| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Laboratoire de Neurobiologie, UMR CNRS 8544, Ecole Normale Supérieure, 46, rue d'Ulm, 75005 Paris, France2 Laboratoire de Physiologie cérébrale, UMR CNRS 8118, Centre Universitaire des Saints Pères, 45 rue des Saints Pères, 75006 Paris, France
 |
Abstract |
|---|
 Top Abstract IntroductionMethodsResultsDiscussionReferences |
|---|
(Received 9 October 2003;
accepted after revision 20 November 2003;
first published online 21 November 2003)
Corresponding author P. Ascher: Laboratoire de Physiologie cérébrale, UMR CNRS 8118, Centre Universitaire des Saints Pères, 45 rue des Saints Pères, 75006 Paris, France. Email: ascher{at}biomedicale.univ-paris5.fr
|
Introduction |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors (at least in the rat cerebellum, and after 15 days) (Llano et al. 1991; Rosenmund et al. 1992; Momiyama et al. 1996). The time course of the AMPA conductance is difficult to evaluate from in vivo voltage recordings, partly because the EPSP is always followed by a di-synaptic GABAergic IPSP. The first detailed analysis of the time course of the excitatory conductance change was performed in voltage-clamp and under conditions in which the inhibitory input could be selectively eliminated. The whole-cell configuration of the patch-clamp technique (Hamill et al. 1981) was first used in cerebellar slices in the early 1990s (Konnerth et al. 1990; Perkel et al. 1990; Llano et al. 1991). In slices taken from young rats (9–15 days old), Llano et al. (1991) observed EPSCs with a fast rising phase (10–90% rise time of about 1.8 ms), a single peak and a monophasic exponential decay (time constant of 6–7 ms at –70 mV). The reversal potential was close to 0 mV. In slices from animals older than 15 days the decay of the EPSC was slower, and the reversal potential was often positive. Several explanations of the time course of the parallel fibre compound EPSC recorded in Purkinje cells have been advanced. It decays more slowly (Llano et al. 1991) than predicted from channel kinetics (Barbour et al. 1994; Häusser & Roth, 1997). The decay is under some conditions limited by dendritic filtering (Llano et al. 1991; Roth & Häusser, 2001), but a long-lasting receptor conductance has also been demonstrated (Barbour et al. 1994). However, none of the mechanisms proposed for generating the compound EPSC are consistent with the observations of Perkel et al. (1990) whose records (their Fig. 2) often displayed ‘bumps’ on the decay phase.
|
|
Methods |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
The animals were anaesthetized either with halothane or with ketamine (75 mg kg-1) and xylazine (0.5 mg kg-1) prior to decapitation. Transverse or para-sagittal cerebellar slices (300 µm) of Wistar rats (aged 15–45 days) were prepared following the method described by Llano et al. (1991). Slices were visualized using either a 60 x or a 40 x water-immersion objective (Axioskop, Carl Zeiss) and infrared optics (illumination filter 750 ± 50 nm; Sony CCD camera).
All experiments were performed at room temperature (18–24°C). The recording chamber was continuously perfused at a rate of 1.5 ml min-1 with a solution containing (mM): NaCl 130, KCl 2.5, CaCl2 2, MgCl2 1, NaH2PO4 1.3, NaHCO3 26, glucose 10, bubbled with 95% O2 and 5% CO2 (pH 7.4). In most experiments 10 µM bicuculline methochloride (and in some cases 1 µM strychnine) were added to the bath solution to block fast inhibitory transmission. The concentration of bicuculline was increased to 20 µM in a few experiments in which the EPSCs were recorded at positive potentials and a residual (di-synaptic) GABAergic current could be detected.
PFs were stimulated by means of a glass pipette (tip diameter 5–10 µm) filled with extracellular Hepes-buffered saline. This stimulation electrode was placed at the surface of the molecular layer at a distance of 100–500 µm from the recorded PC. Stimulation intensity was usually between 3 and 15 V; duration was between 30 and 300 µs. Stimulation frequency was usually 0.1 Hz and consisted of either one or two pulses separated by 20 ms in most cases.
PCs were voltage clamped in the whole-cell configuration. Patch pipettes had resistances of 2.5–4.5 M
. The standard internal solution was a ‘K-based’ solution containing (mM): potassium gluconate 140, Hepes 10, EGTA 1, KCl 6, MgCl2 1, Na2ATP 4 (Na)GTP 0.4, pH adjusted to 7.3 with KOH. In some experiments involving depolarization to positive potentials potassium gluconate was replaced by caesium gluconate and the Ca2+ buffering was increased by adding 10 mM EGTA. Series resistance was maintained between 4 and 10 M then compensated with settings of 95–98%. HEKA software was used for data acquisition and analysis of PC EPSCs. Whole-cell recordings were filtered at 2 kHz and digitized at 10 kHz. Analysis was performed in the IgorPro graphing environment (Wavemetrics Inc., Lake Oswego, OR, USA).
GCs were recorded in loose cell-attached mode with a home-made amplifier (Barbour & Isope, 2000) or with the HEKA amplifier. The pipettes used had a resistance of 15–20 M when filled with Hepes-buffered solution (containing (mM): NaCl 130, KCl 2.5, CaCl2 2, MgCl2 1, Hepes 10; pH 7.3). The same pipettes were used for local applications of muscimol. They were filled with a solution of muscimol at 20 µM. Pressure pulses were made at 2 bars for durations of 50–500 ms.
Means are reported with S.D. 2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo(f)quinoxaline-7-sulphonamide (NBQX) and bicuculline methochloride were purchased from Tocris Cookson. All the other chemicals were from Sigma.
|
Results |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Multi-peak EPSCs were observed in both transverse and parasagittal slices from rats varying in age from 19 to 45 days. In most slices it was possible to find positions of the stimulating electrode and/or intensities of stimulation which elicited simple EPSCs (with a sharp peak and a smooth monophasic decay) and other positions from which EPSCs deviating from this shape were elicited, usually in the form of ‘double-peak’ EPSCs.
The analysis presented below was based on experiments in which the double-peak structure was visible both in single traces and in average traces. Typical examples are illustrated in Figs 1, 2 and 4. The rise time (10–90%) of the first peak (measured on the averaged record) had a mean value of 2.48 ± 0.83 ms (n= 58); the late part of the decay was monotonic and smooth, with a mean time constant of 19.6 ± 7.6 ms (n= 58). However, the second peak could be smaller or larger than the first. It could indent the rising phase or the decay phase, or contribute to the formation of a plateau between the rising phase and the decay phase.
|
|
In some cases the individual records showed more than two peaks but the averaged record showed only two peaks in which the second had a rounded shape, because the jitter in the latencies of the late peaks increased with the number of peaks.
The late peak is not caused by dendritic voltage-activated conductances
We tested two predictions of the hypothesis that the late peaks of the synaptic current could reflect the activation of voltage-dependent conductances in the PC dendrites. The first prediction was that a smaller EPSC should be less able than a large one to trigger a local response in PC dendrites. To reduce the EPSC amplitude we either added NBQX at a subsaturating concentration, or reduced the intensity of the PF stimulation.The second prediction was that changing the membrane potential in the dendrites should alter the behaviour of active conductances in the PC dendrite.
Effects of NBQX At concentrations of 1 µM, NBQX nearly completely eliminated the EPSCs, whether they showed a single peak or multiple peaks. However, in the latter case, during the development of the block, the two components of the response decreased in parallel and were still visible when the response had been reduced by 95%. There was no abrupt disappearance of the late peaks as would have been expected if these peaks corresponded to voltage-activated currents occurring in unclamped dendritic regions.
When the concentration of NBQX was lowered to 0.1 µM, the response stabilized at about 10–30% of the initial amplitude and, again, the shape of the multiple-peak responses was unchanged. One of the three experiments of this type is illustrated in Fig. 1.
Threshold stimulation When the PF stimulation was at threshold for the appearance of a postsynaptic response, the smallest EPSCs were a few tens of picoamps, i.e. in the upper range of the distribution of miniature EPSCs (Barbour, 1993; Sabatini & Regehr, 1997). These small EPSCs were frequently biphasic, as illustrated in Fig. 2B (centre column). It is unlikely that in such records the second hump could be due to a local Ca2+ action potential (for instance), since the size of the current is small. This observation supports the hypothesis that the two components correspond to two successive EPSCs.
Effects of changing the holding potential The reponses showing multiple peaks kept their shape when the holding potential was changed. The constancy of the shape is illustrated in Fig. 2A for a case in which the holding potential was changed from –40 to –60 and –80 mV. In Fig. 2B the potential was changed from –60 to +30 mV. The records are reminiscent of those of Perkel et al. (1990) in which the ‘bumps’ of responses recorded in ‘old’ animals (4–5 weeks) were observed at both negative and positive potentials.
The interpretation of the data obtained at negative potentials could be ambiguous. Hyperpolarization simultaneously increases the synaptic current as well as the difference between holding potential and the activation voltages of any putative voltage-dependent conductances. One could argue that the ability of the EPSC to activate such conductances might not be greatly altered by hyperpolarization. However, the data obtained at positive potentials are unambiguous, since known voltage-dependent conductances which could distort the EPSC are fully inactivated in this range. We conclude that the late peaks do not reflect the activation of voltage-dependent conductances.
The multipeak structure of the EPSCs is due to repetitive firing of the parallel fibres
Since the data presented above suggested that the multipeak structure of the EPSCs is due to repetitive firing of the PFs, we decided to record action potentials from GCs following antidromic stimulation. The PFs were stimulated at 0.1 Hz either with one pulse or with two pulses at a 20 ms interval. This double-pulse protocol, used in the experiments illustrated in Figs 3 and 6, was chosen to interpret an observation which will be described below (Figs 4 and 5), the sensitivity of the late peaks of the PC EPSC to repetitive stimulation of the PFs.
|
|
|
As can be seen in Fig. 3B for a case where the stimulation induced doublets, the latency of the first action potential was very stable, whereas the latency of the second action potential was variable. This variability was even larger for later action potentials, as shown in Fig. 6, in which the PF stimulation elicited in many cases a triplet of action potentials.
In 17 of the cells in which there was more than one action potential the interval between the first two action potentials (tgc) could be measured reliably, and had a mean value of 5.2 ± 1.5 ms.
Effects of repetitive stimulation The late action potentials in the GC as well as the late EPSCs of the PC were very sensitive to the frequency of stimulation. Figure 3 shows the responses of a GC to pairs of pulses separated by 20 ms and repeated 30 times at 0.1 Hz. The first pulse of the pair elicited a doublet of action potentials in 13 out of 30 sweeps. No doublet was seen in response to the second pulse of the pair. Figure 6A (control) corresponds to a case in which the first pulse elicited one, two or three action potentials. The second PF stimulation never produced triplets. In most cases it induced a single action potential and in a few cases a doublet.
The elimination of the late action potentials by a double pulse was quantified by calculating the ratio of the mean number of ‘late action potentials’ elicited by the second PF stimulation over the mean number of late action potentials after the first stimulation. This ratio is 0 in the example illustrated in Fig. 3, where there were no late action potentials in any of the responses to the second pulse. The ratio was 0.17 in the records of Fig. 6A (upper traces, control) where there were a few doublets in responses to the second PF stimulation. The mean ratio for the 13 cells analysed was 0.07 ± 0.09.
The lability of the late action potentials illustrated in Figs 3 and 6 is likely to explain the lability of the late peak(s) of the PC EPSC, which is illustrated in Fig. 4. The first PF stimulation elicited a double-peak EPSC. The second PF stimulation, applied 20 ms after the first, induced an EPSC that was markedly potentiated (paired-pulse facilitation: Konnerth et al. 1990; Perkel et al. 1990; Atluri & Regehr, 1996), but in which the second peak was completely eliminated. This was observed in most experiments, although in a few cases the second peak was only partially occluded. This is in agreement with the fact that in double-pulse experiments the repetitive firing of the GC is always reduced but not always abolished.
When the interval between the two PF stimulations was increased, the occlusion of the late action potentials in GC recordings and of EPSCs in PC recordings became less marked but was still detectable at intervals of 1 s. Figure 5 illustrates three examples of the effect of a 1 Hz stimulation on dual EPSCs. In the case of Fig. 5A, when the rate of stimulation was increased from 0.1 Hz to 1 Hz, the early component was slightly reduced but the late component seemed to be completelty eliminated. In the case of Fig. 5B, the early component was unchanged while the late one seemed to disappear, but at 1 Hz the shape of the rounded peak strongly suggested that the response remained polyphasic. In Fig. 5C both components were reduced at 1 Hz, but the second component was still detectable.
The effect of increasing the stimulation frequency from 0.1 to 1 Hz was also analysed on the responses of GCs. The effect was quantified by calculating the ratio of the mean number of ‘late action potentials’ elicited at 0.1 Hz over the mean number of late action potentials elicited at 1 Hz. The ratio was 1.3 ± 0.1 (n= 14). This is consistent with the observations made on the EPSCs.
Effects of bath-applied muscimol The emission of a burst of action potentials after a brief stimulation is not predicted by classical (Hodgkin–Huxley) models of voltage-dependent conductances and implies that the GC possesses a special set of ‘slow’ depolarizing conductances allowing the development of the late action potentials. Evidence for slow depolarizing conductances in the GCs has been provided by D'Angelo et al. (1998) using direct stimulation of the GC. Hamann et al. (2002) further showed that a burst of action potentials could be elicited in the GCs after an orthodromic stimulation, but only after block of the tonic GABAA-receptor conductance in GCs (Brickley et al. 1996; Wall & Usowicz, 1997). We thus applied muscimol to examine if an increased inhibitory conductance in the GCs reduced their probability of emitting a burst of action potentials after an antidromic stimulation.
Figure 6 illustrates an experiment in which, in the control period, the first PF stimulation induced one, two or three action potentials, and the second PF stimulation only one or two (GABAA receptors were blocked by bicuculline). In the presence of added muscimol (1 µM) (and after washing out bicuculline), both the first and the second PF stimulations triggered only single action potentials. Similar experiments were performed in six cells. The effect was quantified as the ratio of the mean number of action potentials induced by the first PF stimulation measured after 2 min in the presence of muscimol (1 µM) over the same value in control conditions. This ratio was 0.08 in the experiment of Fig. 6 and its mean value was 0.2 ± 0.28 (n= 6).
Figure 7 illustrates the parallel effect of muscimol on EPSCs recorded in a PC. The record obtained in the control solution shows a double EPSC (a). In the presence of muscimol, the EPSC became monophasic (b). The difference between the two records (a–b) shows that the second EPSC (eliminated by muscimol) started 9 ms after the first, had a more rounded peak but a similar speed of decay. The fact that the peak was rounded in this averaged record is likely to reflect the dispersion of the late action potentials of the GCs, visible in Figs 3 and 6.
|
Origin of the action potential burst. The bursts of action potentials in the GC indicate the presence of conductances allowing repetitive activity but do not localize these conductances. We considered two main possibilities (Fig. 8). In the first case, a train of action potentials originates in the PF (at the stimulation site) and propagates along the PF and then down the ascending axon to the soma. In the second case, the PF stimulation triggers a single action potential in the PF which elicits a burst of action potentials only once it reaches the ascending axon (or the soma) of the GC. The first action potential cannot reverberate in the orthodromic direction because the axon is still in its refractory period. But the following action potentials would propagate back along the axon and, when they reach the PF/PC synapse, elicit the late EPSCs.
|
|
The late action potentials can be observed in the absence of GABA-A blockers. Repetitive activity of the GCs, which we observed after antidromic activation of the GCs, has also been observed after orthodromic stimulation of mossy fibres (Hamann et al. 2002). However, these authors only observed the bursts of action potentials in the presence of furosemide, which blocks a large fraction of the tonically active GABAA receptors in GCs. To test if, in our experiments, this tonic activation could prevent the emission of bursts, we repeated the experiments in the absence of bicuculline. In six slices that had never been exposed to this compound, we observed multipeak EPSCs (e.g. Fig. 5C). These EPSCs were not changed by the addition of bicuculline. Similarly, multiple action potentials in GCs were observed in the absence of bicuculline in 23 cells in five slices (e.g. Fig. 9). It thus appears that in our slices the tonic activation of the GABAA receptors in GCs was not sufficient to prevent the repetitive activation of granule cells by an antidromic stimulation.
|
Discussion |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Dendritic filtering undoubtedly slows the EPSCs recorded in animals older than 15 days (Llano et al. 1991; Roth & Häusser, 2001), whether the second peak is present or not. The model of Roth & Häusser (2001) predicts that at P21 a dendritic conductance change rising with an exponential time constant of 0.2 ms and decaying with an exponential time constant of 3 ms will appear in the soma as an EPSC with a 20–80% rise time of up to 3.5 ms and a decay time constant of up to 15 ms. The values that we obtained for the single peak EPSCs (in control conditions or in the presence of muscimol) are in good agreement with these predictions. In contrast, dendritic filtering cannot explain the double-peak EPSCs.
Dendritic voltage escape and active currents
If the late peaks of multiple peak records were due to the activation of voltage-dependent conductances (such as Ca2+ channels), the shape of the multiphasic EPSCs should have been altered by changing the holding potential between –90 and +40 mV and by blocking the postsynaptic receptors (with NBQX). The fact that the shape was not changed indicates that the successive peaks of the EPSCs correspond to successive volleys of action potentials in the PFs.
In a few recordings, individual traces showed postsynaptic ‘action potentiallets’ which differed from the usual late peaks by their fast rise, and their all-or-none character. Records of this type have been shown by Hartell (1996) (his Fig. 1) and interpreted as expressing a local development of active currents, as predicted by Eilers et al. (1995). The occasional presence of these action potentiallets in our experiments indicates that in some cases postsynaptic ‘unclamped’ action potentials may contribute to the complexity of the EPSCs and can make their decay longer and noisier.
The origin of the action potential burst
The effects of local applications of muscimol clearly indicate that the GABA receptors responsible for the effects of bath-applied muscimol are not on the parallel fibres. These experiments also strongly suggest the burst originates in the GC somato-dendritic compartment and/or the ascending axon. D'Angelo et al. (1998) have reported the presence in GCs of two types of TTX-sensitive Na+ currents, which in their experiments triggered a slow depolarization at around –55 mV and were responsible for subthreshold depolarizing potentials around resting potential. These Na+ currents are likely candidates for the observed effects. However, it cannot be completely excluded that a burst-generating mechanism in the PF could be blocked by an electrotonic propagation of a somatic voltage change.
In principle, the comparison of the interval between PC EPSCs (tpc, a first approximation of the interval between the two action potentials arriving at the synapse) with that between successive GC action potentials recorded at the soma (tgc) could give an additional clue regarding the site of origin of the burst. If the second action potential originates in the PF (Fig. 8A), the intervals should be identical and the difference tpc–tgc= 0. If the second action potential originates in the ascending axon or the GC soma (Fig. 8B), the mean interval between the peaks of the PC EPSCs should be slightly longer than the interval between the first and the second action potentials recorded in the GCs. In this case, the difference between tpc and tgc will depend on the relative positions of the stimulating electrode, the branch point of the ascending axon and the synaptic contact. However, in all cases it will include twice the conduction time (ta) from the branching point of the PF to the site of origin of the second GC action potential. If we assume an average conduction velocity at room temperature of about 200 µm ms-1 (Eccles et al. 1966a; Vranesic et al. 1994; D'Angelo et al. 1995) and an average ascending axon length for the stimulated GCs of about 200 µm (Harvey & Napper, 1988), the difference between tpc and tgc should be 2 ms if the second action potential originates in the soma of the GCs.
The mean value of tpc was 6.5 ± 1.3 ms (n= 34). The mean value of tgc was 5.2 ± 1.5 ms (n= 17). The two values are significantly different (Student's t test: t= 3.25, P < 0.001). On the other hand, the difference tpc–tgc= 1.3 ms is not significantly different from 2 ms. Thus, in a first approximation, these results support the hypothesis that the burst does not originate in the PF but in the granule cell or in the ascending axon.
Doublets and LTD induction
In a recent study of LTD at the PF–PC synapse, Casado et al. (2002) induced LTD by coupling PF stimulation with PC depolarization at 1 Hz for 2 min. They found that this protocol was only effective when the PF stimulation was a doublet (stimuli separated by 60 ms). This requirement for a doublet of action potentials was consistent with the proposed involvement of the presynaptic NMDA receptors of the PFs: the glutamate released by the first action potential probably activated the presynaptic NMDA receptors only after the action potential had passed, and this meant that their voltage-dependent magnesium block (Nowak et al. 1984) could only be relieved if a second action potential arrived within a given interval. However, this interpretation is difficult to reconcile with the fact that, in previous publications, coupling PF stimulation and PC depolarization had been found to induce LTD even if the PFs were stimulated at low frequency with a single pulse.
A possible way to reconcile the two sets of data is to suppose that in the experiments using single PF pulses during the induction protocol, the single stimulus actually triggered two action potentials. The duality of the input could have been missed in the experiments using current clamp (e.g. Crepel & Jaillard, 1991; Hartell, 1996). The records illustrating experiments using voltage clamp do not show multiple peaks (e.g. Aiba et al. 1994; Khodakhah & Armstrong, 1997) but many show rounded EPSCs which could correspond to a multicomponent structure smoothed by averaging. It is therefore possible that in some of the experiments in which the induction of LTD used single-pulse stimulation of the PFs, there may have been a covert repetitive activation of the PFs, and that a sufficient fraction of the doublets persisted during the 1 Hz stimulation.
Physiological conditions
Our experiments were aimed primarily at understanding the apparent contradictions in the literature regarding the requirements of LTD induction, as discussed above. Since most of the experiments in this field were performed at room temperature, we analysed the GC doublets and the PF dual EPSCs at room temperature. We have not tried to establish whether the repetitive firing of the GCs would also be observed at higher, more physiological temperatures.
The bursting behaviour of granule cells that we have analysed could be observed in the absence of bicuculline. This appears at first sight to contradict the observations of Hamann et al. 2002) who reported bursting after orthodromic stimulation, but only after blockade of the tonic activation of granule cell furosemide-sensitive GABAA receptors. The difference could be due to a difference between orthodromic and antidromic stimulation. It could also be linked to the fact that the tonic activation of GABAA receptors in granule cells increases with age: Hamann et al. (2002) used animals of 35–45 days, whereas our experiments in the absence of bicuculline were performed on animals aged 21–30 days. Finally, it could also be linked with the different temperatures of the experiments (29 ± 3°C versus 21 ± 3°C).
Although doublets are not necessarily observed in all preparations following antidromic stimulation of PFs (cf. Isope & Barbour, 2002; adult rat slices at 32°C), their possible presence should in future be taken into account when interpreting experiments involving such stimulation.
|
References |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Atluri PP & Regehr W (1996). Determinants of the time course of facilitation at the granule cell to Purkinje synapse. J Neurosci 16, 5661–5671.
Barbour B (1993). Synaptic currents evoked in Purkinje cells by stimulating individual granule cells. Neuron 11, 759–769.[CrossRef][Medline]
Barbour B & Isope P (2000). Combining loose cell-attached stimulation and recording. J Neurosci Meth 103, 199–208.[CrossRef][Medline]
Barbour B, Keller BU, Llano I & Marty A (1994). Prolonged presence of glutamate during excitatory synaptic transmission to cerebellar Purkinje cells. Neuron 12, 1331–1343.[CrossRef][Medline]
Brickley SG, Cull-Candy SG & Farrant M (1996). Development of a tonic form of synaptic inhibition in rat cerebellar granule cells resuling from persistent activation of GABAA receptors. J Physiol 497, 753–759.
Casado M, Isope P & Ascher P (2002). Involvement of presynaptic N-methyl-D-aspartate receptors in cerebellar long-term depression. Neuron 33, 123–130.[CrossRef][Medline]
Crepel F & Jaillard D (1991). Pairing of pre- and postsynaptic activities in cerebellar Purkinje cells induces long-term changes in synaptic efficacy in vitro. J Physiol 432, 123–141.
D'Angelo E, De Filippi G, Rossi P & Taglietti V (1995). Synaptic excitation of individual rat cerebellar granule cells in situ: evidence for the role of NMDA receptors. J Physiol 484, 397–413.
D'Angelo E, De Filippi G, Rossi P & Taglietti V (1998). Ionic mechanism of electroresponsiveness in cerebellar granule cells implicates the action of a persistent sodium current. J Neurophysiol 80, 493–503.
De Schutter E & Bower JM (1994). Simulated responses of cerebellar Purkinje cells are independent of the dendritic location of granule cell synaptic inputs. Proc Natl Acad Sci U S A 91, 4736–4740.
Denk W, Sugimori M & Llinás R (1995). Two types of calcium response limited to single spines in cerebellar Purkinje cells. Proc Natl Acad Sci U S A 92, 8279–8282.
Eccles JC, Llinás R & Sasaki K (1966a). Parallel fiber stimulation and the responses induced thereby in the Purkinje cells of the cerebellum. Exp Brain Res 1, 17–39.[Medline]
Eccles JC, Llinás R & Sasaki K (1966b). Intracellularly recorded responses of the cerebellar Purkinje cells. Exp Brain Res 1, 161–183.[Medline]
Eilers J, Augustine GJ & Konnerth A (1995). Subthreshold synaptic Ca2+ signalling in fine dendrites and spines of cerebellar Purkinje neurons. Nature 373, 155–158.[CrossRef][Medline]
Hamann M, Rossi DJ & Attwell D (2002). Tonic and spillover inhibition of granule cells control information flow through cerebellar cortex. Neuron 33, 625–633.[CrossRef][Medline]
Hamill OP, Marty A, Neher E, Sakmann B & Sigworth FJ (1981). Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches. Pflugers Arch 391, 85–100.[CrossRef][Medline]
Hartell NA (1996). Strong activation of parallel fibers produces localized calcium transients and a form of LTD that spreads to distant synapses. Neuron 16, 601–610.[CrossRef][Medline]
Harvey RJ & Napper RMA (1988). Quantitative study of granule and Purkinje cells in the cerebellar cortex of the rat. J Comp Neurol 274, 151–157.[CrossRef][Medline]
Häusser M & Roth A (1997). Dendritic and somatic glutamate receptor channels in rat cerebellar Purkinje cells. J Physiol 501, 77–95.[Medline]
Isope P & Barbour B (2002). Properties of unitary granule cell –>Purkinje cell synapses in adult rat cerebellar slices. J Neurosci 22, 9668–9678.
Khodakhah K & Armstrong CM (1997). Induction of long-term depression and rebound potentiation by inositol trisphosphate in cerebellar Purkinje neurons. Proc Natl Acad Sci U S A 94, 14009–14014.
Konnerth A, Llano I & Armstrong CM (1990). Synaptic currents in cerebellar Purkinje cells. Proc Natl Acad Sci U S A 87, 2662–2665.
Llano I, Marty A, Armstrong CM & Konnerth A (1991). Synaptic- and agonist-induced excitatory currents of Purkinje cells in rat cerebellar slices. J Physiol 434, 183–213.
Llinás R & Sugimori M (1980). Electrophysiological properties of in vitro Purkinje cell dendrites in mammalian cerebellar slices. J Physiol 305, 197–213.
Momiyama A, Feldmeyer D & Cull-Candy SG (1996). Identification of a native low-conductance NMDA channel with reduced sensitivity to Mg2+ in rat central neurones. J Physiol 494, 479–492.
Nowak L, Bregestovski P, Ascher P, Herbet A & Prochiantz A (1984). Magnesium gates glutamate-activated channels in mouse central neurones. Nature 307, 462–465.[CrossRef][Medline]
Perkel DJ, Hestrin S, Sah P & Nicoll RA (1990). Excitatory synaptic currents in Purkinje cells. Proc R Soc Lond B Biol Sci 241, 116–121.[Medline]
Rosenmund C, Legendre P & Westbrook GL (1992). Expression of NMDA channels on cerebellar Purkinje cells acutely dissociated from newborn rats. J Neurophysiol 68, 1901–1905.
Roth A & Häusser M (2001). Compartmental models of rat cerebellar Purkinje cells based on simultaneous somatic and dendritic patch-clamp recordings. J Physiol 535, 445–472.
Sabatini BL & Regehr WG (1997). Control of neurotransmitter release by presynaptic waveform at the granule cell to Purkinje cell synapse. J Neurosci 17, 3425–3435.
Vranesic I, Ijima T, Ichikawa M, Matsumoto G & Knöpfel T (1994). Signal transmission in the parallel fiber-Purkinje cell system visualized by high-resolution imaging. Proc Natl Acad Sci U S A 91, 13014–13017.
Wall ML & Usowicz MM (1997). Development of action potential-dependent and independent spontaneous GABAA receptor-mediated currents in granule cells of postnatal cerebellum. Eur J Neurosci 9, 533–548.[CrossRef][Medline]
|
Acknowledgements |
|---|
Author's present address
P. Isope: Department of Psychiatry, Kinsmen Laboratory, University of British Columbia, 4N11-2255 Wesbrook Mall, Vancouver, V6T 1Z3, Canada.
This article has been cited by other articles:
|
|
 |
|
  J. Magistretti, L. Castelli, L. Forti, and E. D'Angelo Kinetic and functional analysis of transient, persistent and resurgent sodium currents in rat cerebellar granule cells in situ: an electrophysiological and modelling study J. Physiol., May 15, 2006; 573(1): 83 - 106. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Osorio, G. Alcaraz, F. Padilla, F. Couraud, P. Delmas, and M. Crest Differential targeting and functional specialization of sodium channels in cultured cerebellar granule cells J. Physiol., December 15, 2005; 569(3): 801 - 816. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
