Functional and anatomical organization of floccular zones: A preserved feature in vertebrates

Ever since Cajal’s work, the cerebellum has been an attractive site for systems neuroscience investigation, in part because the circuitry appears to be simple. There are only two major inputs (mossy fibers and climbing fibers), a single output (the Purkinje cells), and few interneurons. Nevertheless, its function still remains elusive. Study of the cerebellar flocculus, in particular, has been important in addressing two major questions in modern neuroscience. The first involves neural transformations, because the flocculus is a site of multimodal sensory and sensory-motor integration important for retinal image stabilization. Visual and vestibular signals converge upon the flocculus, and its main output is to the extraocular muscles. Research by Simpson, Graf, and colleagues has shown that the visual inputs to the flocculus, the semicircular canals, and the extraocular muscles share a common three-dimensional frame of reference. That is, there is a very close correspondence between the axes of rotation of the three pairs of eye muscles, the axes of the three semicircular canal pairs, and the axis of rotation of the visual world that results in maximal modulation of the visual inputs to the flocculus (Simpson and Graf, 1981; see Fig. 3A,B). Second, the flocculus is an ideal site for studying the mechanisms underlying neural plasticity, because the flocculus is important for the adaptive modification of the vestibuloocular reflex (VOR). The flocculus can be subdivided into compartments, each of which monitors rotation of the eye by two of the six extraocular muscles. The compartmentation of the mammalian flocculus has a long history, culminating in the paper by Sugihara et al. (2004) published in this issue of the Journal. This commentary was prompted by recent findings of a very similar arrangement in the avian flocculus, suggesting that this property of the cerebellum is a highly conserved feature (Winship and Wylie, 2003). Many studies of the compartmentation of the flocculus are rooted in Ito’s (1972) hypothesis on the role of the flocculus in long-term adaptation of the VOR. Simultaneous activation of parallel fibers, bearing a signal from the semicircular canals, and climbing fibers from the inferior olive bearing a signal of retinal slip caused by imperfect stabilization of the eyes, supposedly would cause a long-term reduction in the firing rate of the Purkinje cells, upon which the visual and vestibular signals converge. Subsequent disinhibition of vestibuloocular relay cells would compensate for the imperfect stabilization by the VOR. Ito established that stimulation of the flocculus of the rabbit affects six specific canal-ocular pathways. Two of these pathways link the horizontal canal with the medial and lateral recti. The pathway to the ipsilateral medial rectus and the contralateral lateral rectus is excitatory, and the pathway to the ipsilateral lateral rectus and the contralateral medial rectus muscle is inhibitory. Stimulation of the horizontal canal causes adduction of the ipsilateral eye and abduction of the contralateral eye (see Fig. 3A). Stimulation of the flocculus inhibits these pathways and the direction of the evoked eye movement is reversed (see Fig. 3C). The other four pathways arise from the anterior canal. They excite the ipsilateral superior rectus and the contralateral inferior oblique muscles and inhibit their antagonists, the ipsilateral inferior rectus and the contralateral superior oblique (Ito et al., 1973, 1977). These muscles rotate the eye about an axis located in the horizontal plane that is oriented at 135° ipsilateral azimuth/45° contralateral azimuth, i.e., an axis that is approximately orthogonal to plane of the ipsilateral anterior canal. The correspondence of the axis of the anterior canal and the rotation axis of the eyes on stimulation of this canal is illustrated in Figure 3B. The effects of stim-