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The Journal of Neurophysiology Vol. 83 No. 5 May 2000, pp. 3177-3182
Copyright ©2000 by the American Physiological Society
RAPID COMMUNICATION
Division of Neuroscience, John Curtin School of Medical Research, Australian National University, Canberra, ACT 0200, Australia
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ABSTRACT |
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 TOP
 ABSTRACT
 INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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Williams, Stephen R. and Greg J. Stuart. Site Independence of EPSP Time Course Is Mediated by Dendritic Ih in Neocortical Pyramidal Neurons. J. Neurophysiol. 83: 3177-3182, 2000. Neocortical layer 5 pyramidal neurons possess long apical dendrites that receive a significant portion of the neurons excitatory synaptic input. Passive neuronal models indicate that the time course of excitatory postsynaptic potentials (EPSPs) generated in the apical dendrite will be prolonged as they propagate toward the soma. EPSP propagation may, however, be influenced by the recruitment of dendritic voltage-activated channels. Here we investigate the properties and distribution of Ih channels in the axon, soma, and apical dendrites of neocortical layer 5 pyramidal neurons, and their effect on EPSP time course. We find a linear increase (9 pA/100 µm) in the density of dendritic Ih channels with distance from soma. This nonuniform distribution of Ih channels generates site independence of EPSP time course, such that the half-width at the soma of distally generated EPSPs (up to 435 µm from soma) was similar to somatically generated EPSPs. As a corollary, a normalization of temporal summation of EPSPs was observed. The site independence of somatic EPSP time course was found to collapse after pharmacological blockade of Ih channels, revealing pronounced temporal summation of distally generated EPSPs, which could be further enhanced by TTX-sensitive sodium channels. These data indicate that an increasing density of apical dendritic Ih channels mitigates the influence of cable filtering on somatic EPSP time course and temporal summation in neocortical layer 5 pyramidal neurons.
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INTRODUCTION |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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The integration of synaptic potentials to form an
output signal, the action potential, is the most fundamental operation
neurons perform. As excitatory synaptic contacts are made predominantly on the dendrites of central neurons, excitatory postsynaptic potentials (EPSPs) must propagate to the soma and axon to influence action potential initiation (Stuart et al. 1997b
). The
propagation of synaptic potentials from dendrites to the soma is
controlled by both the passive (Rall 1977;
Spruston et al. 1994) and active membrane properties of
the dendritic tree (Yuste and Tank 1996). The influence
of dendritic filtering on EPSP amplitude and time course will be
particularly apparent in neurons with large dendritic trees, such as
layer 5 neocortical pyramidal neurons, where excitatory synaptic
contacts made on apical dendrites can be up to 1 mm from the soma.
Indeed, modeling studies have indicated that EPSPs generated in the
apical tuft of uniformly passive layer 5 neocortical pyramidal neurons
may be attenuated in amplitude by >100 times at the soma, and possess
a time course that greatly outlasts the potential at source
(Cauller and Connors 1992; Stuart and Spruston
1998). Experimentally, however, little relationship between
somatic EPSP time course and the presumed site of generation has been
observed in both neocortical layer 5 and hippocampal CA1 pyramidal
neurons (Andreasen and Lambert 1998; Nicoll et
al. 1993), suggesting either that distal synaptic events have
different time courses at source (Cauller and Connors
1994) or that their propagation to the soma is influenced by
nonuniform membrane properties and/or voltage-activated channels.
Simulations predict that the degree of voltage attenuation from
the soma along the main apical dendrite of layer 5 pyramidal neurons is
best described if a higher membrane conductance and higher density of
hyperpolarization-activated mixed cation channels (Ih) are present in distal apical
dendrites (Stuart and Spruston 1998). These factors
would be expected to influence the time course of EPSPs and suggest
that nonuniform membrane properties and
Ih channel distributions may act to
normalize EPSP time course at the soma. In support of this notion, it
has recently been shown that the density of
Ih channels increases with distance
from the soma in the apical dendrites of CA1 pyramidal neurons
(Magee 1998), where they act to normalize temporal
summation of somatic EPSPs (Magee 1999).
Here we directly investigate the distribution and properties of Ih channels in the apical dendrites of neocortical layer 5 pyramidal neurons and their effect on the relationship between the site of EPSP generation and somatic EPSP time course.
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METHODS |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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Wistar rats (3-6 wk old) were anesthetized by inhalation of
halothane, decapitated, and 300 µm-thick coronal or parasagital neocortical brain slices prepared, according to institutional guidelines. Slices were perfused with oxygenated Ringer solution of the
following composition (in mM): 125 NaCl, 25 NaHCO3, 3 KCl, 1.25 NaH2PO4, 2 CaCl, 1 MgCl,
and 25 glucose. Current-clamp recordings were made at 34-35°C, and
cell-attached recordings were made at either room temperature
(20-24°C) or 34-35°C. Simultaneous somatic (pipette resistance,
2-5 M
) and dendritic (8-12 M) patch-clamp recordings were made
from visually identified large layer 5 pyramidal neurons using two
identical current-clamp amplifiers (Dagan) as previously described
(Williams and Stuart 1999). Somatic, dendritic, and
axonal cell-attached recordings (pipette resistance, 10-12 M) were
made using on-line leak subtraction (P/5) with a patch-clamp amplifier
(Axon Instruments). No differences in the degree or time of negative
pressure applied to the back of pipettes was required to form high
resistance (3-10 G) seals at somatic, dendritic, or axonal sites,
suggesting that similar membrane areas were sampled. For whole cell
recordings patch electrodes were filled with (in mM) 135 K-gluconate, 7 NaCl, 10 HEPES, 0.5 EGTA, 2 Na2-ATP, and 2 MgCl
(pH 7.2 adjusted with KOH; osmolarity, 280 mOsm). All membrane potentials have been corrected for an experimentally determined liquid
junction potential of 
10 mV. For cell-attached recordings, patch
electrodes contained 120 mM KCl, 20 mM tetraethyammonium chloride, 5 mM
4-aminopyridine, 2 mM CaCl, 1 mM MgCl, 1 mM BaCl, 10 mM HEPES, and 1 µM TTX (pH 7.2 adjusted with KOH), and all patch potentials were
corrected for an experimentally determined liquid junction potential of
3 mV. Voltage and current signals were filtered at 10-30 kHz for
whole cell recordings, or 2-5 kHz for cell-attached recordings, and
acquired at 20-100 kHz using an ITC-16 interface (Instrutech)
controlled by an Apple PowerPC. Activation curves were fit with a
single Boltzmann equation of the following form: y = 1/[1 + e(V1/2
V)/k],
where V1/2 is the voltage of
half-maximal activation and k is a constant. The time course
of current activation and deactivation were fit with single or
biexponential functions. Numerical values are given in the text as
means ± SE, unless stated otherwise. Statistical analysis was
performed with Student's t-test (
= 0.05).
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RESULTS |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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Properties and distribution of Ih channels
Cell-attached recordings were made from the axon, soma, and apical
dendrite of layer 5 pyramidal neurons (n = 72) with
pipettes filled with a solution designed to block voltage-activated
potassium and sodium currents. Voltage steps of 100 mV made from a
holding potential set 20 mV positive to resting membrane potential
(RMP) revealed the presence of a slowly activating, noninactivating inward current (Fig. 1A; RMP
determined from current-clamp recordings was found to be on average
75.8 ± 0.5 mV, mean ± SE). The amplitude of this current
was variable from patch to patch, but showed a clear location
dependence (Fig. 1B). Recordings made from axonal and
somatic sites revealed little or no slow inward current, whereas in
patches from apical dendrites the magnitude of this slow inward current
increased as recordings were made more distally from the soma (slope of
linear regression 9 pA/100 µm; Fig. 1B).
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Current-voltage relationships indicated that this slow inward current
first activated at potentials close to 70 mV and increased in
magnitude with potential negativity (Fig. 1C). Tail current analysis revealed that the slow inward current was maximally activated at approximately 110 mV, and that activation could be well fit with a
single Boltzman function with values of
V1/2 of 92 mV and a steepness
coefficient of 6.2 at room temperature (n = 29), and
V1/2 of 91 mV and a steepness
coefficient of 6.1 at 34-35°C (n = 6), indicating
that ~7-8% of maximal Ih current
is activated at the whole cell resting membrane potential (Fig.
1D). The activation properties of the slow inward current
were found to be similar at all dendritic recording locations. The time
course of current activation increased with membrane negativity and
could be well fit with single exponential functions for all voltages
examined (Fig. 1C). The activation time constant was
274 ± 47 ms at 82 mV and decreased exponentially to 55 ± 6 ms at 152 mV when measured at room temperature (n = 19) and were accelerated to 103 ± 20 ms at 82 mV and 18 ± 4 ms at 152 mV at 34-35°C (n = 6; Fig. 1F). Deactivation after maximal activation at 152 mV was
also well described with a single exponential function with values that
decreased exponentially from 275 ± 55 ms at 62 mV to 91 ± 22 ms at 22 mV at room temperature (n = 7) and
30 ± 4 ms at 62 mV and 10 ± 1 ms at 22 mV at 34-35°C
(n = 4; Fig. 1F). The average reversal
potential of the slow inward current, extrapolated from tail currents
following maximal activation, was 7.94 ± 0.77 mV
(n = 6).
These voltage-dependent properties are similar to those described for
Ih currents during whole cell
recording in layer 5 neocortical pyramidal neurons (Solomon et
al. 1993; Solomon and Nerbonne 1993; Spain et al. 1987). Consistent with this, bath
application of the bradycardiac agent ZD7288 (100 µM), which blocks
Ih at an intracellular site in cardiac
cells and central neurons (BoSmith et al. 1993;
Harris and Constanti 1995; Williams et al.
1997) caused a 74.5 ± 2.2% (n = 6)
reduction (measured just before test step termination) in the slow
inward current activated by voltage steps to 152 mV (Fig.
1E). Block by ZD7288 appeared to decrease with time during
maximally activating voltage steps, leading to the appearance of a very
slow inward current that was well fit with a double exponential
function (Fig. 1E). The appearance of a very slow inward
current in the presence of ZD7288 has been previously observed in whole
cell recordings from other central neurons and presumably reflects a
voltage-dependent relief of ZD7288 blockade (BoSmith et al.
1993; Harris and Constanti 1995; Williams
et al. 1997). In summary, we have observed a predominant apical
dendritic distribution of a conductance that by analogy with the
properties of whole cell currents reflects the activation of the mixed
cationic current Ih.
Independence of EPSP time course on dendritic location
Simulated EPSPs (sEPSPs) generated by current injection through
somatic and dendritic whole cell recording pipettes (exponential rise
0.3 ms, decay 3 ms) (Stuart and Sakmann 1995) were used
to explore the location dependence of EPSP time course (Fig.
2A). The time course of sEPSPs
generated by apical dendritic current injection recorded at source and
after propagation to the soma were distinct and demonstrated a
characteristic crossing during their decaying phase (Fig.
2A) (see Stuart and Spruston 1998). The
half-width of somatically and dendritically generated sEPSPs recorded
at the soma were similar regardless of the site of sEPSPs generation
(n = 38; Fig. 2, B and C).
Regression analysis revealed that, as sEPSPs were generated more
distally, the half-width of sEPSPs recorded at the soma increased by
just 0.4 ms/100 µm (Fig. 2C). The 20-80% rise time of
sEPSPs at the soma, however, increased as the site of generation was
more distal (Fig. 2D). These data indicate an independence
of somatic sEPSPs duration with the site of EPSP generation, and a
dissociation between rise and decay kinetics that would not be apparent
in a uniformly passive system (Rall 1977). The
independence of somatic sEPSPs duration on the site of sEPSP generation
collapsed in the presence of the Ih
channel blocker ZD7288 (50 µM; n = 20). In ZD7288 the
half-width of somatic sEPSPs generated by dendritic current injection
outlasted sEPSPs generated by somatic current injection, and increased
as sEPSPs were generated more distally (Fig. 2, B and
C). Furthermore, the crossover between dendritic sEPSPs
recorded at source and after propagation to the soma was abolished (the
ratio of somatic to dendritic sEPSP amplitude at 25 ms was 1.32 ± 0.08 in control and 1.01 ± 0.02 in ZD7288; P < 0.05; n = 20). The rise time of propagated dendritic
sEPSPs was largely unaffected by ZD7288 (Fig. 2D). The
application of ZD7288 hyperpolarized the somatic RMP (by 11.1 ± 1.3 mV; n = 20), indicating that
Ih is active at the RMP. To compensate
for any effect this could have on somatic EPSP time course,
depolarizing current injection was used to maintain somatic membrane
potential in the presence of ZD7288. Furthermore, ZD7288 completely
abolished the depolarizing sag apparent during hyperpolarizing voltage
steps generated at somatic and dendritic recording locations
(n = 20). The small (<5 mV) membrane potential gradient between somatic and dendritic (more depolarized) recording locations (see Stuart et al. 1997a) was also abolished
by ZD7288 (n = 20), indicating that this gradient is
generated by Ih active at RMPs.
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To explore whether these findings were valid for sEPSPs with different time courses, we generated sEPSPs by current injections with a range of exponential rise and decay time constants (rise: 0.2, 0.3, 0.5, 1.0, 2.0 ms; decay: 2, 3, 5, 10, 20 ms; the amplitude of these current injections were varied to maintain the same amplitude of sEPSPs at the soma). Under control conditions the ratio of somatic sEPSP half-width for sEPSPs generated at the soma and those generated at dendritic sites was close to unity for all but the fastest sEPSPs (0.87 ± 0.03, 0.94 ± 0.01, 1.06 ± 0.06, 1.07 ± 0.03, 1.09 ± 0.03, n = 6). In the presence of ZD7288 this ratio decreased to less than one for all sEPSPs (0.68 ± 0.05, 0.79 ± 0.04, 0.93 ± 0.03, 0.93 ± 0.01, 0.93 ± 0.02, n = 6), indicating that the effect of Ih normalization of somatic sEPSP half-width is relatively independent of the time course of the excitatory postsynaptic current.
Ih channels prevent temporal summation of dendritic EPSPs
In a uniformly passive system, distal EPSPs would be expected to show greater somatic temporal summation than proximal or somatic EPSPs because of their slower decay kinetics at the soma. The normalization of sEPSP half-width observed here, however, suggests that this may not occur in layer 5 pyramidal neurons. To test this, a train of five sEPSPs at 50 Hz were generated at somatic and apical dendritic sites, and the integral of the voltage response was measured at the soma after normalization of the amplitude of the first EPSP. Under control conditions we observed that sEPSPs did not appreciably summate when generated from any recording location (Fig. 3, A and B), with the integral of sEPSPs increasing only marginally as the site of sEPSP generation was more distal (3.8 µV · s/100 µm; Fig. 3B). Bath application of ZD7288 (50 µM) unmasked temporal summation of sEPSPs generated at both somatic and dendritic locations (Fig. 3A). In the presence of ZD7288, however, dendritically generated sEPSPs summated to a greater extent than somatically generated sEPSPs, an effect that was more pronounced for more distally generated sEPSPs (Fig. 3, A and B).
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The temporal summation of sEPSPs unmasked by ZD7288 may lead to the
recruitment of other membrane currents, such as the persistent sodium
current, INap, which has been shown to
effect the amplitude and time course of both single and bursts of EPSPs
at depolarized membrane potentials in neocortical layer 5 pyramidal
neurons (Stuart and Sakmann 1995; Williams and
Stuart 1999). Although temporal summation at the soma was
largely absent at RMPs under control conditions (Fig. 3A),
we observed that trains of dendritic sEPSPs generated at depolarized
membrane potentials (on average 8.3 ± 0.8 mV positive to RMP)
showed significant temporal summation (Fig. 3C; increase in
integral of 95 ± 19%; n = 5). This effect of
somatic depolarization was enhanced in the presence of ZD7288 (Fig.
3C). Increased temporal summation of sEPSPs at depolarized potentials in ZD7288 was largely abolished by the addition of the
sodium channel blocker TTX (1µM; n = 5; Fig.
3C). TTX also reduced temporal summation of sEPSPs at the
RMP in ZD7288 (Fig. 3C; decrease in integral 17 ± 7%;
n = 5), indicating that the increased temporal
summation of sEPSPsin the presence of ZD7288 is in part due to the
activation of INap.
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DISCUSSION |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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The main findings of the present investigation are 1) Ih channels are located at a high density in the apical dendrites of neocortical layer 5 pyramidal neurons, 2) somatic EPSP time course is independent of the site of generation, as is temporal summation, and 3) blockade of Ih channels reveals site dependence of somatic EPSP time course and temporal summation.
Under control conditions dendritically generated sEPSPs recorded at
source decayed faster than the propagated sEPSPs recorded at the soma,
leading to a crossover of their decay phase. This behavior is not
expected from a uniformly passive system and is a consequence of a
higher membrane conductance (Gm) at
dendritic sites (London et al. 1999; Stuart and
Spruston 1998). In the present investigation we observed that
crossing of source and propagated sEPSPs was abolished by blockade of
Ih channels, indicating that Ih channels open at the RMP are
responsible for increased Gm in apical
dendrites and are not supplemented by other nonuniform conductances as
previously suggested (Stuart and Spruston 1998). Ih does not, however, operate simply
as a shunt conductance; the crossover of source and propagated sEPSPs
will be further increased as a consequence of the voltage-dependent
deactivation of Ih during EPSPs,
leading to the generation of a net outward current that curtails their decay (Magee 1999; Nicoll et al.
1993). The properties of Ih
observed in cell-attached patches indicates that
Ih deactivation at physiological
temperatures is sufficiently rapid to mediate this effect. At
increasing distal dendritic locations these effects will be greater due
to both the higher density of Ih
channels and the increased local EPSP amplitude. The physiological
consequence of this is site independence of EPSP time course at the
soma. This effect was observed for a wide range of sEPSP kinetics but was less for sEPSPs with fast kinetics.
The pattern of local integration in dendrites will be effected by
Ih channels. At distal dendritic sites
the integration time window, in a uniformly passive system, is shorter
than at the soma as a consequence of the rapid flow of current from
source to neighboring dendritic sites (Koch et al.
1996). The high density of dendritic
Ih channels, observed here, will
further reduce the time window for dendritic integration, decreasing
the likelihood that summation of distal synaptic inputs will reach
threshold for activating dendritic regenerative events
(Andreasen and Lambert 1998; Golding and Spruston
1998; Schiller et al. 1997; Schwindt and
Crill 1997; Stuart et al. 1997a). This will have
the effect of focusing EPSP integration at the level of the soma and axon.
The site independence of EPSP time course and temporal summation
ensures that the temporal nature of synaptic integration at the site of
action potential initiation in the axon of neocortical layer 5 pyramidal neurons will be similar for distal and proximal synaptic
inputs. The nonuniform Gm produced by
Ih and the activation/deactivation properties of Ih should ensure that
temporal integration is normalized across a range of membrane
potentials, EPSP amplitudes, and repetition frequencies (see also
Magee 1999). Under control conditions, however, EPSPs
summate more effectively when generated at somatic membrane potentials
close to firing threshold, due to the activation of INap. Given that
INap has a predominant axosomatic
location (Andreasen and Lambert 1999; Stuart and
Sakmann 1995), and Ih an
apical dendritic location, temporal summation will be increased by
somatic depolarization following the activation of
INap, and by dendritic depolarization through a reduction in Ih
availability, whereas hyperpolarization of these different compartments
will have the opposite effect. Temporal summation of EPSPs at the soma
in layer 5 pyramidal neurons will therefore be determined by the
spatial pattern of excitation and be inhibition as a consequence of
nonuniform distributions of Ih and
INap.
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ACKNOWLEDGMENTS |
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This work was supported by the Wellcome Trust.
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FOOTNOTES |
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Address for reprint requests: G. Stuart, Division of Neuroscience, John Curtin School of Medical Research, Mills Rd., Australian National University, Canberra, ACT 0200, Australia.
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Received 16 December 1999; accepted in final form 4 February 2000.
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REFERENCES |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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M. H.P. Kole, A. U. Brauer, and G. J. Stuart Inherited cortical HCN1 channel loss amplifies dendritic calcium electrogenesis and burst firing in a rat absence epilepsy model J. Physiol., January 15, 2007; 578(2): 507 - 525. [Abstract] [Full Text] [PDF]
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J. A. Goldberg, C. A. Deister, and C. J. Wilson Response Properties and Synchronization of Rhythmically Firing Dendritic Neurons J Neurophysiol, January 1, 2007; 97(1): 208 - 219. [Abstract] [Full Text] [PDF]
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J. J. Letzkus, B. M. Kampa, and G. J. Stuart Learning Rules for Spike Timing-Dependent Plasticity Depend on Dendritic Synapse Location J. Neurosci., October 11, 2006; 26(41): 10420 - 10429. [Abstract] [Full Text] [PDF]
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I. van Welie, M. W. H. Remme, J. A. van Hooft, and W. J. Wadman Different levels of Ih determine distinct temporal integration in bursting and regular-spiking neurons in rat subiculum J. Physiol., October 1, 2006; 576(1): 203 - 214. [Abstract] [Full Text] [PDF]
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J. B. Hardie and R. A. Pearce Active and Passive Membrane Properties and Intrinsic Kinetics Shape Synaptic Inhibition in Hippocampal CA1 Pyramidal Neurons. J. Neurosci., August 15, 2006; 26(33): 8559 - 8569. [Abstract] [Full Text] [PDF]
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Y. Aponte, C.-C. Lien, E. Reisinger, and P. Jonas Hyperpolarization-activated cation channels in fast-spiking interneurons of rat hippocampus J. Physiol., July 1, 2006; 574(1): 229 - 243. [Abstract] [Full Text] [PDF]
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Y. Rateau and N. Ropert Expression of a Functional Hyperpolarization-Activated Current (Ih) in the Mouse Nucleus Reticularis Thalami J Neurophysiol, May 1, 2006; 95(5): 3073 - 3085. [Abstract] [Full Text] [PDF]
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M. H. P. Kole, S. Hallermann, and G. J. Stuart Single Ih Channels in Pyramidal Neuron Dendrites: Properties, Distribution, and Impact on Action Potential Output J. Neurosci., February 8, 2006; 26(6): 1677 - 1687. [Abstract] [Full Text] [PDF]
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A. R. A. Rodrigues and D. Oertel Hyperpolarization-Activated Currents Regulate Excitability in Stellate Cells of the Mammalian Ventral Cochlear Nucleus J Neurophysiol, January 1, 2006; 95(1): 76 - 87. [Abstract] [Full Text] [PDF]
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N. Keren, N. Peled, and A. Korngreen Constraining Compartmental Models Using Multiple Voltage Recordings and Genetic Algorithms J Neurophysiol, December 1, 2005; 94(6): 3730 - 3742. [Abstract] [Full Text] [PDF]
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E. Christophe, N. Doerflinger, D. J. Lavery, Z. Molnar, S. Charpak, and E. Audinat Two Populations of Layer V Pyramidal Cells of the Mouse Neocortex: Development and Sensitivity to Anesthetics J Neurophysiol, November 1, 2005; 94(5): 3357 - 3367. [Abstract] [Full Text] [PDF]
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R. Azouz Dynamic Spatiotemporal Synaptic Integration in Cortical Neurons: Neuronal Gain, Revisited J Neurophysiol, October 1, 2005; 94(4): 2785 - 2796. [Abstract] [Full Text] [PDF]
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N. L Golding, T. J Mickus, Y. Katz, W. L Kath, and N. Spruston Factors mediating powerful voltage attenuation along CA1 pyramidal neuron dendrites J. Physiol., October 1, 2005; 568(1): 69 - 82. [Abstract] [Full Text] [PDF]
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J. Wu and J. J. Hablitz Cooperative Activation of D1 and D2 Dopamine Receptors Enhances a Hyperpolarization-Activated Inward Current in Layer I Interneurons J. Neurosci., July 6, 2005; 25(27): 6322 - 6328. [Abstract] [Full Text] [PDF]
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S. R. Williams Encoding and Decoding of Dendritic Excitation during Active States in Pyramidal Neurons J. Neurosci., June 22, 2005; 25(25): 5894 - 5902. [Abstract] [Full Text] [PDF]
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H. Oviedo and A. D. Reyes Variation of Input-Output Properties along the Somatodendritic Axis of Pyramidal Neurons J. Neurosci., May 18, 2005; 25(20): 4985 - 4995. [Abstract] [Full Text] [PDF]
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C. S. Chan, R. Shigemoto, J. N. Mercer, and D. J. Surmeier HCN2 and HCN1 Channels Govern the Regularity of Autonomous Pacemaking and Synaptic Resetting in Globus Pallidus Neurons J. Neurosci., November 3, 2004; 24(44): 9921 - 9932. [Abstract] [Full Text] [PDF]
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N. A. Otmakhova and J. E. Lisman Contribution of Ih and GABAB to Synaptically Induced Afterhyperpolarizations in CA1: A Brake on the NMDA Response J Neurophysiol, October 1, 2004; 92(4): 2027 - 2039. [Abstract] [Full Text] [PDF]
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W. W. Wu, C. S. Chan, and J. F. Disterhoft Slow Afterhyperpolarization Governs the Development of NMDA Receptor-Dependent Afterdepolarization in CA1 Pyramidal Neurons During Synaptic Stimulation J Neurophysiol, October 1, 2004; 92(4): 2346 - 2356. [Abstract] [Full Text] [PDF]
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 K. Kimura, J. Kitano, Y. Nakajima, and S. Nakanishi Hyperpolarization-activated, cyclic nucleotide-gated HCN2 cation channel forms a protein assembly with multiple neuronal scaffold proteins in distinct modes of protein-protein interaction Genes Cells, July 1, 2004; 9(7): 631 - 640. [Abstract] [Full Text] [PDF]
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T. Berger, W. Senn, and H.-R. Luscher Hyperpolarization-Activated Current Ih Disconnects Somatic and Dendritic Spike Initiation Zones in Layer V Pyramidal Neurons J Neurophysiol, October 1, 2003; 90(4): 2428 - 2437. [Abstract] [Full Text] [PDF]
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S. R. Williams and G. J. Stuart Voltage- and Site-Dependent Control of the Somatic Impact of Dendritic IPSPs J. Neurosci., August 13, 2003; 23(19): 7358 - 7367. [Abstract] [Full Text] [PDF]
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T. Takigawa and C. Alzheimer Interplay Between Activation of GIRK Current and Deactivation of Ih Modifies Temporal Integration of Excitatory Input in CA1 Pyramidal Cells J Neurophysiol, April 1, 2003; 89(4): 2238 - 2244. [Abstract] [Full Text] [PDF]
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M. Rudolph and A. Destexhe A Fast-Conducting, Stochastic Integrative Mode for Neocortical Neurons InVivo J. Neurosci., March 15, 2003; 23(6): 2466 - 2476. [Abstract] [Full Text] [PDF]
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T. Berger and H.-R. Luscher Timing and Precision of Spike Initiation in Layer V Pyramidal Cells of the Rat Somatosensory Cortex Cereb Cortex, March 1, 2003; 13(3): 274 - 281. [Abstract] [Full Text] [PDF]
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D. V. Vasilyev and M. E. Barish Postnatal Development of the Hyperpolarization-Activated Excitatory Current Ih in Mouse Hippocampal Pyramidal Neurons J. Neurosci., October 15, 2002; 22(20): 8992 - 9004. [Abstract] [Full Text] [PDF]
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D. Ulrich Dendritic Resonance in Rat Neocortical Pyramidal Cells J Neurophysiol, June 1, 2002; 87(6): 2753 - 2759. [Abstract] [Full Text] [PDF]
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S. R. Williams and G. J. Stuart Dependence of EPSP Efficacy on Synapse Location in Neocortical Pyramidal Neurons Science, March 8, 2002; 295(5561): 1907 - 1910. [Abstract] [Full Text] [PDF]
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A. J Trevelyan and J. Jack Detailed passive cable models of layer 2/3 pyramidal cells in rat visual cortex at different temperatures J. Physiol., March 1, 2002; 539(2): 623 - 636. [Abstract] [Full Text] [PDF]
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G. Tamas, J. Szabadics, and P. Somogyi Cell Type- and Subcellular Position-Dependent Summation of Unitary Postsynaptic Potentials in Neocortical Neurons J. Neurosci., February 1, 2002; 22(3): 740 - 747. [Abstract] [Full Text] [PDF]
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 Y.-N. Jan and L. Y. Jan Dendrites Genes & Dev., October 15, 2001; 15(20): 2627 - 2641. [Full Text] [PDF]
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G. Gonzalez-Burgos and G. Barrionuevo Voltage-Gated Sodium Channels Shape Subthreshold EPSPs in Layer 5 Pyramidal Neurons From Rat Prefrontal Cortex J Neurophysiol, October 1, 2001; 86(4): 1671 - 1684. [Abstract] [Full Text] [PDF]
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P. A Rhodes and R. R Llinas Apical tuft input efficacy in layer 5 pyramidal cells from rat visual cortex J. Physiol., October 1, 2001; 536(1): 167 - 187. [Abstract] [Full Text] [PDF]
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J. M. Bekkers and A. J. Delaney Modulation of Excitability by {alpha}-Dendrotoxin-Sensitive Potassium Channels in Neocortical Pyramidal Neurons J. Neurosci., September 1, 2001; 21(17): 6553 - 6560. [Abstract] [Full Text] [PDF]
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T. Berger, M. E. Larkum, and H.-R. Luscher High Ih Channel Density in the Distal Apical Dendrite of Layer V Pyramidal Cells Increases Bidirectional Attenuation of EPSPs J Neurophysiol, February 1, 2001; 85(2): 855 - 868. [Abstract] [Full Text] [PDF]
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M. Häusser, G. Major, and G. J. Stuart Differential Shunting of EPSPs by Action Potentials Science, January 5, 2001; 291(5501): 138 - 141. [Abstract] [Full Text]
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I. M. Raman, A. E. Gustafson, and D. Padgett Ionic Currents and Spontaneous Firing in Neurons Isolated from the Cerebellar Nuclei J. Neurosci., December 15, 2000; 20(24): 9004 - 9016. [Abstract] [Full Text] [PDF]
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M. Häusser, N. Spruston, and G. J. Stuart Diversity and Dynamics of Dendritic Signaling Science, October 27, 2000; 290(5492): 739 - 744. [Abstract] [Full Text]
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) and deactivation (
) at different
test potentials. Each point is the mean ± SE and was fit with a
single exponential for recordings made at 20-24°C and 34-35°C.
