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Neonatal pinealectomy induces Purkinje cell loss in the cerebellum of the chick: a stereological study.

Melatonin plays an important role in certain physiological functions and morphological features of various structures. In the current study, the effects of pinealectomy on Purkinje cell number and morphological features of developing cerebellum in the chick were investigated using stereological methods. Fifteen Hybro Broiler newly hatched chicks were divided into three groups: a pinealectomized group (n = 5), sham-operated group (n = 5) and a non-pinealectomized control group (n = 5). Surgical pinealectomy was performed in 3-day-old chicks. In the 8th week, all animals were sacrificed for histopathological evaluation and subsequent stereological analysis. Each layer volume of molecular (+Purkinje cell), granular and white matter in the cerebellum was estimated in all animals. It was found that there was no significant difference for the volume of whole cerebellum and also molecular (+Purkinje cell) layer in these groups (P > 0.05). Nevertheless, the values of granular layer and white matter of sham-operated group were significantly different from those of control and pinealectomized animals (P < 0.01). It was also observed that pinealectomy significantly reduces the Purkinje cell number in cerebellar cortex (P < 0.01). The present study is the first stereological study to demonstrate the histomorphological effects of pinealectomy on the cerebellum in the chick. Our results suggest that pineal gland/melatonin might play an important role in morphological features of the developing cerebellum in the chick.

Animals↗

Differential expression of the estrogen receptors alpha and beta during postnatal development of the rat cerebellum.

Estrogen receptor (ER) beta is a dominant ER subtype in the adult cerebellum. However, it is not known if this is also the case for the developing cerebellum. In the present study, quantitative real-time RT-PCR demonstrated that levels of cerebellar ERalpha mRNA in neonatal pups were significantly higher than in adults. In contrast, expression levels of cerebellar ERbeta mRNA remained significantly unchanged during postnatal development. In situ hybridization and immunohistochemistry demonstrated that ERalpha mRNA and protein were predominantly expressed by Purkinje cells at all ages examined. ERalpha-expressing Purkinje cells were confined to the anterior lobes at postnatal day 7 (P7) but distributed in most lobes at P14 and P21. In the adult cerebellum, however, only a few ERalpha-immunoreactive Purkinje cells were observed. Thus, ERalpha expression was transiently increased during the time when Purkinje cell dendritic growth and synapse formation proceed, suggesting that a role for ERalpha in Purkinje cell differentiation. ERbeta expression occurred in Golgi type neurons in the granular layer at P7, Purkinje cells at P14, and basket cells in the molecular layer at P21 and was detected in all the cell types in the adult cerebellum, suggesting a role for ERbeta associated with neuronal differentiation and maintenance. Furthermore, double-labeled immunofluorescence for ERalpha and ERbeta demonstrated their colocalization in Purkinje cells at P14, suggesting a possibility of their interaction. The discrete expression profiles for ERalpha and ERbeta in the developing cerebellum suggest the two ERs play distinct roles in cerebellar development.

Animals↗

Role of the cerebellum in implicit motor skill learning: a PET study.

To depict neural substrates of implicit motor learning, regional cerebral blood flow was measured using positron emission tomography (PET) in 13 volunteers in the rest condition and during performance of a unimanual two-ball rotation task. Subjects rotated two balls in a single hand; a slow rotation (0.5 Hz) was followed by two sessions requiring as rapid rotation as possible. The process was repeated four times by a single hand (Block 1) and then by the opposite hand (Block 2). One group of volunteers began with the right hand (n = 7), and the other with the left (n = 6). Performance was assessed by both quickness and efficiency of movements. The former was assessed with the maximum number of rotation per unit time, and the latter with the electromyographic activity under constant speed of the movement. Both showed learning transfer from the right hand to the left hand. Activation of cerebrum and cerebellum varied according to hand. Activation common to both hands occurred in the bilateral dorsal premotor cortex and parasagittal cerebellum, right inferior frontal gyms, left lateral cerebellum and thalamus, supplementary motor area, and cerebellar vermis. The left lateral cerebellum showed the most prominent activation on the first trial of the novel task, and hence may be related the early phase of learning, or "what to do" learning. Left parasagittal cerebellum activity diminished with training both in first and second blocks, correlating inversely with task performance. This region may therefore be involved in later learning or "how to do" learning. The activity of these regions was less prominent with prior training than without it. Thus the left cerebellar hemisphere may be related to learning transfer across hands.

Adult↗

Abundant expression of mu and delta opioid receptor mRNA and protein in the cerebellum of the fetal, neonatal, and adult rat.

Opioid receptor proteins and mRNAs have been localized to a variety of regions within the rat brain. It is generally accepted that within the lobes of the rat cerebellum, only delta opioid receptor (DOR) is expressed. This is in contrast to that observed in humans and rabbits which express both mu opioid receptor (MOR) and DOR. In this study, we report detection of MOR as well as DOR protein by immunohistochemical localization, and mRNA by fluorescent in situ hybridization (FISH) within Purkinje cells (PK) and the granular layer of neonatal (P6) and adult rat cerebellum. Expression of MOR mRNA was also detected within cells of the molecular layer, but at lower levels than those seen within the PK cells. Abundant expression of MOR and DOR mRNA was detected in the external germinal layer of the immature cerebellum of the fetal (E16) rat, supporting a role for MOR and DOR in regulating neurogenesis of the cerebellum. In addition, using exon-specific cRNA probes, exons 1 and 4, which are both found in the MOR-1 splice variant mRNA, were detected in PK cells in the cerebellum and also within deep cerebellar nuclei in the adult.

Animals↗

ADC mapping of neurodegeneration in the brainstem and cerebellum of patients with progressive ataxias.

Analysis of the apparent diffusion coefficient (ADC) maps derived from diffusion-weighted MR imaging is emerging as a reproducible, sensitive, and quantitative tool to evaluate brain damage in diseases of the white and gray matter. To explore the potentials of ADC maps analysis in degenerative ataxias, we examined 28 patients and 26 age-matched controls with T1, T2, and diffusion (b values 0-1000 along the three main body axes)-weighted MR images. Twenty-four patients had inherited genetically proven diseases including spinocerebellar ataxia type 1 (SCA1) (n = 9), spinocerebellar ataxia type 2 (SCA2) (n = 8), and Friedreich's ataxia (FA) (n = 7), whereas four patients had sporadic adult onset pure cerebellar ataxia (three idiopathic, one gluten intolerance). Area and linear measurements of the CNS structures contained in the posterior cranial fossa (PCF) preliminary enabled classification of the patients in the three morphological categories reflecting the gross pathology findings, namely olivopontocerebellar atrophy (OPCA) (n = 10: six SCA2 and four SCA1), spinal atrophy (SA) (n = 7: all FA), and cortical cerebellar atrophy (CCA) (n = 4: three idiopathic and one gluten intolerance). Seven patients with SCA1 (n = 5) or SCA2 (n = 2) had morphologic changes reminiscent of OPCA, but their values were still in the lower normal range and were classified as undefined. Mean diffusivity (D) maps of the entire brain were generated and D was measured with regions of interest (ROI) in the medulla, pons, middle cerebellar peduncles, and the peridentate white matter. Moreover, after exclusion of the skull with manual segmentation and of the CSF with application of a threshold value, histograms were obtained for D of the brainstem and cerebellum and for D of the cerebral hemispheres. As compared to controls, a (P < 0.001) increase of D was observed in the medulla, middle cerebellar peduncles, and peridentate white matter in OPCA and undefined patients groups who had also significantly increased values of the 25th and 50th percentiles in the brainstem and cerebellum D histogram. In CCA (P = 0.01), an increase of the 25th and 50th percentile of the D value was observed in the brainstem and cerebellum histograms. The SA group showed (P < 0.001) an increased D in the medulla only. A correlation between clinical severity as assessed with the Inherited Ataxias Clinical Rating Scale (IACRS) and the 50th percentile of the D value in the brainstem and cerebellum histogram (r = 0.69) was observed in patients with SCA1 or SCA2. Diffusion MR imaging reveals variable patterns of increase of D in the brainstem, cerebellum, and cerebral hemispheres in degenerative ataxias that match the known distribution of the neuropathological changes.

Adult↗

[123I]epidepride binding to cerebellar dopamine D2/D3 receptors is displaceable: implications for the use of cerebellum as a reference region.

The low density of cerebellar dopamine D(2)/D(3) receptors provides the basis for using the cerebellum as a representation of free- and non-specifically bound radioligand in positron emission tomography (PET) and single photon emission computed tomography (SPECT) studies. With the development of ultra high-affinity dopamine D(2)/D(3) ligands like [(123)I]epidepride, [(18)F]fallypride, and [(11)C]FLB-457, quantification of extrastriatal low density receptor populations including the cerebellum is possible with important implications for calculation of binding parameters. [(123)I]epidepride-SPECT was performed in 23 patients with schizophrenia before and after 3 months of antipsychotic treatment with either risperidone (n=14) or zuclopenthixol (n=9). In the unblocked situation and partially blocked situation, the average distribution volumes were 5.2+/-1.3 mL/mL and 4.0+/-0.8 mL/mL, respectively. The paired distribution volumes were reduced by 22+/-15% (mean+/-SD) after antipsychotic treatment (p<0.0001, paired Student's t-test). From the paired distribution volumes in cerebellum and extrastriatal regions, the average distribution volume representing free and non-specifically bound [(123)I]epidepride was calculated to be 3.3+/-0.8 mL/mL. Both the % [(123)I]epidepride fraction of plasma radioactivity (p>0.76) and the plasma [(123)I]epidepride concentration (p>0.45) were unchanged after antipsychotic treatment (paired Student's t-test). These results strongly suggest the presence of "non-negligible" specific [(123)I]epidepride binding to dopamine D(2)/D(3) receptors in the cerebellum. Using the cerebellum as a representation of free and non-specifically bound radioligand and neglecting the specifically bound component may lead to results that erroneously imply that antipsychotic drugs bind to extrastriatal dopamine D(2)/D(3) receptors with a higher affinity than to striatal dopamine D(2)/D(3) receptors.

Adult↗

Role of hyperactive cerebellum and motor cortex in Parkinson's disease.

Previous neuroimaging studies have found hyperactivation in the cerebellum and motor cortex and hypoactivation in the basal ganglia in patients with Parkinson's disease (PD) but the relationship between the two has not been established. This study examined whether cerebellar and motor cortex hyperactivation is a compensatory mechanism for hypoactivation in the basal ganglia or is a pathophysiological response that is related to the signs of the disease. Using a BOLD contrast fMRI paradigm PD patients and healthy controls performed automatic and cognitively controlled thumb pressing movements. Regions of interest analysis quantified the BOLD activation in motor areas, and correlations between the hyperactive and hypoactive regions were performed, along with correlations between the severity of upper limb rigidity and BOLD activation. There were three main findings. First, the putamen, supplementary motor area (SMA) and pre-SMA were hypoactive in PD patients. The left and right cerebellum and the contralateral motor cortex were hyperactive in PD patients. Second, PD patients had a significant negative correlation between the BOLD activation in the ipsilateral cerebellum and the contralateral putamen. The correlation between the putamen and motor cortex was not significant. Third, the BOLD activation in the motor cortex was positively correlated with the severity of upper limb rigidity, but the BOLD activation in the cerebellum was not correlated with rigidity. Further, the activation in the motor cortex was not correlated with upper extremity bradykinesia. These findings provide new evidence supporting the hypothesis that hyperactivation in the ipsilateral cerebellum is a compensatory mechanism for the defective basal ganglia. Our findings also provide the first evidence from neuroimaging that hyperactivation in the contralateral primary motor cortex is not a compensatory response but is directly related to upper limb rigidity.

Aged↗

Postsynaptic enrichment of Eps8 at dendritic shaft synapses of unipolar brush cells in rat cerebellum.

Epidermal growth factor receptor pathway substrate 8 (Eps8) is a widely expressed multidomain signaling protein that coordinates two disparate GTPase-dependent mechanisms: actin reorganization via Ras/Rac pathways and receptor trafficking via Rab5. Expression of Eps8, the gene encoding the founding member of the Eps8 family of proteins, was found in cerebellum by virtual Northern analysis and in situ hybridization. Because the cerebellum has a well-known cellular architecture and is a favored model to study synaptic plasticity and actin dynamics, we sought to analyze Eps8 localization in rat cerebellar neurons and synapses by light and electron microscopy. Specificity of Eps8-antibody was demonstrated by immunoblots and in brain sections. In cerebellum, unipolar brush cells (UBCs) were densely Eps8 immunopositive and granule cells were moderately immunostained. In both types of neuron immunoreaction product was localized to the somatodendritic and axonal compartments. Postsynaptic immunostained foci were demonstrated in the glomeruli in correspondence of the synapses formed by mossy fiber terminals with granule cell and UBC dendrites. These foci appeared especially evident in the UBC brush, which contains an extraordinary postsynaptic apparatus of actin microfilaments facing synaptic junctions of the long and segmented varieties. Eps8 immunoreactivity was conspicuously absent in Purkinje cells and their actin-rich dendritic spines, in all types of inhibitory interneurons of the cerebellum, cerebellar nuclei neurons, and astrocytes. In conclusion, Eps8 protein in cerebellum is expressed exclusively by excitatory cortical interneurons and is intracellularly compartmentalized in a cell-class specific manner. This is the first demonstration of the presence of a member of the Eps8 protein family in UBCs and its enrichment at postsynaptic sites.

Adaptor Proteins, Signal Transducing↗

Ontogeny of PACAP receptors in the human cerebellum: perspectives of therapeutic applications.

It is now well established that pituitary adenylate cyclase-activating polypeptide (PACAP) exerts anti-apoptotic and pro-differentiating actions during development of the rodent cerebellum. Cell signaling involved in the neurotrophic effects of PACAP has been precisely investigated. In particular, PACAP is a potent inhibitor of the mitochondrial apoptotic pathway through an ERK- and PKA-dependent mechanism. However, transposition of the neurodevelopmental activities of PACAP to the human cerebellum remains speculative, essentially because of the lack of data concerning the PACAP-ergic system. The present review is based on recent results that provide the first molecular, pharmacological and anatomical characterizations of PACAP receptors in the developing human cerebellum. It is now clearly established that the distribution pattern of PAC1-R and VPAC1-R mRNA in the human cerebellum is very similar to that already described in rodents. [(125)I]PACAP27 binding sites are closely associated with germinative neuroepithelia in fetal stages and with mature granule cells in infants and adults. Pharmacological characterization revealed that, in fetuses, PACAP binding sites exhibit a PAC1-R profile while, in adult patients, they correspond to a heterogeneous population of PAC1-R and VPAC(1/2)-R. Altogether, these data provide the first evidence that PACAP may exert neurodevelopmental functions in the human cerebellum.

Cerebellum↗

Magnetic evoked field associated with transcortical currents in turtle cerebellum.

The neural basis of magnetic evoked fields of the brain was studied with an isolated turtle cerebellum as a model preparation. The turtle cerebellum is a nearly flat tissue with neural processes arranged along three orthogonal axes of symmetry. According to theoretical results, this geometry should enable us to selectively measure the magnetic field due to a subpopulation of nerve cells whose longitudinal axes are perpendicular to the cerebellar surface, by simply placing the cerebellum vertically in the bath so that these cells are horizontal and by measuring the field along the rostrocaudal axis perpendicular to the longitudinal axis of these nerve cells. To elicit neural activity in these cells the dorsal midline was electrically stimulated with a bipolar electrode. Consistent with our expectations, the one-dimensional profile of the field normal to bath surface (Bz) was antisymmetrical along the rostrocaudal axis, implying that the underlying currents were transcortical. Also, the Bz field at a field extremum varied as a cosine of the orientation of the cerebellum when it was rotated about its rostrocaudal axis with the amplitude being zero when the cerebellum was horizontal. The Bz field was dipolar as judged by statistically excellent fits of the dipolar field to the one-dimensional field profile and to the distance function relating the field magnitude at an extremum to measuring distance. This was the case even for the initial component thought to be due to antidromic action currents invading the soma and dendrites of Purkinje cells. We also showed that the dipolar term of the source could be localized within 1 mm of the actual source location in most cases.

Animals↗

Expression of Niemann-Pick type C transcript in rodent cerebellum in vivo and in vitro.

This study assesses the developmental expression of the Niemann-Pick type C mRNA in vivo and in vitro in rat cerebellum. NPC is an autosomal recessive neurovisceral lipid storage disease associated with an alteration in cholesterol trafficking. In the mouse model of NPC and in the early onset form of human NPC, Purkinje neurons are among the first neurological targets, suffering stunted growth during postnatal development and dying, leading to ataxia. Recently, the genes responsible for human (NPC1) and mouse (Npc1) NPC disease have been cloned. Based on a highly homologous domain, we designed primers to look for levels of Npc1 mRNA with a semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) approach using cyclophilin as an internal standard. Total RNA was isolated from various postnatal developmental stages of the rat cerebellum as template for the analyses. Npc1 transcripts were observed at postnatal day 0 and at later stages of development, both in vivo and in vitro from primary cerebellar cultures. To identify the location of Npc1 inside the cerebellum, we performed immunostaining with an anti-Npc1 antibody in primary rat cerebellar cultures identifying reactive Purkinje neurons by double-labeling with the Purkinje specific marker calbindin and sub-populations of glial cells. In summary, Npc1 is expressed in rat cerebellum in vivo and in vitro and is expressed during early postnatal development as well as in the adult cerebellum. Since Npc1 is expressed at similar levels throughout development, the vulnerability of Purkinje neurons to this disease is likely to involve disruption of an interaction with other developmentally-regulated proteins.

Amino Acid Sequence↗

Signals from the cerebellum guide the pathfinding of inferior olivary axons.

During development, inferior olivary axons cross the floor plate and project from the caudal to the rostral hindbrain, whence they grow into the cerebellar plate. We have investigated the axon guidance signals involved in the formation of this projection in vitro. When the cerebellar plate was grafted ectopically along the margin of the hindbrain in organotypic cultures, inferior olivary axons could pathfind to the ectopic cerebellum, establishing a topographically normal projection. Following rostrocaudal reversal of a region of tissue in the axon pathway between the inferior olive and the cerebellum, olivary axons still navigated towards the cerebellum. Moreover, olivary axons could cross a bridging tissue explant (spinal cord) to reach a cerebellar explant. In collagen gel cultures of inferior olive explants, olivary axon outgrowth increased significantly in the presence of cerebellar explants and axons deflected towards the cerebellar tissue. These results show that the cerebellum is a source of diffusible axon guidance signals for olivary axons. We also found that, in organotypic cultures, olivary axons which had crossed the floor plate showed an increased tendency to respond to cerebellar cues. Taken together, these results indicate that the cerebellum is the source of cues that are chemoattractant and growth-promoting for inferior olivary axons; prior exposure to the floor plate increases responsiveness to these cues.

Animals↗

Reciprocal trophic interactions between climbing fibres and Purkinje cells in the rat cerebellum.

In the adult cerebellum both the climbing fibre arbour and the Purkinje cell are very plastic and each element is able to exert a remarkable action on the other one. The adult phenotype of the Purkinje cell is strictly dependent on the presence of its climbing fibre arbour. When the climbing fibre is missing, the Purkinje cell undergoes a hyperspiny transformation and becomes hyperinnervated by the parallel fibres. However, this change is fully reversible. The climbing fibre-deprived Purkinje cell is able to elicit sprouting of nearby located intact climbing fibres and the new arbour is able to fully restore synaptic connections which appear normal both morphologically and functionally. Multiple climbing fibre innervation of a single Purkinje cell persists in the adult hypogranular cerebellum. The different fibres are distributed to separate dendritic regions, suggesting a local competition between the different arbours for their territory. It is postulated that in the intact rat, an activity dependent mechanism of the parallel fibre favours the predominance of one arbour with the elimination of its competitors. When the Purkinje cell is deleted, the climbing fibre arbour becomes heavily atrophic and reduced in size. The analysis of the pattern of this atrophy indicates that the climbing fibre arbour is made by two compartments: a proximal one, whose survival depends on the integrity of the inferior olive, and a distal one, which represents the true pre-synaptic site, which strictly depends on the target. The climbing fibre terminal arbour is able to extend its territory of innervation not only when adult intact climbing fibres are confronted with nearby denervated Purkinje cells, but also when an embryonic cerebellum is grafted onto the surface of an adult unlesioned cerebellum. In this case, collaterals of intact climbing fibre arbours elongate through the pial surface, enter the graft to innervate the Purkinje cells. This growth is likely under the influence of a tropic signal released by the embryonic Purkinje cells. This suggests that the sprouting observed in the adult rat following a subtotal inferior olive lesion is also triggered by a similar factor. The axonal elongation and the consequent synaptogenesis are likely guided by local cues. In this condition, the distribution of the new collateral reinnervation occurs within its projectional map. In addition, when the inferior cerebellar peduncle is sectioned at birth, the climbing fibres of the non-deafferented hemicerebellum emit collaterals which cross the midline and innervate cerebellar strips which are symmetrically positioned relative to the intact side. In the grafting experiments, both the migrated and non-migrated Purkinje cells show the typical electrophysiological properties of the mature cerebellum. These data show that the disappearance of neuronal elements is not a necessary prerequisite to allow new neurones to become fully morphologically and functionally integrated into an adult brain. The reciprocal trophic influence between the climbing fibres and the Purkinje cells shown in the present series of experiments are likely operative in the adult brain not only in pathological conditions and they could give a basic contribution to the synaptic plasticity underlying learned behaviour.

Animals↗

Processing of multiple kinematic signals in the cerebellum and motor cortices.

The cerebellum and motor cortices are hypothesized to make fundamentally different but synergistic contributions to the control of movement. Richly interconnected, these structures must communicate and translate salient parameters of movement. This review examines the similarities and differences in the encoding of multiple limb movement parameters in the cerebellum and motor cortices. Also presented are recent data on direction and speed coding by cerebellar Purkinje cells and primary motor and dorsal premotor cortical neurons during a visually-instructed, manual tracking task. Both similarities and differences have been found in the way that these two motor areas process movement parameters. For example, the two motor control structures encode direction with almost identical depths of modulation, which may simplify the exchange of directional signals. Two major differences between the cerebellum and motor cortices consist of the distribution of the preferred directions and the manner in which direction and speed are jointly signaled within the discharge of individual neurons. First, an anterior-posterior distribution of preferred directions has been shown for both reaching and manual tracking, consistent with an intrinsic reference frame and/or the structure of afferent input. In contrast, neurons in the motor cortices have uniformly distributed preferred directions, consistent with general purpose directional calculations. Secondly, Purkinje cells in the cerebellum and motor cortices combine movement direction and speed information differently. For example, Purkinje cell discharge encodes combinations of direction and speed, a 'preferred velocity', while the motor cortical neurons use a temporal parcellation scheme to encode multiple parameters of movement. These results demonstrate that the cerebellum and motor cortices process and use kinematic information in fundamentally different ways that may underlie the functional uniqueness of the two motor control structures.

Animals↗

Developmental differences in alternative splicing of the NR1 protein in rat cortex and cerebellum.

Expression of the C-terminal cassettes of the NR1 protein was examined using a quantitative Western blot method with cassette-specific antibodies. Measurements were made of the percent of total NR1 protein that contained a specific cassette in both the cerebellum and cortex over development. In the cortex, the C1 cassette was shown to be present in about half of total NR1 protein with no change over development. While about half of total NR1 in the cerebellum at postnatal day 42 (P42) contained the C1 cassette, little NR1 protein with this cassette was seen at young ages. In both the cerebellum and cortex, the C2 and C2' cassettes showed opposite developmental patterns, with the C2 cassette decreasing and the C2' cassette increasing over age. Together with previous data on the expression of the N1 cassette, this study describes the alternatively spliced forms of NR1 protein that are dominant at different ages. In the young cerebellum, the NR1(001) form appeared dominant, while in the young cortex there appeared to be a mix of NR1(001) and NR1(011). The most common splice forms of NR1 protein in the adult cerebellum appeared to be NR1(111) and NR1(100). In the adult cortex, there appeared to be a mix of NR1(001) and NR1(011). These data on the expression of the alternatively spliced forms of NR1 allow predictions on the possible characteristics of NMDA receptors in different regions at specific ages.

Aging↗

Parvalbumin immunoreactivity during the development of the cerebellum of the rainbow trout.

The distribution of parvalbumin immunoreactivity in the developing cerebellum of the rainbow trout was studied by using a specific monoclonal antibody and the avidin-biotin peroxidase method. Parvalbumin immunoreactivity was absent during the embryonic development of the cerebellum. The first immunoreactive elements, identified by their localization and posterior morphological evolution as immature Purkinje cells, appeared at 6 days posthatching in the presumptive corpus cerebelli and lobus vestibulolateralis. The labeling extended throughout the cerebellum following a caudorostral gradient, and in 21 days alevins, parvalbumin immunoreactive Purkinje cells were also observed in the valvula cerebelli. The appearance of parvalbumin-immunostaining in the Purkinje cells was not simultaneous; the labeling was observed initially in the cell body, extending gradually to the dendritic branches and finally to the axon. From 1 year onwards, parvalbumin immunoreactive terminal puncta from the Purkinje cell axons were observed surrounding the cell bodies of eurydendroid cells, that were parvalbumin immunonegative in all developmental stages studied. The spatio-temporal pattern of parvalbumin immunoreactivity in the rainbow trout cerebellum is different to previous observations in the cerebellum of amniotes.

Animals↗

What the cerebellum computes.

The brain is an organ that processes information. Brain systems such as the cerebellum receive inputs from other systems and generate outputs according to their internal rules of information processing. Thus, our understanding of the cerebellum is ultimately best expressed in terms of the information processing it accomplishes and how cerebellar neurons and synapses produce this processing. We review evidence that indicates how Pavlovian eyelid conditioning reveals cerebellar processing to be an example of feedforward control. Eyelid conditioning demonstrates a capacity for learning in the cerebellum that is error driven, associative and temporally specific--as is required for feedforward control. This computation-centered view is consistent with a variety of proposed functions of the cerebellum, including sensory-motor integration, motor coordination, motor learning and timing. Moreover, feedforward processing could be the common link between motor and non-motor functions of the cerebellum.

Animals↗

The temporal and spatial development of CRF binding sites in the postnatal mouse cerebellum.

This study describes the distribution and relative level of labeling of binding sites for corticotrophin releasing factor (CRF) in the postnatal mouse cerebellum. At birth low levels of labeling are present throughout the cerebellum. However, this labeling is most densely distributed in the caudal and lateral aspects of the cerebellum. By P3 CRF binding sites are present throughout the cerebellum, although the greatest level of labeling is in the posterior lobe of the vermis, especially lobules IX and X; this correlates with the early differential pattern of CRF distribution in cerebellar afferents within these same lobules. At P10, the adult pattern of distribution and level of labeling begins to emerge. The presence of CRF and CRF binding sites at birth, and during postnatal growth, suggests that this peptide could play a role in the regulation of developmental events within the cerebellum.

Animals↗