Cerebellar Cortex

Palay, Sanford L.; Chan‐Palay, Victoria

doi:10.1007/978-3-642-65581-4

Cited by 1,664 publications

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“…The short duration of Ca 2+ sparks as measured in muscle fibers (with an estimated duration of Ca 2+ release of about 5 ms) 44 is compatible with the estimated duration of lamIPSCs synchronization (less than 4 ms) derived from our rise time results. Basket cell terminals are elongated structures that contain arrays of release sites spanning several micrometers 27 . Ca 2+ sparks occurring in such structures would reach tens of release sites and could therefore provide the synchronization needed to generate lamIPSCs (up to 1.5 nA) out of individual quantal sizes of ∼60 pA each.…”

Section: Discussionmentioning

confidence: 99%

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Presynaptic calcium stores underlie large-amplitude miniature IPSCs and spontaneous calcium transients

et al. 2000

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articlesThe building block of synaptic transmission is the quantum, the minimal increment of postsynaptic signals 1 . At vertebrate neuromuscular junctions, the quantum may be equated with spontaneous signals obtained in the absence of presynaptic action potentials, called miniature currents (or potentials) and believed to be due to release of one neurotransmitter vesicle. For central synapses, this issue remains an open question, as large miniature currents are suggested to arise from the concerted release of several presynaptic vesicles and to be the sum of several quanta 2-5 . Such multivesicular miniature events could reflect tetrodotoxinresistant action potentials in presynaptic terminals 6 . Another explanation comes from evidence for functional intracellular Ca 2+ stores in presynaptic terminals. First, inositoltrisphosphate (InsP 3 ) receptors are immunolocalized in presynaptic terminals of the deep cerebellar nuclei and retina 7,8 . Second, at the frog neuromuscular junction, agents that affect ryanodine-sensitive Ca 2+ stores also regulate presynaptic intracellular Ca 2+ (Ca 2+ i ) rises and acetylcholine release during high-frequency stimulation 9,10 . Third, action-potential-evoked release of acetylcholine at synapses in Aplysia buccal ganglia is inhibited by ryanodine and augmented by presynaptic injection of cyclic ADP ribose 11 . Fourth, caffeine and/or ryanodine modify presynaptic Ca 2+ i signals in autonomic ganglia 12,13 and in photoreceptors 14 . Finally, in hippocampal pyramidal cells, caffeine or thapsigargin can increase the frequency of miniature IPSCs 15 . Hence, spontaneous Ca 2+ release from presynaptic Ca 2+ stores may provide the synchronization mechanism that leads to multivesicular miniatures. However, except for one study that gave negative results in cultured retinal amacrine cells 16 , this possibility has not been tested systematically.To assess the contribution of intracellular Ca 2+ stores to neurotransmitter release, we monitored the amplitude distribution of miniature synaptic currents while manipulating potential presynaptic Ca 2+ stores. Using cerebellar interneuron-Purkinje cell synapses, in which large miniature synaptic currents are prominent, we found that the largest mIPSCs result from multivesicular release and depend on Ca 2+ mobilization from ryanodine-sensitive presynaptic stores. Further, two-photon confocal microscopy showed ryanodine-sensitive intracellular Ca 2+ i transients highly localized to presumed release sites, which may underlie large miniature currents. RESULTSMiniature IPSCs recorded in cerebellar Purkinje cells, at -60 mV under symmetrical Cl -concentrations and in the presence of tetrodotoxin (TTX) and ionotropic glutamate receptor blockers, showed mean amplitudes of 125 ± 9 pA (n = 28 cells), larger than for most neurons (Fig. 1a). Amplitude histograms had a distinct peak for values less than 200 pA, followed by a long tail with amplitudes up to 1500 pA (Fig. 1b). Spurious summation of independent events did not contribute to the generation of lar...

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Section: Discussionmentioning

confidence: 99%

“…5d). The morphology of these fibers was characteristic of axons and presynaptic terminals of juvenile basket cells 27 . Terminals onto basket cell somata were also strongly labeled (Fig.…”

Section: Rise Time Kineticsmentioning

confidence: 99%

Presynaptic calcium stores underlie large-amplitude miniature IPSCs and spontaneous calcium transients

et al. 2000

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“…Undifferentiated astrocytes could be distinguished from other types of undifferentiated cells in cerebellar explants. Undifferentiated astrocytes were of distinct size (11.8 ± 1.4 μm perikaryal diameter); often had multiple small nucleoli within a nucleus that was eccentrically positioned within the perikarya; and were distributed at the periphery of the outgrowth at a position normally occupied almost exclusively by astrocytes in cerebellar explant cultures after 7 days in vitro 1,23 (Hauser, unpublished 35 , and are of distinct size (7.2 ± 0.7 μm), morphology, and distribution (within the explant) from immature astrocytes. Astrocytes were not labeled for proenkephalin mRNA when pretreated with RNase or an excess of unlabeled probe, or when using an [ 35 S]-labeled RNA probe complementary to prodynorphin mRNA with the same hybridization conditions, exposure time, and specific activity as used for the proenkephalin cRNA probe (Fig.…”

Section: Introductionmentioning

confidence: 99%

Cellular localization of proenkephalin mRNA and enkephalin peptide products in cultured astrocytes

et al. 1990

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To identify the possible cellular sites of opioid gene expression during ontogeny, proenkephalin mRNA and enkephalin peptide expression were examined, respectively, by in situ hybridization and immunocytochemistry in organotypic explants of rat cerebellum and in astrocyte-enriched cultures of murine cerebral hemispheres. High levels of proenkephalin mRNA and enkephalin immunoreactivity were detected in immature cells identified as astrocytes. Double-labeling studies combining in situ hybridization and immunocytochemical localization of the astrocytic marker, glial fibrillary acidic protein, provided direct evidence that proenkephalin mRNA is expressed by astrocytes in culture. Based on previous studies that Met-enkephalin can inhibit astrocyte growth in vitro, the present results suggest that proenkephalin gene expression by astrocytes is important during central nervous system maturation. KeywordsNeural development; In situ hybridization; Endogenous opioids; Proenkephalin A; Glial fibrillary acidic protein; Astrocyte; In vitroThe growth of neuronal and non-neuronal cells of the postnatal rat cerebral cortex, hippocampus, and cerebellum is modified by experimental manipulation of endogenous opioid systems (i.e, endogenous opioids and opioid receptors). Cellular differentiation 17,18 , cell number and packing density 54,55 , and cortical thickness 54,55 are modifiable by treatment with opioid antagonist drugs in vivo. In the cerebellum, [ 3 H]-thymidine incorporation by neuroblasts of the external granular layer (EGL) in 6-day-old rats is inhibited by systemic administration of Met-enkephalin, while treatment with the opioid antagonist naltrexone, at dosages sufficient to completely block opioid receptors, is reported to increase [ 3 H]-thymidine incorporation compared to untreated controls 56 . These and other experiments suggest that endogenous opioids are normally available to cells in the developing CNS in sufficient quantities to tonically inhibit growth 17,18,41,[54][55][56] . In support of this hypothesis, opioid peptide levels and opioid binding are greatly increased in the rat cerebellum 48,49 28,32,43,52 . In the present study, proenkephalin (proenkephalin A) mRNA and enkephalin peptide expression were examined by in situ hybridization and immunocytochemistry, respectively, in primary cultures of the developing CNS (i) to identify the specific cellular sites of proenkephalin gene and peptide expression, and (ii) to determine whether opioids are expressed by replicating astrocytes prior to their reaching confluence. We were particularly interested in determining whether rapidly dividing cells in astrocyte-enriched cultures express the proenkephalin gene prior to reaching confluence, because we have recently found that the proenkephalin peptide product, Met-enkephalin, selectively inhibits type 1 astrocyte proliferation at this time (i.e., at 4 or 6 days in vitro) 46,47 . Initial studies localized high levels of proenkephalin mRNA in cells with astrocytic morphology irrespective of culture conditi...

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“…In the Purkinje cell and granular layers, GAD-positive dots and large patches, which surrounded Purkinje cell bodies (asterisks), are considered to show a pinceau of basket cell axon terminals (Fig. 8A, B) [45]. Ring-shaped profiles stained by GAD-immunohistochemistry show the terminals of Golgi cells in the cerebellar glomeruli.…”

Section: Immunohistochemical Localization Of the Gaba A Receptor αmentioning

confidence: 99%

“…First, we investigated the relationship between presynaptic neurons and α subunits in the postsynaptic neurons. In the normal cerebellum, Purkinje cells receive GABAergic input from stellate and basket cells at dendritic shafts and cell bodies [45], GABAergic transmission at Purkinje cell synapses is mediated by GABA A receptors containing only the α1 subunit but not the remaining five α subunits [28,47,69]. In contrast, Golgi cell axons form synapses with granule cell dendrites within the synaptic glomeruli of the granular layer, and their Second, we investigated the relationship between neuronal maturation and developmental changes in expression of the subunits.…”

Section: Regulatory Mechanisms Underlying the Expression Of The Gamentioning

confidence: 99%

Normal formation of the postsynaptic elements of GABAergic synapses in the reeler cerebellum

Takayama

Inoue

2003

Developmental Brain Research

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Synaptic transmission mediated by γ-amino butyric acid (GABA) plays an important role in inhibition of glutamatergic excitatory transmission and expression of higher brain functions, such as memory, learning and anxiety. To elucidate mechanisms underlying formation of the postsynaptic elements for GABAergic transmission, we employed the reeler mutant mice in this study. In the reeler cerebellum, abnormal cytoarchitecture and an aberrant environment affect the formation of neural networks and maturation of neurons. We examined the expression and localization of GABA A receptor α subunits in the reeler cerebellum and determined whether various abnormalities in the reeler mice affected formation of the postsynaptic elements. In situ hybridization analysis revealed that the specific expression of α subunit mRNAs in each neuronal type was preserved. Abnormal expression of α subunits was not detected, although GABAergic networks were altered and neuronal maturation was severely disturbed. Immunohistochemistry for the α1 and α6 subunits, which were expressed abundantly in the reeler cerebellum, revealed that both subunit-proteins accumulated at positions adjacent to GABAergic terminals. These results, taken together, suggested that expression of the GABA A receptor subunits in postsynaptic neurons might be genetically determined, but trafficking and accumulation of the subunit proteins at the GABAergic synapse may be induced by GABAergic innervation. Classification Terms

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Cerebellar Cortex

Cited by 1,664 publications

References 0 publications

Presynaptic calcium stores underlie large-amplitude miniature IPSCs and spontaneous calcium transients

Presynaptic calcium stores underlie large-amplitude miniature IPSCs and spontaneous calcium transients

Cellular localization of proenkephalin mRNA and enkephalin peptide products in cultured astrocytes

Normal formation of the postsynaptic elements of GABAergic synapses in the reeler cerebellum

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