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Query: UMLS:C0153640 (Cerebellum)
 1,777 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Postsynaptic densities (PSDs) have been isolated from cerebral cortex, midbrain, cerebellum, and brain stem by the Triton X-100 method previously used in the isolation of cerebral PSDs (Cohen et al., 1977, J. Cell Biol. 74:181). These PSDs have been compared in protein composition, protein phosphorylation, and morphology. Thin-section electron microscopy revealed that cerebral cortex and midbrain PSDs were identical, being approximately 57 nm thick and composed of apparent aggregates 20-30 nm in diameter. Isolated cerebellar PSDs appeared thinner (33 nm) than cerebral cortex PSDs and lacked the apparent 20- to 30-nm aggregates, but had a latticelike structure. In unidirectional and rotary-shadowed replicas, the cerebrum and midbrain PSDs were circular in shape with a large central perforation or hole in the center of them. Cerebellum PSDs did not have a large perforation, but did have numerous smaller perforations in a lattice like structure. Filaments (6-9 nm) were observed connecting possible 20- to 30-nm aggregates in cerebrum PSDs and were also observed radiating from one side of the PSD. Both cerebral cortex and midbrain PSDs exhibited identical protein patterns on SDS gel electrophoresis. In comparison, cerebellar PSDs (a) lacked the major 51,000 Mr protein, (b) contained two times less calmodulin, and (c) contained a unique protein at 73,000 Mr. Calcium plus calmodulin stimulated the phosphorylation of the 51,000 and 62,000 Mr bands in both cerebral cortex and midbrain PSDs. In cerebellar PSDs, only the 58,000 and 62,000 Mr bands were phosphorylated. In the PSDs from all brain regions, cAMP stimulated the phosphorylation of Protein Ia (73,000 Mr), Protein Ib (68.000 Mr), and a 60,000 Mr protein, although cerebrum and midbrain PSDs contained very much higher levels of phosphorylated protein than did the cerebellum. On the basis of the morphological criteria, it is possible that PSDs isolated from cerebrum and midbrain were derived from the Gray type I, or asymmetric, synapses, whereas cerebellum PSDs were derived from the Gray type II, or symmetric, synapses. Since there is some evidence that the type I synapses are involved in excitatory mechanisms while the type II are involved in inhibitory mechanisms, the role of the PSD and of some of its proteins in these synaptic responses is discussed.
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PMID:Isolation and characterization of postsynaptic densities from various brain regions: enrichment of different types of postsynaptic densities. 741 Apr 81

Cyclic AMP and cyclic GMP serve as second messengers in a variety of neural cells, modulating their metabolic and electrical activity. The cyclic GMP-stimulated cyclic nucleotide phosphodiesterase, an enzyme whose hydrolytic activity is allosterically regulated by cyclic GMP in peripheral tissues, could play an important role in the regulation of cyclic nucleotide levels in the brain. To study the presence and distribution of cyclic GMP-stimulated phosphodiesterase in the rat brain, we cloned a portion of rat liver cyclic GMP-stimulated phosphodiesterase complementary DNA by polymerase chain reaction, using degenerate phosphodiesterase-specific oligonucleotide primers. Northern blot analysis of rat tissues reveals abundant expression of cyclic GMP-stimulated phosphodiesterase messenger RNA in the brain. Northern blot analysis of brain subregions shows especially strong expression in hippocampus and cortex, modest expression in the remainder of the forebrain and in the midbrain, and little expression in cerebellum and hindbrain. In situ hybridization studies with cyclic GMP-stimulated phosphodiesterase riboprobes confirm these northern blot results, and delineate cell groups with high levels of expression. Medial habenular nucleus is intensely labeled, as is hippocampus in the vicinity of pyramidal and granule cell bodies in areas CA1, CA2, CA3, and dentate gyrus. Other elements of the limbic system also contain cyclic GMP-stimulated phosphodiesterase messenger RNA, including olfactory and entorhinal cortices, subiculum, and amygdala. Additional cortical regions show more diffuse expression of cyclic GMP-stimulated phosphodiesterase messenger RNA, as do the basal ganglia. Cerebellum, thalamus, and hypothalamus do not show appreciable specific labeling. These studies demonstrate the presence of cyclic GMP-stimulated phosphodiesterase messenger RNA in specific regions of the rat brain, and suggest that the cyclic GMP-stimulated phosphodiesterase might modulate neuronal activity by regulating intracellular cyclic AMP levels in response to changes in intracellular cyclic GMP levels.
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PMID:A cyclic GMP-stimulated cyclic nucleotide phosphodiesterase gene is highly expressed in the limbic system of the rat brain. 830 78

Metabotropic glutamate receptors (mGluRs) are a family of proteins that have seven transmembrane segments and that couple to G proteins. They differ from ionotropic glutamate receptors in that they do not form ion channels but instead affect intracellular chemical messenger systems. Eight genes coding for different subtypes of mGluRs have been identified to date and numbered accordingly in the order in which the cDNAs were cloned. Based on their principal signal-transduction capabilities in recombinant expression systems and sequence similarities, the family of mGluR subtypes is subdivided into three groups. Group 1 mGluRs (consisting of mGluR1 and 5) functionally couple to phospholipase C and affect the IP3/Ca2+ signaling pathway. The subtypes of group 2 (mGluR2 and 3) and group 3 (mGluR4, 6 7 and 8) inhibit adenylate cyclase and, thereby, mediate a decrease in cAMP concentration. All mGluR subtypes are found in the cerebellar cortex with the exception of mGluR6 which is exclusively expressed in the retina. At the parallel fiber-Purkinje cell synapses mGluR1 is localized in the peri- and extra-synaptic membrane of Purkinje cells. The main focus of this review deals with the functions of this postsynaptically localized mGluR1. These functions include (i) mediation of an inward current and a slow excitatory postsynaptic potential, and (ii) a role in induction of parallel fiber-Purkinje cell long-term depression. We discuss the mechanism underlying the mGluR1-mediated postsynaptic current as well as current theories on the role of mGluR1 in parallel fiber-Purkinje cell long-term depression.
Cerebellum
PMID:Metabotropic glutamate receptors in the cerebellum with a focus on their function in Purkinje cells. 1287 70

NMDA receptors in cerebellum have specific characteristics that make their function and modulation different from those of NMDA receptors in other brain areas. The properties of the NMDA receptor that modulate its function: Subunit composition, post-translational modifications and synaptic localization are summarized in an accompanying article. In this review we summarize how different signaling molecules modulate the function of NMDA receptors. The function of the receptors is modulated by the co-agonists glycine and serine and this modulation is different in cerebellum than in other areas. The NMDA receptor also has binding sites for polyamines that regulate its function. Other signaling molecules that modulate NMDA receptors function are: cAMP, neurotrophic factors such as BDNF, FGF-2 or neuregulins. These and other molecules allow an interplay between NMDA receptors and other receptors for neurotransmitters that may in this way modulate NMDA receptor function. This has been reported, for example, for metabotropic glutamate receptors. The expression and function of NMDA receptor is also modulated by synaptic activity, allowing an adaptation of the receptors function to the external inputs. NMDA receptors modulate important cerebral processes. NMDA receptors in different brain areas seem to modulate different processes. Cerebellar NMDA receptors play a special role in the modulation of motor learning and coordination. This is also briefly reviewed.
Cerebellum 2005
PMID:Modulation of NMDA receptors in the cerebellum. II. Signaling pathways and physiological modulators regulating NMDA receptor function. 1614 48