Differential Maturation of Climbing Fiber Innervation in Cerebellar Vermis

Abstract

Folding of the brain surface is a general morphological adaptation to maximize surface area in a limited cranial volume. Surface folding is present not only in the neocortex but also in the cerebellar cortex. This folding creates subdivisions of the cortical surface: the sulci, the gyri, and the straight bank region, which is interposed. Is cortical folding only the solution to a surface-volume problem or does it also confer functional differences on the subdivisions that are created by this geometry? Here we have used the innervation of Purkinje cells by climbing fibers as a model system to explore potential functional differences. Purkinje cells are innervated by multiple climbing fibers at birth but undergo an activity-dependent refinement, such that by postnatal day (P) 21, most are contacted by a single climbing fiber. Using whole-cell recording from slices of cerebellar vermis derived from juvenile (P18 -25) or adult (P60 -83) mice, we found that significantly more Purkinje cells in the sulcus were innervated by multiple climbing fibers than in the gyrus or bank subdivisions; however, the basic properties of climbing fiber-Purkinje cell EPSCs such as kinetics, amplitude, and paired-pulse ratio were similar across cortical subdivisions. To search for a morphological correlate of differential multiple climbing fiber innervation, we labeled climbing fibers and performed reconstructions of immunofluorescent images. These revealed that, unlike the bank-gyrus subdivisions, most of the climbing fibers in the sulcus do not innervate the superficial molecular layer. These findings suggest that the subdivisions of the cerebellar cortex produced by folding may create functionally distinct entities.

Neuregulin Signaling Is Dispensable for NMDA- and GABAA-Receptor Expression in the CerebellumIn Vivo

“…Figure 4, B and C, shows the somatic membrane potential change and the dendritic ⌬[Ca 2ϩ ] i signal measured at different stimulating intensities and by concomitant stimulation with the two stim- ] i signal measurements. Thus, the 95% confidence interval for the probability of multiple climbing fiber innervation is 0 Ͻ p Ͻ 0.29, in line with data from wild-type mice (Hashimoto and Kano, 2003;Nishiyama and Linden, 2004). These results indicate that erbb2/erbb4-deficient mice do not have persistent multiple CF innervation above the level of wild-type mice after the critical period of development.…”

Neuronal Nogo-A negatively regulates dendritic morphology and synaptic transmission in the cerebellum

“…To account for strain differences (17) we always compared mutant animals with the WT mice of the corresponding strain. As the cerebellar lobules, and even different regions of the same lobule, mature at different time points (18,19), we always analyzed the bank and gyrus subdivisions of the lobules IV/V, VI/VII, and IX.…”

Impaired Motor Learning in the Vestibulo-Ocular Reflex in Mice with Multiple Climbing Fiber Input to Cerebellar Purkinje Cells

“…The deletion of PKC␥ causes a developmental defect in the elimination of supernumerary climbing fiber-Purkinje cell synapses so that multiple climbing fiber innervation of Purkinje cells persists into adulthood . This multiple climbing fiber innervation can be detected in vitro as the presence of more than one discrete EPSC response in a Purkinje cell when the white matter is stimulated at various intensities to activate the climbing fibers Hashimoto and Kano, 2003;Nishiyama and Linden, 2004). No other abnormalities have been observed in the cerebellum of the PKC␥ Ϫ/Ϫ mice, despite extensive analysis.…”

“…Climbing fiber activity during the induction of learning correlates with changes in behavior, and electrical stimulation of climbing fibers can trigger longlasting changes in the strength of simultaneously active synapses in the cerebellar cortex (Gilbert and Thach, 1977;Ito et al, 1982a;Watanabe, 1984;Mauk et al, 1986;Sears and Steinmetz, 1991;Hartell, 1996;Hesslow and Ivarsson, 1996;Eilers et al, 1997;Katoh et al, 1998;Kim et al, 1998;Raymond and Lisberger, 1998;Jorntell and Ekerot, 2002). A unique feature of the climbing fiber input to the cerebellum is that each Purkinje cell in the cerebellar cortex generally receives input from only a single climbing fiber (Eccles et al, 1967;Kano et al, 1995;Hashimoto and Kano, 2003;Nishiyama and Linden, 2004). To evaluate the functional relevance of this unique architecture, we studied a strain of mice in which Purkinje cells receive multiple climbing fiber inputs.…”

“…A recent study reported that Purkinje cells in cerebellar sulci exhibit some degree of multiple climbing fiber innervation, even in adult, wild-type mice, suggesting that some cerebellar regions may function well with multiple climbing fiber innervation (Nishiyama and Linden, 2004). Eyeblink conditioning, the OKR, and rotorod performance all depend on different regions of the cerebellum (Le Marec and Lalonde, 1997;Katoh et al, 1998;Gerwig et al, 2005;Villarreal and Steinmetz, 2005).…”