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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Experimental brain research 107 (1995), S. 197-204 
    ISSN: 1432-1106
    Keywords: Slowly inactivating potassium currents ; Patch-clamp ; Cortical neurons ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Slowly inactivating outward currents were examined in neurons from rat anterior cortex dissociated at postnatal day 1 and recorded after 7–48 days in vitro by the use of whole-cell patch-clamp technique, in the presence of 0.5–0.8 μM tetrodotoxin (TTX), 50 μM carbachol and 1–5 mM CsCl2. Experiments were often carried out in the additional presence of 1–5 mM CsCl2, which blocks the anomalous, inwardly rectifying I Q, the fast Ca 2 + -dependent K+ current (I C), and 50 μM carbachol, which depresses the I M current. These currents were evoked by depolarizing steps to -40+-5 mV from a conditioning hyperpolarization to -110+-10 mV. Their sensitivity to elevation from 2.5 to 12.5 mM in extracellular K+ concentration, together with their sensitivity to 5–15 mM tetraethylammonium, suggests that they are mainly carried by K+ ions. Their activation and inactivation curves show that the threshold for activation is -65 mV, that their inactivation is achieved at -75 mV and that potentials more negative than -120 mV are needed to abolish it. The time-dependence of de-inactivation gives a maximal current amplitude for conditioning hyperpolarizations of 2 s and is best described by a monoexponential function with a time constant of 0.7 s. Slow, transient K+ currents were depressed by low doses of 4-aminopyridine (30–100 μM), which indicates the occurrence of an I D-type component in the recorded K+ currents. No slowly declining K+ current was expressed when a recording solution containing 10 mM 1,2-bis(2-aminophenoxy)ethane-N, N,N′-N′-tetraacetic acid (BAPTA), instead of 1–5 mM BAPTA, was used. When recorded without Ca2+ chelator in the pipette, slowly declining K+ currents were blocked by bath-applied 40–50 μM BAPTA-aminoethoxy, revealing a large-amplitude, rapidly inactivating outward current. This residual component is insensitive to 50 μM 4-aminopyridine and may include a current more related to the I A-type. Our data provide evidence that, in cultured cortical neurons from rat, the expression of an I D-like K+ current is highly dependent on internal Ca2+ concentration.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Experimental brain research 37 (1979), S. 525-535 
    ISSN: 1432-1106
    Keywords: Cerebellum ; Climbing fibers ; Development
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Correlations between pairs of spontaneous climbing fiber responses (CFRs) recorded from couples of nearby Purkinje cells (PCs) were studied in immature rats by using cross-correlograms between CFR pairs, and compared to those in adult animals. Correlations were found as early as day 3. Some days later, on PN days 7–9, these correlations were higher than in the adult. In most cases, this was apparently not due to the multiple innervation of PC by climbing fibers (CFs) which normally occurs during this immature stage since: 1) temporal relationships between the paired CFRs varied by more than 30 ms and 2) thresholds for pairs of graded CFRs and additional components of the responses evoked in the 2 PCs by juxtafastigial or olivary stimulation were different. Synchronizing mechanisms were therefore likely to be already located at the olivary level. However, in 3 couples of multiply innervated PCs whose spontaneous CF activities were highly correlated, stimulation experiments revealed a common innervation of the 2 cells by branches of the same CF. In multiply innervated cells, spontaneous responses mediated through distinct CFs were also synchronized, suggesting that these fibers originate from neighboring neurons of the inferior olive. Finally, in 7 to 9-day-old rats, correlations among CFR pairs were much more restricted in the longitudinal axis of the folium than in the transverse one. On the whole, the present study indicates that correlations among CFRs of nearby PCs exist as soon as CF-PC synapses are established and the latter are already organized in sagittal strips at early stages of development.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Experimental brain research 14 (1972), S. 463-471 
    ISSN: 1432-1106
    Keywords: Purkinje cells ; Spontaneous firing ; Ontogenesis ; Statistical methods
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The postnatal evolution of the Purkinje cell spontaneous firing (simple spikes) has been studied in the white Rat from 3 days after birth until adulthood using the following parameters: modal interspike interval, mean interspike interval, and ratio of the modal over the mean interspike interval of the discharge. Furthermore, two experimental conditions have been used: rats anaesthetized with Nembutal and rats only locally analgesied, the two preparations being curarized. It is shown that: 1∘) Between 3 and 5 days after birth, the spontaneous activity of many Purkinje cells is only formed by brief bursts of several spike potentials occuring more or less frequently. Evidence is given that some of these bursts are climbing fiber responses, the others being presumably elicited in Purkinje cells by parallel fibers activation. 2∘) After 5 days, the firing pattern (simple spikes) of Purkinje cells become more subtained and is formed by a more or less regular succession of spikes. Experimental conditions significantly change for all ages studied this firing pattern, and also change the time course of the evolution of all the considered parameters excepted for the modal interspike interval. 3∘) As a whole, Purkinje cells look immature until 8 days after birth. They rapidly mature between days 10 and 20. After the end of the 3rd postnatal week they show no significant differences when compared to the spontaneous firing of adult Purkinje cells, at least for the unanaesthetized preparations. At all ages a good correlation exist between Purkinje cells spontaneous firing (simple spikes) and data from the litterature concerning synaptogenesis in the cerebellum (parallel fibers Purkinje cells synapses).
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Experimental brain research 14 (1972), S. 472-479 
    ISSN: 1432-1106
    Keywords: Purkinje cell ; Spontaneous firing ; Ontogenesis ; Hypothyroidism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effects of thyroid deficiency are tested on the cerebellar Purkinje cells spontaneous firing (simple spikes) of young rats. Hypothyroidism is obtained by giving the mothers Propylthiouracile (P.T.U.) during the first postnatal month. Animals are studied between 5 days after birth and the middle of the 3rd postnatal month by comparison with controls: normally maturing rats and P.T.U. young rats also submitted to a daily administration of 2 micrograms of D.L. Thyroxine during the first postnatal month. Two experimental conditions are used: rats anaesthetized with Nembutal and rats only locally analgesied, the 2 preparations being curarized. It is shown that: 1∘) After the tenth postnatal day, hypothyroidism leads to a significant (P=0,05) decrease of both the mean and the modal frequencies of Purkinje cells spontaneous firing (simple spikes) when compared to normal values for the same ages. 2∘) The steadiness of the Purkinje cells firing is more accentuated in hypothyroidic rats than in normal rats at the end of the first postnatal month. 3∘) Hypothyroidism leads to a delay in the maturation of the “complex spikes”. All these differences are transitory. They have disappeared spontaneously about on the middle of the third postnatal month (P.T.U. administration is stopped at the end of the first postnatal month). Additionnai D.L. Thyroxine totally prevents the effects of P.T.U. These results are compared to histochemical and histological available data from the literature and they are discussed in their light.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Experimental brain research 20 (1974), S. 403-420 
    ISSN: 1432-1106
    Keywords: Cerebellum ; Maturation ; Hypothyroidism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The functional maturation of the cerebellum has been studied in normal rats from 3 days after birth until adulthood and over the same period in animals rendered hypothyroidic through propylthiouracile injections. Evoked field potentials and unitary activities were recorded from the cerebellar nuclei and from the molecular layer and Purkinje cell (P.C.) layer of the cerebellar cortex. The following observations are reported: 1. a few P.C. axons are functional and presumably connected to subcortical neurons as early as 3 days after birth. However the maturation of the bulk of P.C. axons only occurs after the 6th day; 2. climbing fiber responses of the P.C. (C.F.Rs) are also present on day 3, although the dendritic components of the response only appear several days later. C.F.R. maturation is achieved at the end of the first postnatal month and is only slightly disturbed by hypothyroidism; 3. some connections between mossy fibers (M.F.), granule cells and P.C. also seem to exist on days 3 to 4, but the functional maturation of the parallel fibers occurs principally during the 10th to 30th day period. This maturation is delayed to a considerable extent by hypothyroidism: 4. the efficiency of parallel fibers to excite P.C. increases strongly from the 10th to the 20th day; this evolution is also markedly slowed down in hypothyroid rats; 5. some inhibitory action can already be characterized in the cerebellar cortex on day 10, but most inhibitory interneurones and their synapses on P.C. become mature from the 10th to the 15th day. Furthermore, inhibition exerted by these cells on P.C. is more prolonged in the immature rat than in the adult. Hypothyroidism markedly delays the maturation of these inhibitory processes.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    European journal of neuroscience 8 (1996), S. 0 
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The effects of glutamate, aspartate and N-methyl-d-aspartate (NMDA) on Purkinje cells and interneurons were investigated in cerebellar slice cultures using the whole-cell configuration of the patch-clamp technique. l-Glutamate and l-aspartate induced inward currents in Purkinje cells voltage-clamped at -60 mV. In standard external solution, the amplitude of the responses induced by these two amino-acids was a linear function of the membrane potential. l-Aspartate-induced currents were inhibited by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), a selective antagonist of non-NMDA receptors. NMDA, a selective agonist of NMDA receptors, had no effect of its own on the excitability of Purkinje cells, but was effective in blocking the responses induced by aspartate in Purkinje cells in a voltage-independent manner. In contrast, d-(–)-2-amino-5-phosphonovaleric acid (d-APV), a selective antagonist of NMDA receptors, had no effect on aspartate-induced responses. d-Aspartate also induced responses in Purkinje cells, and the amplitude of these responses was a linear function of the membrane potential. Currents induced by l- and d-aspartate were inhibited by dihydrokainate, a glutamate uptake blocker. In sodium-free external solution, glutamate still induced outward currents in Purkinje cells, whereas l- and d-aspartate no longer evoked any current. When sodium was replaced by lithium in the external medium, no change in the holding current could be detected in Purkinje cells maintained at -60 mV; moreover, in this bathing medium l-aspartate no longer evoked any current whereas glutamate-induced responses were still present. In contrast, interneurons were sensitive to both NMDA and aspartate applications, and these responses were antagonized by d-APV. In addition, aspartate still induced an outward current in sodium-free external solution. This study presents rather direct evidence in favour of l-aspartate as being a very selective NMDA receptor agonist in the cerebellum. l-Aspartate-induced currents in Purkinje cells are not due to activation of mixed NMDA/non-NMDA receptors, but are probably due to the release of l-glutamate induced by aspartate through glutamate uptake.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    European journal of neuroscience 5 (1993), S. 0 
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: In patch-clamped Purkinje cells, bath application of the nitric oxide synthase inhibitor NG-methyl-l-arginine consistently prevents the induction of long-term depression (LTD) of parallel fibre-mediated excitatory postsynaptic potentials (EPSPs) induced by their pairing with calcium spikes. On the other hand, bath application of nitric oxide donors and of 8-bromoguanosine 3′:5’cyclic monophosphate is able to reproduce an LTD-like phenomenon. LTD of parallel fibre-mediated EPSPs also occurs when nitric oxide donors or guanosine 3′:5’cyclic monophosphate are directly dialysed into Purkinje cells, and this effect partially occludes LTD induced by pairing protocols. These results show that nitric oxide does play a role in LTD induction, and demonstrate for the first time that its site of action is probably the soluble guanylate cyclase of Purkinje cells.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    European journal of neuroscience 4 (1992), S. 0 
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The in vitro slice preparation of rat prefrontal cortical cells was used to analyse the presence and characteristics of a slowly inactivating outward current and its effect on the delayed integration of synaptic inputs. Pyramidal cells were identified as regular firing or bursting cells. In a fraction of these cells a depolarizing current pulse to –40 mV from a holding potential of –95 mV evoked the fast outward IA current followed by a slower outward current (IKs) which inactivated slowly during the 3-s pulse. This slowly inactivating outward current was completely inactivated at holding potentials near –40 mV and was fully deinactivated by large hyperpolarizing pulses of 1 s duration. It was sensitive to micromolar concentrations of 4-aminopyridine and to 10 mM tetraethylammonium. In current clamp experiments, when the cells were maintained at –80 mV, they responded to subliminal depolarizing current pulses by a slow rising depolarization which reached threshold for spike firing after a delay of several seconds. This delay was considerably reduced either by maintaining the cell at less hyperpolarized potentials or by bath application of 40 μM 4-aminopyridine, or by repeated application of depolarizing pulses. The inactivation of IKs by the last procedure also led to plateau depolarization of the cell. These results suggest that the activation of the slowly inactivating outward current IKs can shunt excitatory inputs, preventing the cell from reaching spike threshold as long as it is not largely inactivated.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    European journal of neuroscience 5 (1993), S. 0 
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The effects of noradrenaline on pyramidal cells of layer V of the prefrontal cortex were examined in rat brain slices in vitro. Bath administration of noradrenaline (10 μM) reduced synaptic transmission of afferent inputs from layer 1. The decrease affected all the components of the evoked response and particularly the monosynaptic excitatory postsynaptic potential (EPSP) as evidenced by a reduction of its initial rising slope (mean slope: 71 ± 11% of its control). Pharmacological dissociation of the NMDA- and non-NMDA-receptor components of the EPSP showed that noradrenaline reduced both (mean EPSP slopes were 71 ± 8% and 73 ± 10% of their control, respectively). Alpha1-, but not α-2- or β-adrenoceptor antagonists prevented the noradrenaline-induced decrease in synaptic efficacy. However, the effect of noradrenaline was not reproduced by α1-adrenoceptor agonists. Lastly, noradrenaline acting through β-adrenoceptors reduced the slow hyperpolarization that follows a train of action potentials.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    European journal of neuroscience 2 (1990), S. 0 
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: In vitro sagittal slices of immature rat cerebellum were used to study the development of the sensitivity of Purkinje cells (PC) to L-glutamate (Glu) and N-methyl-D-aspartate (NMDA). In 8-day-old animals, all PCs recorded in magnesium-free medium responded to iontophoretic applications of both agonists by transient and dose dependent inward currents which, in both cases, were heavily contaminated by a Glu and NMDA-induced synaptic noise. When 5 × 10−6 M tetrodotoxin (TTX) was added to the perfusing medium, this evoked synaptic noise was completely abolished in most cells whereas clear-cut inward currents induced in PCs by Glu and NMDA applications on their dendrites were still visible. These responses were selectively antagonized by the non-NMDA glutamate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and by the NMDA receptor antagonist D-2-aminophosphono-5-valeric acid (2APV) respectively. Excitatory responses induced by aspartate in 8– 10-day-old PCs were also markedly antagonized by CNQX. At this stage, the sensitivity of PCs to NMDA was about one order of magnitude less than that to Glu. In 15–20-day-old animals, all PCs were still responsive to Glu whereas only 70% of them were still excited by NMDA in the presence of TTX in the bath. Furthermore, the sensitivity of PCs to Glu was higher than at 8 days of age, whereas that to NMDA was significantly lower, even when considering only those cells which still responded to this agonist. This trend was still accentuated later on since at 2 months of age, only 25% of PCs were excited by NMDA whereas their sensitivity to Glu was similar to that observed in 15–20-day-old animals. Therefore, the present results are fully consistent with the view that PCs have a transient expression of NMDA receptors during development.
    Type of Medium: Electronic Resource
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