scholarly journals CEREBELLAR GRANULE CELLS IN VITRO

1970 ◽  
Vol 45 (2) ◽  
pp. 212-220 ◽  
Author(s):  
Fredrick J. Seil ◽  
Robert M. Herndon
Keyword(s):  
Granule Cell ◽  
Granular Layer ◽  
Granule Cells ◽  
Cerebellar Granule Cells ◽  
Light And Electron Microscopy ◽  
Newborn Mouse ◽  
Newborn Mice ◽  
Cerebellar Cultures

The behavior of granule cells in mature cerebellar cultures derived from newborn mice was studied by light and electron microscopy. Many granule cells remained in the explants as an external granular layer. These cells were differentiated, as evidenced by formation of bundles of parallel fibers and by development of synapses between granule cell axons and Purkinje cell branchlet spines, and between Golgi cell axons and granule cell dendrites. Although the over-all architecture of the cerebellar explants after 18–33 days in vitro was similar to that of the newborn mouse, the evident differentiation of the granule cells suggested that interneuronal relationships resemble those of the mature cerebellum in vivo.

scholarly journals Deletion of Jdp2 enhances Slc7a11 expression in Atoh-1 positive cerebellum granule cell progenitors in vivo

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Chia-Chen Ku ◽  
Kenly Wuputra ◽  
Kohsuke Kato ◽  
Jia-Bin Pan ◽  
Chia-Pei Li ◽  
...  
Keyword(s):  
Granule Cell ◽  
Granule Cells ◽  
Apoptotic Cell ◽  
Redox Homeostasis ◽  
Critical Role ◽  
Glutamate Transporter ◽  
Developmental Abnormalities ◽  
Oxidative Stresses

Abstract Background The cerebellum is the sensitive region of the brain to developmental abnormalities related to the effects of oxidative stresses. Abnormal cerebellar lobe formation, found in Jun dimerization protein 2 (Jdp2)-knockout (KO) mice, is related to increased antioxidant formation and a reduction in apoptotic cell death in granule cell progenitors (GCPs). Here, we aim that Jdp2 plays a critical role of cerebellar development which is affected by the ROS regulation and redox control. Objective Jdp2-promoter-Cre transgenic mouse displayed a positive signal in the cerebellum, especially within granule cells. Jdp2-KO mice exhibited impaired development of the cerebellum compared with wild-type (WT) mice. The antioxidation controlled gene, such as cystine-glutamate transporter Slc7a11, might be critical to regulate the redox homeostasis and the development of the cerebellum. Methods We generated the Jdp2-promoter-Cre mice and Jdp2-KO mice to examine the levels of Slc7a11, ROS levels and the expressions of antioxidation related genes were examined in the mouse cerebellum using the immunohistochemistry. Results The cerebellum of Jdp2-KO mice displayed expression of the cystine-glutamate transporter Slc7a11, within the internal granule layer at postnatal day 6; in contrast, the WT cerebellum mainly displayed Sla7a11 expression in the external granule layer. Moreover, development of the cerebellar lobes in Jdp2-KO mice was altered compared with WT mice. Expression of Slc7a11, Nrf2, and p21Cip1 was higher in the cerebellum of Jdp2-KO mice than in WT mice. Conclusion Jdp2 is a critical regulator of Slc7a11 transporter during the antioxidation response, which might control the growth, apoptosis, and differentiation of GCPs in the cerebellar lobes. These observations are consistent with our previous study in vitro.

In Vivo Intracellular Analysis of Granule Cell Axon Reorganization in Epileptic Rats

1999 ◽  
Vol 81 (2) ◽  
pp. 712-721 ◽  
Author(s):  
Paul S. Buckmaster ◽  
F. Edward Dudek
Keyword(s):  
Granule Cell ◽  
Granule Cells ◽  
Molecular Layer ◽  
Axon Collateral ◽  
Cell Axon ◽  
Recurrent Excitation ◽  
The Difference ◽  
Intracellular Analysis

In vivo intracellular analysis of granule cell axon reorganization in epileptic rats. In vivo intracellular recording and labeling in kainate-induced epileptic rats was used to address questions about granule cell axon reorganization in temporal lobe epilepsy. Individually labeled granule cells were reconstructed three dimensionally and in their entirety. Compared with controls, granule cells in epileptic rats had longer average axon length per cell; the difference was significant in all strata of the dentate gyrus including the hilus. In epileptic rats, at least one-third of the granule cells extended an aberrant axon collateral into the molecular layer. Axon projections into the molecular layer had an average summed length of 1 mm per cell and spanned 600 μm of the septotemporal axis of the hippocampus—a distance within the normal span of granule cell axon collaterals. These findings in vivo confirm results from previous in vitro studies. Surprisingly, 12% of the granule cells in epileptic rats, and none in controls, extended a basal dendrite into the hilus, providing another route for recurrent excitation. Consistent with recurrent excitation, many granule cells (56%) in epileptic rats displayed a long-latency depolarization superimposed on a normal inhibitory postsynaptic potential. These findings demonstrate changes, occurring at the single-cell level after an epileptogenic hippocampal injury, that could result in novel, local, recurrent circuits.

scholarly journals Bone Morphogenetic Protein-6 Promotes Cerebellar Granule Neurons Survival by Activation of the MEK/ERK/CREB Pathway

2009 ◽  
Vol 20 (24) ◽  
pp. 5051-5063 ◽  
Author(s):  
Bruna Barneda-Zahonero ◽  
Alfredo Miñano-Molina ◽  
Nahuai Badiola ◽  
Rut Fadó ◽  
Xavier Xifró ◽  
...  
Keyword(s):  
Bone Morphogenetic Proteins ◽  
Granule Cells ◽  
Cerebellar Granule Cells ◽  
Neuroprotective Effect ◽  
High Potassium ◽  
Cerebellar Granule ◽  
Low Potassium ◽  
Creb Pathway

Bone morphogenetic proteins (BMPs) have been implicated in the generation and postnatal differentiation of cerebellar granule cells (CGCs). Here, we examined the eventual role of BMPs on the survival of these neurons. Lack of depolarization causes CGC death by apoptosis in vivo, a phenomenon that is mimicked in vitro by deprivation of high potassium in cultured CGCs. We have found that BMP-6, but not BMP-7, is able to block low potassium–mediated apoptosis in CGCs. The neuroprotective effect of BMP-6 is not accompanied by an increase of Smad translocation to the nucleus, suggesting that the canonical pathway is not involved. By contrast, activation of the MEK/ERK/CREB pathway by BMP-6 is necessary for its neuroprotective effect, which involves inhibition of caspase activity and an increase in Bcl-2 protein levels. Other pathways involved in the regulation of CGC survival, such as the c-Jun terminal kinase and the phosphatidylinositol 3-kinase (PI3K)-Akt/PKB, were not affected by BMP-6. Moreover, failure of BMP-7 to activate the MEK/ERK/CREB pathway could explain its inability to protect CGCs from low potassium–mediated apoptosis. Thus, this study demonstrates that BMP-6 acting through the noncanonical MEK/ERK/CREB pathway plays a crucial role on CGC survival.

The absence of pleiotrophin modulates gene expression in the hippocampus in vivo and in cerebellar granule cells in vitro

2016 ◽  
Vol 75 ◽  
pp. 113-121 ◽  
Author(s):  
Celia González-Castillo ◽  
Daniel Ortuño-Sahagún ◽  
Carolina Guzmán-Brambila ◽  
Ana Laura Márquez-Aguirre ◽  
Rita Raisman-Vozari ◽  
...  
Keyword(s):  
Gene Expression ◽  
Granule Cells ◽  
Cerebellar Granule Cells ◽  
Cerebellar Granule

SDF-1α induces chemotaxis and enhances Sonic hedgehog-induced proliferation of cerebellar granule cells

Development ◽  
2001 ◽  
Vol 128 (11) ◽  
pp. 1971-1981 ◽  
Author(s):  
Robyn S. Klein ◽  
Joshua B. Rubin ◽  
Hilary D. Gibson ◽  
Elliot N. DeHaan ◽  
Xavier Alvarez-Hernandez ◽  
...  
Keyword(s):  
Sonic Hedgehog ◽  
Granule Cell ◽  
Granule Cells ◽  
Cerebellar Granule Cells ◽  
Cell Number ◽  
Calcium Flux ◽  
Neuronal Responses ◽  
And Migration ◽  
Activity Dependent

The chemokine SDF-1α (CXC12) and its receptor CXCR4 have been shown to play a role in the development of normal cerebellar cytoarchitecture. We report here that SDF-1α both induces chemotactic responses in granule precursor cells and enhances granule cell proliferative responses to Sonic hedgehog. Chemotactic and proliferative responses to SDF-1α are greater in granule cells obtained from cerebella of animals in the first postnatal week, coinciding with the observed in vivo peak in cerebellar CXCR4 expression. SDF-1α activation of neuronal CXCR4 differs from activation of CXCR4 in leukocytes in that SDF-1α-induced calcium flux is activity dependent, requiring predepolarization with KCl or pretreatment with glutamate. However, as is the case in leukocytes, neuronal responses to SDF-1α are all abolished by pretreatment of granule cells with pertussis toxin, suggesting they occur through Gαi activation. In conclusion, SDF-1α plays a role in two important processes of granule cell maturation – proliferation and migration – assisting in the achievement of appropriate cell number and position in the cerebellar cortex.

scholarly journals Synaptic Inputs to Granule Cells of the Dorsal Cochlear Nucleus

2008 ◽  
Vol 99 (1) ◽  
pp. 208-219 ◽  
Author(s):  
Veeramuthu Balakrishnan ◽  
Laurence O. Trussell
Keyword(s):  
Granule Cell ◽  
Cochlear Nucleus ◽  
Granule Cells ◽  
Cerebellar Granule Cells ◽  
Dorsal Cochlear Nucleus ◽  
Excitatory Postsynaptic Currents ◽  
Synaptic Inputs ◽  
Postsynaptic Currents ◽  
Cell Circuit

The mammalian dorsal cochlear nucleus (DCN) integrates auditory nerve input with nonauditory signals via a cerebellar-like granule cell circuit. Although granule cells carry nonauditory information to the DCN, almost nothing is known about their physiology. Here we describe electrophysiological features of synaptic inputs to granule cells in the DCN by in vitro patch-clamp recordings from P12 to P22 rats. Granule cells ranged from 6 to 8 μm in cell body diameter and had high-input resistance. Excitatory postsynaptic currents consisted of both AMPA receptor-mediated and N-methyl-d-aspartate receptor-mediated currents. Synaptically evoked excitatory postsynaptic currents ranged from −25 to −140 pA with fast decay time constants. Synaptic stimulation evoked both short- and long-latency synaptic responses that summated to spike threshold, indicating the presence of a polysynaptic excitatory pathway in the granule cell circuit. Synaptically evoked inhibitory postsynaptic currents in Cl−-loaded cells ranged from −30 to −1,021 pA and were mediated by glycine and, to a lesser extent, GABAA receptors. Unlike cerebellar granule cells, DCN granule cells lacked tonic inhibition by GABA. The glycinergic synaptic conductance was mediated by heteromeric glycine receptors and was far stronger than the glutamatergic conductance, suggesting that glycinergic neurons may act to gate nonauditory signals in the DCN.

scholarly journals Reduced Granule Cell Proliferation and Molecular Dysregulation in the Cerebellum of Lysosomal Acid Phosphatase 2 (ACP2) Mutant Mice

2021 ◽  
Vol 22 (6) ◽  
pp. 2994
Author(s):  
Xiaodan Jiao ◽  
Maryam Rahimi Balaei ◽  
Ejlal Abu-El-Rub ◽  
Filippo Casoni ◽  
Hassan Pezeshgi Modarres ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Acid Phosphatase ◽  
Granule Cell ◽  
Granule Cells ◽  
Mutant Mice ◽  
Lysosomal Acid ◽  
Protein Synthesis Machinery

Lysosomal acid phosphatase 2 (Acp2) mutant mice (naked-ataxia, nax) have a severe cerebellar cortex defect with a striking reduction in the number of granule cells. Using a combination of in vivo and in vitro immunohistochemistry, Western blotting, BrdU assays, and RT-qPCR, we show downregulation of MYCN and dysregulation of the SHH signaling pathway in the nax cerebellum. MYCN protein expression is significantly reduced at P10, but not at the peak of proliferation at around P6 when the number of granule cells is strikingly reduced in the nax cerebellum. Despite the significant role of the SHH–MycN pathway in granule cell proliferation, our study suggests that a broader molecular pathway and additional mechanisms regulating granule cell development during the clonal expansion period are impaired in the nax cerebellum. In particular, our results indicate that downregulation of the protein synthesis machinery may contribute to the reduced number of granule cells in the nax cerebellum.

Ectocellular in vitro and in vivo metabolism of cADP-ribose in cerebellum

1996 ◽  
Vol 320 (2) ◽  
pp. 665-671 ◽  
Author(s):  
Antonio DE FLORA ◽  
Lucrezia GUIDA ◽  
Luisa FRANCO ◽  
Elena ZOCCHI ◽  
Mario PESTARINO ◽  
...  
Keyword(s):  
Intracellular Calcium ◽  
Calcium Release ◽  
Granule Cells ◽  
Cerebellar Granule Cells ◽  
Adult Rat ◽  
Transmembrane Glycoprotein ◽  
Adp Ribosyl Cyclase ◽  
Calcium Induced Calcium Release

CD38, a type II transmembrane glycoprotein predominantly expressed in blood cells, is a bifunctional ectoenzyme directly involved in the metabolism of cADP-ribose (cADPR). This is a potent Ca2+ mobilizer in several types of cells. The relationship between the ectocellular site of cADPR production and its intracellular calcium-related functions is poorly understood. Cultured rat cerebellar granule cells showed both enzymic activities of CD38, ADP-ribosyl cyclase and cADPR hydrolase, at a ratio of 16 to 1 respectively, and were immunostained by the anti-(human CD38) monoclonal antibody IB4. In these cells externally added cADPR and β-NAD+ (the precursor of cADPR), but not α-NAD+ or ADP-ribose, enhanced the peak of the depolarization-induced rise in intracellular Ca2+ concentration. This effect was inhibited by 1 µM ryanodine, suggesting a potentiation of calcium-induced calcium release by cADPR. CD38 ectoenzyme activities, ADP-ribosyl cyclase and cADPR hydrolase, were also demonstrated in vivo by microdialysis of adult rat cerebellum, where IB4 bound to granule neurons selectively. Trace amounts (11.5±3.8 nM) of NAD+ were detected by microdialysis sampling and sensitive assays in the basal interstitial fluid of the cerebellum. These results provide a link between ectocellular cADPR turnover and intracellular calcium mobilization in cerebellum.

scholarly journals Control of cerebellar granule cell output by sensory-evoked Golgi cell inhibition

2015 ◽  
Vol 112 (42) ◽  
pp. 13099-13104 ◽  
Author(s):  
Ian Duguid ◽  
Tiago Branco ◽  
Paul Chadderton ◽  
Charlotte Arlt ◽  
Kate Powell ◽  
...  
Keyword(s):  
Granule Cell ◽  
Granule Cells ◽  
Mossy Fiber ◽  
Feed Forward ◽  
Sensory Responses ◽  
Sensory Evoked ◽  
Cell Inhibition ◽  
Feed Forward Inhibition

Classical feed-forward inhibition involves an excitation–inhibition sequence that enhances the temporal precision of neuronal responses by narrowing the window for synaptic integration. In the input layer of the cerebellum, feed-forward inhibition is thought to preserve the temporal fidelity of granule cell spikes during mossy fiber stimulation. Although this classical feed-forward inhibitory circuit has been demonstrated in vitro, the extent to which inhibition shapes granule cell sensory responses in vivo remains unresolved. Here we combined whole-cell patch-clamp recordings in vivo and dynamic clamp recordings in vitro to directly assess the impact of Golgi cell inhibition on sensory information transmission in the granule cell layer of the cerebellum. We show that the majority of granule cells in Crus II of the cerebrocerebellum receive sensory-evoked phasic and spillover inhibition prior to mossy fiber excitation. This preceding inhibition reduces granule cell excitability and sensory-evoked spike precision, but enhances sensory response reproducibility across the granule cell population. Our findings suggest that neighboring granule cells and Golgi cells can receive segregated and functionally distinct mossy fiber inputs, enabling Golgi cells to regulate the size and reproducibility of sensory responses.

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