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

Regional brain GABA distribution studies show that after administration of sodium n dipropylacetate, a competitive inhibitor of GABA transaminase, the concentration of GABA increases in some regions i.e. Olfactory Bulbs, Hypothalamus, Cortex, Cerebellum. The GABA level remains unchanged in Caudate Nucleus, Pons Medulla, Hippocampus in our experimental conditions. These variations do not correlate with the initial GABA level.
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PMID:[Effects of sodium n-dipropylacetate on the GABA level in various areas of the mouse brain]. 14 Jul 50

Inferior olivary neurons receive extensive glutamatergic and GABAergic innervation. Yet, because of the membrane properties of olivary neurons these neurotransmitters can produce only small changes in the firing rates of these cells. Moreover, olivary neurons can generate spontaneous spike activity in the absence of excitatory glutamatergic input. These facts suggest that glutamate and GABA have additional roles within the olivocerebellar system beyond simply modulating single cell firing probability. Indeed, one of the characteristics of the olivocerebellar system is its ability to generate synchronous complex spike activity across populations of Purkinje cells. The pattern of synchronous activity changes rapidly, and is thought to reflect the momentary distribution of effective electrotonic coupling between olivary neurons as shaped by afferent input to the inferior olive. However, it also possible that synchronous olivocerebellar activity is the result of synchrony inherent in the afferent activity itself. The issue of the origin of complex spike synchrony, and the role of glutamatergic olivary afferents in modulating its distribution were recently studied using multiple electrode recordings from Purkinje cells. The results of these studies, reviewed here, demonstrate that synchronous complex spike activity occurs in the absence of glutamatergic (and GABAergic) input to the inferior olive, and therefore indicate that synchronization of complex spike activity primarily results from the electrotonic coupling of olivary neurons, rather than from synchronization present within their afferents. Instead of triggering synchronous discharges directly, the results suggest that the function of tonic excitatory activity is to modulate the effective coupling of spike activity between olivary neurons. Blocking glutamate within the inferior olive causes an enhancement of the normal banding pattern of complex spike synchrony, with higher synchrony among parasagittally aligned Purkinje cells and less synchrony between non-aligned cells. This is in contrast to the more uniform synchrony distribution that follows block of GABAergic olivary afferents. Thus, GABA and glutamate play critical, and complementary, roles in determining the patterns of synchronous complex spike activity that are likely central to the functioning of the olivocerebellar system.
Cerebellum 2003
PMID:Excitatory afferent modulation of complex spike synchrony. 1450 65

The effect of kainate, an agonist selective for ionotropic AMPA/kainate type of glutamate receptors, on GABAA receptor subunit expression in cultured mouse cerebellar granule cells was studied using quantitative RT-PCR, ligand binding and electrophysiology. Chronic kainate treatment, without producing excitotoxicity, resulted in preferential, dose- and time-dependent down-regulation of alpha1, alpha6 and beta2 subunit mRNA expression, the expression of beta3, gamma2 and delta subunit mRNAs being less affected. The down-regulation was reversed by DNQX, an AMPA/kainate-selective glutamate receptor antagonist. A 14-day kainate treatment resulted in 46% decrease of total [3H]Ro 15-4513 binding to the benzodiazepine sites. Diazepam-insensitive [3H]Ro 15-4513 binding was decreased by 89% in accordance with very low amount of alpha6 subunit mRNA present. Diazepam-sensitive [3H]Ro 154513 binding was decreased only by 40%, contrasting >90% decrease in alpha1 subunit mRNA expression. However, this was consistent with lower potentiation of GABA-evoked currents in kainate-treated than control cells by the alpha1-selective benzodiazepine site ligand zolpidem, suggesting compensatory expression of alpha5 (and/or alpha2 or alpha3) subunits producing diazepam-sensitive but zolpidem-insensitive receptor subtypes. In conclusion, chronic kainate treatment of cerebellar granule cells selectively down-regulates oil, alpha6 and beta2 subunits resulting in altered GABAA receptor pharmacology.
Cerebellum 2004
PMID:Kainate down-regulates a subset of GABAA receptor subunits expressed in cultured mouse cerebellar granule cells. 1507 65

Activity driven Ca2+ signaling is an important regulator of neuronal development. Early developing Purkinje neurons (postnatal day 5-7) prior to the stage of dendritic development express a somatic Ca2+ signaling pathway that is electrically driven and communicates information from the cell membrane to the cytosol and nucleus. In the current studies, we examined the properties and potential functional role of this pathway using acutely isolated Purkinje neurons from postnatal day 5-7 rat pups and brief K+ stimulation to activate the pathway. Results show that the amplitude of the nuclear Ca2+ signal increases as a function of the cytosolic Ca2+ signal but is larger than the cytosolic Ca2+ signal at strong K+ stimulations. Both L-type and P-type Ca2+ channels contribute to the Ca2+ signal. We also show using semiquantitative immunohistochemical methods that activation of this Ca2+ signaling pathway results in activation the transcription factor CREB and that L-type Ca2+ channels play a prominent role in this effect. The level of cfos, a transcription factor whose expression is regulated by CREB, was also increased by K+ stimulation. K+ stimulation also altered the level of the Ca2+ binding protein calbindin, an effect that involved L-type Ca2+ channels. The relationship between increases in Ca2+ and calbindin expression was bell-shaped, with high levels of Ca2+ decreasing calbindin expression. The level of the transmitter GABA was also increased by K+ stimulation but this effect was not dependent on L-type Ca2+ channels. Taken together, these results support a role for L-type channels in the phenotypic expression of Purkinje neuron properties during early development and suggest that the different activity patterns of early developing Purkinje neurons could be one mechanism for signaling the induction of specific genes through differences in cytosolic or nuclear Ca2+.
Cerebellum 2005
PMID:Contribution of L-type channels to Ca2+ regulation of neuronal properties in early developing purkinje neurons. 1603 95

There is considerable evidence that the transition metal zinc plays an important role in mammalian neural development, physiology and pathology. The most compelling evidence for a synaptic role for zinc comes from hippocampal studies: zinc is concentrated in the synaptic vesicles of some glutamatergic neurons, zinc can be released during neural activity and zinc can modulate postsynaptic GABA and glutamate receptors. The possibility that zinc is involved in cerebellar synaptic transmission is supported by the expression of specific zinc transporters (ZnT, including the synaptic vesicle transporter ZnT-3) in the cerebellar cortex. Furthermore, some subtypes of neurotransmitter receptors, expressed by cerebellar neurones, are highly sensitive to low concentrations of exogenous zinc. However there appears to be little chelatable (synaptic) zinc in the cerebellum, deletion of the ZnT-3 gene has no effect on motor phenotype and there is currently no evidence that zinc is released from cerebellar neurones to have physiological actions. Thus it is possible that the different types of zinc transporter found in the cerebellum play a neuroprotective rather than a signalling role.
Cerebellum 2005
PMID:A role for zinc in cerebellar synaptic transmission? 1632 77

Gamma-aminobutyric acid (GABA) and nitric oxide are two key-transmitters in cerebellar nuclei, the major output of cerebellar circuitry. The aims of this study were to investigate the effects of acute intra-cerebellar administration of ethanol (20 mM) on extra-cellular levels of GABA and on the NMDA-induced nitric oxide (NO) production using microdialysis in the rat. We also studied: (i) the effects of a pre-administration of DNQX, a specific antagonist of AMPA receptors, on NO production, (ii) the effects of a pre-administration of 7-NI (7-nitroindazole, an inhibitor of neuronal nitric oxide synthase NOS) and APV (D-2-amino-5-phosphonovaleric acid, a specific blocker of the NMDA type glutamate receptors) on the actions of alcohol/NMDA on glutamate receptors, and (iii) the in vivo interaction between DNQX, ethanol and NMDA receptor activation. We found that ethanol decreased the amount of extra-cellular GABA, and that this effect was counterbalanced by administration of tiagabine 1 mg/kg, a potent inhibitor of GAT-1 GABA transporter, given by the i.p. route. In loco administration of NMDA increased the levels of NO, as previously reported. A pre-administration of DNQX (500 microM) increased significantly the production of NO up to toxic levels, as well as ethanol administration. A pre-administration of 7-NI or APV reduced significantly the amounts of NO when NMDA and alcohol were infused simultaneously. The combination of ethanol with DNQX was associated with a marked enhancement of the concentrations of NO. The activity of GAT-1 in cerebellar nuclei and around this target, including in glial cells expressing GAT-1 activated by ambient GABA, seems to be spared by ethanol. Tiagabine could be considered as a candidate for future investigational treatments of acute ethanol-induced dysfunction of cerebellar nuclei. We found a potentiation of the production of NO when AMPA antagonists are given simultaneously to ethanol. The hypothesis of AMPA neurotoxicity, which has convincing arguments during chronic exposure, is challenged in this model of acute cerebellar nuclear toxicity of alcohol.
Cerebellum 2005
PMID:Depression of extra-cellular GABA and increase of NMDA-induced nitric oxide following acute intra-nuclear administration of alcohol in the cerebellar nuclei of the rat. 1632 78

In tetrapods, cerebellar efferent systems are mainly mediated via the cerebellar nuclei. In teleosts, the cerebellum lacks cerebellar nuclei. Instead, the cerebellar efferent neurons, termed eurydendroid cells, are arrayed within and below the ganglionic layer. Tracer injections outside of the cerebellum, which retrogradely label eurydendroid cells demonstrate that most eurydendroid cells possess two or more primary dendrites which extend broadly into the molecular layer. Some eurydendroid cells mostly situated in caudal portions of the cerebellum have only one primary dendrite. The eurydendroid cells receive inputs from the Purkinje cells and parallel fibers, but apparently do not receive inputs from the climbing fibers. Eurydendroid cells of the corpus cerebelli and medial valvula project to many brain regions, from the diencephalon to the caudal medulla. A few eurydendroid cells in the valvula project directly to the telencephalon. About half of the eurydendroid cells are aspartate immunopositive. Anti-GABA and anti-zebrin II antibodies that are known as markers for the Purkinje cells in mammals also recognize the Purkinje cells in the teleost cerebellum, but do not recognize the eurydendroid cells. These results suggest that the eurydendroid cells receive GABAergic inputs from the Purkinje cells. This relationship between the eurydendroid and Purkinje cells is similar to that between the cerebellar nuclei and Purkinje cells in mammals. The eurydendroid cells of teleost have both dissimilar as well as similar features compared to neurons of the cerebellar nuclei in tetrapods.
Cerebellum 2006
PMID:Cerebellar efferent neurons in teleost fish. 1713 89

GABAA receptors form heteromeric GABA-gated chloride channels assembled from a large family of subunit genes. In cerebellum, distinct GABAA receptor subtypes, differing in subunit composition, are segregated between cell types and synaptic circuits. The cerebellum therefore represents a useful system to investigate the significance of GABAA receptor heterogeneity. For instance, studies of mice carrying targeted deletion of major GABAA receptor subunit genes revealed the role of alpha subunit variants for receptor assembly, synaptic targeting, and functional properties. In addition, these studies unraveled mandatory association between certain subunits and demonstrated distinct pharmacology of receptors mediating phasic and tonic inhibition. Although some of these mutants have a profound loss of GABAA receptors, they exhibit only minor impairment of motor function, suggesting activation of compensatory mechanisms to preserve inhibitory networks in the cerebellum. These adaptations include an altered balance between phasic and tonic inhibition, activation of voltage-independent K+ conductances, and upregulation of GABAA receptors in interneurons that are not affected directly by the mutation. Deletion of the alpha1 subunit gene leads to complete loss of GABAA receptors in Purkinje cells. A striking alteration occurs in these mice, whereby presynaptic GABAergic terminals are preserved in the molecular layer but make heterologous synapses with spines, characterized by a glutamatergic-like postsynaptic density. During development of alpha1(0/0) mice, GABAergic synapses are initially formed but are replaced upon spine maturation. These findings suggest that functional GABAA receptors are required for long-term maintenance of GABAergic synapses in Purkinje cells.
Cerebellum 2006
PMID:Molecular and synaptic organization of GABAA receptors in the cerebellum: Effects of targeted subunit gene deletions. 1713 90

Our understanding of GABAergic and glutamatergic neurotransmission in the CNS has been greatly influenced with the discovery and subsequent investigations of the metabotropic gamma-aminobutyric acid (B) (GABA(B)) receptors. These G-protein coupled receptors mediate slow inhibitory neurotransmission and are widely expressed and distributed in the cerebellum, where they play critical roles in neuronal excitability and modulation of synaptic neurotransmission. Their function is modulated by interaction with effector ion channels, notably inwardly rectifying K(+) channels and voltage-gated Ca(2+) channels. The receptors are encoded by two distinct subunits, GABA(B1) and GABA(B2), both of which are required in order to function normally in vivo, as shown in recombinant expression systems and in GABA(B1) -/- mice. The GABA(B1) and GABA(B2) subunits exhibit overlapping distributions in the cerebellar cortex, both at pre- and postsynaptic sites, during development and adulthood. They are in particular abundant in Purkinje cells prior to synaptogenesis and throughout postnatal development. Using high-resolution immunohistochemical techniques at the electron microscopic level in combination with quantitative analysis and three-dimensional reconstructions, it has recently been demonstrated that GABA(B) receptors undergo changes in localization on the surface of Purkinje cell dendrites and spines during postnatal development in association with the establishment and maturation of excitatory synapses. Due to this dynamic regulation, the highest densities of GABA(B1) and GABA(B2) subunits occur around the glutamatergic synapses between Purkinje cell spines and parallel fibre varicosities. This review highlights recent studies that have shed further light on the subcellular localization during postnatal development and the cell surface dynamics of GABA(B) receptors.
Cerebellum 2007
PMID:Subcellular regulation of metabotropic GABA receptors in the developing cerebellum. 1751 Sep 12

Despite the apparent uniformity in cellular composition of the adult mammalian cerebellar cortex, it is actually highly compartmentalized into transverse zones, and within each zone the cortex is further subdivided into a reproducible array of parasagittal stripes. The most extensively studied compartmentation antigen is zebrin II/aldolase c, which is expressed by a subset of Purkinje cells forming parasagittal stripes. Gamma-aminobutyric acid B receptors (GABABRs) are G-protein-coupled receptors that mediate a slow, prolonged form of inhibition in many brain areas. This study examines the localization of GABABR2 in the mouse cerebellum by using whole mount and section immunohistochemistry. The data reveal that GABABR2 immunoreactivity is expressed strongly in the dendrites of a subset of Purkinje cells that form a reproducible array of transverse zones and parasagittal stripes. By using double immunostaining, the striped pattern of GABABR2 expression was shown to be identical to that revealed by anti-zebrin II and complementary to that of phospholipase Cbeta4. This finding supports previous functional studies showing that inhibitory neurotransmission is highly patterned in the cerebellar cortex.
Cerebellum 2008
PMID:Compartmentation of GABA B receptor2 expression in the mouse cerebellar cortex. 1841 71


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