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1 INSERM EMI 0224, CHU Pitié-Salpêtrière, Université Paris VI, 105 boulevard de l'Hôpital, 75013 Paris, France2 Institut für Physiologie der Charité, Abteilung Neurophysiologie, Tucholskystr. 2, 10117 Berlin, Germany
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Abstract |
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(Received 28 July 2003;
accepted after revision 8 January 2004;
first published online 14 January 2004)
Corresponding author R. Miles: CHU Pitié-Salpêtrière, UPMC, 105 boulevard de l'Hôpital, 75013 Paris, France. Email: rmiles{at}chups.jussieu.fr
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Introduction |
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The temporal precision of action potential generation in response to afferent excitation varies between different neurones. Spike timing tends to be most precise when postsynaptic cells receive biphasic excitatory–inhibitory signals. The inhibitory component may be extrinsic, such as an inhibitory synaptic potential (Pouille & Scanziani, 2001; Galarreta & Hestrin, 2001). Alternatively, an EPSP may activate intrinsic voltage-dependent K+ currents (Cassell & McLachlan, 1986; Brew & Forsythe, 1995; Martina et al. 1998; Ramakers & Storm, 2002) which by limiting synaptically induced depolarizations can constrain EPSP–spike coupling to be temporally precise (Csicsvari et al. 1998; Fricker & Miles, 2000).
In neocortical and hippocampal pyramidal cells, small EPSPs initiate voltage-dependent currents which are largely inward near threshold (Stuart & Sakmann, 1995; Fricker & Miles, 2000). These inward currents tend to prolong synaptic depolarizations so that action potentials may be initiated at long, variable latencies. On the other hand, noisy stimuli in vitro (Mainen & Sejnowski, 1995) or natural stimuli in vivo (Azouz & Gray, 2000) can induce temporally precise firing. These studies showed that action potentials were most precisely generated by depolarizing transients emerging from a hyperpolarized level, and suggested that the dynamic properties of voltage-dependent currents near threshold were responsible. Such precise coupling is important for theories on how pyramidal cells code information and generate synchrony (König et al. 1996) as well as on how synaptic plasticity depends on spike timing (Abbott & Nelson, 2000).
In this study, we attempt to reconcile the divergence in findings on the temporal precision of pyramidal cell firing by examining intrinsic currents activated by EPSP-like waveforms in CA1 pyramidal cells in vitro. First, we asked how the activation of intrinsic currents was related to temporal variability of spike firing in response to these waveforms. Then we compared the timing of action potentials and intrinsic currents elicited by noisy stimuli of variable frequency composition and amplitude. Low amplitude stimuli were found to induce largely inward currents in CA1 pyramidal cells and generate temporally imprecise firing. In contrast when stimulus amplitude was increased, intrinsic K+ currents were activated and the temporal precision of action potential generation was enhanced.
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Methods |
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Experiments were performed according to local regulations, on hippocampal slices obtained from 9- to 14-day-old Sprague-Dawley rats. Animals were anaesthetized by intraperitoneal injection of a mixture of ketamine (200mgkg-1) and xylazine (800mgkg-1). After decapitation, the hippocampal formation was removed from the brain and cut into slices of 250µm thickness using a tissue slicer (Dosaka, Kyoto, Japan). Slices were maintained at room temperature in physiological saline bubbled with a mixture of 95% O2 and 5% CO2, before transfer into a heated chamber (32°C) for recording.
Solutions
Slices were prepared in and continuously superfused with a solution containing (mM): NaCl 130, KCl 3, CaCl2 2, MgCl2 2, NaH2PO4 1.3, NaHCO3 26, glucose 27.7, and saturated with 95% O2 and 5% CO2. Drugs were applied by bath application. Pipettes were filled with solutions containing (mM): potassium methylsulphate (KMeSO4) 150, Hepes 10, EGTA 0.1, ATP-Mg 4, GTP-Na 0.2, pH adjusted to 7.3 with KOH, osmolarity 290 mosmol l-1. Potassium methylsulphate was preferred to potassium gluconate to avoid the suppression of some K+ conductances, which is reported with gluconate as the major intracellular anion (Velumian et al. 1997). Na+ currents were measured in the presence of 500µM 4-aminopyridine (4-AP) in the extracellular solution. The addition of 100µM NiCl2, 1mM tetraethyl ammonium (TEA) and 2mM CsCl had no further effect on inward current amplitudes or kinetics. K+ currents were measured in the presence of 2µM tetrodotoxin (TTX) and 100µM nickel. In a few experiments 20µM 1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzol[f]quinoxaline-7-sulphonamide (NBQX) was added to suppress synaptic currents mediated by AMPA receptors, but synaptic transmission was usually left intact. Blocking synaptic excitation and synaptic inhibition increases cellular input resistance, which might affect the integration of currents in different cellular compartments (Destexhe & Pare, 1999). Potassium methylsulphate was obtained from ICN (Orsay, France), NBQX from Tocris Cookson (Fisher Bioblock, Illkirch, France) and all other chemicals were purchased from Sigma (Lyon, France).
Recordings
Patch pipettes were prepared (ESF electrode puller, Göttingen, Germany) from borosilicate glass of external diameter 1.5mm (Harvard Apparatus Ltd., Edenbridge, UK). Their resistance when filled with recording solution varied from 3 to 5M
. Recordings were made from pyramidal cells of the CA1 area of the hippocampus. Cells were identified visually using a Nikon microscope equipped with differential interference contrast (DIC) optics and a 40 x objective. Slices were illuminated with light passed through a high pass filter of cut-off 700 nm and images were obtained with a camera sensitive to infrared light (Hamamatsu C3077, Massy, France).
Whole-cell records were made with an Axopatch 200A amplifier operating in the fast current clamp or the voltage clamp mode (Axon Instruments, Union City, CA, USA). Stimulation and data acquisition were controlled by pCLAMP software (Axon Instruments). Signals were filtered at 5 kHz, digitized with a Digidata interface (Axon Instruments) at a sampling interval of 20µs, and stored on a computer. Leakage and capacitive currents were subtracted using a P/6 protocol with six correction pulses of amplitude one-sixth of the test pulse and opposite polarity. We noted no significant differences between a P/6 and a P/10 subtraction protocol. The holding potential was systematically used as the reference potential.
Whole-cell recordings were obtained by advancing a pipette through the slice under positive pressure until it was seen to distort the pyramidal cell body. Negative pressure was applied to form a high resistance seal and whole-cell access was established by applying a brief negative pressure pulse. Recordings were accepted when pyramidal cells had input resistances in the whole-cell configuration of 100–300M and an access resistance of less than 10% of the input resistance. We waited for at least 5 min after whole-cell recording was established, to allow for perfusion of the cell with the pipette solution. Cells were excluded from analysis if either their input or access resistance, measured from responses to small hyperpolarizing pulses, changed by more than 20% during a recording.
Injections of simulated synaptic waveforms
Both single synaptic events and synaptic noise were simulated by somatic injection of waveforms created in the MATLAB programming environment (The Mathworks, Sèvres, France). The form of simulated synaptic potentials or currents follows the expression (1 – e-t/ton)e-t/toff with ton= 0.2ms and toff= 0.8ms. While these somewhat rapid kinetics were chosen to avoid inactivation of intrinsic cellular currents during the rising phase of injected events, we also systematically explored events with slower rising phases (Figs 2 and 5). Gaussian white noise was generated in the MATLAB programming environment at a frequency of 10 kHz and then low-pass filtered at 50 or 100 Hz with an analog filter (Frequency Devices, Haverhill, MA, USA). The frequency and amplitude composition of injected noise waveforms were close to those used by Mainen & Sejnowski (1995) and were chosen to mimic membrane potential fluctuations observed in recordings from the intact animal (Paréet al. 1998; Destexhe & Paré, 1999).
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Results |
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Na+ and K+ current responses to small steps at subthreshold voltages
We first examined currents induced by stimuli of different amplitudes at varying holding potentials. Summed currents elicited by steps of 10mV (Fig. 1A) from holding potentials ranging between –80 and -50mV were recorded (Fig. 1B). These experiments revealed a voltage-dependent transition from a net outward current to a net inward current as the holding potential was shifted into the subthreshold range (Fig. 1B). At hyperpolarized potentials, small steps induced net outward currents, while at more depolarized potentials currents were largely inward (n= 5). The responses were dissected into inward (Fig. 1C) and outward components (Fig. 1D) by using either 4-AP (500µM, n= 4) or TTX (1µM, n= 4). The increase in peak amplitude of the Na+ current with depolarization was faster than that of K+ currents. Furthermore a significant maintained inward current (French & Gage, 1985) was evoked by steps from immediately subthreshold potentials (Fig. 1C). Its amplitude was usually larger than that of outward currents (Fig. 1D) resulting in a summed current that was entirely depolarizing at subthreshold potentials.
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EPSPs vary in rise time as well as in amplitude. Rapidly rising synaptic depolarizations are suggested to initiate firing with high precision (Mainen & Sejnowski, 1995; Azouz & Gray, 2000). More slowly rising synaptic events may inactivate inward or outward currents (Martina & Jonas, 1997; Martina et al. 1998; Fricker et al. 1999) and so increase firing threshold and reduce the precision of EPSP to spike coupling. To investigate how EPSP rise time affects the activation of inward and outward currents governing the precision of firing, we examined currents induced by injecting pulses of rise times, measured at half height, in the range of 0.7–19.3ms (Fig. 2). The amplitude of pulses was 10mV and after reaching a peak potential was maintained to avoid the effects of incomplete activation. Summed current responses to these pulses injected from a holding potential of -55mV were inward throughout their time course. The contributions of inward (n= 4) and outward currents (n= 4) to summed responses were dissected in experiments with appropriate antagonists (4-AP, TEA, Cs+ and Ni2+ for Na+ currents and TTX and Ni2+ for K+ currents). The pulses with the fastest rise times initiated a rapid component of the Na+ current (Fig. 2B). For both Na+ and K+ currents, the peak current initiated by the most slowly rising ramp was about 60% of that initated by a square pulse (Fig. 2B and C). These data suggest that inactivation has relatively little effect on inward or outward currents during times corresponding to the kinetics of fast EPSPs.
Na+ and K+ currents elicited by synaptic waveforms
These data show that depolarizing pulses of amplitudes up to 5–6mV, injected near threshold, always activate inward currents, and that outward currents are only evident when stimuli of larger amplitude (
10mV) are injected from more hyperpolarized holding potentials. We asked whether similar behaviour was evident in responses to simulated EPSP waveforms (Fig. 3).
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EPSPs are prolonged when outward currents are not activated
Current clamp records were used to explore the consequences for spike timing of this difference in synaptic activation of intrinsic currents. Synaptic waveforms of different amplitude were injected at different potentials. As shown in Fig. 4A, events induced by small amplitude currents were prolonged at subthreshold potentials (n= 9). Action potentials could be initiated from the rising phase of these events, but were also triggered at longer, variable latencies from a depolarizing plateau. The mean action potential latency measured from the onset of the stimulus was 125.4 ± 124.8ms. Figure 4B shows the voltage dependence of the decay of these responses, measured as the time from 90% to 10% of the peak. The latency distribution follows a continuous distribution with no evidence for two separate peaks. It resembles the voltage dependence of Na+ current activation, suggesting that the prolongation of synaptic waveforms may depend on activation of Na+ channels (Stuart & Sakmann, 1995; Fricker & Miles, 2000).
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Dependence of spiking precision on EPSC rise time
Our voltage clamp data show that the activation of subthreshold inward and outward currents is relatively independent of stimulus rise time (Fig. 2). We explored the effect of EPSC rise time on spike initiation in current clamp experiments by examining responses to injections of synaptic waveforms with rise times between 1.2 and 90ms (Fig. 5A). The larger charge transfer associated with waveforms of the same peak current but slower kinetics resulted in significantly larger depolarizations and a more effective activation of voltage-dependent conductances. We therefore adjusted intensity so that currents with different rise times elicited voltage responses of similar amplitude from a holding potential of -60mV (Fig. 5B). The threshold for action potential discharge was independent of the EPSC rise time (correlation coefficient r2= 0.21). As expected, slower waveforms initiated action potentials at longer latencies (Fig. 5B and C). However, the precision of firing, measured as the standard deviation of action potential latency, did not depend on the rise time of the stimulus (Fig. 5C). Note that in Fig. 4 not only the mean latency of discharges, but also their variability depended on the amplitude of the injected synaptic waveform, resulting in a broader distribution of latencies for small synaptic waveforms. The data presented in Fig. 5 suggest that the rise time of synaptic waveforms has little influence on the temporal precision for action potential generation in CA1 pyramidal cells.
White noise with higher variance induces more precise spiking than noise with lower variance
These data establish relations between active currents initiated by isolated synaptic waveforms and the timing of action potential discharge. We next asked whether similar relations exist during more complex patterns of synaptic inputs (Destexhe & Pare, 1999). Temporally complex barrages of EPSCs, were mimicked using white noise stimuli resembling synaptic events (Mainen & Sejnowski, 1995). Noise stimuli were filtered with a low-pass cut-off at 50 or 100 Hz and noise waveforms (Fig. 6A) were scaled to provide stimuli of low, medium and high variance, with standard deviations in the range 5–20 pA.
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Differential activation of inward and outward currents by noise with low and high variance
We attempted to dissect inward and outward currents initiated by noise waveforms in order to determine their influence on the timing of spike initiation. We examined voltage clamp responses to the same waveforms, rather than their time derivative, so that we could compare precisely currents in voltage clamp records with action potentials generated in current-clamp experiments. Figure 7 shows membrane current responses to voltage noise stimuli. We examined responses to noise waveforms of different levels of variance (with standard deviations 1.8, 3.7 and 6.9mV) at progressively more depolarized holding potentials (n= 9). We varied holding potentials over a range between hyperpolarized values at which no currents were induced, and potentials that were 1–2mV below action current threshold. We note that potentials corresponding to features in current responses (as in Fig. 7) were always comparable, since larger peak voltage stimuli were obtained in the high variance than in the medium or low variance waveforms. At hyperpolarized holding potentials, low variance noise (Fig. 7A) evoked no currents. As the holding potential was depolarized, evoked currents were largely inward with small outward components. Similarly, noise stimuli of medium variance evoked no response at hyperpolarized potentials. As membrane holding potential was depolarized, sequences of inward followed by outward currents emerged, but with further depolarization current responses were largely inward (Fig. 7B). In contrast, when the holding potential was depolarized to levels at which currents were elicited, large variance noise stimuli first elicited purely outward currents (Fig. 7C). As the holding potential was further depolarized, mixed inward and outward currents were elicited. While inward currents predominated in responses to low variance waveforms, larger outward currents than inward currents were elicited by the high variance noise. These results are comparable to those obtained with isolated EPSP waveforms (Fig. 3). They show that while small synaptic events may elicit purely inward postsynaptic currents, larger amplitude stimuli initiate sequences of inward currents followed and curtailed by outward currents.
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Finally we compared the timing and properties of intrinsic currents activated by noise stimuli to the initiation and temporal precision of action potentials evoked by the same stimuli (Fig. 8A–C). Current and voltage clamp responses to the low, medium and high variance versions of the same waveforms were compared in nine cells. Action potentials were typically initiated at time points corresponding to inward current transients in companion voltage clamp responses. Low variance noise waveforms induced largely inward currents and the timing of action potential initiation was rather dispersed (Fig. 6). In contrast, high variance waveforms resulted in sequences of inward followed by outward currents. In current clamp experiments with the same waveforms, action potentials were generated with a reduced temporal dispersion. Figure 8D plots the temporal variability in action potential generation calculated as the standard deviation of spike occurrence at all points corresponding to the occurrence of inward currents in voltage clamp experiments with a given noise waveform. The mean amplitude of all inward and outward currents generated by low, medium and high variance waveforms (up to 15 currents per traces, n= 9 cells) at the most depolarized holding potential just below threshold is shown in Fig. 8E. Outward currents increased with the variance of the noise waveform, while the peak amplitude of inward currents was reduced in parallel as the waveform variance increased. This comparison of action potential timing and membrane currents suggests that outward currents which succeeded inward currents, prevented the delayed initiation of action potentials and so enhanced the precision of action potential generation.
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Discussion |
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We injected current pulses and synaptic waveforms via a somatic electrode and recorded responses with the same electrode. EPSPs impinge on dendritic membrane of CA1 pyramidal cells and action potentials are probably generated at axonal sites distant from the soma (Colbert & Johnston, 1996; Colbert & Pan, 2002). Our studies probably therefore underestimated contributions of conductances activated by EPSPs at dendritic sites and errors may have been introduced in measurements of the timing of action potential discharges at their initiation site. Whole cell studies on cells with an extended morphology probably suffer from an imperfect space clamp. However, since our study was limited to the effects of somatically generated waveforms on action potential generation, these errors were probably minimized. Both the density and biophysical properties of currents expressed by hippocampal neurones change during development (Spigelman et al. 1992; Falk et al. 2003). Our work was done on tissue from young animals, so results are strictly applicable to this age range. However, the relations between the properties of Na+ and K+ currents and timing of action potential generation probably apply more generally.
A voltage-dependent switch in net currents near firing threshold
Our data show that a voltage-dependent switch occurs in the net current elicited by small pulses as membrane potential is depolarized towards firing threshold (Fig. 1). Inward currents always preceded outward currents. However, while net currents were largely outward at hyperpolarized potentials, summed currents were completely inward near threshold potentials. This behaviour seems to result from the combination of an increased maintained component of Na+ current together with a voltage-dependent increase in the steady state inactivation of K+ currents.
The voltage dependence of intrinsic currents induced by EPSP-shaped waveforms (Fig. 3) was similar to that of step commands, and may explain the firing precision observed with simulated synaptic currents of different kinetics (Fig. 4). Small stimuli elicited largely inward currents, which were blocked by tetrodotoxin and so were carried by voltage-dependent Na+ channels. These Na+ currents showed relatively little inactivation (Fig. 2). Similar behaviour in this potential range in a number of cell types has been attributed to a persistent Na+ current (French et al. 1990; Fleidervish & Gutnick, 1996; Magistretti & Alonso, 1999), although recent work (Taddese & Bean, 2002) suggests that it may not be necessary to invoke a separate current. Na+ channel availability is significantly reduced at near threshold potentials (Fricker et al. 1999; Taddese & Bean, 2002). In conditions of low availability, the stochastic behaviour of single channels becomes important (Schneidman et al. 1998) and this seems likely to be one factor underlying the variability in timing of action potentials (Fig. 4A).
Larger stimuli delivered from more hyperpolarized potentials activated in addition an outward current which was suppressed by 4-aminopyridine and so corresponds to inactivating voltage-dependent potassium channel. A role for transient K+ currents in accelerating EPSP decay was first noted at synapses made with sympathetic ganglion cells (Cassell & McLachlan, 1986). These K+ currents may ensure that only a short time window is available for action potential discharge (Brew & Forsythe, 1995; Fricker & Miles, 2000; Ramakers & Storm, 2002). At other synapses, however, inactivating K+ currents may have opposite effects so that EPSPs initiate firing at long, and variable, latencies. For instance, dendro-dendritic EPSPs impinging on mitral cells of the olfactory bulb activate a transient potassium current with similar kinetics to the AMPA component of the EPSP. Mitral cell discharge is thus initiated at long-latency by the NMDA component of the synaptic event (Schoppa & Westbrook, 1999). For inactivating K+ currents to ensure delayed firing, depolarizing influences, such as a long-lasting NMDA receptor mediated synaptic excitation or a substantial Na+ current must be maintained. Delayed firing cannot occur, if the excitation decays more quickly than the outward current inactivates, as in the present experiments.
EPSC rise time and the precision of CA1 pyramidal cell firing
In neocortical pyramidal cells, the rate of membrane depolarization affects the probability of action potential generation (Nowak et al. 1997) and, by some measures, their threshold (Azouz & Gray, 2000). This effect is suggested to depend on the rate of transition of Na+ channels into their inactivated state. Slower synaptic events of rise times similar to the kinetics of Na+ channel inactivation might then initiate action potentials at more depolarized potentials, and with longer, more variable latencies (Harsch & Robinson, 2000). However, the time constants of inactivation for Na+ currents are close to 20ms at subthreshold potentials (authors' unpublished observations; Martina & Jonas, 1997; Fricker et al. 1999). Furthermore inward currents induced by step depolarizations to subthreshold potentials had substantial persistent components (Fig. 1). AMPA receptor-mediated EPSPs recorded from CA1 pyramidal cells have a time to peak of 4–8ms and so Na+ channel inactivation should be far from complete. However, an alternative explanation for the enhanced efficacy with which rapid depolarizations initiate firing may lie in our observation (Fig. 2) that waveforms with rapid kinetics initiate a transient inward current which is absent from responses to more slowly rising EPSP waveforms. Our data suggest that depolarizations with rise times slower than about 10ms induce largely maintained inward currents (cf. Fleidervish & Gutnick, 1996; Magistretti & Alonso, 1999).
EPSPs with slower rise times often have a slow decay. In our experiments we used ramps rather than EPSP-like waveforms to explore the influence of EPSP kinetics in an attempt to avoid effects due to deactivation and incomplete activation. The data shown in Fig. 2A suggest that fast EPSPs only partially activate Na+ and K+ currents.
Comparison of responses to noisy stimuli and to single synaptic waveforms
Our comparison of the variability in spike timing with intrinsic currents elicited in response to the same waveforms seems to resolve a paradox. Noisy current stimuli injected into layer V cortical pyramidal cells evoke precise spike timing (Mainen & Sejnowski, 1995). In contrast, EPSP waveforms injected into the same cells, activate intrinsic Na+ currents, which prolong synaptic events and initiate action potentials at long, variable latencies (Stuart & Sakmann, 1995). In CA1 pyramidal cells, our data suggest that action potentials may be initiated either precisely or with poor temporal precision according to the amplitude of the stimulus. Small stimuli activate currents that are largely inward and induce firing with variable timing. In contrast, larger stimuli induce firing more precisely since they evoke biphasic sequences of inward–outward currents.
Our comparison of the relation between the mode of cellular firing and intrinsic currents generated by noise stimuli of different variances complements previous data suggesting that action potentials are most precisely initiated by rapid depolarizations from hyperpolarized potentials (Mainen & Sejnowski, 1995; Azouz & Gray, 2000). Our voltage clamp data suggest that rapidly rising waveforms are more likely to initiate a transient component of inward current. Furthermore, in our current clamp experiments increasing the variance of the test waveform tended to augment hyperpolarizing as well as depolarizing transients. Hyperpolarizing transients should tend to remove K+ current inactivation and thus enhance the probability that a succeeding depolarizing current transient would initiate a biphasic inward–outward sequence of intrinsic currents.
In vivo, action potentials are induced by membrane fluctuations resulting from the summation of multiple synaptic events. We attempted to analyse this process using first simple stimuli, then waveforms similar to synaptic events of variable kinetics and amplitude and finally with noise stimuli. Summed synaptic events in vivo may be characterized according to amplitude, frequency content and membrane potential. Our use of white noise stimuli let us avoid assumptions on the exact nature of these fluctuations Identical noise waveforms were injected in current and voltage clamp experiments, so that the precision of spike generation could be compared directly to cellular currents elicited by the same waveform. It might be argued that a better comparison would be made by injecting in current clamp the differential of a given waveform. However, in our experiments, values for the membrane time constant were significantly shorter than the frequency of our injected noise signal chosen to fit the frequency range of natural synaptic events (Mainen & Sejnowski, 1995). We found that the potential fluctuations resulting from injections of current noise at hyperpolarized potentials where intrinsic currents were little activated were better correlated with the injected waveform than with its integral (data not shown). In other conditions, with injected noise signals of higher frequency components, or with neurones of long time constant, injection of the integral of the current clamp waveform as the test stimulus in voltage clamp might provide a better comparison.
Functional significance of the temporal precision in EPSP–spike coupling
Our results suggest that CA1 pyramidal cells discharge precisely when large afferent stimuli arrive at hyperpolarized potentials. It seems that excitatory synaptic inputs which induce precise firing must consist of multiple, synchronous EPSPs (Stevens & Zador, 1998; Harsch & Robinson, 2000). As shown by Pouille & Scanziani (2001), the sequential occurrence of an EPSP followed at short latency by a feedforward inhibition is another way by which CA1 pyramidal cell firing can be restricted to a short time window. However, small EPSPs arriving in isolation at depolarized potentials should induce firing at variable and often long latencies. Such long latency firing seems likely to underly the maintenance of reverberating neuronal population activities (Burns, 1954), which may be important in several types of neuronal operations (Aksay et al. 2001; Wang, 2002).
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 M. J. Higley and D. Contreras Balanced Excitation and Inhibition Determine Spike Timing during Frequency Adaptation J. Neurosci., January 11, 2006; 26(2): 448 - 457. [Abstract] [Full Text] [PDF]
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 F. J Veredas, F. J Vico, and J.-M. Alonso Factors determining the precision of the correlated firing generated by a monosynaptic connection in the cat visual pathway J. Physiol., September 15, 2005; 567(3): 1057 - 1078. [Abstract] [Full Text] [PDF]
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S. A. Prescott and Y. De Koninck Integration Time in a Subset of Spinal Lamina I Neurons Is Lengthened by Sodium and Calcium Currents Acting Synergistically to Prolong Subthreshold Depolarization J. Neurosci., May 11, 2005; 25(19): 4743 - 4754. [Abstract] [Full Text] [PDF]
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W. B. Wilent and D. Contreras Stimulus-Dependent Changes in Spike Threshold Enhance Feature Selectivity in Rat Barrel Cortex Neurons J. Neurosci., March 16, 2005; 25(11): 2983 - 2991. [Abstract] [Full Text] [PDF]
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J. Munoz-Cuevas, H. Vara, and A. Colino Characterization of release-independent short-term depression in the juvenile rat hippocampus J. Physiol., July 15, 2004; 558(2): 527 - 548. [Abstract] [Full Text] [PDF]
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