 |
 Previous Article | Next Article 
The Journal of Neuroscience, February 15, 2000, 20(4):1307-1317
Action Potential Backpropagation and Somato-dendritic
Distribution of Ion Channels in Thalamocortical Neurons
Stephen R.
Williams and
Greg J.
Stuart
Division of Neuroscience, John Curtin School of Medical Research,
Australian National University, Canberra, A.C.T. 0200, Australia
 |
ABSTRACT |
Thalamocortical (TC) neurons of the dorsal thalamus integrate
sensory inputs in an attentionally relevant manner during wakefulness and exhibit complex network-driven and intrinsic oscillatory activity during sleep. Despite these complex intrinsic and network functions, little is known about the dendritic distribution of ion channels in TC
neurons or the role such channel distributions may play in synaptic
integration. Here we demonstrate with simultaneous somatic and
dendritic recordings from TC neurons in brain slices that action
potentials evoked by sensory or cortical excitatory postsynaptic
potentials are initiated near the soma and backpropagate into the
dendrites of TC neurons. Cell-attached recordings demonstrated that TC
neuron dendrites contain a nonuniform distribution of sodium but a
roughly uniform density of potassium channels across the
somatodendritic area examined that corresponds to approximately half
the average path length of TC neuron dendrites. Dendritic action
potential backpropagation was found to be active, but compromised by
dendritic branching, such that action potentials may fail to invade
relatively distal dendrites. We have also observed that calcium
channels are nonuniformly distributed in the dendrites of TC neurons.
Low-threshold calcium channels were found to be concentrated at
proximal dendritic locations, sites known to receive excitatory
synaptic connections from primary afferents, suggesting that they play
a key role in the amplification of sensory inputs to TC neurons.
Key words:
sodium channel; calcium channel; potassium channel; burst
firing; patch clamp; dendrite; thalamus
| |
INTRODUCTION |
Thalamocortical (TC) neurons of the
dorsal thalamus integrate synaptic input from the periphery, neocortex,
and brainstem to convey sensory information to the neocortex in an
attentionally relevant and state-dependent manner (Steriade and
Deschenes, 1984 ; McCormick, 1992; Steriade et al., 1993; Guido and
Weyand, 1995; Sherman and Guillery, 1996). The complex
electrophysiological properties of TC neurons serve to highlight their
important integrative role (McCormick, 1992). Anatomical studies have
revealed a precise organization of excitatory inputs from sensory and
cortical inputs to the stem and relatively distal dendrites of TC
neurons, respectively (Ralston and Herman, 1969; Sherman and Guillery,
1996). A similar anatomical segregation of inhibitory inputs from
intrinsic and extrinsic GABAergic neurons may facilitate complex
synaptic interactions in the dendrites of TC neurons (Sherman and
Guillery, 1996). This synaptic organization highlights the need to
directly investigate dendritic function in TC neurons.
Recent advances in recording techniques have allowed investigation of
the distribution of voltage-activated channels that influence synaptic
integration in the dendrites of several types of central neurons
(Johnston et al., 1996; Stuart et al., 1997b). The complex radial,
multi-branched fine caliber dendritic arbor of TC neurons (Grossman et
al., 1973; Bloomfield et al., 1987; Havton and Ohara, 1993; Ohara and
Havton, 1994; Ohara et al., 1995; Warren and Jones, 1997), however, has
until now precluded direct analysis. Imaging, anatomical, and
modeling studies have indicated that the dendrites of TC neurons
contain voltage-activated calcium currents (Munsch et al., 1997; Zhou
et al., 1997; Budde et al., 1998; Destexhe et al., 1998); however, the
distribution and properties of these channels are unknown.
Simultaneous dendritic and somatic recording would allow investigation
of the site(s) of action potential generation in TC neurons (Stuart et
al., 1997b). Furthermore, once generated, action potentials may
backpropagate into TC dendrites, where the complex dendritic branching
of these neurons may influence action potential invasion (Spruston et
al., 1995). Recent modeling studies have indicated that the geometry of
the dendritic tree plays a key role in controlling the extent of active
backpropagation of action potentials, with complex multi-branched
dendritic arbors compromising this form of retrograde information
transfer (Hausser et al., 1998). Similarly, modeling studies of
branched cable and axonal structures have demonstrated that propagation
of action potentials may fail or be compromised at branch points
(Goldstein and Rall, 1974; Luscher and Shiner, 1990; Manor et al.,
1991). The multi-branched structure of TC neuron dendrites, therefore,
allows direct investigation of the role of dendritic branch points in
the control of action potential backpropagation. The failure of action
potential invasion into parts of a multi-branched dendritic tree may
have important functional outcomes. For example, backpropagating action
potentials may invade some areas of the dendritic tree resetting
synaptic integration but fail to influence activity in others (Spruston et al., 1995; Magee and Johnston, 1997; Stuart et al., 1997b; Stuart
and Hausser, 1998).
Here we directly address these issues by making simultaneous whole-cell
and cell-attached patch-clamp recordings from the soma and dendrites of
TC neurons in slices of the dorsal lateral geniculate nucleus (dLGN).
| |
MATERIALS AND METHODS |
Experiments were performed according to methods approved by the
Animal Experimentation Ethics Committee of the Australian National
University. Wistar rats (postnatal day 16-22) were decapitated, and
300-µm-thick brain slices of the dorsal lateral geniculate nucleus
were prepared either in the plane of the optic tract (Crunelli et al.,
1987b; Williams et al., 1996) or parasagittally (Turner and Salt,
1998). At this age, the synaptic, morphological, and electrophysiological properties of rat TC neurons are similar to those
of adult animals (Perez Velazquez and Carlen, 1996; Warren and Jones,
1997; Warren et al., 1997; Golshani et al., 1998).
Slices were perfused with oxygenated Ringer's solution of the
following composition (in mM): 125 NaCl, 25 NaHCO3, 3 KCl, 1.25 NaH2PO4, 2 CaCl2, 1 MgCl2, and 10 glucose. Experiments on action potential backpropagation were performed
at 31-33°C; all other experiments were conducted at room temperature
(20-24°C). Simultaneous somatic (pipette resistance 2-7 M ) and
dendritic (pipette resistance 10-15 M) patch-clamp recordings were
made from visually identified TC neurons using two identical
current-clamp amplifiers (Dagan) as previously described (Stuart and
Sakmann, 1994). If the formation of a dendritic recording altered the
somatic membrane potential or input resistance, both recordings were
abandoned. A patch-clamp amplifier (Axon Instruments) was used in
voltage and fast current-clamp mode for experiments involving the
generation of a somatic action potential waveform in the presence of
tetrodotoxin (TTX). Synaptic potentials were evoked with the use of a
metal bipolar electrode or a patch pipette (1-2 M) placed within
the optic tract, within the nucleus reticularis thalami to stimulate
fibers of the cortical backprojection, or close (within 100 µm) to
the recorded neuron. Synaptic responses were evoked at low frequency
(0.1-0.5 Hz), usually in the presence of the
GABAA receptor antagonist bicuculline methiodide.
Somatic and dendritic cell-attached recordings (pipette resistance
12-15 M) were made using on-line leak subtraction (P/4), and
careful adjustment of pipette capacitance neutralization was made. 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 and dendritic sites, suggesting that similar membrane
areas were sampled. For whole-cell recordings, patch electrodes were
filled with the following (in mM): 135 K-gluconate, 7 NaCl,
10 HEPES, 0.5 EGTA, 2 Na2-ATP, 0.3 Na2-GTP, 10 Na2-phosphocreatine, and 2 MgCl (pH 7.2 adjusted
with KOH; osmolarity 270 mOsm). No correction was made for liquid
junction potentials. For cell-attached recordings of Na and K currents,
patch electrodes contained (in mM): 135 NaCl, 3 KCl, 1 CaCl2, 2 MgCl2, 3 NiCl2, 0.5 CdCl2,10 HEPES,
and 10 glucose, pH 7.2; whereas for recordings of
Ca2+ currents, electrodes contained 140 mM tetraethylammonium chloride (TEA), 10 mM
BaCl2, 2 mM
MgCl2, 1 mM
CsCl2, 3 mM 4-aminopyridine, 1 µM TTX, and 10 mM HEPES (pH 7.2 adjusted with
Tris-base solution) (Mouginot et al., 1997). For whole-cell recordings,
voltage and current signals were filtered at 10 or 30 kHz, whereas for
cell-attached recordings current signals were filtered at 2-5 kHz.
Signals were acquired at 20-100 kHz, using an ITC-16 interface
(Instrutech Corporation, Long Island, NY) controlled by an Apple
PowerPC implementing Axograph acquisition and analysis software (kindly
supplied by Dr. J. Clements, Division of Neuroscience, Australian
National University). Maximal conductance was calculated with an
equation of the form g = I/(VT  Vrev), where I is the
recorded current, VT is the test
voltage, and Vrev is the reversal
potential extrapolated from current-voltage relationships.
Steady-state activation and inactivation curves were fit with a single
Boltzmann equation of the form: y = 1/(1 + e(V1/2  V)/k), where
V1/2 is the voltage of half-maximal
activation or inactivation, and k is a constant. The rise
and decay of outward currents were fit with an equation of the form
y = a (1 e(t/ rise))G · (e(t/decay) + c), where t is time,
 rise and decay are
the time constants of rise and decay, b is the power of the
activation process (Huguenard et al., 1991), and a and
c are scaling factors. Numerical values are given in the
text as mean ± SEM, unless stated otherwise. Statistical analysis
was performed with either Student's t test or ANOVA,
with statistical significance determined with  = 0.05.
| |
RESULTS |
The dendritic morphology of TC neurons is well preserved in slices
of the rat dLGN (Crunelli et al., 1987b; Williams et al., 1996). These
neurons exhibit radial dendritic trees, with 3-10 stem dendrites, that
branch to form second to seventh order terminal dendrites (Williams et
al., 1996). The dendritic path length (length from origin to
termination) has been found to be on average 151 µm (range 58-193
µm) in TC neurons of the adult rat somatosensory thalamus (Ohara and
Havton, 1994). In the present investigation, dLGN TC neurons were
visually identified using interference contrast video microscopy (see
Fig. 5B) by their relatively large round somata and the
presence of three or more stem dendrites, which had diameters of
~1-3 µm. This method of identification was confirmed by somatic
whole-cell recordings that revealed characteristic electrophysiological
properties of TC neurons, namely a robust low-threshold calcium
potential and a highly rectified voltage-current relationship
(Williams et al., 1996).
Initiation and backpropagation of action potentials
Simultaneous whole-cell current-clamp recordings were made from
the soma and dendrites of TC neurons. Electrical stimulation of the
sensory input (optic tract) (n = 6) or cortical
backprojection (n = 8) evoked EPSPs that led to
the generation of either a single or high-frequency burst of action
potentials in a voltage-dependent manner (Fig.
1A,C).
This corresponds to the two action potential firing modes of TC neurons
(Deschenes et al., 1982; Llinas and Jahnsen, 1982). Burst firing is
known to be driven by the activation of low-threshold calcium
(IT) channels, which form a transient depolarizing potential termed a low-threshold calcium potential (LTCP)
(Crunelli et al., 1987a; Llinas, 1988; Coulter et al., 1989;
Hernandez-Cruz and Pape, 1989; McCormick, 1992; Steriade et al., 1993).
This LTCP has recently been suggested to be generated by
IT channels located in the distal
dendrites of TC neurons (Destexhe et al., 1998). Activation of these
calcium channels may therefore lead to dendritic depolarization
sufficient to evoke dendritic action potential initiation, as has been
shown in other central neurons after intense distal dendritic
depolarization (Schiller et al., 1997; Stuart et al., 1997a; Golding
and Spruston, 1998).
View larger version (23K):
[in this window]
[in a new window]
|
Figure 1.
EPSPs evoke action potentials that backpropagate
into the dendrites of TC neurons. A, Simultaneous
somatic and stem dendritic (25 µm from the soma/dendritic
intersection) recording of action potentials evoked by electrical
stimulation of fibers of the optic tract. EPSPs led to the generation
of a single or a burst discharge of action potentials, in a
voltage-dependent manner. Membrane potential (indicated to the
left of traces) was controlled by the tonic
passage of current through the somatic electrode. The
inset shows the first somatic and dendritic
(thick trace) action potential at a faster time base.
Note that action potentials are recorded first at the soma.
B, Repetitive stimulation (5 stimuli at 100 Hz) of optic
tract fibers evoked EPSPs that depress during the train. The top
inset shows superposed somatic and dendritic action potentials,
and the bottom inset the rising phase of the first EPSP
of the train. Note that the EPSP rise time is faster in the dendritic
recording made from a secondary dendrite 37 µm from the
soma/dendritic intersection. C, Action potential
discharge evoked by electrical stimulation of fibers of the
corticothalamic tract. The dendritic recording was made from a stem
dendrite 35 µm from the soma/dendritic intersection. The
inset shows the first somatic and dendritic
(thick trace) action potential at a faster time base.
Note that action potentials are recorded first at the soma.
D, Repetitive stimulation of this pathway evoked
EPSPs that showed frequency-dependent facilitation. The top
inset shows superposed somatic and stem dendritic (30 µm from
the soma/dendritic intersection) action potentials, and the
bottom inset shows slow regenerative potentials at a
faster time base.
|
|
Under all conditions, EPSPs led to the generation of single or
LTCP-driven bursts of action potentials that were always recorded first
at the somatic recording electrode (n = 14) (Fig.
1A,C, insets). In an
attempt to depolarize the dendrites of TC neurons to a greater extent
to search for dendritic action potential initiation, we repetitively
stimulated the sensory and cortical inputs (Fig. 1B,D). Repetitive stimulation of
the sensory input led to profound frequency-dependent depression of
EPSPs (Fig. 1B); the summated series of EPSPs,
however, always evoked action potentials that were recorded first
somatically (n = 6) (Fig. 1B,
inset). In contrast, repetitive stimulation of the cortical
backprojection led to frequency-dependent facilitation, where each EPSP
of a train increased in amplitude (Fig. 1D). This
form of input depolarized neurons to such an extent that action
potentials were inactivated and replaced by the generation of slower
regenerative events (Fig. 1D, bottom
inset) (Turner and Salt, 1998). Despite this powerful form of
distal dendritic depolarization, all action potentials and slow
regenerative events were recorded first from somatic sites
(n = 8) (Fig. 1D), indicating that
action potential initiation does not occur in TC neuron dendrites.
To further explore the site of action potential initiation in TC
neurons, we evoked action potentials by the injection of current at the
soma or at the dendritic recording site (n = 40) (Fig.
2A). In all neurons
examined, action potentials were first recorded at the soma and then
backpropagated into the dendritic tree. Action potential
backpropagation was found to be decremental, with the degree of
attenuation related to the dendritic recording location. The effects of
recording location are summarized in Figure 2A, where
dendritic recordings were sequentially made at the first dichotomous
branch point, from its stem dendrite, and from one of its daughter
dendrites of the same neuron. Note that the amplitude and shape of
backpropagating dendritic action potentials are dramatically altered at
and after the dendritic branch point. Pooled data derived from
simultaneous somatic and dendritic recordings (n = 27)
demonstrated that when dendritic recordings were made from a stem
dendrite, the amplitude of dendritic action potentials decreased, on
average, by 3.8% per 10 µm (distances from soma/dendrite intersection) (Fig. 2B,  ). Dendritic recordings
made from higher order (second or third) dendrites (n = 13) revealed that action potential attenuation was increased after
dendritic branching, proceeding with a steeper average slope of 9% per
10 µm (Fig. 2B,  ). To ascertain in any given
dendrite whether a branch point-induced decrease in action potential
backpropagation occurred, recordings were made from the same dendrite
at sites before and after a branch. For an average dendritic electrode
separation of 16.5 µm, an average decrease in action potential
amplitude of 27.4% was observed (Fig. 2B,
inset). This value is greater than that found for action
potential attenuation along an unbranched dendrite, emphasizing the
deleterious effects of dendritic branching on action potential
backpropagation. The attenuation of slower voltage changes of the
membrane were measured by plotting the degree of steady-state voltage
attenuation from soma to dendrite (determined at the termination of
small, negative, 200-500 msec somatic current steps that evoked
voltage deviations of <5 mV at the soma). The degree of steady-state
attenuation was found to be 2.9% per 10 µm along stem dendrites and
4% per 10 µm when recordings were made after dendritic branching
(Fig. 2C), indicating that steady-state attenuation is not
noticeably effected by dendritic branching. The relationship between
action potential and steady-state voltage attenuation was found to be close to 1 for recordings made from stem dendrites, but <1 for recordings made after dendritic branching (Fig. 2D).
This suggests that action potential backpropagation is active; that is,
it is reliant on the activation of dendritic voltage-activated ionic currents, because a near-unity relationship between action potential and steady-state attenuation in stem dendrites would not be expected for a passive system.
View larger version (27K):
[in this window]
[in a new window]
|
Figure 2.
Action potential backpropagation into the
dendrites of TC neurons. A, Simultaneous somatic and
dendritic recordings of action potentials evoked by somatic current
injection. Dendritic recordings were sequentially made from the first
branch point of a stem dendrite (35 µm from the soma/dendrite
intersection), from the stem dendrite (20 µm), and from one of its
daughter dendrites (62 µm). Note changes in action potential onset,
the abrupt decrease in amplitude, and increase in action potential
duration for recordings made at and after the dendritic branch point.
B, Pooled data demonstrate the relationship between
action potential amplitude and dendritic recording location for
recordings made from stem () and higher order () dendrites. All
data from simultaneous somatic and dendritic recordings. The average
amplitude of somatic action potentials (±SD) is shown as the
filled square. Lines represent regression
analysis, constrained to the average somatic action potential
amplitude. The inset shows the degree of reduction of
action potential amplitude for recordings made before () and after
() a branch point from the same dendrite. C,
Normalized steady-state attenuation of small negative voltage responses
evoked at the soma for recordings made from stem () and higher order
dendrites (). Lines represent regression analysis,
constrained at origin to 1. D, Relationship between
normalized steady-state attenuation and normalized action potential
attenuation for recordings made from stem () and higher order
dendrites (); the line has a slope of 1.
|
|
Distribution of sodium and potassium channels
Somatic and dendritic cell-attached recordings (n = 46) were used to map the distribution and basic properties of sodium
and potassium channels. From a pipette voltage of 0 mV [i.e., from the
resting membrane potential (RMP) of the cell], a 40 mV, 500 msec
prepulse was used to remove steady-state inactivation, followed by a
positive test pulse to +90 mV. The mean whole-cell RMP of neurons was
73 ± 1 mV; therefore, the voltage change of the membrane will
be from approximately 113 mV to +17 mV. When the contribution of a
liquid-junction and Donnan equilibrium potentials are considered (Verheugen et al., 1999), however, the true resting potential of
neurons is probably closer to 80 mV. Figure
3 demonstrates examples of cell-attached
patch currents during steps to these test potentials, which were
characterized by a fast transient inward current followed by a
bi-phasic outward current. This ensemble channel activity was variable
from trial to trial (Fig. 3A). An incremental series (+30 to + 150 mV) of positive test pulses were used to establish the nature of
these currents (Fig. 3B). The fast inward current first
activated ~40 mV positive to RMP, peaked close to ~80 mV positive
to RMP, and demonstrated voltage-dependent activation kinetics (Fig.
3B,D). This current was
substantially inactivated by omitting the hyperpolarizing prepulse or
applying small positive (20 mV) prepulses (data not shown). Given that calcium currents were blocked under our recording conditions, this
cell-attached inward current is most likely a fast sodium current
(INa) (Parri and Crunelli, 1998). The
amplitude of INa was found to be
variable from patch to patch, but on average it was similar for
recordings made from the soma, stem dendrites, and at the first
dendritic branch point (Fig. 3C). The average amplitude of
INa in recordings made from higher
order dendrites was found, however, to be relatively smaller than those
recorded from the soma (p < 0.05, t
test) (Fig. 3C). At the test potential used to assess sodium
channel density, the amplitude of the fast inward current was minimally
distorted by the presence of outward currents because the activation of
outward currents was relatively slow and possessed a sigmoidal time
course. The predicted time course of the outward current is shown by
extrapolation from fits made to the rise and decay of the outward
current in Figure 3A,B. Note that
at the peak of INa little outward
current is activated.
View larger version (26K):
[in this window]
[in a new window]
|
Figure 3.
Properties and somato-dendritic distribution of
sodium channels. A, Three consecutive single sweeps of
cell-attached patch currents recorded from a stem dendrite. Note the
clear appearance of a fast inward current followed by a slower outward
current. The bottom trace is an average
(n = 30 trials), and the dashed line
represents a fit to the rising and decaying phase of the outward
current (see Materials and Methods). Note that extrapolation of this
fit indicates that there is no significant outward current activation
at the time of the peak of the inward current. The voltage protocol is
shown as an inset. B, Superposed averaged
(n = 5 trials) cell-attached current records
demonstrate the voltage dependence of activation of the fast inward
current; data were obtained from a dendritic primary branch point. The
dashed lines represent fits made to the rise and decay
of the outward current. The voltage protocol is shown as an
inset. C, Pooled data demonstrating the
somato-dendritic distribution of the fast inward (sodium) current
during test pulses to +90 mV, as shown in A. The
line is an unconstrained regression fit. Filled
squares show mean (±SD) current as a function of distance from
the soma (±SD) for recordings made from the soma, stem dendrites,
primary branch points. and higher order dendrites (from
left to right, respectively). Note that
for higher order dendrites the amplitude of the fast inward (sodium)
current is on average reduced. D, Normalized
current-voltage relationship. Families of currents for a single neuron
were normalized to the maximal value, and then data from different
neurons were pooled (n = 13).
|
|
INa was followed by a bi-phasic
outward current, which was characterized by a relatively fast transient
component that, in turn, was followed by a more sustained component
(Fig.
4A,B). The relative fraction of these kinetically distinct components was
variable at different locations in the same neuron (Fig.
4A). The amplitude of the transient current was
calculated by subtraction of the value of the steady-state current at
the end of the test pulse (used to measure the sustained current) from
the peak of the current. We observed that some patches appeared to
contain only one of these components (data not shown). On average,
however, despite a large degree of interpatch variability, these
channels were found to be uniformly distributed on the soma, stem, and higher order dendrites (Fig. 4C,D). The uniform
density of outward currents is in contrast to that of
INa, indicating that any contamination of INa measurement by potassium
currents would be similar at all somato-dendritic locations. The
kinetic properties (Fig. 4B) of these ensemble
channel activities are similar to the transient IA-like and more slowly inactivating
delayed rectifier potassium currents identified by whole-cell recording
in TC neurons (Huguenard and Prince, 1991; Huguenard et al., 1991).
Furthermore, the transient component of the current was found to
activate from more hyperpolarized membrane potentials (Fig.
4B), as is the case for whole-cell
IA-like currents. It should be noted,
however, that the voltage dependence of activation of this transient
outward current may have been shifted in the depolarized direction by
the inclusion of calcium channel blockers in the patch pipette-filling
solution (Mayer and Sugiyama, 1988; Klee et al., 1995). In summary,
cell-attached recordings demonstrate that potassium channels are
localized in the dendrites of TC neurons at densities similar to those
of the soma.
View larger version (30K):
[in this window]
[in a new window]
|
Figure 4.
Properties and somato-dendritic distribution of
potassium channels. A, Averaged (n = 30 trails) cell-attached patch currents obtained from the indicated
somato-dendritic locations of a single neuron. Note that the amplitude
and the relative contribution of the transient and sustained outward
currents is variable from patch to patch. B, A family of
superposed cell-attached patch currents demonstrate the
voltage-dependent activation properties of the transient and sustained
outward currents, obtained from a stem dendritic patch. The voltage
protocol is shown as an inset. C, Pooled
data demonstrating the somato-dendritic distribution of the transient
outward current. The line is an unconstrained regression
fit. Filled squares show mean (±SD) current as a
function of distance from the soma (±SD) for recordings made from the
soma, stem dendrites, primary branch points, and higher order dendrites
(from left to right, respectively).
D, Pooled data demonstrating the somato-dendritic
distribution of the sustained outward current, as in
C.
|
|
Active action potential backpropagation
To directly test the influence of dendritic voltage-activated
channels on backpropagation of action potentials, we made simultaneous whole-cell somatic and dendritic recordings under control conditions, and then for each neuron examined (n = 16) we used the
somatically recorded action potential as a somatic voltage-clamp
command waveform to ascertain action potential attenuation in the
presence of the sodium channel blocker TTX (Stuart and Sakmann, 1994).
In these experiments care was taken to achieve stable, low series
resistance somatic recordings (<8 M, pipette resistance 2-3 M,
which was compensated for by >95%, in the presence of lag values of
<3 µsec). Using this technique we observed that the blockade of
sodium channels by bath application of TTX greatly reduced the
amplitude of dendritic action potentials (Fig.
5A,C),
decreasing the slope of action potential attenuation with distance from
4.3% per 10 µm to 11.9% per 10 µm. To verify the voltage change
at the soma produced by the injection of action potential
voltage-command waveforms, we made subsequent double somatic recordings
in 10 of 16 neurons and observed that the voltage change produced was
on average 95.8% of the original somatic action potential amplitude
(Fig. 5A,C). These findings,
therefore, directly demonstrate that action potential backpropagation
in TC neurons is active and dependent on dendritic sodium channel
activation.
View larger version (44K):
[in this window]
[in a new window]
|
Figure 5.
Active dendritic action potential backpropagation.
A, The top traces show simultaneous
somatic and dendritic whole-cell current-clamp recordings demonstrating
action potential attenuation under control conditions. The soma was
then voltage-clamped, and the control somatic action potential was used
as a voltage command. The middle traces demonstrate the
relatively small dendritic voltage response evoked by the somatic
action potential voltage command in the presence of the sodium channel
blocker tetrodotoxin (TTX). The bottom
traces show the actual voltage deviation produced at the soma
by the somatic action potential voltage command (thick
trace) during double somatic recording. B, Video
image of the neuron and the location of somatic and dendritic
(white asterisk) recording electrodes. The white
arrows show the location of major dendritic branch points, and
the black arrow indicates a small collateral dendrite.
C, Pooled data from 16 experiments showing the ratio of
dendritic action potential amplitude in the presence of TTX versus that
in control at different dendritic locations. The ratio of voltage
changes recorded at the soma during control and in TTX, obtained during
double somatic recordings, is shown as open circles. The
line represents the result of linear regression
analysis.
|
|
Dendritic filtering of action potential burst firing
During burst firing, the attenuation of the first action potential
of a burst mirrored that of action potentials evoked in single-spike
firing mode (slope reduction along stem dendrites 4.2% per 10 µm;
after branch points 9.1% per 10 µm). Each action potential of a
burst was recorded first at soma. Surprisingly, however, we observed
that when backpropagating action potentials were recorded after
dendritic branch points, the degree of attenuation of subsequent action
potentials in a burst was less than that of the first (Fig.
6A). When recorded from
the soma, later action potentials in a burst showed a reduction in
amplitude and a slowing of rise and decay times (Fig.
6A). Backpropagating action potentials recorded after
dendritic branch points, however, showed an apparent equalization of
amplitude, where the first action potential of a burst was attenuated
to the greatest extent (slope reduction along stem dendrites for third
action potential of a burst 3.7% per 10 µm; after branch points
7.4% per 10 µm) (Fig. 6A). This effect is
quantified in Figure 6B by plotting the difference in amplitude of the first and third action potentials recorded at the
soma, relative to their differential amplitude when recorded dendritically. Along stem dendrites, a near unity relationship exists
that collapses after dendritic branching (Fig. 6B).
These effects were not a consequence of sodium channel
activation/inactivation because they were also observed in the presence
of TTX, after the injection of a voltage-clamp waveform composed of an
action potential burst at the soma. Furthermore, scaling of this burst voltage-clamp waveform by one-half did not modify the normalization of
dendritic action potential amplitude (data not shown), suggesting that
these effects are not dependent on the influence of potassium or
calcium channels but are likely to reflect the more effective passive
propagation through dendritic branch points of the slowly rising and
broader action potentials that occurred later in the burst.
View larger version (16K):
[in this window]
[in a new window]
|
Figure 6.
Filtering of action potential burst firing by
dendritic branch points. A, Top,
Simultaneous somatic (thin trace) and secondary
dendritic (thick trace) whole-cell recordings during a
burst of action potentials evoked by somatic current injection. Note
that the amplitude of somatic action potentials decreases during the
burst, but the amplitude of dendritic action potentials increases.
Bottom, This effect is shown more clearly at a faster
time base, where the first dendritic action potential (thick
trace) has been scaled to equal the amplitude of the first
somatic action potential. B, The relative difference in
first and third action potential amplitude, when measured from the soma
and dendrite. Note a near-unity relationship exists for recordings made
from stem dendrites (), but this relationship collapses after
dendritic branching ().
|
|
Properties of calcium channels in cell-attached patches
Cell-attached recordings, made in the presence of TTX and with a
TEA-based, barium-rich pipette solution (n = 60),
demonstrated that an isolated transient inward current was evoked in
both the soma and dendrites in response to voltage steps from
approximately 113 to 33 mV (Fig.
7A). This cell-attached
current was of low amplitude, variable from trial to trial, but clearly
discernible in single trials (Fig. 7A). An increase in test
pulse amplitude led to the additional appearance of a sustained inward
current in some patches (Fig. 7B). The construction of
current-voltage relationships revealed that this transient inward
current was first activated from potentials ~20 mV positive to RMP,
reaching a peak at ~75 mV positive to RMP, whereas the sustained
component was first activated from potentials ~50 mV positive to RMP
(Fig. 8A,C).
The kinetics of activation and inactivation of the transient current
were found to be voltage dependent (Fig. 8A).
Furthermore, the transient inward current could be steady-state
inactivated by applying prepulses (1 sec duration) of varying amplitude
(Fig. 8B). We constructed steady-state activation and
inactivation curves for ensemble IT currents
recorded from the majority of patches (Fig. 8D). When
pooled from all recording sites, steady-state activation and
inactivation curves were found to be well fit with single Boltzmann
functions, with slopes of 13.6 and 11.8, respectively. A better
approximation of the steady-state activation curve could be made,
however, by raising the Boltzmann function to the third power (Fig.
8D). A considerable voltage overlap was found between these curves, indicating that under ideal voltage-clamp conditions a
non-negligible window current exists (Fig. 8D)
(Williams et al., 1997). Furthermore, the slope of these steady-state
curves was found to be shallower than those reported for whole-cell
recordings made from intact or dissociated TC neurons (Coulter et al.,
1989; Crunelli et al., 1989; Destexhe et al., 1998). This was not a product of data pooling because we observed steepness values of between
5.5 to 16.6 (activation) and 7.6 to 19.9 (inactivation) in individual
recordings, indicating that previous estimates of these parameters may
have been compromised by the recording configuration and conditions
(Destexhe et al., 1998). These voltage-dependent and kinetic properties
identify the transient inward current as a low-threshold calcium
current, IT, and the sustained current as a high-threshold calcium current (Coulter et al., 1989; Crunelli et
al., 1989; Hernandez-Cruz and Pape, 1989; Mouginot et al., 1997).
View larger version (33K):
[in this window]
[in a new window]
|
Figure 7.
Calcium channel activation in the dendrites of TC
neurons. A, Cell-attached patch currents recorded from a
secondary dendrite with pipette solutions designed to block sodium and
potassium currents (see Materials and Methods). Three sequential single
trials demonstrate the presence of an isolated transient inward
current, which is shown more clearly in the average
(n = 50 trials). The voltage protocol is shown as
an inset. B, An additional sustained
current was evoked by increasing the magnitude of the test pulse.
|
|
View larger version (34K):
[in this window]
[in a new window]
|
Figure 8.
Steady-state properties of low-threshold calcium
channels. A, Superposed cell-attached current traces
used for the construction of steady-state activation curves during test
pulses from +15 to +65 mV in 5 mV steps. Each trace is an average of
five trials. The inset shows the voltage-dependent
activation kinetics of the current at a faster time base.
B, A family of current traces used for the construction
of steady-state inactivation curves during prepulses from 40 to 40 mV
in 10 mV steps. The insets show the voltage-dependent
kinetics of this current at a faster time base. C,
Current-voltage relationship of the current shown in A
when measured at peak amplitude () or immediately before the
termination of the test pulse (). D, Pooled
steady-state activation () and inactivation () curves; each point
represents mean ± SEM. The solid curves were fit
with single Boltzmann functions (see Material and Methods). A better
approximation of the activation curve was found by raising the
Boltzmann function to the third power (dashed line).
Note the voltage overlap between curves. Voltages are relative to
resting membrane potential.
|
|
Distribution of low-threshold calcium channels
We mapped the distribution of IT
channels and observed that the kinetic properties of these channels
were similar in patches derived from the soma, stem, and higher order
dendrites (Fig. 9A). The
amplitude of ensemble currents, however, was found to be on average
significantly larger (ANOVA, p < 0.05) in recordings made from the stem dendrite compared with somatic and higher order dendritic locations (Fig. 9B). To our surprise we obtained
many somatic patches that did not show any, or demonstrated very
little, calcium channel activity. Furthermore, little calcium channel activity was found in our most distal dendritic recordings (Fig. 9B).
View larger version (26K):
[in this window]
[in a new window]
|
Figure 9.
Somato-dendritic distribution and properties of
low-threshold calcium channels. A, Selected averaged
traces demonstrating the relationship between current amplitude and
recording location. Note that the transient inward current is of the
same kinetics at each recording location, but of relatively greater
amplitude when recorded from stem dendrites. Somatic and stem dendritic
patches were taken from the same neuron. B, Pooled data
quantifying the relationship between current density and dendritic
location. Each recording is shown as an open circle.
Filled squares show mean (±SD) current as a function of
distance from the soma (±SD) for recordings made from the soma, stem
dendrites, primary branch points, and higher order dendrites (from
left to right, respectively).
C, Steady-state activation and inactivation curves
constructed from data pooled by recording location, as shown in the
inset. Note that more distal dendritic recordings yield
activation and inactivation curves that are shifted to the right along
the voltage axis. Voltages are relative to resting membrane
potential.
|
|
When the voltage dependence of activation and steady-state inactivation
were examined at different somato-dendritic locations, we observed a
small parallel shift in the midpoint values of steady-state activation
and inactivation curves (soma: 52.9 mV, activation, 4.5 mV,
inactivation; primary dendrite branch: 59.6 mV, activation, 11.92 mV,
inactivation; all potentials are relative to RMP) in the depolarized
direction for recordings made from the most distal sites (i.e., at
dendritic branch points and from higher order dendrites) (Fig.
9C). These effects were not produced by differences in RMP
between somatic and dendritic sites because we observed no noticeable
differences in RMP across the somato-dendritic area examined. In
summary, these data directly demonstrate that low-threshold calcium
channels have a predominant dendritic distribution and that the profile
of this distribution is nonuniform and highest in stem dendrites.
Local dendritic regenerative activity
We sought to explore whether a predominate dendritic location of
IT channels led to any unique effects
when current was directly injected into the dendrites of TC neurons
(Fig. 10). Simultaneous somatic and
dendritic current-clamp recordings demonstrated that as the somatic
membrane potential was changed by tonic somatic current injection, the
firing response of TC neurons in response to small positive somatic
current steps changed from single spike to the burst firing of action
potentials in a voltage-dependent manner, as has been described
previously (Deschenes et al., 1982; Llinas and Jahnsen, 1982). This
transformation was produced by the activation of an LTCP. When this
experiment was repeated by controlling membrane potential with tonic
current injection through the dendritic pipette and voltage responses
were evoked by small positive dendritic current steps, a similar
transformation of firing pattern was observed. The charging pattern of
the membrane was altered (Fig. 10, right,
arrows), however, in 5 of 30 recordings during dendritic
current steps, as a consequence of the generation of smaller amplitude
transient depolarizing potential that proceeded the full blown LTCP.
This potential was of greatest amplitude when recorded locally in the
dendrite and was significantly attenuated at the somatic recording site
(Fig. 10). The voltage dependence of this local transient depolarizing
potential was similar to that of the LTCP, suggesting that it is
mediated by the activation of dendritic
IT channels. These data, therefore,
suggest that local voltage-dependent processes can occur in relative
isolation in the dendrites of TC neurons.
View larger version (21K):
[in this window]
[in a new window]
|
Figure 10.
Local regenerative activity in the dendrites of
TC neurons. All traces were recorded during simultaneous somatic
(thin traces) and secondary dendritic recording. The
membrane potential was controlled by tonic current injection through
the somatic (left) or dendritic (right)
electrode, and voltage responses were evoked by 100 pA current steps
(bottom traces) delivered to either the somatic
(left) or dendritic (right) recording
electrode. In response to somatic current injection the neuron showed a
voltage-dependent firing pattern, characterized by the generation of a
low-frequency train of action potentials at the most depolarized
membrane potential and a burst of action potentials crowning a
low-threshold calcium potential at more hyperpolarized membrane
potentials. In response to dendritic current injection, low-threshold
calcium potentials are proceeded by a smaller transient depolarizing
potential (arrows). This potential could be evoked in
isolation at the most hyperpolarized test potential. Note the degree of
attenuation of this transient depolarizing potential from dendrite to
soma. The resting membrane potential of this neurons was 70 mV.
|
|
| |
DISCUSSION |
We show that action potentials evoked by sensory or cortical EPSPs
are initiated near the soma and actively backpropagate into the
dendrites of TC neurons. Backpropagation is compromised, however, by
the properties of dendritic branches coupled with a declining density
of dendritic sodium channels, indicating that backpropagation may fail
to effect synaptic integration in the distal dendrites of TC neurons.
We further show that low-threshold calcium channels are nonuniformly
distributed in TC neuron dendrites. A high density of these channels at
sites that are known to receive excitatory synaptic connections from
primary afferents suggests that IT
channels play a key role in the amplification of sensory input to TC neurons.
Site of action potential initiation and active
dendritic backpropagation
Our simultaneous recordings demonstrated that action potentials
were recorded first at the soma and subsequently in the dendrites of TC
neurons. Because the axon of rat dLGN TC neurons arises from the soma
(Grossman et al., 1973; Williams et al., 1996), these data indicate
that action potentials are probably initiated at axonal sites, as shown
in other central neurons (Stuart et al., 1997b). After axonal
initiation, dendritic action potential backpropagation has been shown
to be reliant on the activation of dendritic voltage-activated sodium
channels in a number of central neurons (Johnston et al., 1996; Stuart
et al., 1997b). The density of sodium channels in TC neurons was on
average constant across recordings made from the soma to the first
branch point of stem dendrites. In daughter dendrites, however, we
observed a reduction in sodium channel density. The density of
potassium channels underlying a fast transient
(IA-like) current and more slowly
inactivating delayed rectifier type current was found to be on average
constant across the somatodendritic area examined, which corresponds to
approximately one-half the path length of TC neuron dendrites. Such
channel distributions appear to be unique, because in pyramidal neurons
of the hippocampus and neocortex, potassium channels with different
properties are differentially distributed between the soma and
dendrites (Hoffman et al., 1997; Bekkers and Stuart, 1998). The
measured channel densities should therefore be considered in future
dendritic models of TC neurons (Lytton et al., 1996; Antal et al.,
1997). The active nature of action potential backpropagation in TC
neurons was confirmed by comparing dendritic voltage responses in the
absence and presence of TTX. A decrease in sodium channel density in
daughter dendrites may help to explain the observation that action
potential backpropagation is compromised after the branching of stem
dendrites. The control of action potential backpropagation, however, is
influenced not only by channel densities but also by dendritic morphology.
Influence of dendritic geometry
Modeling studies have demonstrated that action potential
propagation through branched cable structures is critically dependent on cable geometry (Goldstein and Rall, 1974; Luscher and Shiner, 1990;
Manor et al., 1991; Hausser et al., 1998). Action potential propagation
through a dichotomously branched uniformly excitable cable occurs
without amplitude degradation if the input impedance of the parent
cable matches that of the daughter cables (Goldstein and Rall, 1974).
For a cable of infinite length, this relationship holds if the diameter
of the cables after the branch raised to the power 3/2 equals that of
the parent cable raised to the power 3/2, yielding a geometrical ratio
(GR) that equals 1 (Goldstein and Rall, 1974). If GR is greater than 1, a time-delay and decrease in action potential amplitude at and after
the branch point occurs (Goldstein and Rall, 1974; Luscher and Shiner,
1990; Manor et al., 1991). It should be noted that invasion of a
particular branch of an axon or dendrite is influenced not only by the
GR of the branch point that an action potential immediately encounters
but by the GR of other more distal branch points, within certain
electrotonic limits (Manor et al., 1991; Hausser et al., 1998), and
that the summed influence of such mismatches is supralinear (Manor et
al., 1991). Consistent with a deleterious effect of dendritic branching on action potential backpropagation, we find that a shallower relationship exists, on average, between backpropagating action potential amplitude and distance of dendritic recordings from soma
along unbranched stem dendrites as compared with those made after
branch points (Fig. 2). Furthermore, recordings made from the same
dendrite before and after a branch point indicate that attenuation of
action potentials over a finite distance is greater for a branching
dendrite than for an unbranched dendrite.
Anatomical studies have demonstrated that the dichotomously branched
dendrites of TC neurons do not obey Ralls power law (Kniffki et al.,
1993; Ohara et al., 1995). The degree of variation from GR = 1 is
dependent on the branch number; stem dendrites of TC neurons branch
many times (average values between 7 and 25, depending on species and
nuclei) to form a large number (1 to >40) of terminal dendrites
(Havton and Ohara, 1993; Kniffki et al., 1993; Ohara and Havton, 1994;
Ohara et al., 1995). Average GR values of near 1 (but with scatter from
0.7-1.3) (Bloomfield et al., 1987), 1.4 (Ohara et al., 1995), and 1.72 (Kniffki et al., 1993) have been obtained at the first stem to
nonterminal dendritic branch, whereas values >4-5 have been observed
for more distal fifth to seventh order branches (Kniffki et al., 1993;
Ohara et al., 1995). These data are therefore compatible with our
electrophysiological findings and suggest that action potential
backpropagation is controlled in TC neurons according to the following
scheme: (1) impedance mismatch at dendritic branch points directly
compromises backpropagation; (2) as a corollary more highly branched
dendrites hamper backpropagation to a greater extent and (3) combined
with the lower sodium channel density in daughter dendrites this forms
a situation in which lower amplitude action potentials are less likely
to activate a decreasing number of sodium channels. Backpropagating
action potentials may therefore fail to invade the most distal
dendrites of TC neurons. The filtering effects of dendritic branch
points on action potentials of different rise and decay times generated during action potential burst firing are consistent with this scheme,
because slower rising events will be expected to be filtered less by
impedance mismatches at dendritic branch points.
One key function of backpropagating action potentials is thought to be
the resetting of synaptic integration, produced as a consequence of the
depolarization of dendrites decreasing the driving force for excitatory
synaptic currents, and by shunting produced by the conductance changes
associated with action potential generation (Stuart and Sakmann, 1994;
Stuart et al., 1997b; Stuart and Hausser, 1998). Backpropagating action
potentials in TC neurons may be capable of effecting the dendritic
integration of the primary afferent and intrageniculate inhibitory
inputs to these cells, which are made on stem dendrites or at sites
close to the first dendritic branch points but may fail to effect
inputs from cortical neurons made at distal dendritic sites (Sherman
and Guillery, 1996). Backpropagation of action potentials in TC neurons
might therefore lead to the resetting of dendritic integration of
synaptic inputs that primarily determine the receptive field properties of TC neurons (Sherman and Guillery, 1998) while sparing inputs from
the cortex that are thought to produce slower membrane potential changes that control response mode (i.e., single or burst firing of
action potentials) (Sherman and Guillery, 1998).
Distribution of calcium channels
The low-threshold calcium current underlies many of the complex
electrophysiological properties of TC neurons, including the generation
of action potential burst firing, periodic oscillatory activity, and
membrane potential bistability (Llinas, 1988; Steriade et al., 1993;
Williams et al., 1997). Furthermore,
IT has been shown to amplify
subthreshold EPSPs and IPSPs (von Krosigk et al., 1993; Turner et al.,
1994; Williams et al., 1997; Kim and McCormick, 1998). Our dendritic
recordings indicate that IT channels are at a high density in stem dendrites and stem dendritic branch points of TC neurons, with a lower and more patchy distribution at the
soma. Furthermore, we failed to detect
IT channels in more distal secondary
dendrites. Supportive of these findings, calcium imaging experiments
have indicated the presence of low- and high-threshold calcium
channel-mediated signals in the stem dendrites of TC neurons (Munsch et
al., 1997; Zhou et al., 1997). The voltage dependence of steady-state
activation and inactivation processes of dendritic IT channels was found to be shifted in
the depolarized direction at more distal recording locations. These
properties would allow dendritic IT
channels to be activated at membrane potentials nearer firing
threshold, and so extend the role of dendritic
IT channels in the amplification of
synaptic inputs. Recent modeling studies have indicated that the
electrophysiological properties of TC neurons may be reproduced if
IT channels are distributed
dendritically with a uniform high density throughout their arbor
(Destexhe et al., 1998). Our data, however, indicate that
IT channels are nonuniformly distributed. More extensive computer simulations are therefore required
to ascertain the consequences of a nonuniform dendritic distribution of
IT channels.
In conclusion, we have directly demonstrated that the dendrites of TC
neurons contain various voltage-activated ion channels and can support
active backpropagation of action potentials and the generation of local
dendritic regenerative activity. These channel distributions extend the
functional repertoire of TC neurons and indicate that during
wakefulness and sleep dendritic ion channels will influence synaptic
integration and the generation of oscillatory activity in TC neurons.
| |
FOOTNOTES |
Received Sept. 17, 1999; revised Nov. 15, 1999; accepted Nov. 24, 1999.
Correspondence should be addressed to Dr. Greg Stuart, Division of
Neuroscience, John Curtin School of Medical Research, Mills Road,
Australian National University, Canberra, A.C.T. 0200, Australia. E-mail: Greg.Stuart{at}anu.edu.au.
This work was supported by the Wellcome Trust and the Human Frontiers
Science Program.
| |
REFERENCES |
-
Antal K,
Emri Z,
Toth TI,
Crunelli V
(1997)
Model of a thalamocortical neurone with dendritic voltage-gated ion channels.
NeuroReport
8:1063-1066[Web of Science][Medline].
-
Bekkers JM,
Stuart G
(1998)
Distribution and properties of potassium channels in the soma and apical dendrites of layer 5 cortical pyramidal neurons.
Soc Neurosci Abstr
24:807.8.
-
Bloomfield SA,
Hamos JE,
Sherman SM
(1987)
Passive cable properties and morphological correlates of neurones in the lateral geniculate nucleus of the cat.
J Physiol (Lond)
383:653-692[Abstract/Free Full Text].
-
Budde T,
Munsch T,
Pape HC
(1998)
Distribution of L-type calcium channels in rat thalamic neurones.
Eur J Neurosci
10:586-597[Web of Science][Medline].
-
Coulter DA,
Huguenard JR,
Prince DA
(1989)
Calcium currents in rat thalamocortical relay neurones: kinetic properties of the transient, low-threshold current.
J Physiol (Lond)
414:587-604[Abstract/Free Full Text].
-
Crunelli V,
Kelly JS,
Leresche N,
Pirchio M
(1987a)
On the excitatory post-synaptic potential evoked by stimulation of the optic tract in the rat lateral geniculate nucleus.
J Physiol (Lond)
384:603-618[Abstract/Free Full Text].
-
Crunelli V,
Kelly JS,
Leresche N,
Pirchio M
(1987b)
The ventral and dorsal lateral geniculate nucleus of the rat: intracellular recordings in vitro.
J Physiol (Lond)
384:587-601[Abstract/Free Full Text].
-
Crunelli V,
Lightowler S,
Pollard CE
(1989)
A T-type Ca2+ current underlies low-threshold Ca2+ potentials in cells of the cat and rat lateral geniculate nucleus.
J Physiol (Lond)
413:543-561[Abstract/Free Full Text].
-
Deschenes M,
Roy JP,
Steriade M
(1982)
Thalamic bursting mechanism: an inward slow current revealed by membrane hyperpolarization.
Brain Res
239:289-293[Web of Science][Medline].
-
Destexhe A,
Neubig M,
Ulrich D,
Huguenard J
(1998)
Dendritic low-threshold calcium currents in thalamic relay cells.
J Neurosci
18:3574-3588[Abstract/Free Full Text].
-
Golding NL,
Spruston N
(1998)
Dendritic sodium spikes are variable triggers of axonal action potentials in hippocampal CA1 pyramidal neurons.
Neuron
21:1189-1200[Web of Science][Medline].
-
Goldstein SS,
Rall W
(1974)
Changes of action potential shape and velocity for changing core conductor geometry.
Biophys J
14:731-757.
-
Golshani P,
Warren RA,
Jones EG
(1998)
Progression of change in NMDA, non-NMDA, and metabotropic glutamate receptor function at the developing corticothalamic synapse.
J Neurophysiol
80:143-154[Abstract/Free Full Text].
-
Grossman A,
Lieberman AR,
Webster KE
(1973)
A Golgi study of the rat dorsal lateral geniculate nucleus.
J Comp Neurol
150:441-466[Web of Science][Medline].
-
Guido W,
Weyand T
(1995)
Burst responses in thalamic relay cells of the awake behaving cat.
J Neurophysiol
74:1782-1786[Abstract/Free Full Text].
-
Hausser M,
Vetter P,
Roth A
(1998)
Action potential backpropagation depends on dendritic geometry.
Soc Neurosci Abstr
24:719.1.
-
Havton LA,
Ohara PT
(1993)
Quantitative analyses of intracellularly characterized and labelled thalamocortical projection neurons in the ventrobasal complex of primates.
J Comp Neurol
336:135-150[Web of Science][Medline].
-
Hernandez-Cruz A,
Pape HC
(1989)
Identification of two calcium currents in acutely dissociated neurons from the rat lateral geniculate nucleus.
J Neurophysiol
61:1270-1283[Abstract/Free Full Text].
-
Hoffman DA,
Magee JC,
Colbert CM,
Johnston D
(1997)
K+ channel regulation of signal propagation in dendrites of hippocampal pyramidal neurons.
Nature
387:869-875[Medline].
-
Huguenard JR,
Prince DA
(1991)
Slow inactivation of a TEA-sensitive K current in acutely isolated rat thalamic relay neurons.
J Neurophysiol
66:1316-1328[Abstract/Free Full Text].
-
Huguenard JR,
Coulter DA,
Prince DA
(1991)
A fast transient potassium current in thalamic relay neurons: kinetics of activation and inactivation.
J Neurophysiol
66:1304-1315[Abstract/Free Full Text].
-
Johnston D,
Magee JC,
Colbert CM,
Cristie BR
(1996)
Active properties of neuronal dendrites.
Annu Rev Neurosci
19:165-186[Web of Science][Medline].
-
Kim U,
McCormick DA
(1998)
The functional influence of burst and tonic firing mode on synaptic interactions in the thalamus.
J Neurosci
18:9500-9516[Abstract/Free Full Text].
-
Klee R,
Ficker E,
Heinemann U
(1995)
Comparison of voltage-dependent potassium currents in rat pyramidal neurons acutely isolated from hippocampal regions CA1 and CA3.
J Neurophysiol
74:1982-1995[Abstract/Free Full Text].
-
Kniffki K-D,
Pawlak M,
Vahle-Hinz C
(1993)
Scaling behavior of the dendritic branches of thalamic neurons.
Fractals
1:171-178.
-
Llinas R
(1988)
The intrinsic electrophysiological properties of mammalian neurons: insights into central nervous system function.
Science
242:1654-1664[Abstract/Free Full Text].
-
Llinas R,
Jahnsen H
(1982)
Electrophysiology of mammalian thalamic neurones in vitro.
Nature
297:406-408[Medline].
-
Luscher HR,
Shiner JS
(1990)
Simulation of action potential propagation in complex terminal arborizations.
Biophys J
58:1389-1399[Web of Science][Medline].
-
Lytton WW,
Destexhe A,
Sejnowski TJ
(1996)
Control of slow oscillations in the thalamocortical neuron: a computer model.
Neuroscience
70:673-684[Web of Science][Medline].
-
Magee JC,
Johnston D
(1997)
A synaptically controlled, associative signal for Hebbian plasticity in hippocampal neurons.
Science
275:209-213[Abstract/Free Full Text].
-
Manor Y,
Koch C,
Segev I
(1991)
Effect of geometrical irregularities on propagation delay in axonal trees.
Biophys J
60:1424-1437[Web of Science][Medline].
-
Mayer ML,
Sugiyama K
(1988)
A modulatory action of divalent cations on transient outward current in cultured rat sensory neurones.
J Physiol (Lond)
396:417-433[Abstract/Free Full Text].
-
McCormick DA
(1992)
Neurotransmitter actions in the thalamus and cerebral cortex and their role in neuromodulation of thalamocortical activity.
Prog Neurobiol
39:337-388[Web of Science][Medline].
-
Mouginot D,
Bossu JL,
Gahwiler BH
(1997)
Low-threshold Ca2+ currents in dendritic recordings from Purkinje cells in rat cerebellar slice cultures.
J Neurosci
17:160-170[Abstract/Free Full Text].
-
Munsch T,
Budde T,
Pape HC
(1997)
Voltage-activated intracellular calcium transients in thalamic relay cells and interneurons.
NeuroReport
8:2411-2418[Web of Science][Medline].
-
Ohara PT,
Havton LA
(1994)
Dendritic architecture of rat somatosensory thalamocortical projection neurons.
J Comp Neurol
341:159-171[Web of Science][Medline].
-
Ohara PT,
Ralston H,
Havton LA
(1995)
Architecture of individual dendrites from intracellularly labelled thalamocortical projection neurons in the ventral posterolateral and ventral posteromedial nuclei of cat.
J Comp Neurol
358:563-572[Web of Science][Medline].
-
Parri HR,
Crunelli V
(1998)
Sodium current in rat and cat thalamocortical neurons: role of a non-inactivating component in tonic and burst firing.
J Neurosci
18:854-867[Abstract/Free Full Text].
-
Perez Velazquez JL,
Carlen PL
(1996)
Development of firing patterns and electrical properties in neurons of the rat ventrobasal thalamus.
Brain Res Dev Brain Res
91:164-170[Medline].
-
Ralston H,
Herman MM
(1969)
The fine structure of neurons and synapses in ventrobasal thalamus of the cat.
Brain Res
14:77-97[Web of Science][Medline].
-
Schiller J,
Schiller Y,
Stuart G,
Sakmann B
(1997)
Calcium action potentials restricted to distal apical dendrites of rat neocortical pyramidal neurons.
J Physiol (Lond)
505:605-616[Abstract/Free Full Text].
-
Sherman SM,
Guillery RW
(1996)
Functional organization of thalamocortical relays.
J Neurophysiol
76:1367-1395[Abstract/Free Full Text].
-
Sherman SM,
Guillery RW
(1998)
On the actions that one nerve cell can have on another: distinguishing "drivers" from "modulators".
Proc Natl Acad Sci USA
95:7121-7126[Abstract/Free Full Text].
-
Spruston N,
Schiller Y,
Stuart G,
Sakmann B
(1995)
Activity-dependent action potential invasion and calcium influx into hippocampal CA1 dendrites.
Science
268:297-300[Abstract/Free Full Text].
-
Steriade M,
Deschenes M
(1984)
The thalamus as a neuronal oscillator.
Brain Res
320:1-63[Medline].
-
Steriade M,
McCormick DA,
Sejnowski TJ
(1993)
Thalamocortical oscillations in the sleeping and aroused brain.
Science
262:679-685[Abstract/Free Full Text].
-
Stuart G,
Hausser M
(1998)
Shunting of EPSPs by action potentials.
Soc Neurosci Abstr
24:718.3.
-
Stuart GJ,
Sakmann B
(1994)
Active propagation of somatic action potentials into neocortical pyramidal cell dendrites.
Nature
367:69-72[Medline].
-
Stuart G,
Schiller J,
Sakmann B
(1997a)
Action potential initiation and propagation in rat neocortical pyramidal neurons.
J Physiol (Lond)
505:617-632[Abstract/Free Full Text].
-
Stuart G,
Spruston N,
Sakmann B,
Hausser M
(1997b)
Action potential initiation and backpropagation in neurons of the mammalian CNS.
Trends Neurosci
20:125-131[Web of Science][Medline].
-
Turner JP,
Salt TE
(1998)
Characterization of sensory and corticothalamic excitatory inputs to rat thalamocortical neurones in vitro.
J Physiol (Lond)
510:829-843[Abstract/Free Full Text].
-
Turner JP,
Leresche N,
Guyon A,
Soltesz I,
Crunelli V
(1994)
Sensory input and burst firing output of rat and cat thalamocortical cells: the role of NMDA and non-NMDA receptors.
J Physiol (Lond)
480:281-295[Abstract/Free Full Text].
-
Verheugen JA,
Fricker D,
Miles R
(1999)
Noninvasive measurements of the membrane potential and GABAergic action in hippocampal interneurons.
J Neurosci
19:2546-2555[Abstract/Free Full Text].
-
von Krosigk M,
Bal T,
McCormick DA
(1993)
Cellular mechanisms of a synchronized oscillation in the thalamus.
Science
261:361-364[Abstract/Free Full Text].
-
Warren RA,
Jones EG
(1997)
Maturation of neuronal form and function in a mouse thalamo-cortical circuit.
J Neurosci
17:277-295[Abstract/Free Full Text].
-
Warren RA,
Golshani P,
Jones EG
(1997)
GABA(B)-receptor-mediated inhibition in developing mouse ventral posterior thalamic nucleus.
J Neurophysiol
78:550-553[Abstract/Free Full Text].
-
Williams SR,
Turner JP,
Anderson CM,
Crunelli V
(1996)
Electrophysiological and morphological properties of interneurones in the rat dorsal lateral geniculate nucleus in vitro.
J Physiol (Lond)
490:129-147[Abstract/Free Full Text].
-
Williams SR,
Toth TI,
Turner JP,
Hughes SW,
Crunelli V
(1997)
The "window" component of the low threshold Ca2+ current produces input signal amplification and bistability in cat and rat thalamocortical neurones.
J Physiol (Lond)
505:689-705[Abstract/Free Full Text].
-
Zhou Q,
Godwin DW,
O'Malley DM,
Adams PR
(1997)
Visualization of calcium influx through channels that shape the burst and tonic firing modes of thalamic relay cells.
J Neurophysiol
77:2816-2825[Abstract/Free Full Text].
Copyright © 2000 Society for Neuroscience 0270-6474/00/2041307-11$05.00/0
This article has been cited by other articles:
|
|
|
|
 
E. Calixto, E. J. Galvan, J. P. Card, and G. Barrionuevo
Coincidence detection of convergent perforant path and mossy fibre inputs by CA3 interneurons
J. Physiol.,
June 1, 2008;
586(11):
2695 - 2712.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. J. Lacey, J. P. Bolam, and P. J. Magill
Novel and Distinct Operational Principles of Intralaminar Thalamic Neurons and Their Striatal Projections
J. Neurosci.,
April 18, 2007;
27(16):
4374 - 4384.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. C. Sincich, D. L. Adams, J. R. Economides, and J. C. Horton
Transmission of Spike Trains at the Retinogeniculate Synapse
J. Neurosci.,
March 7, 2007;
27(10):
2683 - 2692.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. J. Gentet and S. R. Williams
Dopamine Gates Action Potential Backpropagation in Midbrain Dopaminergic Neurons
J. Neurosci.,
February 21, 2007;
27(8):
1892 - 1901.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
X. Chen, L.-L. Yuan, C. Zhao, S. G. Birnbaum, A. Frick, W. E. Jung, T. L. Schwarz, J. D. Sweatt, and D. Johnston
Deletion of Kv4.2 Gene Eliminates Dendritic A-Type K+ Current and Enhances Induction of Long-Term Potentiation in Hippocampal CA1 Pyramidal Neurons.
J. Neurosci.,
November 22, 2006;
26(47):
12143 - 12151.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Miyata and K. Imoto
Different composition of glutamate receptors in corticothalamic and lemniscal synaptic responses and their roles in the firing responses of ventrobasal thalamic neurons in juvenile mice
J. Physiol.,
August 15, 2006;
575(1):
161 - 174.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. R. Llinas and M. Steriade
Bursting of Thalamic Neurons and States of Vigilance
J Neurophysiol,
June 1, 2006;
95(6):
3297 - 3308.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. W. Hughes and V. Crunelli
Thalamic Mechanisms of EEG Alpha Rhythms and Their Pathological Implications
Neuroscientist,
August 1, 2005;
11(4):
357 - 372.
[Abstract]
[PDF]
|
|
|
|
|
|
|
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]
|
|
|
|
|
|
|
P. M Joksovic, D. A Bayliss, and S. M Todorovic
Different kinetic properties of two T-type Ca2+ currents of rat reticular thalamic neurones and their modulation by enflurane
J. Physiol.,
July 1, 2005;
566(1):
125 - 142.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. A Rhodes and R. Llinas
A model of thalamocortical relay cells
J. Physiol.,
June 15, 2005;
565(3):
765 - 781.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. D. Traub, D. Contreras, M. O. Cunningham, H. Murray, F. E. N. LeBeau, A. Roopun, A. Bibbig, W. B. Wilent, M. J. Higley, and M. A. Whittington
Single-Column Thalamocortical Network Model Exhibiting Gamma Oscillations, Sleep Spindles, and Epileptogenic Bursts
J Neurophysiol,
April 1, 2005;
93(4):
2194 - 2232.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Martin, S. Puig, A. Pietrzykowski, P. Zadek, P. Emery, and S. Treistman
Somatic Localization of a Specific Large-Conductance Calcium-Activated Potassium Channel Subtype Controls Compartmentalized Ethanol Sensitivity in the Nucleus Accumbens
J. Neurosci.,
July 21, 2004;
24(29):
6563 - 6572.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Leresche, J. Hering, and R. C. Lambert
Paradoxical Potentiation of Neuronal T-Type Ca2+ Current by ATP at Resting Membrane Potential
J. Neurosci.,
June 16, 2004;
24(24):
5592 - 5602.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Massaux, G. Dutrieux, N. Cotillon-Williams, Y. Manunta, and J.-M. Edeline
Auditory Thalamus Bursts in Anesthetized and Non-Anesthetized States: Contribution to Functional Properties
J Neurophysiol,
May 1, 2004;
91(5):
2117 - 2134.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. C. McIntyre, W. M. Grill, D. L. Sherman, and N. V. Thakor
Cellular Effects of Deep Brain Stimulation: Model-Based Analysis of Activation and Inhibition
J Neurophysiol,
April 1, 2004;
91(4):
1457 - 1469.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. DESTEXHE and T. J. SEJNOWSKI
Interactions Between Membrane Conductances Underlying Thalamocortical Slow-Wave Oscillations
Physiol Rev,
October 1, 2003;
83(4):
1401 - 1453.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
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]
|
|
|
|
|
|
|
L. Noonan, B. Doiron, C. Laing, A. Longtin, and R. W. Turner
A Dynamic Dendritic Refractory Period Regulates Burst Discharge in the Electrosensory Lobe of Weakly Electric Fish
J. Neurosci.,
February 15, 2003;
23(4):
1524 - 1534.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Doiron, L. Noonan, N. Lemon, and R. W. Turner
Persistent Na+ Current Modifies Burst Discharge By Regulating Conditional Backpropagation of Dendritic Spikes
J Neurophysiol,
January 1, 2003;
89(1):
324 - 337.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. R. Chen, G. Y. Shen, G. M. Shepherd, M. L. Hines, and J. Midtgaard
Multiple Modes of Action Potential Initiation and Propagation in Mitral Cell Primary Dendrite
J Neurophysiol,
November 1, 2002;
88(5):
2755 - 2764.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Brecht and B. Sakmann
Whisker maps of neuronal subclasses of the rat ventral posterior medial thalamus, identified by whole-cell voltage recording and morphological reconstruction
J. Physiol.,
January 15, 2002;
538(2):
495 - 515.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y.-N. Jan and L. Y. Jan
Dendrites
Genes & Dev.,
October 15, 2001;
15(20):
2627 - 2641.
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Doiron, A. Longtin, R. W. Turner, and L. Maler
Model of Gamma Frequency Burst Discharge Generated by Conditional Backpropagation
J Neurophysiol,
October 1, 2001;
86(4):
1523 - 1545.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Vetter, A. Roth, and M. Hausser
Propagation of Action Potentials in Dendrites Depends on Dendritic Morphology
J Neurophysiol,
February 1, 2001;
85(2):
926 - 937.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. R. Williams and G. J. Stuart
Backpropagation of Physiological Spike Trains in Neocortical Pyramidal Neurons: Implications for Temporal Coding in Dendrites
J. Neurosci.,
November 15, 2000;
20(22):
8238 - 8246.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
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]
|
|
|
|
TOP
ABSTRACT
INTRODUCTION
