloarchitecture, cortico-nuclear and olivo-cerebellar connections, particularly in the pioneering work of Oscarsson and Voogd. From these studies a number of cerebellar compartments were identified, each consisting of a cortical zone receiving climbing fibre afferents from a specific part of the inferior olive and projecting to an efferent nucleus through which it controls a specific motor function. Later studies have shown that these compartments consist of smaller 'modules' (Ekerot et al. 1997). The cortical microzone of a module receives a homogenous climbing fibre input from a specific peripheral receptive field and each module controls a simple movement through a private set of efferent neurones. The climbing fibre cutaneous receptive field of a module seems to be closely related to the controlled movement. Studies on the vestibulo-occular reflex (VOR), a relatively simple motor system controlled by the cerebellum, have shown that climbing fibres projecting to cerebellar zones controlling this reflex are strongly activated when images of large objects move across the retina. This occurs during movements if the gain of the reflex is incorrect (see Ito, 1984). Furthermore, several studies on behaving animals have shown that climbing fibres that are easily activated by stimuli in a passive animal are not activated when similar stimuli result from active movement (i.e. during locomotion), but may discharge in response to unexpected stimuli (see Andersson & Armstrong, 1987). The paper of Apps & Lee (1999) and previous papers from the Bristol group are of great relevance to one of the most important issues concerning climbing fibres, namely how they evaluate motor performance. The C1/C3 zones consist of 30-40 microzones (Ekerot et al. 1997) and control movements via the rubrospinal and corticospinal tracts. Examples of climbing fibre receptive fields from microzones of the C3 zone of the cat are shown in Fig. 1B. From their location it is evident that many of them would be stimulated during normal locomotion. In previous investigations the excitability of climbing fibre pathways to the forelimb area of the C1 zone in the anterior lobe was studied during locomotion (see Apps & Lee, 1999). Climbing fibre field potentials evoked by stimulation of cutaneous superficial radial nerve afferents were used as a measure of the excitability. At most recording sites climbing fibres had their highest excitability during the swing phase and lowest during the stance phase. Interestingly, the present study shows that most recording sites in the C1 and C3 zones in the cerebellar posterior lobe (paramedian lobule) have a different pattern with peak excitability during the stance phase (Apps & Lee, 1999). Thus, the excitability of climbing fibres to the C1/C3 zones is not uniformly controlled during locomotion. Since receptive fields of climbing fibres projecting to different microzones differ at different rostro-caudal levels, the different phase relations of gating of climbing fibre transmission to a microzone could be a function of the location of the climbing fibre receptive field. If this is true the gating of climbing fibre pathways during locomotion could be an efficient way to eliminate self-generated activation of climbing fibres during normal locomotion and to facilitate responses to inputs occurring during movement phases when no peripheral input is expected. The results of Apps & Lee and studies of the VOR suggest that different strategies, specifically adapted to the function of the controlled motor system, are used by climbing fibres to evaluate motor performance.

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