Functional Meaning of the Patterns of Synaptic Connections in the Cerebellum

FUNCTIONAL MEANING OF THE PATTERNS OF SYNAPTIC CONNECTIONS IN THE CEREBELLUM SIR JOHN ECCLES* Ever since their first detailed investigations on the structure ofthe central nervous system, the neuroanatomists, and particularly Ramón y Cajal, have been meditating on the mode ofoperation ofthe complex patterns ofneuronal arrangements that they were discovering. These patterns appeared to be so different in the various regions ofthe nervous system, yet there seemed to be some underlying principles of organization which could dimly be perceived. Ramón y Cajal himselfdid not hesitate to draw conjectural diagrams of all the major neuronal assemblages that he investigated , and he proposed many modes ofneuronal interaction. But inherent in all these was the fatal defect that inhibitory synaptic action was ignored. Neuroanatomists have, I think, generally recognized that the cerebellum provides the greatest challenge in our initial efforts to discern functional meaning in neuronal patterns, because there is such a beautiful geometrical arrangement ofits unique neuronal constituents. Presumably, it is for this reason that we are fortunate in possessing the most refined knowledge of microstructure that is available in the central nervous system. The pioneer investigations ofRamón y Cajal have led in recent times to fascinating developments concerning microstructure, geometricalarrangements, and numerical assessment, notably by Professors Fox and Szentágothai. When one considers the cerebellum in relation to the rest ofthe nervous system, interesting speculations in the field of comparative morphology can be developed. It appears that the cerebellum originally arose in relation to the vestibular and lateral line receptor organs of primitive vertebrates * Australian National University, Canberra, Australia. This paper was presented as the Fourth Annual AntonJ. Carlson Memorial Lecture at the University ofChicago, November 19, 1964. 289 [?]. With each further evolutionary development ofthe brain, this same cerebellar organization seemed to be a necessary adjunct, presumably because it possessed some unique mode of processing information. Hence, these newly developed areas ofthe brain colonized or developed areas of the cerebellum for this purpose; and most lately ofall, the cerebral hemispheres have called forth the great development of the cerebellar lobes. With the evolutionary growth ofthe brain, the cerebellar hypertrophy has matchedthehypertrophyofthe cerebrum. This evolutionary storycertainly gives rise to the concept that there is some highly significant and unique functional meaning in the neuronal patterns ofthe cerebellum and in the processing ofinformation that is accomplished thereby. My present purpose is to give an account ofthe structure and functional properties and ofthe various pathways into and through the mammalian cerebellum (actually the vermis ofthe cat) from the simplest to the most complex and then to integrate these mechanisms, first, at local zones of action and, second, in the wider geometrical fields of action that derive from their three-dimensional structure. In this way I will endeavor to formulate some tentative conceptsabout the meaningand significance ofthese unique neuronal arrangements in the cerebellum. Professors Fox and Szentágothai have already pioneered this approach in relation to the anatomical organization; and in these present physiological investigations I am also greatly indebted to my colleagues Doctors Andersen, Llinás, Voorhoeve, and Sasaki. Only a small fraction ofthis work has as yet been published [2-5]. I. Introductory Morphology It is generally accepted that there arejust two kinds ofafferent fiber conveying information to the cerebellum—the climbing fibers and the mossy fibers; and that there is only one type ofefferent fiber from the cerebellum —the axons ofthe Purkinje cells, which for the most part terminate in the cerebellar nuclei, as shown in the beautiful drawing (Fig. 1) that has been published by Professor C. A. Fox [6]. In this initialattempt to see functional meaning in the synaptic connections in the cerebellar cortex, I will concentrate on the major functional connections and neglect those that seem to have either subsidiary action or to be aberrancies in structural development . Figure ? shows a perspective drawing ofa section ofa typical cerebellar 290 SirJohn Eccles · Synaptic Connections in the Cerebellum Perspectives in Biology and Medicine · Spring ipfy folium cut both transversely and longitudinally. The transverse section shows the planar arrangement of the great branching dendritic tree ofa Purkinjecell (pc) andofthelesserdendritictreesofthebasket cells (bc) and stellate cells (sc). It also shows how each climbing fiber (cf) uniquely twines around the many branches...