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Mossy Fibre (mossy + fibre)
Selected AbstractsDistribution of mossy fibre rosettes in the cerebellum of cat and mice: evidence for a parasagittal organization at the single fibre levelEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2001Fahad SultanArticle first published online: 20 DEC 200 Abstract Mossy fibres are the main afferent input to the granular layer of the cerebellar cortex. In this study, the spatial distribution of the mossy fibres' presynaptic enlargements , the so-called rosettes , were analysed on the single fibre level. Data obtained from the cerebella of cat and mice were compared to look for species differences, and the cerebella of the adult and young mice were also compared to look for developmental changes. The results show that there is a spatial anisotropy in all mossy fibres studied, with neighbouring rosettes being about three times further away from each other along the parasagittal axis and closer to each other in the mediolateral direction. Furthermore, these results suggest that this anisotropy is established at an early developmental stage. The anisotropic orientation of mossy fibres at the single fibre level supports the hypothesis of a timing mechanism in cerebellar function. [source] Characterization in vivo of bilaterally branching pontocerebellar mossy fibre to Golgi cell inputs in the rat cerebellumEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 2 2009Tahl Holtzman Abstract Golgi cells regulate the flow of information from mossy fibres to the cerebellar cortex, through a mix of feedback and feedforward inhibitory actions on granule cells. The aim of the current study was to examine mossy fibre input to Golgi cells, in order to assess their impact on switching Golgi cells into feedforward behaviour. In urethane-anaesthetized rats, extracellular recordings were made from Golgi cells in Crus II (n = 18). Spikes were evoked in all Golgi cells by microstimulation within the contralateral hemispheral cortex, via branches of mossy fibres that terminate in both cerebellar hemispheres. The latencies of these responses were very short, consistent with a monosynaptic mossy fibre contact [average onset latency 2.3 ± 0.1 ms (SEM)]. The same stimuli had no measurable effect on spike responses of nearby Purkinje cells (n = 12). Systematic mapping in the contralateral cerebellar hemisphere (Crus Ib, IIa, IIb and the paramedian lobule) usually revealed one low-intensity stimulus ,hotspot' (12,35 ,A) from which short-latency spikes could be evoked in an individual Golgi cell. Microinjections of red and green retrograde tracers (latex beads, ,50,150 nL injection volume) made at the recording site and the stimulation hotspot resulted in double-labelled neurons within the pontine nuclei. Overall, this suggests that subsets of pontine neurons supply mossy fibres that branch to both hemispheres, some of which directly target Golgi cells. Such an arrangement may provide a common feedforward inhibitory link to temporally couple activity on both sides of the cerebellum during behaviour. [source] NMDA receptor subunits GluR,1, GluR,3 and GluR,1 are enriched at the mossy fibre,granule cell synapse in the adult mouse cerebellumEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2001Kazuyuki Yamada Abstract Cerebellar N -methyl- d -aspartate (NMDA) receptors are concentrated in the granular layer and are involved in motor coordination and the induction of long-term potentiation at mossy fibre,granule cell synapses. In the present study, we used immunohistochemistry to examine the distribution of NMDA receptor subunits in the adult mouse cerebellum. We found that appropriate pepsin pretreatment of sections greatly enhanced the sensitivity and specificity of immunohistochemical detection. As a result, intense immunolabelling for GluR,1 (NR2A), GluR,3 (NR2C), and GluR,1 (NR1) all appeared in synaptic glomeruli of the granular layer. Double immunofluorescence showed that these subunits were colocalized in individual synaptic glomeruli. Within the glomerulus, NMDA receptor subunits were located between centrally-located huge mossy fibre terminals and peripherally-located tiny Golgi axon terminals. By immunoelectron microscopy, all three subunits were detected at the postsynaptic junction in granule cell dendrites, forming synapses with mossy fibre terminals. Consistent with the known functional localization, GluR,1, GluR,3, and GluR,1 are, thus, anatomically concentrated at the mossy fibre,granule cell synapse. By contrast, immunohistochemical signals were very low in Purkinje cell somata and dendrites in the molecular layer. The lack of GluR,1 immunolabelling in Purkinje cells was unexpected because the cells express GluR,1 mRNA at high levels and high levels of GluR,1 protein in the molecular layer were revealed by immunoblot. As Purkinje cells are exceptionally lacking GluR, expression, the discrepant result may provide in vivo evidence suggesting the importance of accompanying GluR, subunits in synaptic localization of GluR,1. [source] Encoding of whisker input by cerebellar Purkinje cellsTHE JOURNAL OF PHYSIOLOGY, Issue 19 2010Laurens W. J. Bosman The cerebellar cortex is crucial for sensorimotor integration. Sensorimotor inputs converge on cerebellar Purkinje cells via two afferent pathways: the climbing fibre pathway triggering complex spikes, and the mossy fibre,parallel fibre pathway, modulating the simple spike activities of Purkinje cells. We used, for the first time, the mouse whisker system as a model system to study the encoding of somatosensory input by Purkinje cells. We show that most Purkinje cells in ipsilateral crus 1 and crus 2 of awake mice respond to whisker stimulation with complex spike and/or simple spike responses. Single-whisker stimulation in anaesthetised mice revealed that the receptive fields of complex spike and simple spike responses were strikingly different. Complex spike responses, which proved to be sensitive to the amplitude, speed and direction of whisker movement, were evoked by only one or a few whiskers. Simple spike responses, which were not affected by the direction of movement, could be evoked by many individual whiskers. The receptive fields of Purkinje cells were largely intermingled, and we suggest that this facilitates the rapid integration of sensory inputs from different sources. Furthermore, we describe that individual Purkinje cells, at least under anaesthesia, may be bound in two functional ensembles based on the receptive fields and the synchrony of the complex spike and simple spike responses. The ,complex spike ensembles' were oriented in the sagittal plane, following the anatomical organization of the climbing fibres, while the ,simple spike ensembles' were oriented in the transversal plane, as are the beams of parallel fibres. [source] Impaired development of hippocampal mossy fibre synapses in mouse mutants for the presynaptic scaffold protein BassoonTHE JOURNAL OF PHYSIOLOGY, Issue 12 2010Frederic Lanore Bassoon, a protein highly concentrated at the synaptic active zone, is thought to participate in the organization of the cytomatrix at the site of neurotransmitter release. Bassoon is amongst the first proteins to accumulate at newly formed synaptic junctions, raising the question of the functional role of this protein in the early stages of synaptic development. Here we show that the course of synaptic maturation of hippocampal mossy fibre (MF) synapses (glutamatergic synapses with multiple release sites) is markedly altered during the first 2 weeks of postnatal development in mutant mice lacking the central region of Bassoon (Bsn,/, mice). At postnatal day 7 (P7), Bsn,/, mice display large amplitude MF-EPSCs with decreased paired pulse ratios, an abnormality which may be linked to deficits in the organization of the presynaptic active zone. Surprisingly, 1 week later, decreased MF-EPSCs amplitude is observed in Bsn,/, mice, consistent with the inactivation of a subset of synaptic release sites. Finally, at more mature states a decreased posttetanic potentiation is observed at MF-synapses. These results support the notion that Bassoon is important for organizing the presynaptic active zone during the postnatal maturation of glutamatergic synapses. [source] Coincidence detection of convergent perforant path and mossy fibre inputs by CA3 interneuronsTHE JOURNAL OF PHYSIOLOGY, Issue 11 2008Eduardo Calixto We performed whole-cell recordings from CA3 s. radiatum (R) and s. lacunosum-moleculare (L-M) interneurons in hippocampal slices to examine the temporal aspects of summation of converging perforant path (PP) and mossy fibre (MF) inputs. PP EPSPs were evoked from the s. lacunosum-moleculare in area CA1. MF EPSPs were evoked from the medial extent of the suprapyramidal blade of the dentate gyrus. Summation was strongly supralinear when examining PP EPSP with MF EPSP in a heterosynaptic pair at the 10 ms ISI, and linear to sublinear at longer ISIs. This pattern of nonlinearities suggests that R and L-M interneurons act as coincidence detectors for input from PP and MF. Summation at all ISIs was linear in voltage clamp mode demonstrating that nonlinearities were generated by postsynaptic voltage-dependent conductances. Supralinearity was not detected when the first EPSP in the pair was replaced by a simulated EPSP injected into the soma, suggesting that the conductances underlying the EPSP boosting were located in distal dendrites. Supralinearity was selectively eliminated with either Ni2+ (30 ,m), mibefradil (10 ,m) or nimodipine (15 ,m), but was unaffected by QX-314. This pharmacological profile indicates that supralinearity is due to recruitment of dendritic T-type Ca2+channels by the first subthreshold EPSP in the pair. Results with the hyperpolarization-activated (Ih) channel blocker ZD 7288 (50 ,m) revealed that Ih restricted the time course of supralinearity for coincidently summed EPSPs, and promoted linear to sublinear summation for asynchronous EPSPs. We conclude that coincidence detection results from the counterbalanced activation of T-type Ca2+ channels and inactivation of Ih. [source] Visualization of transmitter release with zinc fluorescence detection at the mouse hippocampal mossy fibre synapseTHE JOURNAL OF PHYSIOLOGY, Issue 3 2005Jing Qian Exocytosis of synaptic vesicle contents defines the quantal nature of neurotransmitter release. Here we developed a technique to directly assess exocytosis by measuring vesicular zinc release with the zinc-sensitive dye FluoZin-3 at the hippocampal mossy fibre (MF) synapse. Using a photodiode, we were able to clearly resolve the zinc fluorescence transient ([Zn2+]t) with a train of five action potentials in mouse hippocampal brain slices. The vesicular origin of [Zn2+]t was verified by the lack of zinc signal in vesicular zinc transporter Znt3-deficient mice. Manipulating release probability with the application of neuromodulators such as DCG IV, 4-aminopyridine and forskolin as well as a paired train stimulation protocol altered both the [Zn2+]t and the field excitatory postsynaptic potential (fEPSP) coordinately, strongly indicating that zinc is co-released with glutamate during exocytosis. Since zinc ions colocalize with glutamate in small clear vesicles and modulate postsynaptic excitability at NMDA and GABA receptors, the findings establish zinc as a cotransmitter during physiological signalling at the mossy fibre synapse. The ability to directly visualize release dynamics with zinc imaging will facilitate the exploration of the molecular pharmacology and plasticity of exocytosis at MF synapses. [source] Characterization in vivo of bilaterally branching pontocerebellar mossy fibre to Golgi cell inputs in the rat cerebellumEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 2 2009Tahl Holtzman Abstract Golgi cells regulate the flow of information from mossy fibres to the cerebellar cortex, through a mix of feedback and feedforward inhibitory actions on granule cells. The aim of the current study was to examine mossy fibre input to Golgi cells, in order to assess their impact on switching Golgi cells into feedforward behaviour. In urethane-anaesthetized rats, extracellular recordings were made from Golgi cells in Crus II (n = 18). Spikes were evoked in all Golgi cells by microstimulation within the contralateral hemispheral cortex, via branches of mossy fibres that terminate in both cerebellar hemispheres. The latencies of these responses were very short, consistent with a monosynaptic mossy fibre contact [average onset latency 2.3 ± 0.1 ms (SEM)]. The same stimuli had no measurable effect on spike responses of nearby Purkinje cells (n = 12). Systematic mapping in the contralateral cerebellar hemisphere (Crus Ib, IIa, IIb and the paramedian lobule) usually revealed one low-intensity stimulus ,hotspot' (12,35 ,A) from which short-latency spikes could be evoked in an individual Golgi cell. Microinjections of red and green retrograde tracers (latex beads, ,50,150 nL injection volume) made at the recording site and the stimulation hotspot resulted in double-labelled neurons within the pontine nuclei. Overall, this suggests that subsets of pontine neurons supply mossy fibres that branch to both hemispheres, some of which directly target Golgi cells. Such an arrangement may provide a common feedforward inhibitory link to temporally couple activity on both sides of the cerebellum during behaviour. [source] Brief exposure to NMDA produces long-term protection of cerebellar granule cells from apoptosisEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2005Xavier Xifro Abstract Cerebellar granule cells (CGCs) require excitatory inputs to survive during their postnatal migration from the external to the internal granule cell layers. The lack of innervation of mossy fibres induces CGC death by apoptosis. In vitro, CGCs die by apoptosis in the presence of physiological concentrations of KCl (5 mm or K5) but they survive in the presence of depolarizing concentrations of KCl (25 mm or K25) or N -methyl- d -aspartate (NMDA) by a mechanism dependent on calcium influx. The addition of NMDA or K25, for only 24 h, to immature CGCs cultures [2 days in vitro (DIV)] was able to produce a remarkable and long-term protection until 8 DIV. Moreover, our data show that NMDA and K25-mediated long-lasting protection was related to an inhibition of caspase-3 activity. By using different protein kinase inhibitors, we have shown that the inhibition of caspase-3 activation by NMDA was dependent on the activation of tyrosine kinases and phosphatidylinositol 3-kinase (PI3-kinase). Moreover, an impairment in NMDA-mediated neuroprotection and caspase-3 inhibition was observed when the action of brain-derived neurotrophic factor (BDNF) was blocked. By contrast, K25-mediated neuroprotection was BDNF-independent and was mediated by a mitogen-activated protein kinase- and PI3-kinase-dependent inhibition of caspase-3. [source] Degeneration of pontine mossy fibres during cerebellar development in weaver mutant miceEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2002Miwako Ozaki Abstract In weaver mutant mice, substitution of an amino acid residue in the pore region of GIRK2, a subtype of the G-protein-coupled inwardly rectifying K+ channel, changes the properties of the homomeric channel to produce a lethal depolarized state in cerebellar granule cells and dopaminergic neurons in substantia nigra. Degeneration of these types of neurons causes strong ataxia and Parkinsonian phenomena in the mutant mice, respectively. On the other hand, the mutant gene is also expressed in various other brain regions, in which the mutant may have effects on neuronal survival. Among these regions, we focused on the pontine nuclei, the origin of the pontocerebellar mossy fibres, projecting mainly into the central region of the cerebellar cortex. The results of histological analysis showed that by P9 the number of neurons in the nuclei was reduced in the mutant to about one half and by P18 to one third of those in the wild type, whereas until P7 the number were about the same in wild-type and weaver mutant mice. Three-dimensional reconstruction of the nuclei showed a marked reduction in volume and shape of the mutant nuclei, correlating well with the decrease in neuronal number. In addition, DiI (a lipophilic tracer dye) tracing experiments revealed retraction of pontocerebellar mossy fibres from the cerebellar cortex after P5. From these results, we conclude that projecting neurons in the pontine nuclei, as well as cerebellar granule cells and dopaminergic neurons in substantia nigra, strongly degenerate in weaver mutant mice, resulting in elimination of pontocerebellar mossy fibres during cerebellar development. [source] Distribution of mossy fibre rosettes in the cerebellum of cat and mice: evidence for a parasagittal organization at the single fibre levelEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2001Fahad SultanArticle first published online: 20 DEC 200 Abstract Mossy fibres are the main afferent input to the granular layer of the cerebellar cortex. In this study, the spatial distribution of the mossy fibres' presynaptic enlargements , the so-called rosettes , were analysed on the single fibre level. Data obtained from the cerebella of cat and mice were compared to look for species differences, and the cerebella of the adult and young mice were also compared to look for developmental changes. The results show that there is a spatial anisotropy in all mossy fibres studied, with neighbouring rosettes being about three times further away from each other along the parasagittal axis and closer to each other in the mediolateral direction. Furthermore, these results suggest that this anisotropy is established at an early developmental stage. The anisotropic orientation of mossy fibres at the single fibre level supports the hypothesis of a timing mechanism in cerebellar function. [source] Repeated long-term potentiation induces mossy fibre sprouting and changes the sensibility of hippocampal granule cells to subconvulsive doses of pentylenetetrazolEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2000Hadir Hassan Abstract Electrical and chemical kindling induces sprouting of the mossy fibre system and potentiation of evoked field potentials in the dentate gyrus. It has been postulated that such changes may also be induced by repeated induction of long-term potentiation (LTP) with tetanic stimulation of the perforant pathway. LTP was induced in rats chronically implanted with stimulation electrodes in the ipsilateral and contralateral angular bundles and with a recording electrode in the ipsilateral dorsal dentate gyrus. The animals were stimulated 10 times on 10 consecutive days but with different tetanization strengths. Sprouting of the mossy fibres terminating in the CA3 region was significantly induced only in the group of ,strongly' tetanized animals, but not in that of ,weakly' tetanized animals, or in low-frequency stimulated animals. Additionally, a novel form of potentiation which was previously found in pentylenetetrazol (PTZ)-kindled animals was also observed in the group of ,strongly' and ,weakly' tetanized rats. Differences in duration of this potentiation were found between the two groups of animals tetanized with different strengths. The results further demonstrate that morphological and functional changes in the hippocampus, similar to those seen after kindling, can also occur in an activation paradigm leading to long-lasting synaptic plasticity but not accompanied by seizure activity. [source] |