Development and developmental disorders of the human cerebellum

The human cerebellum develops over a long time, extending from the early embryonic period until the first postnatal years. This protracted development makes the cerebellum vulnerable to a broad spectrum of developmental disorders. The development of the cerebellum occurs in four basic steps: 1) characterization of the cerebellar territory at the midbrain-hindbrain boundary; 2) formation of two compartments for cell proliferation: first, the Purkinje cells and the deep cerebellar nuclei arise from the ventricular zone of the metencephalic alar plate; second, granule cell precursors are formed from a second compartment of proliferation, i. e. the upper rhombic lip; 3) inward migration of the granule cells: granule precursor cells form the external granular layer, from which (and continuing into the first postnatal year), granule cells migrate inwards to their definite position in the internal granular layer, and 4) formation of cerebellar circuitry and further differentiation. The precerebellar nuclei, i. e. the pontine nuclei and the inferior olive, arise from the lower rhombic lip. Developmental disorders of the cerebellum are often accompanied by malformations of the precerebellar nuclei. In this review the development of the cerebellum and some of its more frequent developmental disorders, such as the Dandy-Walker and related midline malformations, and the pontocerebellar hypoplasias, are discussed.     

Embryonic development of the rat cerebellum. II. Translocation and regional distribution of the deep neurons

In thymidine radiograms and plastic-embedded sections, the migration of cerebellar deep neurons was traced from their germinal source to their final settling sites. The route proved to be roundabout and three developmental events could be distinguished during the process. First, between days E14 and E16, transversely oriented cells of the nuclear transitory zone move in an arc from the ventrolateral neuroepithelium of the lateral cerebellar primordium in a medial direction. Second, between days E16 and E18, the cells of the rostral component of the nuclear transitory zone assume a longitudinal orientation. We postulated that this is the period of axonogenesis, the longitudinally oriented cells issuing efferents that join the superior cerebellar peduncle ipsilaterally and the transversely oriented cells (representing the neurons of the caudal fastigial nucleus) sending decussating fibers to the uncinate fasciculus (the hook bundle of Russell). Third, between days E18 and E21, the earlier-produced superficial cells of the nuclear transitory zone and the later-produced deep cells of the cortical transitory zone (the young Purkinje cells) exchange positions. The descent of the deep neurons is in the direction of the fibers of the inferior cerebellar peduncle, which becomes distributed throughout the cerebellum on day E17. The ascent of the Purkinje cells is in the direction of the external germinal layer, which begins to spread from caudal to rostral on day E17. The three deep nuclei, the lateral (dentate), interpositus, and medial (fastigial), can be distinguished before their descent into the depth of the cerebellum, and by day E22 a small-celled and a large-celled subdivision is identifiable in each nucleus.     

Development of the olfactory pathways in platypus and echidna

The two groups of living monotremes (platypus and echidnas) have remarkably different olfactory structures in the adult. The layers of the main olfactory bulb of the short-beaked echidna are extensively folded, whereas those of the platypus are not. Similarly, the surface area of the piriform cortex of the echidna is large and its lamination complex, whereas in the platypus it is small and simple. It has been argued that the modern echidnas are derived from a platypus-like ancestor, in which case the extensive olfactory specializations of the modern echidnas would have developed relatively recently in monotreme evolution. In this study, the development of the constituent structures of the olfactory pathway was studied in sectioned platypus and echidna embryos and post-hatchlings at the Museum für Naturkunde, Berlin, Germany. The aim was to determine whether the olfactory structures follow a similar maturational path in the two monotremes during embryonic and early post-hatching ages or whether they show very different developmental paths from the outset. The findings indicate that anatomical differences in the central olfactory system between the short-beaked echidna and the platypus begin to develop immediately before hatching, although details of differences in nasal cavity architecture emerge progressively during late post-hatching life. These findings are most consistent with the proposition that the two modern monotreme lineages have followed independent evolutionary paths from a less olfaction-specialized ancestor. The monotreme olfactory pathway does not appear to be sufficiently structurally mature at birth to allow olfaction-mediated behaviour, because central components of both the main and accessory olfactory system have not differentiated at the time of hatching.     

Late granule cell genesis in quail cerebellum

Proliferation of avian cerebellar neurons, including granule cells, is thought to be completed during embryonic life, and aspects of cell addition in cerebellar lobules in posthatching life are unknown. The present study tested the hypothesis that cell genesis in late embryonic and posthatching stages of quail cerebellum occurs in parallel with the performance of motor programs. After exposure to bromodeoxyuridine, short (20 hours) and long survival time points were selected to investigate survival and migration of labeled cells. Quantitative analysis of the lobular distribution of labeled cells was performed with the stereological disector method. External granular layer (EGL) proliferation did not cease after hatching, indicating that there is an extended posthatching period, lasting until P20, when cells can be added into the internal granular layer, modifying the cerebellar circuitry and function. Indeed, long survival experiments suggested that EGL-labeled cells migrated into the internal granular layer and survived for a prolonged time, although many of the progenitor cells remained in the EGL for days. Double-labeling experiments revealed that most of the late-generated granule cells were NeuN positive, but only few expressed nitric oxide synthase. In addition to granule cells, the white matter and a glutamic acid decarboxylase (GAD)-positive cell population in the molecular layer around Purkinje somata showed bromodeoxyuridine labeling. Although all lobules showed significant posthatching proliferation, an anteroposterior gradient was evident. The index of granule cell production and survival supports a spatiotemporal pattern, in correlation with the functional division of cerebellum into anterior and posterior domains.     

Prenatal development of the cerebellar system in the rat. I. Cytogenesis and histogenesis of the deep nuclei and the cortex of the cerebellum

Prenatal cerebellar development was investigated with three approaches. In normal embryos sectioned in three planes morphological and cytological changes were determined at daily intervals beginning on embryonic day 13 (E13). A similar series of X-irradiated embryos was used to study changes in neuroepithelial organization and in the location of primitive (radiosensitive) or differentiated cells. Finally, to quantify the time of origin of different classes of cerebellar neurons with the progressively delayed labelling procedure, we used autoradiograms from adult rats whose mothers were injected with two successive daily doses of ³H-thymidine on overlapping days from day E13 on. The cerebellar anlage was delineated in the dorsal metencephalon by the collapse of its ventricular lining after X-irradiation. This “collapsing neuroepithelium” was located laterally on day E13, then it spread medially and reached the midline on day E16. Deep nuclear neurons began to differentiate on day E13, with two-thirds forming on day E14; Purkinje cell formation peaked on day E15, with a few cells still forming on day E16. It was postulated that the deep nuclear neurons settled first in the superficial “nuclear zone,” and that the Purkinje cells gathered temporarily in the underlying “transitory zone,” adjacent to the collapsing neuroepithelium. In the next period of cerebellar development four major events were recognized. (1) Beginning on day E17 the cells of the nuclear and transitory zones became intermingled. It was postulated that the Purkinje cells were migrating radially through the ranks of the stationary deep nuclear neurons and assembled under the spreading canopy of a fibrous plexus and the external germinal layer. (2) It was also on day E17 that the external germinal layer began to form as one of the prongs of the “germinal trigone” in the posteroventral aspect of the cerebellum. On the succeeding days the external germinal layer spread over the surface of the cerebellum; in the vermis in a rostral direction. (3) Two cell types destined to settle in the future granular layer, the pale cells and the Golgi cells, began to form at a relatively slow rate on day E19. Chronological considerations suggested that they were generated in the regressing, noncollapsing neuroepithelium of the cerebellar ventricle. (4) From the beginning (day E17) of its genesis posteroventrally, the primitive cerebellar cortex bridged the midline. As the fused cortex spread rostrally, the vertical ventricular cleft separating the underlying portions of the cerebellum became shallower and then disappeared; the process was completed in the anterior cerebellum by day E22. By the time of birth the maturation of the neurons of the deep nuclei appeared advanced but the maturation of the prenatally produced neurons of the cortex does not start until after birth when a new class of neurons is generated in the external germinal layer.     

Neural control of hatching: fate of the pattern generator for the leg movements of hatching in post-hatching chicks

Chicks from 0 to 61 days post-hatching were gently folded into the hatching position and placed in artificial glass eggs. Within 0 to 2 min they began to produce a behavior that qualitatively resembled normal hatching. Furthermore, quantitative analysis of electromyographic records showed that under these conditions the intralimb and interlimb leg motor output patterns produced during each hatching episode (the episode motor program) were those typical of normal hatching. The only major change associated with increasing post-hatching age was a gradual increase in inter-episode interval. Therefore, we conclude that the neural pattern-generating circuitry which produces the motor program for the leg movements of hatching remains functional in post-hatching chicks despite the fact that, under normal conditions, hatching behavior is never used again.     

Neural control of limb coordination. I. Comparison of hatching and walking motor output patterns in normal and deafferented chicks

Previous work has shown that the neural circuits underlying the leg movements of walking and hatching coexist in post-hatching chicks (Bekoff and Kauer, 1984). In the present study, quantitative analysis of leg EMGs shows that there are some similarities, but also significant differences, in the motor output patterns of walking and hatching. This study examines the effect of removing sensory feedback from the legs on the production of the distinctive leg motor patterns. The temporal characteristics and interlimb coordination of hatching and walking are little affected. However, major changes in intralimb motor output patterns are seen when compared to records from normal chicks. These changes fall into one of 2 categories. Some parameters show similar changes in both behaviors after deafferentation (e.g., increases in flexor burst durations and cycle period). This suggests that certain features of sensory input from the legs normally modulate the hatching and walking pattern-generating circuitry in similar ways. Other parameters show convergence. That is, these aspects of the 2 intralimb motor patterns become more similar to each other after removal of sensory input. This is consistent with the hypothesis that some feature of sensory input from the legs normally modulates one set of multiuse intralimb circuitry to produce different output patterns. In general, the walking pattern becomes more like hatching after deafferentation, rather than the reverse, which suggests that the hatching pattern is a more basic one. The maintenance of some residual differences in intralimb motor patterns after leg deafferentation suggests that other sources of modulation must also be involved, or that there are some additional elements of circuitry that are called into play during the normal production of walking and hatching.     

Embryonic development of the rat cerebellum. I. Delineation of the cerebellar primordium and early cell movements

Short-survival and long-survival thymidine radiograms, and methacrylate-embedded tissue from normal and X-irradiated rat embryos were used to delineate the neuroepithelial source of the cerebellum and trace the earliest cell movements. The cerebellar anlage, crescent shaped, is demarcated by two ventricular landmarks, the anterior extension of the tela choroidea of the fourth ventricle and the embryonic cerebellar fissure. The cerebellar tela choroidea extends from the medullary fourth ventricle posteromedially to the lateral recess of the pontine fourth ventricle anterolaterally. The embryonic cerebellar fissure begins caudally as a single midline incision beneath the fused posterior cerebellar primordium, then splits to follow the unfused cerebellar halves, first separating each from the isthmus then from the pons. The cerebellar primordium is divided into three parts. The lateral cerebellar primordium caps the lateral recess of the fourth ventricle; it is contiguous with the pons medially and separated ventrally from the anlage of the cochlear nuclei by the tela choroidea. The subisthmal cerebellar primordium is situated beneath the isthmus, medially lining the isthmus canal. Laterally and posteriorly, it is continuous with the lateral and postisthmal primordia. The postisthmal cerebellar primordium caps the postisthmal recess of the fourth ventricle and extends to the medullary fourth ventricle. As we shall describe later, each of these primordia is a source of different components of the developing cerebellum. Most cells of the superficially located nuclear transitory zone are labeled with 3H-thymidine administered on day E14 but not thereafter. A high proportion of the cells of the deeper cortical transitory zone could still be labeled on day E15. This supports the assumption made earlier that the first is composed of differentiating deep neurons, the second of Purkinje cells. The cells of the nuclear transitory zone originate in the lateral cerebellar primordium near the junction with the tela choroidea prior to the formation of the germinal trigone and migrate in a superficial position medially. Beginning on day E16, the nuclear transitory zone splits into two components. One has transversely oriented cells that seem to be the source of a decussating fiber tract, presumably the hook bundle of Russell. The other is composed of longitudinally oriented cells that apparently contribute fibers to the ipsilateral superior cerebellar peduncle. The translocation of the cells of the nuclear transitory zone from the cerebellar surface to its depth, to form the deep nuclei, and the radial migration of the cells of the cortical transitory zone to the surfa     

Distinct development of the cerebral cortex in platypus and echidna

Both lineages of the modern monotremes have distinctive features in the cerebral cortex, but the developmental mechanisms that produce such different adult cortical architecture remain unknown. Similarly, nothing is known about the differences and/or similarities between monotreme and therian cortical development. We have used material from the Hill embryological collection to try to answer key questions concerning cortical development in monotremes. Our findings indicate that gyrencephaly begins to emerge in the echidna brain shortly before birth (crown-rump length 12.5 mm), whereas the cortex of the platypus remains lissencephalic throughout development. The cortices of both monotremes are very immature at the time of hatching, much like that seen in marsupials, and both have a subventricular zone (SubV) within both the striatum and pallium during post-hatching development. It is particularly striking that in the platypus, this region has an extension from the palliostriatal angle beneath the developing trigeminoreceptive part of the somatosensory cortex of the lateral cortex. The putative SubV beneath the trigeminal part of S1 appears to accommodate at least two distinct types of cell and many mitotic figures and (particularly in the platypus) appears to be traversed by large numbers of thalamocortical axons as these grow in. The association with putative thalamocortical fibres suggests that this region may also serve functions similar to the subplate zone of Eutheria. These findings suggest that cortical development in each monotreme follows distinct paths from at least the time of birth, consistent with a long period of independent and divergent cortical evolution.     

Norepinephrine levels in developing pigeon brain: effect of monocular deprivation on the Wulst noradrenergic system

The endogenous level of norepinephrine (NE) was measured in discrete brain areas of the pigeon during post-hatching development. The pontine tegmentum showed the highest NE content, which remained constant during the post-hatching period. On the contrary, the NE content in the Wulst and cerebellum gradually decreased from hatching to 6 days. After this period, the Wulst NE level did not change significantly. In fact, there was no significant difference between NE values at 6 days and those at 6 months of age. In contrast, the difference between the cerebellar NE level at 6 days and that at the adult stage was highly significant. The NE content in the Wulst could be related to noradrenergic afferents originating in the ipsilateral locus coeruleus and substantia grisea centralis, since an electrolytic lesion of the pontine tegmentum caused a 60% reduction in the NE level in the ipsilateral Wulst. In line with the hypothesis that NE plays an important role in cortical plasticity, effects of early monocular deprivation on the Wulst NE content were also observed. After monocular deprivation during the first 6 months of life, the NE level increased by 40% in the Wulst ipsilateral to the deprived eye in comparison to the other side, where the NE level was normal. Monocular deprivation performed in adult animals did not affect the NE content in the Wulst. These results indicate that noradrenergic systems in the Wulst are affected by early, but not late visual deprivation.     

Histamine-N-methyltransferase activity of the nervous system of the chick during development

The developmental course of histamine-N-methyltransferase activity was determined in the chick pineal gland, thalamus, cerebral hemispheres, cerebellum and sciatic nerve from the 13-day embryo to 1-week post-hatching. In each tissue, low levels of enzyme activities were detectable in the 13-day embryo. Thereafter, to the stage of hatching activity rose rapidly in the pineals, thalamus and peripheral nerve. Enzyme activity in the pineals decreased after hatching and remained at a relatively low pre-hatch level in the 7-day chick. In the sciatic nerve and thalamus activity also dropped slightly after hatching. The increase of enzyme activity in the cerebellum and cerebral hemispheres was very gradual after the 13th day of embryonic stage and maximum activities were obtained only 2 days after hatching. Highest specific activities of the enzyme were detected in the sciatic nerve, pineals and thalamus at each developmental stage. The K_m values for histamine and S-adenosyl-l-methionine and the behavior towards certain drugs of the enzyme in the pineals and sciatic nerve did not change significantly during development.     

Distinct development of peripheral trigeminal pathways in the platypus (Ornithorhynchus anatinus) and short-beaked echidna (Tachyglossus aculeatus)

The extant monotremes (platypus and echidnas) are believed to all be capable of electroreception in the trigeminal pathways, although they differ significantly in the number and distribution of electroreceptors. It has been argued by some authors that electroreception was first developed in an aquatic environment and that echidnas are descended from a platypus-like ancestor that invaded an available terrestrial habitat. If this were the case, one would expect the developmental trajectories of the trigeminal pathways to be similar in the early stages of platypus and short-beaked echidna development, with structural divergence occurring later. We examined the development of the peripheral trigeminal pathway from snout skin to trigeminal ganglion in sectioned material in the Hill and Hubrecht collections to test for similarities and differences between the two during the development from egg to adulthood. Each monotreme showed a characteristic and different pattern of distribution of developing epidermal sensory gland specializations (electroreceptor primordia) from the time of hatching. The cross-sectional areas of the trigeminal divisions and the volume of the trigeminal ganglion itself were also very different between the two species at embryonic ages, and remained consistently different throughout post-hatching development. Our findings indicate that the trigeminal pathways in the short-beaked echidna and the platypus follow very different developmental trajectories from the earliest ages. These findings are more consistent with the notion that the platypus and echidna have both diverged from an ancestor with rudimentary electroreception and/or trigeminal specialization, rather than the contention that the echidna is derived from a platypus-like ancestor.     

IL1RAPL1 controls inhibitory networks during cerebellar development in mice

Abnormalities in the formation and function of cerebellar circuitry potentially contribute to cognitive deficits in humans. In the adult, the activity of the sole output neurons of the cerebellar cortex – the Purkinje cells (PCs) – is shaped by the balance of activity between local excitatory and inhibitory circuits. However, how this balance is established during development remains poorly understood. Here, we investigate the role of interleukin-1 receptor accessory protein-like 1 (IL1RAPL1), a protein linked to cognitive function which interacts with neuronal calcium sensor 1 (NCS-1) in the development of mouse cerebellum. Using Il1rapl1 -deficient mice, we found that absence of IL1RAPL1 causes a transient disinhibition of deep cerebellar nuclei neurons between postnatal days 10 and 14 (P10/P14). Upstream, in the cerebellar cortex, we found developmental perturbations in the activity level of molecular layer interneurons (MLIs), resulting in the premature appearance of giant GABAA-mediated inhibitory post-synaptic currents capable of silencing PCs. Examination of feed-forward recruitment of MLIs by parallel fibres shows that during this P10/P14 time window, MLIs were more responsive to incoming excitatory drive. Thus, we conclude that IL1RAPL1 exerts a key function during cerebellar development in establishing local excitation/inhibition balance.     

Postnatal taurine deficiency in the kitten results in a persistence of the cerebellar external granule cell layer: correction by taurine feeding

Dietary deprivation of taurine in pregnant cats from approximately 1 week prior to giving birth is sufficient to reduce substantially the taurine concentration in feline milk but does not result in any abnormalities in kittens at birth. Kittens nursing on this low taurine milk have a lower growth rate than normal, have lower tissue taurine concentrations, and 8 weeks after birth have a persistence of cells in the cerebellar external granule cell layer. Mitotic figures are present also, indicating that cell division is occurring still, an event which normally is completed 3-4 weeks after birth. Daily oral supplementation with 40 mumoles taurine increases the growth rate almost to the level of normally nurtured kittens and results in normal tissue taurine concentrations and apparently normal migration of cells in the cerebellum. These findings indicate that nutritional taurine supplied in the milk is involved in the normal ontogeny of the cerebellum and that a taurine deficiency at this stage of development results in a maturational delay.     

Microglia development in the quail cerebellum

We used the QH1 antibody to study changes in the morphological features and distribution of microglial cells throughout development in the quail cerebellum. Few microglial precursors were present in the cerebellar anlage before the ninth incubation day (E9), whereas many precursors apparently entered the cerebellum from the meninges in the basal region of the cerebellar peduncles between E9 and E16. From this point of entry into the nervous parenchyma, they spread through the cerebellar white matter, forming a ‘stream’ of labeled cells that could be seen until hatching (E16). The number of microglial cells in the cerebellar cortex increased during the last days of embryonic life and first posthatching week, whereas microglial density within the white matter decreased after hatching. As a consequence, the differences in microglial cell density observed in the cerebellar cortex and the white matter during embryonic life diminished after hatching, and microglia showed a nearly homogeneous pattern of distribution in adult cerebella. Ameboid and poorly ramified microglial cells were found in developing stages, whereas only mature microglia appeared in adult cerebella. Our observations suggest that microglial precursors enter the cerebellar anlage mainly by traversing the pial surface at the basal region of the peduncles, then migrate along the white matter, and finally move radially to the different cortical layers. Differentiation occurs after the microglial cells have reached their final position. In other brain regions the development of microglia follows similar stages, suggesting that these steps are general rules of microglial development in the central nervous system. J. Comp. Neurol. 389:390–401, 1997. © 1997 Wiley-Liss, Inc.     

Development and aging of noradrenergic cell bodies and axon terminals in the chicken

Tyrosine hydroxylase activity was measured in the region of locus coeruleus, cerebellum, cervical spinal cord, lumbar sympathetic ganglia, and iris throughout most of the life span of the chicken (8 days of incubation to 5 years) to compare developmental trends in tyrosine hydroxylase activity in noradrenergic cell bodies and in axon terminals in both the central and peripheral nervous system. Fluorescence histochemistry and retrograde transport of horseradish peroxidase were used to characterize further the coeruleo-cerebellar projections. Tyrosine hydroxylase activity was detected in the cerebellum as early as 8 days of incubation, which is the earliest stage so far reported. The greatest increase in total tyrosine hydroxylase activity in the region of the locus coeruleus and cerebellum occurred during the embryonic period. There was a more pronounced increase in the cerebellum than in the locus coeruleus region. This is in contrast to the cervical spinal cord where tyrosine hydroxylase activity increased at approximately the same rate during the embryonic and post-hatching periods. Moreover, the cerebellum and cervical spinal cord, two locus coeruleus target sites, displayed different trends in tyrosine hydroxylase activity throughout development and aging. In both structures examined in the peripheral nervous system, the greatest increase in total tyrosine hydroxylase activity occurred during the post-hatching period, with a greater rise in the cell bodies of the lumbar sympathetic ganglia than in the noradrenergic terminals of the iris. In both the central and peripheral nervous system, total tyrosine hydroxylase activity continued to increase in noradrenergic terminals long after hatching reaching the highest levels at 7 months when the chicken is considered fully mature. During aging, 16 months to 5 years, there was a greater decrease in total tyrosine hydroxylase activity in the terminals of noradrenergic neurons than in the cell bodies in both the central and peripheral nervous system, a phenomenon that was more marked in the peripheral nervous system than in the brain.     

小鼠小脑皮质的生长发育

目的：探讨小鼠小脑皮质的组织发生过程。方法：应用光镜和电镜技术对胚胎和生后小脑皮质进行形态学观察,对各层厚度和细胞密度进行测量。结果：胚胎12d（E12）小脑原基有室管膜层、套层和边缘层构成,约出生当日（P0）出现外颗粒层、分子层、Purkinje细胞层和内颗粒层。外颗粒层P6／7达最厚,至P20消失。P0至P30内颗粒层细胞逐步分化发育成熟,Purkinje细胞树突树逐渐形成,约P7时Purkinje细胞排列成单层。结论：E12至P0片层化小脑主要经历了细胞增殖、分化与迁移;P0至P30片层化结构逐渐发育成熟,外颗粒层消亡以细胞迁移和凋亡为主,其他各层细胞主要经历了分化发育与凋亡。     

Presynaptic plasticity at cerebellar parallel fiber terminals

The cerebellum plays a role in the control of sensorimotor functions and possibly also of higher cognitive processing. The granule cells, which are abundant and unique in their characteristic dendritic morphology, allow the cerebellum to combine the advantages of sparse coding with a high sensitivity for individual afferents at the input stage. Plastic changes in the granular layer circuitry may thus control instant transformation of inputs as well as long-term modifications so as to support procedural memory formation. Over recent decades, substantial research has been done to explore the mechanisms of postsynaptic changes that may sustain learning processes in the cerebellum, especially bidirectional plasticity at the parallel fiber to Purkinje cell synapse. In contrast, the presynaptic occurrence of synaptic plasticity has been relatively neglected. Here we review the current models of granular layer processing in the framework of cerebellar functioning with special emphasis on the presynaptic modulations of operations at the parallel fiber to Purkinje cell synapse. We argue that the wide range of possible mechanisms that can strengthen the parallel fiber to Purkinje cell synapse at the presynaptic level endows the cerebellar cortex with optimal computational capacities to potentiate both spatial and temporal cues that are relevant for fine-regulating memory formation.     

Comparative morphology of the avian cerebellum: I. Degree of foliation

Despite the conservative circuitry of the cerebellum, there is considerable variation in the shape of the cerebellum among vertebrates. One aspect of cerebellar morphology that is of particular interest is the degree of folding, or foliation, of the cerebellum and its functional significance. Here, we present the first comprehensive analysis of variation in cerebellar foliation in birds with the aim of determining the effects that allometry, phylogeny and development have on species differences in the degree of cerebellar foliation. Using both conventional and phylogenetically based statistics, we assess the effects of these variables on cerebellar foliation among 91 species of birds. Overall, our results indicate that allometry exerts the strongest effect and accounts for more than half of the interspecific variation in cerebellar foliation. In addition, we detected a significant phylogenetic effect. A comparison among orders revealed that several groups, corvids, parrots and seabirds, have significantly more foliated cerebella than other groups, after accounting for allometric effects. Lastly, developmental mode was weakly correlated with relative cerebellar foliation, but incubation period and fledging age were not. From our analyses, we conclude that allometric and phylogenetic effects exert the strongest effects and developmental mode a weak effect on avian cerebellar foliation. The phylogenetic distribution of highly foliated cerebella also suggests that cognitive and/or behavioral differences play a role in the evolution of the cerebellum.     

Expression of Rho GTPases Rho-A and Rac1 in the adult and developing gerbil cerebellum

Rho GTPases proteins are essential for cytoskeletal reorganization and play important roles in the development of neuronal dendrites and axons. Several studies have implicated two members of the Rho GTPase family Rho-A and Rac1 activities in the neuronal polarization and the formation of axons and dendrites. In order to correlate cellular expressions of Rho-A and Rac1 with neuronal polarity (axons versus dendrite formation) in the central nervous system, the cerebellum and immunochemical techniques have been chosen. In the adult cerebellar cortex differential pattern of distribution between Rho-A and Rac1 was observed. While Rac1 expression was restricted to Purkinje cell (somata, dendrites and axons), Rho-A was ubiquitously distributed within the cerebellar cortex. Rac1 was localized in the Purkinje cell dendritic arborization (largest and tiny dendrites) and in their axons. This pattern of distribution was also observed during the postnatal development and followed the dendritic morphogenesis of Purkinje cell. Rho-A was highly expressed in the adult Purkinje cells somata, in cells of the granular layer, in glia within the white matter and in axons. Intense staining was observed in Bergmann glia cell bodies and processes. In the developing cerebellum, Rho-A was highly present in cells of the external and internal granule layers and in the Purkinje cell layer. Bergmann glia cell bodies and processes had the most intense staining during the development. The present study reveals a high expression of Rac1 and Rho-A during Purkinje cell neurites outgrowth period which occurred after birth in the cerebellum. In addition Rho-A is highly expressed in granule cell progenitor cells present in the external granular layer and therefore may play an important role in granule cell progenitor migration.