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1.
The spontaneous discharge frequency of the fastigial and interpositus nuclei was evaluated in three experimental conditions in Rat: (a) in the "intact" animal; (b) in animals with total and selective destruction of the inferior olive, depriving the Purkinje cells of their afferent climbing fiber; (c) in animals having inferior olive destruction and cryocoagulation of the cerebellar cortex, destroying Purkinje cells innervating the neurones of the fastigial and interpositus nuclei. Unit activity was high in group (a) (32.9 +/- 22.9/s); it was markedly reduced in group (b) (1.1 +/- 1.3/s); it was higher in group (c) than in group (a) (43.7 +/- 25.5/s). Suppression of the inferior olive thus increases the Purkinje cell inhibitory action upon neurones of the cerebellar nuclei.  相似文献   

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The spontaneous frequency of discharge of the red nucleus neurones has been evaluated in the rat before and after total and bilateral destruction of the inferior olive by 3-acetylpyridine. The suppression of the inferior olive increasing the cerebellar inhibition, produces, as a consequence, a consequence, a disfacilitation of the activity of the red nucleus neurones. The process persists for a few days, then a progressive compensation takes place. A month later the average frequency of discharge is recovered but a normal unit activity and motor behaviour are not restaured.  相似文献   

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The relationship between complex and simple spikes of Purkinje cells from vermis cerebelli of guinea pigs has been investigated. The ratio of complex spikes innervated by the processes of one and the same liana-like fiber ("twins cells") has also been studied. Three types of complex spikes in each Purkinje cell from vermis cerebelli of guinea pigs (n = 44) have been differentiated, which differ in duration. It was found that long (10.28 +/- 0.27 ms) complex spikes in all cells lead to a more pronounced inhibition of simple spikes than complex spikes of short duration (6.08 +/- 0.25 ms). It was shown that the dynamics of duration of complex spikes coordinates with changes in the activity of some Purkinje cells and their local groups: (a) complex spikes generated before the onset of pauses of simple spikes are longer than complex spikes generated before the termination of pauses; (b) in "twins cells" innervated by one liana-like fiber, the properties of complex spikes change simultaneously; (c) The degree of synchronism of complex spikes in closely-spaced (to 150 microm) Purkinje cells receiving the inputs from different liana-like fibers increases with their duration. A possible functional role and the mechanisms of generation of complex spikes are discussed.  相似文献   

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In experiments on guinea pigs (from newborn to adults), studies have been made on the extensor, support and lift reactions, as well as on the activity of cerebellar Purkinje cells in the same animals. First signs of immature lift, extensor and support reactions were observed already 12th after birth. At this period, mean discharge frequency in Purkinje cells was significantly lower than in the adult animals, reaching 11.5 +/- 1.2 imp/s for simple spikes and 0.45 +/- 0.05 imp/s for complex ones. Complete maturation of lift, extensor and support reactions takes place to the beginning of the 2nd week (8-9 days) of postnatal life. Within this period, significant changes in the activity of Purkinje cells were observed: mean discharge frequency of simple and complex spikes increased correspondingly up to 17.9 +/- 2.3 and 1.48 +/- 0.25 imp/s. At the same time, the mean discharge frequency in Purkinje cells, the average duration of inhibition pause, and the response latency became more stable.  相似文献   

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Inferior olive neurons (IONs) have rich dynamics and can exhibit stable, unstable, periodic, and even chaotic trajectories. This paper presents an analysis of bifurcation of periodic orbits of an ION when its two key parameters (a, μ) are varied in a two-dimensional plane. The parameter a describes the shape of the parabolic nonlinearity in the model and μ is the extracellular stimulus. The four-dimensional ION model considered here is a cascade connection of two subsystems (S(a) and S(b)). The parameter plane (a - μ) is delineated into several subregions. The ION has distinct orbit structure and stability property in each subregion. It is shown that the subsystem S(a) or S(b) undergoes supercritical Poincare-Andronov-Hopf (PAH) bifurcation at a critical value μ(c)(a) of the extracellular stimulus and periodic orbits of the neuron are born. Based on the center manifold theory, the existence of periodic orbits in the asymptotically stable S(a), when the subsystem S(b) undergoes PAH bifurcation, is established. In such a case, both subsystems exhibit periodic orbits. Interestingly when S(b) is under PAH bifurcation and S(a) is unstable, the trajectory of S(a) exhibits periodic bursting, interrupted by periods of quiescence. The bifurcation analysis is followed by the design of (i) a linear first-order filter and (ii) a nonlinear control system for the synchronization of IONs. The first controller uses a single output of each ION, but the nonlinear control system uses two state variables for feedback. The open-loop and closed-loop responses are presented which show bifurcation of orbits and synchronization of oscillating neurons.  相似文献   

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The versatility of stem cells has only recently been fully recognized. There is evidence that upon adoptive bone marrow (BM) transplantation (BMT), donor-derived cells can give rise to neuronal phenotypes in the brains of recipient mice. Yet only few cells with the characteristic shape of neurons were detected 1-6 mo post-BMT using transgenic or newborn mutant mice. To evaluate the potential of BM to generate mature neurons in adult C57BL/6 mice, we transferred the enhanced green fluorescent protein (GFP) gene into BM cells using a murine stem cell virus-based retroviral vector. Stable and high level long-term GFP expression was observed in mice transplanted with the transduced BM. Engraftment of GFP-expressing cells in the brain was monitored by intravital microscopy. In a long-term follow up of 15 mo post-BMT, fully developed Purkinje neurons were found to express GFP in both cerebellar hemispheres and in all chimeric mice. GFP-positive Purkinje cells were also detected in BM chimeras from transgenic mice that ubiquitously express GFP. Based on morphologic criteria and the expression of glutamic acid decarboxylase, the newly generated Purkinje cells were functional.  相似文献   

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Matsuda S  Launey T  Mikawa S  Hirai H 《The EMBO journal》2000,19(12):2765-2774
Cerebellar long-term depression (LTD) is thought to play an important role in certain types of motor learning. However, the molecular mechanisms underlying this event have not been clarified. Here, using cultured Purkinje cells, we show that stimulations inducing cerebellar LTD cause phosphorylation of Ser880 in the intracellular C-terminal domain of the AMPA receptor subunit GluR2. This phosphorylation is accompanied by both a reduction in the affinity of GluR2 to glutamate receptor interacting protein (GRIP), a molecule known to be critical for AMPA receptor clustering, and a significant disruption of postsynaptic GluR2 clusters. Moreover, GluR2 protein released from GRIP is shown to be internalized. These results suggest that the dissociation of postsynaptic GluR2 clusters and subsequent internalization of the receptor protein, initiated by the phosphorylation of Ser880, are the mechanisms underlying the induction of cerebellar LTD.  相似文献   

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A secondary ion mass spectrometry (SIMS) microscope was used to detect intracellular stores of calcium, magnesium, sodium and potassium. Measurements were made in semithin sections of fixed tissues of normal and climbing fiber deafferented cerebellar cortex. Quantitative data were collected from 150 microns diameter image fields in the molecular and granule layers. The results indicate smaller quantities of both calcium and magnesium in the deafferented cerebellar cortex compared to the normals, the molecular as well as the granule layer being affected. The results are discussed in terms of the usefulness and limitations of the SIMS microscope for histological preparations.  相似文献   

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Moore's method used for the examination of chromatin template activity in Purkinje and granule cells of 7, 14, 30 days and 3 months old rate cerebellar cortex has shown the age-dependent changes during differentiation period. The histograms for Purkinje cells have demonstrated that all neurons were distributed into 3 groups of activity according to their nuclear labelling. The cell percentage in each group varied during ontogenesis.  相似文献   

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Spike encoding at GABAergic neurons plays an important role in maintaining the homeostasis of brain functions for well-organized behaviors. The rise of intracellular Ca2+ in GABAergic neurons causes synaptic plasticity. It is not clear how intracellular Ca2+ influences their spike encoding. We have investigated this issue at GFP-labeled GABAergic cortical neurons and cerebellar Purkinje cells by whole-cell recording in mouse brain slices. Our results show that an elevation of intracellular Ca2+ by infusing adenophostin-A lowers spike encoding at GABAergic cortical neurons and enhances encoding ability at cerebellar Purkinje cells. These differential effects of cytoplasmic Ca2+ on spike encoding are mechanistically associated with Ca2+-induced changes in the refractory periods and threshold potentials of sequential spikes, as well as with various expression ratios of CaM-KII to calcineurin in GABAergic cortical neurons and cerebellar Purkinje cells.  相似文献   

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The cells that comprise the cerebellum perform a complex integration of neural inputs to influence motor control and coordination. The functioning of this circuit depends upon Purkinje cells and other cerebellar neurons forming in the precise place and time during development. Zebrafish provide a useful platform for modeling disease and studying gene function, thus a quantitative metric of normal zebrafish cerebellar development is key for understanding how gene mutations affect the cerebellum. To begin to quantitatively measure cerebellar development in zebrafish, we have characterized the spatial and temporal patterning of Purkinje cells during the first 2 weeks of development. Differentiated Purkinje cells first emerged by 2.8 days post fertilization and were spatially patterned into separate dorsomedial and ventrolateral clusters that merged at around 4 days. Quantification of the Purkinje cell layer revealed that there was a logarithmic increase in both Purkinje cell number as well as overall volume during the first 2 weeks, while the entire region curved forward in an anterior, then ventral direction. Purkinje cell dendrites were positioned next to parallel fibers as early as 3.3 days, and Purkinje cell diameter decreased significantly from 3.3 to 14 days, possibly due to cytoplasmic reappropriation into maturing dendritic arbors. A nearest neighbor analysis showed that Purkinje cells moved slightly apart from each other from 3 to 14 days, perhaps spreading as the organized monolayer forms. This study establishes a quantitative spatiotemporal map of Purkinje cell development in zebrafish that provides an important metric for studies of cerebellar development and disease. © 2015 Wiley Periodicals, Inc. Develop Neurobiol 75: 1174–1188, 2015  相似文献   

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Two intracellular calcium-release channel proteins, the inositol trisphosphate (InsP3), and ryanodine receptors, have been identified in mammalian and avian cerebellar Purkinje neurons. In the present study, biochemical and immunological techniques were used to demonstrate that these proteins coexist in the same avian Purkinje neurons, where they have different intracellular distributions. Western analyses demonstrate that antibodies produced against the InsP3 and the ryanodine receptors do not cross-react. Based on their relative rates of sedimentation in continuous sucrose gradients and SDS-PAGE, the avian cerebellar InsP3 receptor has apparent native and subunit molecular weights of approximately 1,000 and 260 kD, while those of the ryanodine receptors are approximately 2,000 and 500 kD. Specific [3H]InsP3- and [3H]ryanodine-binding activities were localized in the sucrose gradient fractions enriched in the 260-kD and the approximately 500-kD polypeptides, respectively. Under equilibrium conditions, cerebellar microsomes bound [3H]InsP3 with a Kd of 16.8 nM and Bmax of 3.8 pmol/mg protein; whereas, [3H]ryanodine was bound with a Kd of 1.5 nM and a capacity of 0.08 pmol/mg protein. Immunolocalization techniques, applied at both the light and electron microscopic levels, revealed that the InsP3 and ryanodine receptors have overlapping, yet distinctive intracellular distributions in avian Purkinje neurons. Most notably the InsP3 receptor is localized in endomembranes of the dendritic tree, in both the shafts and spines. In contrast, the ryanodine receptor is observed in dendritic shafts, but not in the spines. Both receptors appear to be more abundant at main branch points of the dendritic arbor. In Purkinje neuron cell bodies, both the InsP3 and ryanodine receptors are present in smooth and rough ER, subsurface membrane cisternae and to a lesser extent in the nuclear envelope. In some cases the receptors coexist in the same membranes. Neither protein is observed at the plasma membrane, Golgi complex or mitochondrial membranes. Both the InsP3 and ryanodine receptors are associated with intracellular membrane systems in axonal processes, although they are less abundant there than in dendrites. These data demonstrate that InsP3 and ryanodine receptors exist as unique proteins in the same Purkinje neuron. These calcium-release channels appear to coexist in ER membranes in most regions of the Purkinje neurons, but importantly they are differentially distributed in dendritic processes, with the dendritic spines containing only InsP3 receptors.  相似文献   

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Phenothiazine derivatives were examined as potential antagonists of the inhibitory noradrenergic synapses from the nucleus locus coeruleus to rat cerebellar Purkinje cells. Fluphenazine, and its thioxanthine analogue, flupenthixol, antagonized the inhibitory action of norepinephrine, when iontrophoretically applied to single cells. Alpha-flupenthixol was generally more active than the beta isomer. Fluphenazine had no appreciable effect on inhibitions induced by iontophoresis of GABA or cyclic AMP. Parenteral fluphenazine also blocked the inhibition of Purkinje cells produced by the stimulation of the noradrenergic pathway from locus coeruleus, but basket and stellate cell inhibitory inputs to Purkinje cells were unaffected. These data suggest that fluphenazine can specifically block a known central adrenergic inhibitory pathway.  相似文献   

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Cerebellar Purkinje neurons (PNs) receive two main excitatory inputs, from climbing fibers and parallel fibers, and inhibitory inputs, from GABAergic interneurons. The synapses formed by parallel fibers and by inhibitory interneurons on PNs are able to undergo long-lasting in efficacy. Thus, the excitatory parallel fiber-PN synapse undergoes long-term fibers. Synaptic inhibition can be potentiated by climbing fiber activity by a mechanism named rebound potentiation, resulting in a more powerful inhibitory effect of GABAergic interneurons. The induction of both long-term depression and rebound potentiation requires a transient elevation of the cytoplasmic calcium concentration ([Ca2+]i). The [Ca2+]i-transient is caused by Ca2+ entry through voltage-gated Ca2+ channels and, possibly, by release of Ca2+ from IP3- and ryanodine-sensitive stores. Direct Ca2+ entry through synaptic AMPA receptor channels seems not to contribute significantly to the Ca2+ signal mediating the induction of both long-term depression and rebound potentiation.  相似文献   

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