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Ontogeny of proenkephalin mRNA and enkephalin peptide expression in the cerebellar cortex of the rat: spatial and temporal patterns of expression follow maturational gradients in the external granular layer and in Purkinje cells.

Proenkephalin mRNA and peptide products were examined in developing cells of the postnatal rat cerebellar cortex using in situ hybridization and immunocytochemistry. On day 7, proenkephalin mRNA was first detected as discrete cellular labeling in Golgi cells and as a diffuse hybridization signal over the Purkinje cell layer. On day 14, proenkephalin mRNA and peptide products primarily appeared in distinct subpopulations of Purkinje cells present in the posterior and lateral cerebellum. Similarly, in the external granular layer (EGL), enkephalin immunoreactivity was present only in the posterior and lateral portions of the cerebellum on day 14. However, proenkephalin mRNA was not detected in enkephalin-immunoreactive EGL cells. On day 21, the subset of Purkinje cells that expressed proenkephalin mRNA and peptides were distributed more uniformly throughout the cerebellum. On day 28, a few enkephalin-immunoreactive Purkinje cells were uniformly present throughout the cerebellum, but proenkephalin mRNA was not detected in most of these cells. The spatial gradients in proenkephalin mRNA expression evident in the Purkinje cells of younger rats were no longer present in 28-day-old rats. These findings are important, because endogenous opioids such as enkephalin have been previously shown to inhibit the growth of Purkinje cell dendrites and dendritic spines, and inhibit the rate of mitosis in EGL neuroblasts. Cells do not develop at uniform rates within the cerebellum. There are regional differences in the timing of the formation of the EGL, and in the morphogenesis of Purkinje cells. In conjunction with previous work, the present findings suggest that during development, the pattern of enkephalin immunoreactivity in Purkinje and EGL cells closely follows the spatial and temporal gradients of maturation in both these cell types. The emergence and disappearance of enkephalin immunoreactivity in Purkinje and EGL cells is spatially and temporally related, and coincides with proenkephalin mRNA expression in Purkinje cells. Thus, the transient and coordinated appearance of enkephalin in cerebellar Purkinje and EGL cells may contribute to regional differences in the rate of cerebellar maturation, and may help synchronize the developmental interactions between these two cell types.

Animals↗

[Cytospectrophotometric study of GABA-transaminase in the rat cerebellar cortex].

Modification of the histochemical method for detection of GABA-transaminase activity is suggested. Optimal concentrations of the substrates and cofactors are chosen on the basis of kinetic study of the enzymatic reaction in the cryostat sections of the rat cerebellar cortex by the quantitative microspectrophotometric method. The method is intended for the quantitative histochemical analysis of GABA-transaminase activity in the brain sections.

4-Aminobutyrate Transaminase↗

Transient accumulations of glycosaminoglycans in rat and chicken cerebellar cortex during development.

Modifications of glycosaminoglycans at neuropile of rat and chicken cerebellum during development were histochemically studied. The application of Alcian Blue staining techniques and enzymatic degradations permitted to reveal in both species that in earlier stages of cerebellar development hyaluronic acid is present throughout neuropile of entire cerebellum but it accumulated preferentially at the medullary region and around precursory Purkinje cells where it showed a mucoid-like appearance. This substance was related with cell migration and aligning processes. At the middle of cerebellar development, around 2nd postnatal week in rat and 12-16 embryonary days in chick, a new polyanionic transient accumulation, presumably chondroitinsulphate, became present at the medullary region following the longitudinal axis of folium and limiting the forming granular layer, being this substance mainly related with polarity processes by controlling or guiding the growing cones of afferent fibers, which enter massively to cerebellar cortex. It disappeared as myelination progressed. Also from the middle stage of development onward, beside glycosaminoglycans, other polyanionic substances were present at the molecular and granular layer neuropile and at the cytoplasm of some nerve cells. These macromolecules were rather related with nerve cell differentiation and maturation.

Alcian Blue↗

[Morphological and cytochemical analysis of neuronal populations in the ganglion cell layer of the cerebellar cortex in birds and mammals living in similar habitats].

Neuron populations of ganglion cell layer of cerebellar cortex were studied in birds and mammals, which were living in similar habitats: air-land habitat (squirrel--Sciurus vulgaris and sparrow--Passer domesticus) and land-water habitat (nutria--Myocastor coypus and goose--Anser domesticus). The following morpho-cytochemical indices were analyzed: density of Purkinje cell distribution per unit gyms length, area parameters, tinctorial properties, protein content of neuron populations of ganglion cell layer. Evaluation of neuronal tinctorial properties has revealed general consistent patterns in the organization of cerebellar ganglion cell layer in vertebrates, while an analysis of protein metabolism has demonstrated specific features characteristic for definite classes irrespective of their habitat.

Adaptation, Physiological↗

GABA-like immunoreactivity in different cellular populations of cerebellar cortex of rats before and after treatment with amino-oxyacetic acid.

The postembedding immunogold procedure was used to detect changes in the levels of gamma-aminobutyric acid (GABA)-like immunoreactivity at the ultrastructural level in the cerebellar cortex of control rats and rats treated with the GABA transaminase inhibitor, amino-oxyacetic acid (AOAA), in order to increase the levels of GABA. GABA-immunoreactive structures were labelled using an antiserum directed against GABA coupled to bovine serum albumin and a secondary antibody conjugated to colloidal gold. The density of gold particles per square micron of tissue was taken as a measure of GABA-like immunoreactivity. In separate groups of control and AOAA-treated animals, the levels of GABA were assessed biochemically in the cerebellum, the cortex, the ventral mesencephalon and the striatum. Six hours after treatment with AOAA the GABA levels in the cerebellum, the cortex, the ventral mesencephalon and the striatum. Six hours after treatment with GABA immunoreactivity of the Golgi and basket cell terminals was significantly greater than that of mossy fibres, granule cell dendrites and perikarya and glial cells. The value obtained for Golgi terminals was the highest of all the structures examined and was twice that of their perikarya. Six hours after treatment with AOAA the GABA immunoreactivity in Golgi and basket cell terminals and in glial cells was greatly enhanced. The drug treatment slightly enhanced the immunoreactivity in mossy fibres and granule cell dendrites but induced no change in granule cell bodies. Thus, in both control and treated rats, the highest GABA immunoreactivity was present in the terminals of GABAergic cells, and the lowest in putative glutamatergic cells. The results demonstrate that there is a high degree of selectivity in the changes in GABA levels following the inhibition of GABA transaminase in the cerebellum. They also confirm the potential of the use of postembedding methods for the quantification of endogenous amino acid at cellular and subcellular levels, in relative and possibly also absolute terms.

4-Aminobutyrate Transaminase↗

Regressive modifications of climbing fibres following Purkinje cell degeneration in the cerebellar cortex of the adult rat.

The role of postsynaptic neurons in the maintenance of adult terminal axon arbours was investigated in the rat olivocerebellar system. The degeneration of Purkinje cells, the main target of olivary axons in the cerebellar cortex, was obtained by intraparenchymal application of kainate. The structural features of target-deprived climbing fibres, visualized by Phaseolus vulgaris leucoagglutinin tracing, were examined from two days to six months after the lesion. Following the degeneration of its Purkinje cell, the climbing fibre underwent remarkable regressive modifications involving the disappearance of most of the terminal arborization. Never the less, atrophic arbours still spanned through the molecular layer six months after the lesion. Morphometric evaluations showed that, one week after kainate application, total arbour length was already reduced to 52% of control, whereas the number of branches and of varicosities had both dropped around 40%. This retraction process progressed in the following stages to reach its maximum at about one month after the lesion, when total length was 30% of control and only 10% of branches and varicosities were still present. Only a slight tendency to a further decrease of the values could be detected at longer survival times. Branching pattern analysis revealed that such regressive phenomena mainly involved the distal compartment of the climbing fibres, the one made of fine varicose branchlets, while sparing the proximal thick branches. In addition, the whole process appeared to follow some rather strict guiding principles leading to an ordered branch retraction, from the periphery of the arbour inwards. Finally, in order to rule out the possibility that the observed changes could be due to a direct action of kainate on climbing fibres, we designed an alternative method of killing Purkinje cells by intraparenchymal injection of propidium iodide. The structural features of climbing fibres deprived of their target by such a procedure were very similar to those shown by arbours from time-matched kainate-lesioned animals at both qualitative and quantitative levels. Our results show that target deprivation induces remarkable structural modifications in the climbing fibre, leading to the retraction of most of the arbour. Never the less, the integrity of the Purkinje cell is not necessary for the maintenance of the whole arborization since its proximal compartment is maintained in the molecular layer for several months after target degeneration. It is proposed that the Purkinje cell, most likely by acting through a contact factor, directly controls the formation and the maintenance of the distal climbing fibre branches with their varicosities, which represent the presynaptic compartment of the axonal arbour.

Animals↗

Granule neuron DNA damage following deafferentation in adult rats cerebellar cortex: a lesion model.

Neuronal programmed cell death is regulated by a neurotrophic supply from targets and afferent inputs. The relative contribution of each component varies according to neuronal type and age. We have previously reported that primary cultures of cerebellar granule cells undergo apoptosis when deprived of depolarising KCl concentrations, suggesting a significant role of afferent inputs in the control of cerebellar granule cells survival. This issue was investigated by setting up various in vivo lesional paradigms in order to obtain partial or total deafferentation of the cerebellar granule layer in adult rats. At different times after surgery, cerebellar sections were subjected to TUNEL staining in order to detect possible DNA damage. One week after unilateral pedunculotomy, few scattered groups of apoptotic granule neurons were observed in the homolateral hemisphere. On the contrary, total deafferentation obtained by a new experimental paradigm based on an "L-cut" lesion induced massive and widespread apoptotic death in the granule layer of the deafferentated area. The time window of DNA fragmentation in granule layer was one to seven days after the "L-cut". Selective Purkinje cell deafferentation obtained by 3-acetylpyridine injection did not result in TUNEL staining in the cerebellar cortex. The current finding that mossy fiber axotomy induces granule cell apoptotic death points out for the first time the crucial role of afferent inputs in mature granule cell survival. Moreover, the in vivo lesional model described here may prove to be an useful tool for investigating cellular and molecular mechanisms of neuronal death triggered by deafferentation.

Afferent Pathways↗

The effects of early hypo- and hyperthyroidism on the development of rat cerebellar cortex. III. Kinetics of cell proliferation in the external granular layer.

The effects of early hypo- and hyperthyroidism on the rates of cell acquisition and proliferation have been studied in the external granular layer (EGL) of the developing rat cerebellar cortex at 10 days of age using quantitative autoradiographic methods. Both altered thyroid states reduce the rate of cell acquisition in the EGL, but appear to do so for different reasons. Hyperthyroidism shortens the average length of the cell cycle by decreasing the duration of the pre-DNA synthetic phase (G1), indicating that excess thyroxine may exert a direct effect on the EGL. This action involves the early onset of neuronal differentiation (cessation of proliferation)46 which presumably leads to the observed decrease in the rate of cell acquisition (increased doubling time). Such differentiating cells do not, however, leave the proliferative zone or the EGL prematurely, resulting in a reduced labeling index, mitotic index, and growth fraction as non-dividing cells dilute the proliferating cell population. Hypothyroidism, on the other hand, leads to no significant change in the length of the cell cycle or in the mitotic index, but causes a decreased labeling index and growth fraction, as well as a reduced rate of cell acquisition (increased doubling time). No significant change in the amount of cell death in the EGL could be found to explain this apparent discrepancy between the rate of cell proliferation (cell cycle length) and cell acqusiition. The answer to this puzzle appears to lie in the mitotic index, which is not affected to the same extent as the labeling index, although it is also slightly reduced. If cells were to remain longer in mitosis, this could result in a decreased labeling index and growth fraction but nearly normal mitotic index and cell cycle length (as measured using the % labeled mitoses method), since those cells dropping out of the cycling population would be counted as mitoses...

Animals↗

Compartmentation of the mouse cerebellar cortex by neuronal calcium sensor-1.

Neuronal calcium sensor-1 (NCS-1) is a member of the EF-hand calcium-binding protein superfamily, which is considered to modulate synaptic transmission and plasticity. The detailed distribution of NCS-1 was analyzed in the mouse cerebellar cortex. In coronal sections, the NCS-1 immunostaining displayed characteristic parasagittal banding pattern in the Purkinje cell layer and molecular layer, while there were no apparent bands in the granule cell layer. The alternating positively and negatively NCS-1-labeled Purkinje cell clusters contributed to this cerebellar compartmentation. In contrast, stellate-basket cells were uniformly NCS-1-positive throughout the cerebellum. Immunofluorescent double staining showed that NCS-1 and zebrin II exhibited a similar parasagittal banding pattern. Then, we performed mapping of NCS-1- and/or zebrin II-labeled Purkinje cell somata using seven sequential coronal sections. NCS-1-positive/zebrin II-positive Purkinje cell clusters were seen throughout the cerebellum, but NCS-1-positive/zebrin II-negative Purkinje cells were exceedingly rare. On the other hand, NCS-1-negative/zebrin II-positive Purkinje cell clusters were found in anterior lobule vermis and paraflocculus, whereas they were rarely seen in posterior lobules. The digitized quantitative analysis showed close relationship between NCS-1 and zebrin II immunoreactivity in the molecular layer. The correspondence between NCS-1 and zebrin II demonstrated here indicates a novel anteroposterior difference of cerebellar compartmentation and provides fundamental information of cerebellar organization.

Animals↗

Antigenic map of the rat cerebellar cortex: the distribution of parasagittal bands as revealed by monoclonal anti-Purkinje cell antibody mabQ113.

Both anatomical and physiological mapping methods have revealed that the mammalian cerebellar cortex consists of a family of parasagittal bands of cells, each band with its own pattern of afferent and efferent axons. Monoclonal antibody mabQ113 recognizes an unknown polypeptide antigen that is confined to a subset of rat cerebellar Purkinje cells. Immunoreactive cells are arranged into parasagittal bands extending throughout the vermis and hemispheres. Expression of the Q113 epitope by individual Purkinje cells may not be all-or-nothing, since the bands tend to be more strongly stained in the vermis than the hemispheres. The band display is symmetrical about the midline and reproducible from individual to individual. Whole-mount immunocytochemistry and serial reconstruction reveal a median band of mabQ113+ Purkinje cells adjacent to the midline (P1+) and six other positive bands disposed symmetrically at either side (P2+ to P7+). Bands are distinct throughout most of the cortex but tend to fuse ventrally and caudally. There are two sources of interindividual differences. Firstly, most animals express supernumerary "satellite" bands in the vermis. Satellite bands are usually only one cell wide, are not bilaterally symmetrical, and differ in position and number from individual to individual. Secondly, the precise position of an individual band can differ, perhaps according to the variable cortical lobulation, for example, the position of P4+ in lobules VIII/IX and P6+ in lobule VII. While a scheme of parasagittal bands is a good description of the vermian organization, the distribution of mabQ113+ and mabQ113- Purkinje cells in the hemispheres may be better described as a checkerboard of antigenic patches.

Animals↗

Specimen preparation of the human cerebellar cortex for scanning electron microscopy using a t-butyl alcohol freeze-drying device.

A freeze-drying device was applied to t-butyl alcohol substituted nerve cells, fibers and synaptic terminals. Ten percent formalin-fixed human cerebellar cortex specimens were postfixed in 2.5% glutaraldehyde in 0.1 M cacodylate buffer solution and were rinsed three times in 5% sucrose solution in the same buffer. After the postfixed specimens were dehydrated using a graded series of ethanols and then transferred into a graded series of t-butyl alcohols (freezing point 25.4 degrees C), the t-butyl alcohol substituted specimens were freeze-dried at 15 degrees C and at high vacuum (5 x 10(-2) Torr). The freeze-dried specimens were sputter coated with gold. Scanning electron microscopy revealed synaptic terminals on the surfaces of a Golgi cell and a small flat polygonal cell. Rough somatic surfaces of granule cells were also observed.

Aged↗

Light and electron microscopic study on cerebellar cortex of macular mutant mouse as a model of Menkes kinky hair disease.

The macular mouse is a mutant mouse, the hemizygotes of which show clinical and biochemical abnormalities similar to those in Menkes kinky hair disease (MKHD) in humans. The cerebellar cortex of this mutant suckling mouse was examined by light and electron microscopy. In hemizygotes, the Purkinje cells showed a delay in the maturation of dendrites and somatic spines. Somal sprouts, abnormal mitochondria, and filamentous cytoplasmic inclusions were observed on these cells on day 13. Axonal swellings, containing abnormal mitochondrias were also seen in the inner granular layer. These findings correspond with those of MKHD in humans and those of the brindled mouse, another model mouse of MKHD.

Animals↗

[Assessment of the contribution of complex and simple Purkinje cell impulses to local potentials of the cerebellar cortex].

Potentials amplitude decrement with the distance between referent cell and test electrode is estimated by means of potential averaging synchronous with complex and simple spikes of the referent Purkinje cell. Anisotropy of recorded fields in accordance with natural planes of anisotropy of cerebellar cortex and temporal parameters of complex and simple spikes has been described. Use of synchronous averaging for increase of a probability of finding of Purkinje cells pairs controlled with the same climbing fiber is discussed.

Action Potentials↗

Potentiation of gamma-aminobutyric acid-mediated inhibition by isoproterenol in the cerebellar cortex: receptor specificity.

A large body of electrophysiological data has supported the hypothesis that an important role of norepinephrine in the central nervous system is to modulate the actions of other transmitter systems, particularly those utilizing the amino acid neurotransmitters. Noradrenergic potentiation of inhibitory responses, induced by locally-applied or synaptically-released gamma-aminobutyric acid (GABA) on cerebellar Purkinje neurons, has been observed by a number of investigators, who have suggested that activation of beta-adrenergic receptors plays a critical role in mediating this modulatory effect of norepinephrine (NE). Two postsynaptic receptors for GABA, termed A and B, have been identified and both subtypes have been found in the cerebellum of the rat. The purposes of this investigation were first to identify the subtype(s) of GABA receptor responsible for mediating the inhibitory effects of locally-applied GABA in the cerebellar cortex and second to identify which subtype of GABA receptor is modulated by a beta-adrenergic input. Inhibitory responses of cerebellar Purkinje neurons, in urethane-anesthetized rats, to iontophoretic or pressure-applied isoguvacine, a selective GABAA agonist, to baclofen, a GABAB agonist or to GABA itself, were examined before, during and after local application of isoproterenol or norepinephrine. Isoguvacine, but not baclofen, induced consistent and dose-dependent inhibition of the firing of Purkinje cells. At ejection currents that had no effect on spontaneous firing rate, iontophoretically-applied isoproterenol potentiated isoguvacine-induced inhibition. These data suggest that GABAA, rather than GABAB receptors, mediate GABA-induced inhibitions of cerebellar Purkinje neurons. Moreover, it appears that the modulation of GABA function by beta adrenergic agonists involves an interaction between a beta-adrenergic input and the GABAA receptor complex.

Action Potentials↗

Localization of hexokinase in neural tissue: electron microscopic studies of rat cerebellar cortex.

The distribution of hexokinase (ATP:D-hexose 6-phosphotransferase, EC 2.7.1.1) in the rat cerebellar cortex has been studied at the electron microscopic level using the peroxidase-antiperoxidase procedure. Extensive staining of cytoplasmic regions, with some increased staining at mitochondrial profiles, was seen in the cell bodies of both neurons (basket, stellate, Lugaro, Golgi, and granule cells) and astrocytes. Oligodendrocytes showed little or no detectable staining. Purkinje cell perikarya were much less intensely stained than were the perikarya of other neurons. The initial portion of the Purkinje dendrite was, like the perikaryon from which it emerged, lightly stained. More intense staining was seen in the secondary and tertiary branches of the Purkinje dendrite, but the terminal branches were devoid of stain. Granule cell dendrites were well stained in their initial portions but devoid of stain in their terminal dendritic digits which form part of the cerebellar glomeruli. In contrast to the unstained granule cell dendritic digits, the central mossy fiber nerve terminal of the glomerulus exhibited intense staining of the mitochondrial profiles and of synaptic vesicles adjacent to the mitochondria. Axons of basket cells showed intense staining in the segments adjacent to the Purkinje cell soma, while terminal twigs of the basket axons in the pinceau surrounding the (unstained) initial segment of the Purkinje axon showed markedly decreased staining intensity. These results indicate that there may be substantial variation in hexokinase levels between the various regions of neuronal processes. Hexokinase was seen at both cytoplasmic and mitochondrial locations in a variety of cells. It does not appear likely that location of hexokinase can be directly correlated with cell type, i.e., with neurons versus glia.

Animals↗

Scanning electron microscopy of vertebrate cerebellar cortex.

In this study, the Golgi method for light microscopy, transmission and conventional scanning electron microscopy, the ethanol-cryofracturing technique, the freeze-fracture method for SEM, and the freeze-etching method have been used in conjuction to analyze the three-dimensional cytoarchitectonic arrangement and intracortical circuits of vertebrate cerebellar cortex. Approximately more than 100 specimens of mice, rat, teleost fishes and human cerebelli were processed by the above mentioned techniques. A chronological review of other methods for studying hidden surfaces of cerebellar nerve cell has been also described. The three-dimensional morphology, outer and inner surfaces of granule, Golgi, Purkinje and stellate cells were reviewed by means of a correlative and comparative study. The cerebellar circuits formed by mossy and climbing fibers with granule cell dendrites and Purkinje cell-granule cell synapses have been traced by ethanol-cryofracturing technique, freeze-fracture method for SEM and freeze-etching technique. These findings have been correlated with previous light and electron microscope findings published in the last century. Some advantages and limitations of each method are pointed out. The review emphasizes the paramount importance of correlating light microscope Golgi method with ethanol-cryofracturing and slicing techniques for SEM. The correlation between freeze-fracture method for SEM and freeze-etching technique provides a new approach for studying three-dimensional morphology of nerve cells at cellular and macromolecular levels. This modern methodology of three-dimensional analysis offers new potential areas for future experimental investigation in embryology and pathology of the central nervous system.

Animals↗

Projections from the pontine nuclei proper and reticular tegmental nucleus onto the cerebellar cortex in the cat. An autoradiographic study.

After injections of 0.5 microliter of tritiated leucine and/or proline into various parts of the pontine nuclei proper or the pontine tegmental reticular nucleus (N.r.t.) of 34 cats, labeled terminals of pontocerebellar fibers were found in the cerebellar cortex. Fibers from the pontine nuclei and N.r.t. terminate as mossy fibers in the granular layer of the cerebellum, and no evidence is obtained of labeled fibers in the molecular layer. The pontocerebellar projection is, in general, bilateral with a contralateral preponderance, and a complex organization has been shown to exist in the cat. Clear evidence of divergence of this projection from a small pontine area has been demonstrated. Thus, the dorsolateral nucleus has a heavy projection to lobule VII, besides modest projections to lobules VI, VIII, and IX, crus I and II, paraflocculus, and paramedian lobule. On the other hand, a particular cerebellar region receives afferent fibers from several pontine regions, confirming previous HRP studies. For example, lobule VII receives heavy projections from parts of the dorsolateral, peduncular, and paramedian nuclei, less heavy projections from the lateral part of the lateral nucleus, and some from other parts of the pontine nuclei. This is a convergent feature of the pontocerebellar projections. In addition, small adjoining areas within a pontine subdivision have different patterns of cerebellar projections, shwing preferential sites of terminations. This suggests some degree of localization within the pontine nuclei. The cerebellar projection from the N.r.t. shows an essentially similar organization as the projection from the pontine nuclei proper, an apparent difference being only that the former is more extensive in the fields of termination than the latter. Some evidence for a parasagittal termination of pontocerebellar projections to the paramedian lobule has been found in this study. However, this is not as clear-cut as such patterns in the cerebellar projections from the spinal cord, cuneate nucleus, and lateral reticular nucleus shown recently in rat and cat.

Amino Acids↗

Integrative versus delay line characteristics of cerebellar cortex.

In order to determine which of two general models ("tapped delay line" or "integrator") provides a more accurate desciption of mammalian Purkinje cell (P-cell) activation by natural stimulation, the spatial and temporal characteristics of a population of neurons in cerebellar cortex responsive to small controlled stretches of forelimb muscles were examined in awake, locally anesthetized cats. Stretch of a single wrist muscle excited P-cells over a distance of about 1 mm in the long axis of a folium, a span which is at most half the length of parallel fibers. Both granule cells and molecular layer interneurons were excited over a wider zone than P-cells. Furthermore, P-cells across a response zone all fired on the average at the same time, as determined by computing peristimulus cross-interval histograms from pairs of simultaneously recorded neurons. Consistent delays could only be demonstrated in the minimal response latencies as measured from peristimulus time histograms. These delays, however, were longer than could be ascribed to parallel fiber conduction velocity. No evidence, therefore, was found in cat cerebellum to support the "tapped delay line" model, which postulates the successive activation of P-cells as an excitatory volley travels along a parallel fiber beam. Instead, an integrative mode of operation seems to predominate: a relatively wide substratum of activated granule cells simultaneously activates a narrower focus of P-cells centrally situated with respect to the granule cell population. The role of inhibitory interneurons in promoting the "integrator" model is discussed.

Animals↗