Structural Basis of Cerebellar Microcircuits in the Rat

Abstract

The topography of the cerebellar cortex is described by at least three different maps, with the basic units of each map termed "microzones," "patches," and "bands." These are defined, respectively, by different patterns of climbing fiber input, mossy fiber input, and Purkinje cell (PC) phenotype. Based on embryological development, the "one-map" hypothesis proposes that the basic units of each map align in the adult animal and the aim of the present study was to test this possibility. In barbiturate anesthetized adult rats, nanoinjections of bidirectional tracer (Retrobeads and biotinylated dextran amine) were made into somatotopically identified regions within the hindlimb C1 zone in copula pyramidis. Injection sites were mapped relative to PC bands defined by the molecular marker zebrin II and were correlated with the pattern of retrograde cell labeling within the inferior olive and in the basilar pontine nuclei to determine connectivity of microzones and patches, respectively, and also with the distributions of biotinylated dextran amine-labeled PC terminals in the cerebellar nuclei. Zebrin bands were found to be related to both climbing fiber and mossy fiber inputs and also to cortical representation of different parts of the ipsilateral hindpaw, indicating a precise spatial organization within cerebellar microcircuitry. This precise connectivity extends to PC terminal fields in the cerebellar nuclei and olivonuclear projections. These findings strongly support the one-map hypothesis and suggest that, at the microcircuit level of resolution, the cerebellar cortex has a common plan of spatial organization for major inputs, outputs, and PC phenotype.

Redefining the cerebellar cortex as an assembly of non-uniform Purkinje cell microcircuits

“…Given the remarkable relationship between zebrin II expression and cerebellar afferent and efferent connectivity and patterns of expression of many other molecular markers, this issue has been addressed mainly by using zebrin II expression as a reference 10, 14, 15, 77, 79, 85–88 .…”

“…It remains to be established whether they operate independently or co-operatively, given that pairs of zebrin II+ and zebrin II− bands have been found to form functional units in relation to patterns of optic flow 163 . But given the precise spatial organization that exists between climbing fibre and mossy fibre inputs and individual zebrin bands (the ‘one-map hypothesis’ 10, 77 ), it is possible that at least some inputs could be processed independently. In other words, since some projections target either positive or negative bands 76 , including olivo-cerebellar projections arising from ascending or descending sources 15, 82, 83 , such inputs have the potential to have different computations performed upon them.…”

How the cerebellum may monitor sensory information for spatial representation

“…Recent descriptions of the cerebellar micro-circuit features (Cerminara et al, 2013) led to the proposal of an updated and more generalistic model of the cerebellar function as an adaptive filter (Dean and Porrill, 2010). …”

Systematic Regional Variations in Purkinje Cell Spiking Patterns

“…In mammals and birds, regions in which Purkinje cells (PCs, the sole output neurons of the cerebellar cortex) express zebrin (Z+) alternate with ones that do not (Z−), subdividing much of the cerebellar cortex into longitudinally running alternating Z+ and Z− bands [11]–[15]. This zebrin banding pattern is particularly useful as a frame of reference because it shows at least some correspondence with the topographies of the afferent (particularly the olivocerebellar zonal system) and efferent projections to and from the cortex [8], [16]–[24]. Moreover, the expression patterns of a number of other genes can be straightforwardly mapped onto that of zebrin, and many of these likely affect neuronal activity.…”