Minicerebellum, now available for reductionists' functional study.

Abstract

The cerebellum is a neuronal machine that is composed of numerous uniform modules called “microcomplexes.” The cerebellum plays an essential role for adaptive motor learning by providing the motor control system with an “internal model.” The internal models are formed by integration of calculations performed by microcomplexes in which the input-output relationship is adaptively modified by the “error signals” conveyed into Purkinje cells by climbing fibers (1, 2). Despite the long history of the cerebellum research, much of the mechanism on how each microcomplex works and how the calculations of microcomplexes are integrated to form internal models still remains to be studied as this research has been hampered by the difficulty in observing and manipulating a too large number of microcomplexes either at once or individually. One possible way to overcome this difficulty is to take a reductionist approach, i.e., to study the “smallest” cerebellum. In PNAS, the report by Matsui et al. (3), together with recently published works by others (4⇓⇓–7), demonstrates that the tiny cerebellum of the larva of teleost zebrafish (Danio rerio) can be a suitable model for this purpose, because it is much smaller in size with much smaller number of microcomplexes than in mammals and is still amenable to various genetic manipulations. Transparency of larva enables the whole-brain neural activity imaging with single-cell resolution by use of modern cellular activity imaging technology such as two-photon microscopy in combination with various intracellular calcium indicators (3⇓⇓⇓–7).