Ultrastructural analysis of climbing fiber–Purkinje cell synaptogenesis in the rat cerebellum

Morara, Stefano; Want, J.J.L. van der; Weerd, Henk de; Provini, L.; Rosina, A.

doi:10.1016/s0306-4522(01)00433-x

Cited by 76 publications

(76 citation statements)

References 58 publications

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“…After reaching the cerebellum at late embryonic stages (Chedotal and Sotelo, 1992;Morara et al, 2001), CFs exhibit distinct modes of PC innervation (Ramon y Cajal, 1911;Chedotal and Sotelo, 1993). In the creeper stage, CFs creep between immature PCs and form a few synapses on apical dendrites.…”

Section: Temporal Profile Of the Perisomatic Cf Synapsementioning

confidence: 99%

“…PCs are unique in that perisomatic innervation by basket cell fibers (BFs) in adulthood is preceded by transient innervation by glutamatergic climbing fibers (CFs) (Larramendi, 1969;Altman, 1972). From around at birth, CFs form synapses on to perisomatic protrusions or thorns of PCs and constitute a dense plexus called the pericellular nest or nid (Ramon y Cajal, 1911;Larramendi, 1969;Altman, 1972;Sotelo, 1992, 1993;Morara et al, 2001). The nest represents innervation by multiple CFs to individual PCs (Hashimoto et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

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Developmental Switching of Perisomatic Innervation from Climbing Fibers to Basket Cell Fibers in Cerebellar Purkinje Cells

Ichikawa

Yamasaki²,

Miyazaki³

et al. 2011

J. Neurosci.

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In early postnatal development, perisomatic innervation of cerebellar Purkinje cells (PCs) switches from glutamatergic climbing fibers (CFs) to GABAergic basket cell fibers (BFs). Here we examined the switching process in C57BL/6 mice. At postnatal day 7 (P7), most perisomatic synapses were formed by CFs on to somatic spines. The density of CF-spine synapses peaked at P9, when pericellular nest around PCs by CFs was most developed, and CF-spine synapses constituted 88% of the total perisomatic synapses. Thereafter, CF-spine synapses dropped to 63% at P12, 6% at P15, and Ͻ1% at P20, whereas BF synapses increased reciprocally. During the switching period, a substantial number of BF synapses existed as BF-spine synapses (37% of the total perisomatic synapses at P15), and free spines surrounded by BFs or Bergmann glia also emerged. By P20, BF-spine synapses and free spines virtually disappeared, and BF-soma synapses became predominant (88%), thus attaining the adult pattern of perisomatic innervation. Parallel with the presynaptic switching, postsynaptic receptor phenotype also switched from glutamatergic to GABAergic. In the active switching period, particularly at P12, fragmental clusters of AMPA-type glutamate receptor were juxtaposed with those of GABA A receptor. When examined with serial ultrathin sections, immunogold labeling for glutamate and GABA A receptors was often clustered beneath single BF terminals. These results suggest that a considerable fraction of somatic spines is succeeded from CFs to BFs and Bergmann glia in the early postnatal period, and that the switching of postsynaptic receptor phenotypes mainly proceeds under the coverage of BF terminals.

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Section: Temporal Profile Of the Perisomatic Cf Synapsementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Developmental Switching of Perisomatic Innervation from Climbing Fibers to Basket Cell Fibers in Cerebellar Purkinje Cells

Ichikawa

Yamasaki²,

Miyazaki³

et al. 2011

J. Neurosci.

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“…105 Finally, CGRP may modulate neuronal function through interaction with glial CGRP receptors. 106 CGRP is thought to be secreted by neurons and then to activate the surrounding glia cells to express molecules such as nitric oxides, which in turn can activate many pronociceptive mediators This modulating effect of CGRP on glial function is not only limited to trigeminal ganglia, but has also been demonstrated in other brain areas, such as the cerebellum [107][108][109][110] and neuromuscular junctions. 25 The cerebellum is known to be important in modulating many cortical motor and sensory inputs.…”

Section: How Do Cgrp Antagonists Act In Migraine?mentioning

confidence: 99%

CGRP Receptor Antagonism and Migraine

Edvinsson

2010

Neurotherapeutics

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Summary: Calcitonin gene-related peptide (CGRP) is expressed throughout the central and peripheral nervous systems, consistent with control of vasodilatation, nociception, motor function, secretion, and olfaction. ␣CGRP is prominently localized in primary spinal afferent C and A⌬ fibers of sensory ganglia, and ␤CGRP is the main isoform in the enteric nervous system. In the CNS there is a wide distribution of CGRP-containing neurons, with the highest levels occurring in striatum, amygdala, colliculi, and cerebellum. The peripheral projections are involved in neurogenic vasodilatation and inflammation, and central release induces hyperalgesia. CGRP is released from trigeminal nerves in migraine. Trigeminal nerve activation results in antidromic release of CGRP to cause non-endothelium-mediated vasodilatation. At the central synapses in the trigeminal nucleus caudalis, CGRP acts postjunctionally on second-order neurons to transmit pain signals centrally via the brainstem and midbrain to the thalamus and higher cortical pain regions. Recently developed CGRP receptor antagonists are effective at aborting acute migraine attacks. They may act both centrally and peripherally to attenuate signaling within the trigeminovascular pathway.

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“…Immunolabeling was performed on 0.2-mm-thick gelatin sections by using anti-Stwl antibody incubated overnight (1:40 diluted), followed by biotinylated Rab-anti Rat antibodies (Vector Laboratories, Burlingame, CA) (1:200 diluted) for 2 h. Immunoreactivity was visualized with the ATP-binding cassette method by using a Vectastain kit (Vector Laboratories). The standard gold-substituted silver-intensified peroxidase (GSSP) technique was used in which the diaminobenzidine reaction product is first intensified with silver and then substituted for gold as described previously (van den Pol and Gorcs, 1986;Morara et al, 2001). The GSSP reaction product, at sites where Stwl antibody is localized, is visible as dense black precipitates with sharply defined contours.…”

Section: Electron Microscopic Analysismentioning

confidence: 99%

Stwl Modifies Chromatin Compaction and Is Required to Maintain DNA Integrity in the Presence of Perturbed DNA Replication

Vries

Siudeja

et al. 2009

MBoC

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Hydroxyurea, a well-known DNA replication inhibitor, induces cell cycle arrest and intact checkpoint functions are required to survive DNA replication stress induced by this genotoxic agent. Perturbed DNA synthesis also results in elevated levels of DNA damage. It is unclear how organisms prevent accumulation of this type of DNA damage that coincides with hampered DNA synthesis. Here, we report the identification of stonewall (stwl) as a novel hydroxyureahypersensitive mutant. We demonstrate that Stwl is required to prevent accumulation of DNA damage induced by hydroxyurea; yet, Stwl is not involved in S/M checkpoint regulation. We show that Stwl is a heterochromatin-associated protein with transcription-repressing capacities. In stwl mutants, levels of trimethylated H3K27 and H3K9 (two hallmarks of silent chromatin) are decreased. Our data provide evidence for a Stwl-dependent epigenetic mechanism that is involved in the maintenance of the normal balance between euchromatin and heterochromatin and that is required to prevent accumulation of DNA damage in the presence of DNA replication stress. INTRODUCTIONCell cycle checkpoint pathways and DNA damage response pathways are essential mechanisms that control the order and timing of all cell cycle transitions and that ensure that critical events such as DNA replication and chromosome segregation are performed with high fidelity (Hartwell and Weinert, 1989;Elledge, 1996;Hurley and Bunz, 2007). In case these mechanisms fail, genetic abnormalities could be passed on to the following generations of cells, and this could lead to genomic instability and diseases such as cancer (Dasika et al., 1999;Houtgraaf et al., 2006). Cell cycle checkpoint and DNA repair genes have initially been identified using forward genetic screens in budding yeast (Saccharomyces cerevisiae) and fission yeast (Schizosaccharomyces pombe) (reviewed in O'Connell et al., 2000;Carr, 2002). Subsequently, forward genetic screens were also performed in Drosophila melanogaster and resulted in the identification of Ͼ30 mutagen-hypersensitive (mus) genes (Boyd et al., 1976(Boyd et al., , 1981Henderson et al., 1987). Several of these mus genes have been cloned, and their function has been assigned to checkpoint regulation or DNA damage repair (Harris et al., 1996;Oshige et al., 1999;Brodsky et al., 2000;Yamamoto et al., 2000). More recently, using additional screens or by comparing Drosophila homologues with other species (Sibon et al., 1997(Sibon et al., , 1999Price et al., 2000;LaRocque et al., 2007;McVey et al., 2007;Wei and Rong, 2007;Klovstad et al., 2008), several other genes were identified that are implicated in proper cell cycle checkpoint function or DNA damage repair. Although discrepancies in survival pathways among different organisms do exist, it can be concluded that many genes involved in responses to DNA damage, and their pathways, are highly conserved (Henderson, 1999;Rhind and Russell, 2000;Sekelsky et al., 2000).Hydroxyurea (HU) is a compound that inhibits ribonucleoside dephosphate redu...

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Ultrastructural analysis of climbing fiber–Purkinje cell synaptogenesis in the rat cerebellum

Cited by 76 publications

References 58 publications

Developmental Switching of Perisomatic Innervation from Climbing Fibers to Basket Cell Fibers in Cerebellar Purkinje Cells

Developmental Switching of Perisomatic Innervation from Climbing Fibers to Basket Cell Fibers in Cerebellar Purkinje Cells

CGRP Receptor Antagonism and Migraine

Stwl Modifies Chromatin Compaction and Is Required to Maintain DNA Integrity in the Presence of Perturbed DNA Replication

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