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Fibre Stimulation (fibre + stimulation)
Selected AbstractsDynamics of Ca2+ and Na+ in the dendrites of mouse cerebellar Purkinje cells evoked by parallel fibre stimulationEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 10 2003Akinori Kuruma Abstract Ca2+ and Na+ play important roles in neurons, such as in synaptic plasticity. Their concentrations in neurons change dynamically in response to synaptic inputs, but their kinetics have not been compared directly. Here, we show the mechanisms and dynamics of Ca2+ and Na+ transients by simultaneous monitoring in Purkinje cell dendrites in mouse cerebellar slices. High frequency parallel fibre stimulation (50 Hz, 3,50-times) depolarized Purkinje cells, and Ca2+ transients were observed at the anatomically expected sites. The magnitude of the Ca2+ transients increased linearly with increasing numbers of parallel fibre inputs. With 50 stimuli, Ca2+ transients lasted for seconds, and the peak [Ca2+] reached ,100 µm, which was much higher than that reported previously, although it was still confined to a part of the dendrite. In contrast, Na+ transients were sustained for tens of seconds and diffused away from the stimulated site. Pharmacological interventions revealed that Na+ influx through ,-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors and Ca2+ influx through P-type Ca channels were essential players, that AMPA receptors did not operate as a Ca2+ influx pathway and that Ca2+ release from intracellular stores through inositol trisphosphate receptors or ryanodine receptors did not contribute greatly to the large Ca2+ transients. [source] Exogenous nitric oxide causes potentiation of hippocampal synaptic transmission during low-frequency stimulation via the endogenous nitric oxide,cGMP pathwayEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2001Christelle L. M. Bon Abstract Nitric oxide (NO) is a putative participant in synaptic plasticity and demonstrations that exogenous NO can elicit the same plastic changes have been taken to support such a role. The experiments, carried out on the CA1 region of rat hippocampal slices, were aimed at testing this interpretation. A major component of tetanus-induced long-term potentiation (LTP) was lost in response to l -nitroarginine, which inhibits NO synthase, and 1H -[1,2,4]oxadiazolo[4,3- a]quinoxalin-1-one (ODQ), which inhibits NO-sensitive soluble guanylyl cyclase (sGC). At 0.2 Hz afferent fibre stimulation, exogenous NO produced, concentration-dependently, a synaptic depression that reverted on washout to a persistent potentiation that occluded tetanus-induced LTP. The NO concentrations necessary (estimated in the 100-nm range), however, were mostly supramaximal for stimulating hippocampal slice sGC activity. Nevertheless the potentiation, but not the preceding depression, was blocked by ODQ. l -nitroarginine and an NMDA antagonist were similarly effective, indicating mediation by the endogenous NMDA receptor,NO synthase,sGC pathway. At a concentration normally too low to affect synaptic transmission but sufficient to stimulate sGC (estimated to be 50 nm), exogenous NO reversed the effect of l -nitroarginine and caused a potentiation which was blocked by ODQ. At a concentration inducing the depression/potentiation sequence, NO partially inhibited hippocampal slice oxygen consumption. It is concluded that, at physiological levels, exogenous NO can directly elicit a potentiation of synaptic transmission through sGC, provided that the synapses are suitably primed. At higher concentrations, NO inhibits mitochondrial respiration, which can result in an enduring synaptic potentiation due to secondary activation of the endogenous NO,cGMP pathway. [source] Deficient long-term synaptic depression in the rostral cerebellum correlated with impaired motor learning in phospholipase C ,4 mutant miceEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 10 2001Mariko Miyata Abstract Long-term depression (LTD) at parallel fibre,Purkinje cell synapse of the cerebellum is thought to be a cellular substrate for motor learning. LTD requires activation of metabotropic glutamate receptor subtype 1 (mGluR1) and its downstream signalling pathways, which invariably involves phospholipase C,s (PLC,s). PLC,s consist of four isoforms (PLC,1,4) among which PLC,4 is the major isoform in most Purkinje cells in the rostral cerebellum (lobule 1 to the rostral half of lobule 6). We studied mutant mice deficient in PLC,4, and found that LTD was deficient in the rostral but not in the caudal cerebellum of the mutant. Basic properties of parallel fibre,Purkinje cell synapses and voltage-gated Ca2+ channel currents appeared normal. The mGluR1-mediated Ca2+ release induced by repetitive parallel fibre stimulation was absent in the rostral cerebellum of the mutant, suggesting that their LTD lesion was due to the defect in the mGluR1-mediated signalling in Purkinje cells. Importantly, the eyeblink conditioning, a simple form of discrete motor learning, was severely impaired in PLC,4 mutant mice. Wild-type mice developed the conditioned eyeblink response, when pairs of the conditioned stimulus (tone) and the unconditioned stimulus (periorbital shock) were repeatedly applied. In contrast, PLC,4 mutant mice could not learn the association between the conditioned and unconditioned stimuli, although their behavioural responses to the tone or to the periorbital shock appeared normal. These results strongly suggest that PLC,4 is essential for LTD in the rostral cerebellum, which may be required for the acuisition of the conditioned eyeblink response. [source] Climbing fibre-dependent changes in Golgi cell responses to peripheral stimulationTHE JOURNAL OF PHYSIOLOGY, Issue 20 2008W. Xu Golgi cells are important elements of the cerebellar cortex, controlling the flow of mossy fibre information to other cells via granule cells. Several anatomical reports suggest that climbing fibre afferents contact Golgi cells, and electrophysiological studies suggest that they depress Golgi cell firing. We reinvestigated this issue and, given that climbing fibres mediate synaptic plasticity in the cerebellar cortex, we have examined the effects of conjunctive stimulation of peripheral afferents and climbing fibres on Golgi cell responses. The results confirm that climbing fibre stimulation depresses Golgi cell firing at short latency. Golgi cells responded to stimulation of peripheral afferents with longer latency depressions of firing and after conjunctive stimulation with climbing fibres these were significantly reduced. The reductions developed progressively over 20 min of conjunctive stimulation and were persistent (up to 84 min). Temporal conjunction of the inputs was important because non-synchronous stimulation of climbing fibres and peripheral afferents failed to alter the peripheral afferent-evoked response in Golgi cells. In control experiments using either the same climbing fibre stimulation alone, or peripheral afferent stimulation paired with brainstem stimulation that did not activate climbing fibres, responses were not depressed. The results thus show that conjunctive stimulation of climbing fibres with other inputs to Golgi cells can induce long-term changes in Golgi cell responses in vivo. This raises the possibility that changes in Golgi cell peripheral responses mediated by climbing fibres can potentially contribute to cerebellar motor learning. [source] Alterations in connexin expression in the bladder of patients with urge symptomsBJU INTERNATIONAL, Issue 4 2005Jochen Neuhaus OBJECTIVE To compare the formation of gap junctions between detrusor smooth muscle cells in situ and the distribution of connexin (Cx)40, Cx43 and Cx45 expressions in bladder biopsies from a control group (with bladder tumour) and from patients with urge symptoms, as smooth muscle cells of the human detrusor muscle communicate via gap junctions and express several connexin subtypes, alterations of which may be involved in the causes of lower urinary tract symptoms. MATERIALS AND METHODS Connexin expression is prominent in myofibroblast-like cells, supposedly involved in afferent signalling pathways of the bladder. Their strategic position directly beneath the urothelium suggests they are a link between urothelial ATP signalling during bladder filling and afferent A,-fibre stimulation for co-ordination of bladder tonus and initialization of the micturition reflex. Modification of their coupling characteristics may have profound impact on bladder sensation. Bladder tissue probes of patients undergoing cystectomy or transurethral tumour resection for bladder cancer were used as controls. Tissue samples from patients with severe idiopathic urge symptoms were taken for exclusion diagnostics of interstitial cystitis (IC) and carcinoma in situ. The formation of functional syncytia between detrusor smooth muscle cells were examined in dye-coupling experiments by injecting with Lucifer Yellow. The morphology and structure of gap junctions were assessed by transmission electron microscopy and immunogold labelling of Cx43 and Cx45. The expression of connexin subtypes Cx40, Cx43 and Cx45 was compared by indirect immunofluorescence, and confocal laser scanning microscopy used for semiquantitative analysis. RESULTS There was dye coupling between smooth muscle cells of the detrusor in situ. Electron microscopy and immunogold labelling showed very small gap junctional plaques. These findings were confirmed by confocal immunofluorescence. Semiquantitative analyses showed significantly higher Cx43 expression in the detrusor muscle, and a tendency to higher Cx45 expression in the suburothelial layer associated with urge symptoms, whereas Cx40 expression was unaffected. CONCLUSIONS Smooth muscle cells of the human detrusor muscle are coupled by classical gap junctions, forming limited local functional syncytia. Both Cx43 and Cx45 are expressed at low levels in normal detrusor. Up-regulation of Cx43 in patients with urge incontinence supports the possibility of functional changes in the syncytial properties of detrusor smooth muscle cells in this condition. In addition, the observed increase of Cx45 in the myofibroblast cell layer supports the idea that alterations in sensory signalling are also involved. Comparison with previous reports implies that the pathophysiology of urgency is distinct from that of the unstable bladder and other forms of incontinence. [source] | ||||||||||