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The Journal of Neuroscience, May 15, 1998, 18(10):3919-3928
Dendritic Spikes Are Enhanced by Cooperative Network Activity in
the Intact Hippocampus
Anita
Kamondi,
László
Acsády, and
György
Buzsáki
Center for Molecular and Behavioral Neuroscience, Rutgers, The
State University of New Jersey, Newark, New Jersey 07102
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ABSTRACT |
In vitro experiments suggest that dendritic fast
action potentials may influence the efficacy of concurrently active
synapses by enhancing Ca2+ influx into the
dendrites. However, the exact circumstances leading to these effects in
the intact brain are not known. We have addressed these issues by
performing intracellular sharp electrode recordings from
morphologically identified sites in the apical dendrites of CA1
pyramidal neurons in vivo while simultaneously
monitoring extracellular population activity. The amplitude of
spontaneous fast action potentials in dendrites decreased as a function
of distance from the soma, suggesting that dendritic propagation of
fast action potentials is strongly attenuated in vivo.
Whereas the amplitude variability of somatic action potentials was very small, the amplitude of fast spikes varied substantially in distal dendrites. Large-amplitude fast spikes in dendrites occurred during population discharges of CA3-CA1 neurons concurrent with field sharp
waves. The large-amplitude fast spikes were associated with bursts of
smaller-amplitude action potentials and putative
Ca2+ spikes. Both current pulse-evoked and
spontaneously occurring Ca2+ spikes were always
preceded by large-amplitude fast spikes. More spikes were observed in
the dendrites during sharp waves than in the soma, suggesting that
local dendritic spikes may be generated during this behaviorally
relevant population pattern. Because not all dendritic spikes produce
somatic action potentials, they may be functionally distinct from
action potentials that signal via the axon.
Key words:
plasticity; calcium spikes; long-term potentiation; spike
propagation; signaling; action potentials
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INTRODUCTION |
Experiments using extracellular
techniques, intracellular recordings with sharp electrodes, and
patch-clamp pipettes have led to competing but not necessarily mutually
exclusive scenarios regarding the initiation and active propagation of
action potentials (Johnston et al., 1996 ; Yuste and Tank, 1996; Stuart
et al., 1997). According to one view, fast (Na+)
action potentials are initiated in the axon, and active dendritic Na+ conductances facilitate their back-propagation
into the dendritic tree (Turner et al., 1991; Jaffe et al., 1992;
Stuart and Sakmann, 1994; Magee and Johnston, 1995; Spruston et al.,
1995). Actively back-propagating fast action potentials may affect the
efficacy of concurrently active synapses and may influence synaptic
plasticity by enhancing Ca2+ influx into the cell
(Yuste and Denk, 1995; Christie et al., 1996; Jester et al., 1996;
Magee and Johnston 1997; Markram et al., 1997). An alternative view is
that strong excitatory synaptic activation may lead to action
potentials generated within the dendrites independent of the soma or
axon initial segment (Spencer and Kandel, 1961; Llinás and
Nicholson, 1971; Wong et al., 1979; Herreras 1990; Turner et al., 1991;
Wong and Stuart, 1992; Regehr et al., 1993). Because most experiments
in this area of research have been done in the slice preparation, the
argument can be made that the amount of depolarization produced by
electrical stimulation of presynaptic fibers for the demonstration of
dendritic spike initiation is artificial, and such synchrony never
exists under physiological conditions (Mainen et al., 1995; Stuart et
al., 1997). Besides factors intrinsic to the neuron, such as channel density and branching pattern of the dendritic tree, various network factors can exert an important effect on dendritic
Na+ conductances and associated
Ca2+ electrogenesis in the in vivo
situation, including synaptic inhibition, the extracellular milieu, the
discharge frequency of the neuron, and cooperative synchronized
depolarization of dendritic segments (Kim et al., 1995; Buzsáki
et al., 1996; Miles et al., 1996; Tsubokawa and Ross, 1996). It is
therefore important to investigate the rules of dendritic
electrogenesis and its modification by physiologically relevant network
events in the intact brain (Svoboda et al., 1997).
In the behaving animal, two physiologically antagonistic population
patterns are known in the hippocampus: theta waves and sharp waves
(Buzsáki et al., 1983). During theta activity, somata of
pyramidal cells, in general, are hyperpolarized and rarely fire (Leung
and Yim, 1986; Fox, 1989; Soltész and Dechénes, 1993;
Ylinen et al., 1995b). In contrast, pyramidal cells are depolarized
during sharp waves (SPW) (Ylinen et al., 1995a) and often fire
"complex-spike" bursts (Spencer and Kandel, 1961; Ranck, 1973).
SPWs are large-amplitude (1-3 mV) aperiodic field potentials (40-100
msec) observed in stratum radiatum of the CA1 region (Buzsáki, 1986, 1989; Suzuki and Smith, 1987) present during awake immobility, consummatory behaviors, and slow-wave sleep. Field SPWs result from the
excitation of the dendritic fields of CA1 pyramidal cells and
interneurons by their CA3 Schaffer collateral input. The ramp-like depolarization of CA1 neurons induces a dynamic interaction between interneurons and pyramidal cells, the result of which is a short-lived oscillatory field potential (ripple) within stratum pyramidale and a
phase-related discharge of the CA1 network at 200 Hz (Buzsáki et
al., 1992; Ylinen et al., 1995a). In association with field SPWs,
~40,000-60,000 cells discharge in concert in the
CA3-CA1-subiculum-presubiculum-layer V entorhinal cortex axis
(Chrobak and Buzsáki, 1996). In summary, the SPW burst is the
most powerful depolarizing population pattern in the hippocampal
formation. We reasoned therefore that if active properties of dendrites
are critically influenced by synaptic inputs, then their physiological
relevance in the intact brain could be investigated during the
occurrence of SPW-associated population bursts.
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MATERIALS AND METHODS |
Surgery and recording. Ninety-three rats of the
Sprague Dawley strain (250-350 gm) were anesthetized with urethane
(1.3-1.5 gm/kg) and placed in a stereotaxic apparatus. The body
temperature of the rat was kept constant by a small-animal
thermoregulation device. The scalp was removed, and a small (1.2 × 0.8 mm) bone window was drilled above the hippocampus
(anteroposterior at  3.3 mm from anteromedial edge and lateral at 2.2 mm from bregma) for extracellular and intracellular recordings. The
cisterna magna was opened, and the CSF was drained to decrease
pulsation of the brain. A pair of stimulating electrodes (100 µm
each, with 0.5 mm tip separation) was inserted into the left
fimbria-fornix (anteroposterior at 1.3, lateral at 1.0, and ventral
at 4.1) to stimulate the commissural inputs. An extracellular recording
electrode (20 µm insulated tungsten wire) was placed into the CA1
pyramidal layer 0.5-1.0 mm anterior to the intracellular electrode.
Positioning of the recording electrode in the CA1 pyramidal layer was
aided by the presence of multiple-unit activity and the commissurally evoked responses. After the extracellular and intracellular recording electrodes were inserted into the brain, the bone window was covered by
a mixture of paraffin and paraffin oil to prevent drying of the brain
and to decrease pulsation.
Micropipettes for intracellular recordings were pulled from 2.0 mm
capillary glass. They were filled with 1 M
K+-acetate in 50 mM Tris buffer, pH 7.2, containing 2% biocytin for intracellular labeling. In vivo
electrode impedances varied from 60 to 100 M . Once stable,
intracellular recordings were obtained and evoked, and passive
physiological properties of the cell were determined. Only neurons with
a resting potential more negative than 55 mV were included in this
study. Because the resting membrane potential fluctuates in
vivo, we used the voltmeter readings of the amplifier
(Axoclamp-2B; Axon Instruments, Foster City, CA) to obtain an average
value integrated over time. Input resistance of the neurons varied
between 17 and 67 M. Field activity recorded through the
extracellular electrode was filtered between 1 Hz and 5 kHz. The
intracellular activity and the extracellular field unit activity were
digitized at 10 kHz with 12 bit precision (ISC-16 board; RC
Electronics, Santa Barbara, CA). The electrophysiological data were
stored on optical disks. In three rats, bicuculline meth-Cl (5 mg/kg)
was injected intraperitoneally after baseline recordings ( 15 min),
and recordings continued for 30-140 min.
Data analysis. The data were analyzed off-line. The
extracellular trace was digitally filtered at 120 dB/octave to separate the fast-ripple waves (50-200 Hz) and unit activity (500 Hz-5 kHz).
Cross-correlograms between intracellular spikes and extracellular unit
activity were performed using a selected amplitude or pattern of
intracellular spikes as reference signals. Extracellular units were
detected by amplitude discriminator software. For the amplitude measurements of intracellular fast spikes, the intracellular trace was
filtered (50 Hz-5 kHz) to eliminate synaptic potentials and slow
spikes. These discriminated spikes were used to construct amplitude
histograms, interspike interval histograms, and waveform averages using
the original unfiltered traces. Spike amplitude, rate of rise, rate of
decay, amplitude of spike afterpotential, and half-amplitude width were
determined for each recorded neuron.
Histological analysis. After the completion of the
physiological data collection, biocytin was injected through a bridge
circuit using 500 msec depolarizing pulses at 0.6-2 nA at 1 Hz for
10-60 min. Neuronal activity was followed throughout the procedure, and the current was reduced if the electrode was blocked and/or the
condition of the neuron deteriorated. Two to 12 hr after the injection,
the animals were given a urethane overdose and then perfused
intracardially with 100 ml of physiological saline followed by 400 ml
of 4% paraformaldehyde and 0.2% glutaraldehyde dissolved in PBS, pH
7.2. The brains were then removed and stored in the fixative solution
overnight. Sixty- or 100-µm-thick coronal sections were cut and
processed for biocytin labeling (Sik et al., 1995). The labeled neurons
were reconstructed with the aid of a drawing tube. Double- and
multiple-labeled neurons were discarded from the analysis. The
histological sections were also used to verify the position of the
extracellular recording electrodes and the track made by the recording
pipette. Both physiological and histological methods were used to
localize the tip of the recording electrode. During the experiment the
micrometer readings of the microstepper (Inchworm; Burleigh Inc.,
Fishers, NY) indicated the depth from the pyramidal layer. The
pyramidal layer was recognized by the high density of impaled somata.
After the withdrawal of the pipette from the dendrite, extracellular
averaged evoked responses to commissural stimulation were obtained at
50 µm steps from the recording site to the pyramidal layer. The
polarity reversal of the extracellular field response at the border of
strata radiatum and pyramidale provided an additional landmark for the
pyramidal layer. The location of dendritic penetration was determined
from the distance between the pyramidal layer and the recording site (measured in a straight line) during the experiment and from the anatomical reconstruction of the electrode track and the dendritic tree
of the filled neuron. After the field potential recordings, the pipette
was moved up and down several times at a faster speed. This procedure
aimed to sever capillaries and to release red blood cells for filling
the recording track. In some experiments, the glass pipette was glued
to the surface of the brain with cyanoacrylic. The pipette was broken
above the glue, and the brain was perfused with the pipette left
in situ. During sectioning, the pipette was cut above the
corpus callosum by a fine scalpel blade, the upper part of the pipette
was removed, and the hippocampus was sectioned with the glass tip
remaining in the hippocampus.
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RESULTS |
Properties of dendritic action potentials vary with distance
from soma
All recordings in this study were made from biocytin-injected and
morphologically identified CA1 pyramidal cells. Double- and
multiple-labeled neurons were discarded from the analysis. Stable
measurements (30 min-4 hr; resting membrane potential less than 55
mV) were made from 56 dendrites at distances of up to 400 µm from the
pyramidal layer. Somatic recordings were available from 28 additional
neurons. Somatic recordings were characterized by short (0.98 ± 0.09 msec half-amplitude width) overshooting action potentials with
little amplitude variance, undershooting spike afterhyperpolarization,
frequency of spontaneous firing <2 Hz, and the lack of slow spikes
(see below) in response to depolarizing pulses.
During the experiment, the location of the recorded dendrite was
estimated from the travel distance of the recording pipette from the
pyramidal layer. In addition, after the withdrawal of the pipette from
the dendrite the extracellular averaged evoked responses to commissural
stimulation were obtained at 50 µm steps from the site of dendritic
impalement to the pyramidal layer. The polarity reversal of the
extracellular field response at the border of strata radiatum and
pyramidale provided a clearcut landmark for the pyramidal layer
(Andersen et al., 1971). Anatomical verification of the recording track
was available in 26 cases. In several instances, the exact location of
the impalement could also be verified from the recording track and the
reconstructed dendritic tree (Fig. 1A). Occasionally,
bulging of the dendrite or the presence of biocytin-filled astrocytic
processes further assisted the determination of the location of
dendritic impalement.
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Figure 1.
Properties of evoked and spontaneous dendritic
events. A, Photograph of the electrode track and the
biocytin-filled neuron and its camera lucida reconstruction. Recording
was made from the principal apical shaft at the border of strata
radiatum (rad) and lacunosum-moleculare
(l-m). The electrode was moved beyond the dendrite
during the experiment. The electrode track is filled with red blood
cells. pyr, Pyramidal layer. B, Current
step-induced responses (0.3 and 1.0 nA). Note amplitude decrement of
fast spikes (bottom trace). Note also large fast spike
(arrow), slow spike (asterisk), and
transient cessation of fast spikes (top trace).
Inset, Temporal detail of the fast and slow spikes.
C, Responses to commissural input stimulation
(arrow). Traces were evoked using the same stimulus
intensity. Note that the spike can precede or follow the peak
depolarization (arrows). D, Spontaneous
spike burst with decrementing amplitude spikes.
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Recordings from apical dendrites of CA1 pyramidal cells replicated
several features of dendritic action potentials described in
vitro (Wong et al., 1979; Wong and Stuart, 1992; Spruston et al.,
1995; Tsubokawa and Ross, 1996). The amplitude of fast action potentials was always smaller than that recorded from the soma (Fig.
2A). Depolarizing
pulses in dendrites evoked a train of action potentials with
progressively decrementing amplitude. The recordings shown in Figure 1
were obtained from the distal part of a primary dendritic shaft in the
outer third of stratum radiatum. Low-intensity current steps (<0.4 nA)
induced a moderate spike frequency adaptation and amplitude decrement
of the action potentials. Larger current steps induced a more complex
pattern associated with three additional changes. First, a
large-amplitude slow spike, likely reflecting high-threshold
Ca2+ currents (Wong et al., 1979; Wong and Stuart,
1992; Magee and Johnston, 1995), was evoked. Second, the slow spikes
were associated with a burst of fast spikes, one of which was often
much larger in amplitude (Fig. 1B, arrow)
than those evoked by smaller currents. Third, large-amplitude slow
spikes were followed by suppression of fast spikes, likely attributable
to activation of Ca2+-mediated increase of
K+ conductance (Fig. 1) (Hotson and Prince, 1980;
Schwartzkroin and Stafstrom, 1980). Synaptically evoked postsynaptic
potentials in dendrites were of larger amplitude, and the latency of
evoked action potential varied more than in the soma. Action potentials could occur before or after the peak of the evoked EPSP (Fig. 1C).
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Figure 2.
Properties of spontaneous dendritic action
potentials in CA1 pyramidal cells in vivo. A, Amplitude
of action potentials (measured from the inflection point to the peak)
as a function of the distance from the cell body. Each
point is an average of at least 50 spontaneous single
spikes. The average somatic spike amplitude is indicated by a single
point (mean ± SD; n = 25).
Insets, Examples of averaged spikes
(n = 50). Filled triangles,
Anatomically verified dendritic locations; open circles,
dendritic recording sites are estimated from the distance from the cell
body layer during the recording session. B, Spike
amplitude, rate of rise, rate of decay, half-amplitude width
(half A), fast spike afterpotential
(SAP), and resting membrane potential
(RMP) in the soma (pyr) and at
dendritic sites (mean ± SD). The stratum radiatum was arbitrarily
divided into three equal layers: proximal (prox),
middle (mid), and distal (dist).
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In addition to the above differences, dendritic and somatic fast action
potentials were different in several more respects. The amplitude of
spontaneously occurring single action potentials decreased as a
function of the distance from the soma (Fig. 2). Several other
parameters of spontaneously occurring spikes, including the rate of
rise and decay, the width at half-amplitude, and the spike
afterpotential, also correlated with the location of the dendritic
recording (Fig. 2B). The undershooting spike
afterhyperpolarization observed in somatic recordings was absent or, in
fact, was depolarizing in the dendrite. The resting membrane potential
was slightly but significantly more hyperpolarized in the dendrites
(65.2 ± 2.2 mV) than in the soma (61.2 ± 1.9 mV;
t = 3.26; p < 0.002). However, the
resting membrane potential did not change with distance from the
soma.
The amplitude of spontaneous spikes in dendrites was rather constant
from the soma up to ~250 µm from the somatic layer (Fig. 2A). This was followed by a step-wise amplitude
decrement in the distal third of stratum radiatum. Regression lines
fitted to the proximal-middle group (<280 µm) and distal group
intercepted the y-axis at 55 and 48 mV, respectively.
However, the slopes of the linear regression lines were significantly
different (F(6,30); p < 0.015). In only one case was the spike amplitude <15 mV in the
proximal two-thirds of stratum radiatum. In this single case (Fig. 2,
triangle at 220 µm), the recordings were made from an
anatomically verified second-order branch.
Network influence on dendritic spikes
A striking difference between somatic-proximal dendritic and
distal dendritic recordings was the large range of spike amplitudes in
distal dendrites. Although recordings at distal locations typically revealed small action (<15 mV) potentials, large-amplitude (20-50 mV)
spontaneous spikes were also observed as part of a burst (Fig. 3). When action potentials were evoked by
intradendritic current pulses, the amplitude of the first few evoked
spikes was often larger than that of the spontaneously occurring action
potentials. Spikes evoked by suprathreshold afferent stimulation were
also larger in amplitude than the spontaneously occurring spikes. This was in sharp contrast to somatic recordings, because the amplitude of
evoked spikes in the soma was always 10-30% smaller than that of the
spontaneously occurring action potentials, likely attributable to a
shunting effect of IPSPs mediated by the feed-forward activation of
basket cells (Sik et al., 1995; Miles et al., 1996). Subthreshold afferent stimulation combined with intradendritic current-induced depolarization often evoked large-amplitude spikes (Fig.
3C). These findings indicated that local regeneration of
fast spikes can be enhanced by depolarization of the dendrite.
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Figure 3.
Sharp wave burst-induced amplitude enhancement of
fast spikes. A, Reconstructed dendritic tree. The
micropipette points to the anatomically verified penetrated dendrite.
B, Responses to hyperpolarizing (0.5 nA) and
depolarizing (left, 0.5 nA; right, 0.6 nA) current steps. Arrow, Large-amplitude fast spike
(LAS); asterisk, putative calcium spike.
C, Responses to commissural (c)
stimulation. Note large-amplitude-evoked fast spike
(arrow) and absence of spike (bottom
trace) with and without concurrent direct depolarization of the
dendrite, respectively. The same stimulus intensity was used in both
cases. D, E, Relationship between
extracellularly recorded multiple unit activity (MUA)
and field ripples from CA1 pyramidal layer and intradendritic activity
(dendrite). There is a 45 sec gap between
traces in D and E.
Cross-correlogram (burst vs MUA) between intradendritic
bursts as defined by repeating spikes at <10 msec, interspike
intervals, and extracellular MUA activity illustrates that the
incidence of intradendritic bursts was highest during ripple-related
MUA. E, left inset, Large-amplitude fast spikes were
present exclusively during MUA bursts. Note that the slow potential
associated with the large fast spike is larger than the
stimulation-evoked EPSP shown in C. Right
inset, Cross-correlogram between large-amplitude (>30 mV)
spikes and MUA activity (LAS vs MUA).
Ordinate, Number of units per bin.
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After studying dendritic events in response to current injections and
electrically evoked synaptic responses, we questioned whether the
magnitude of dendritic depolarization required for these events is ever
achieved under physiological conditions by comparing the intracellular
spike events with the extracellularly recorded field and multiple unit
activity. Field activity was characterized by either rhythmic theta
waves (2-6 Hz) or irregularly occurring sharp wave events (SPW)
associated with a fast field oscillation in the pyramidal layer
(ripple) and population discharge of a large number of neurons (Ylinen
et al., 1995a). Dendritic action potential bursts occurred most
consistently during SPWs, although they were occasionally observed
during theta activity and between the irregularly occurring SPWs. All
recordings illustrated in the present work were obtained during SPW
(nontheta) state. The relationship between intracellular events and the
extracellularly recorded multiple unit activity (MUA) was quantified by
cross-correlating these events. As was the case with somatically
recorded action potentials (Ylinen et al., 1995), SPW-associated field
ripples and MUA correlated with dendritic bursts of action potentials (Fig. 3E, left inset). A burst of action
potentials was defined as repeating spikes at <10 msec interspike
intervals for these calculations. In each animal with a sufficient
number of SPW bursts (>10) for the construction of cross-correlograms
(n = 17), the large peaks in the cross-correlograms
indicated that intradendritic bursts occurred preferentially during the
SPW-associated population events.
Similar to the current injection-induced events, large-amplitude spikes
never occurred in isolation but were always part of a dendritic burst.
In distal dendrites the amplitude of the small and large spikes could
easily be distinguished. To study the role of network activity in the
generation of the large-amplitude events, the large-amplitude spikes
were cross-correlated with the simultaneously recorded MUA (Fig.
3E, right inset). The peaks in the
cross-correlograms indicated that large-amplitude spikes occurred
preferentially during the SPW-associated population events
(n = 6 distal dendrites). In four cases, spontaneous
large-amplitude spikes were present exclusively during SPW bursts.
SPW-associated large, fast spikes, similar to current pulse-induced
events, arose from wide depolarizing potentials. These wide
depolarizing potentials probably reflected a combination of
synaptically induced postsynaptic potentials and
Ca2+ spikes, because their amplitude was often
larger than that of the commissurally evoked depolarization (Figs.
3C,E, 4). In
addition, the rate of decay of these wide events was faster than their
rate of rise, similar to the current step-induced
Ca2+ spikes. Putative calcium spikes occurred very
rarely (<0.2/min) at the resting potential, but steady depolarization
of the dendrite (<10 mV) significantly increased the incidence of
putative calcium spikes and revealed them in neurons in which no such
events were observed at rest (50-350%; t = 2.45;
p < 0.05; n = 12). These observations
indicate that at least part of the SPW-associated large depolarizing
events reflect Ca2+ spikes. In an attempt to
increase the incidence of large-amplitude fast spikes and associated
putative Ca2+ spikes, the frequency of sharp wave
bursts was increased by reducing inhibition. Systemic injection
of the GABAA receptor blocker bicuculline (5 mg/kg,
i.p.) increased the amplitude of the commissurally evoked population
spike and the incidence of SPW bursts (Buzsáki, 1986). Parallel
with these network changes, the incidence of large-amplitude spikes
also increased (Fig. 5). The distribution
of spike amplitude was bimodal, and bicuculline disproportionately
increased the number of large-amplitude spikes (Fig. 5,
arrows). Similar to the predrug condition, the large-amplitude
fast spikes occurred most often in association with SPWs (Fig.
6). The large-amplitude fast spikes, in
turn, were associated with putative Ca2+ spikes.
Averages triggered by the large-amplitude fast spikes (n = 3 rats with bicuculline treatment;
n = 4 rats with no drug treatment) revealed that fast
spikes preceded the peaks of the putative Ca2+
spikes (Figs. 6D,
7B2). In four control rats,
only the vehicle (0.9% NaCl) was injected after 20-60 min of dendrite
impalement. This injection procedure had no effect on the
electrophysiological properties of the recorded neurons.
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Figure 4.
Recording from a first-order dendrite in the
middle third of stratum radiatum. A, Reconstructed
dendritic tree. The arrow (enlargement of the
boxed area) shows a labeled astrocytic process at the
site of electrode penetration. B, Relationship between
extracellularly recorded multiple unit activity (MUA)
and field ripples from CA1 pyramidal layer and intradendritic activity.
C, D, Intradendritic
(dendrite)-evoked potential in response to commissural
(c) stimulation and extracellular response
(extra) after the pipette was withdrawn from the
dendrite. E, Current step-induced responses (0.4, 0.8, and 1.0 nA). Asterisks, Putative calcium spikes. Note
that the commissurally evoked response (C) is
smaller than the large depolarization associated with the sharp wave
burst in B. Note also the similarity of the spontaneous
and current-induced bursts.
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Figure 5.
Augmentation of fast spike amplitude by
attenuating GABAergic inhibition. Amplitude histograms of action
potentials in three dendrites (A-C)
before (gray) and after (black)
bicuculline administration (5 mg/kg, i.p.). Note bimodal distribution
of dendritic spike amplitude in all three cells. Arrows
indicate large-amplitude spikes. Note also the increased incidence of
large-amplitude spikes after drug administration.
Insets, Action potential averages before
(gray) and after (black)
bicuculline in the indicated time window. The postdrug average is
slightly shifted upward in B. A and
C are midapical dendrites. C (also shown
in Fig. 6) is recorded from a distal dendrite.
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Figure 6.
Augmentation of spike amplitude by attenuating
GABAergic inhibition. Recordings from a distal dendrite 350 µm from
the soma. A, Relationship between extracellularly
recorded multiple unit activity (MUA) and field ripple
from CA1 pyramidal layer and intradendritic activity 11 min after drug
injection. B, Cross-correlation between large-amplitude
fast spikes (LAS in A; >20 mV) and MUA.
C, Large-amplitude fast spike-triggered average of
intradendritic events (n = 8). D,
Current step (0.5 nA)-induced response before drug administration.
E, Two superimposed evoked potentials in response to
commissural (c) stimulation at threshold
intensity 110 min after drug administration. Only one of the stimuli
evoked a spike. Bottom trace, Extracellular response
after the pipette was withdrawn from the dendrite.
Arrows, Large-amplitude spikes;
asterisks, putative calcium spikes.
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Figure 7.
Fast spikes may be initiated at multiple
locations. A1, Simultaneous recording of field ripple
and intracellular response from soma. Note burst of fast spikes with
similar amplitude. A2, Autocorrelogram of fast spikes.
Note refractory period of >8 msec. Inset, Averaged
somatic spike. B1, Simultaneous recording of field
ripple and intracellular response from dendrite. Note the presence of
small-amplitude (filled arrow) and
large-amplitude (LAS, open arrow) fast
spikes. B2, Autocorrelogram of fast large spikes
(top) and all spikes (bottom). Note lack
of a refractory period when all spikes were included.
Inset, Averaged waveforms triggered by large amplitude
fast spikes (LAS) and all spikes
(all).
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Action potentials may be initiated at multiple sites
SPW bursts were typically associated with a single spike in the
soma, and the number of somatic spikes during bursts never exceeded
four (mean ± SD = 1.2 ± 0.21; n = 9;
Fig. 7A). In contrast, SPW events often evoked multiple
spike bursts with as many as seven fast action potentials in dendrites
(mean ± SD = 3.3 ± 0.65; n = 16;
t = 4.56; p < 0.001). In addition,
comparison of spike autocorrelograms revealed significantly longer
refractory periods of somatic spikes (6.9 ± 1.1 msec) than of
dendritic action potentials (2.7 ± 0.52 msec; t = 2.87; p < 0.01). In distal dendritic recordings the
refractory period could be as short as the action potential when small-
and large-amplitude spikes were all considered (Fig. 7A,B). When only large-amplitude
spikes recorded in distal dendrites were considered, interspike
intervals were long (Fig. 7B). These observations are
compatible with the view that action potentials can emanate from
multiple locations.
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DISCUSSION |
Our results demonstrate that (1) the propagation of fast action
potentials in dendrites is strongly suppressed in vivo; (2) large-amplitude dendritic fast spikes occur during SPW bursts; (3)
large-amplitude dendritic fast spikes are associated with spike bursts
and putative Ca2+ spikes; and (4) fast spikes may be
initiated in dendrites and may not invade the soma.
Spike amplitude attenuation in dendrites
Our in vivo observations of the amplitude decrease of
fast spikes with distance from the soma revealed similarities to
previous in vitro results (Spruston et al., 1995; Tsubokawa
and Ross, 1996; Magee and Johnston, 1997; Jung et al., 1997). However,
in in vitro measurements the first spike of the current
step-induced train showed little amplitude decrement with distance from
the soma, and only subsequent action potentials were attenuated
(Callaway and Ross, 1995; Spruston et al., 1995; Tsubokawa and Ross,
1996). This is in contrast to the in vivo situation, because
the majority of spontaneous spikes in dendrites were much smaller than
in the soma. Thus, the somadendritic amplitude gradient of spontaneous single action potentials in vivo was similar to the later
action potentials in evoked trains in vitro. These findings
therefore indicate that dendritic propagation of fast action potentials in the intact hippocampus is under a strong tonic suppression. Such
suppression of dendritic activity may be brought about by inhibitory interneurons innervating the dendrites of pyramidal cells (Buzsáki et al., 1996; Miles et al., 1996; Tsubokawa
and Ross, 1996).
Simultaneous patch-clamp recordings from the soma and different-caliber
dendrites showed a step-like reduction in the imaged Ca2+ signal at dendritic branch points (Spruston et
al., 1995). Our observations on spontaneously occurring spikes are
compatible with the suggestion that dendritic branch points play a
critical role in the regulation of action potential back propagation.
Although spike amplitudes were somewhat smaller in the middle third of stratum radiatum than in the proximal third, a large step-wise amplitude reduction was evident in the distal third. Most of our anatomically verified impalements were made in the main apical shaft,
which in CA1 pyramidal neurons extends up to the distal third of
stratum radiatum (Ishizuka et al., 1995). In only one rat was the
dendritic spike amplitude <15 mV in the middle third of stratum
radiatum. In this case, the recording was made from a histologically
verified second-order thin branch. Because all branches in the outer
third of the stratum radiatum and in stratum lacunosum-moleculare are
second- or higher-order branches, the small-amplitude spikes recorded
from dendrites in this layer were thin dendritic segments. These
observations suggest that it is the branching order, and consequently
the increased density of A-type K+ channels (Hoffman
et al., 1997), that may determine the degree of spike attenuation in
the dendritic tree rather than the metric distance from the soma.
Sharp wave bursts facilitate dendritic electrogenesis
Of all known physiological patterns, SPWs are associated with the
most powerful depolarization of pyramidal cells. Although most
interneurons also show intense spiking, their population synchrony is
severalfold less than that of the pyramidal cells (Csicsvari et al.,
1997). Therefore, during SPWs there is a net increase of synaptic
excitation. Dendritic recordings revealed three correlated events
during SPWs: bursts of spikes, large-amplitude fast spikes, and wide
putative Ca2+ spikes. Large-amplitude action
potentials typically occurred with small spike bursts, and large fast
spikes were associated with putative Ca2+ spikes. In
fact, large-amplitude fast spikes always preceded the peak of the
Ca2+ spikes, suggesting that the depolarization
produced by the enhanced-amplitude spike is a necessary condition for
the activation of high-threshold Ca2+ channels.
Although large-amplitude fast spikes in distal dendrites occurred
almost exclusively during SPWs, only a portion of SPWs (12%) was
associated with large amplitude spikes. Spontaneous Ca2+ spikes occurred even more rarely (<0.2/min).
The discrepancy between the relative regularity of the population event
(SPW) and the rare events in the dendrites may be explained by assuming that coincident presynaptic activity only rarely converges on the
recorded dendritic segment. In any case, the amplitude variability of
dendritic spikes suggests that action potentials are under the control
of local factors. Enhancement of fast spike amplitude may reflect
facilitated back-propagation of the action potential from the soma to
the recorded dendrite or a locally generated event. Indeed, the average
size of action potential decreased progressively toward the distal
dendrites. Nevertheless, when convergent network excitation was
powerful enough during SPW bursts, large-amplitude spikes were also
present in distal dendrites. The enhancement of fast spike amplitude
may reflect facilitated back-propagation of the action potential from
the soma to the recorded dendrite or a locally generated event. The
observation that current-induced intradendritic depolarization enhanced
spike amplitude in response to synaptic activation indicates that the magnitude of local membrane depolarization and the speed at which these
changes take place are both critical factors.
A general requirement of synaptic plasticity is that afferent activity
is present during periods of large postsynaptic depolarization and
intradendritic increase of Ca2+ (Bliss and
Collingridge, 1993). Recent fluorescent imaging studies indicate the
possible involvement of voltage-gated Ca2+ channels
in synaptic plasticity (Jaffe et al., 1992; Miyakawa et al., 1992;
Regehr and Tank, 1992). Pairing of afferent stimulation with dendritic
action potentials can induce a robust Ca2+ influx
and long-term modification of the active synapses (Christie et al.,
1996; Magee and Johnston 1997; Markram et al., 1997). In light of these
experiments, the present observations indicate that in the intact
hippocampus these conditions may be present during physiological SPW
bursts. During the time window of the SPW, intracellular
Ca2+ may be increased by several cooperative
mechanisms. Bursts of Na+-dependent action
potentials may lead to Ca2+ influx through
voltage-gated Ca2+ channels (Jaffe et al., 1992;
Miyakawa et al., 1992; Christie et al., 1995; Svoboda et al., 1997).
Wide Ca2+ spikes may further increase intracellular
Ca2+ levels (Jaffe et al., 1992). The temporal
overlap of presynaptic activity and postsynaptic spiking during SPW may
result in supralinear summation of Ca2+ signals in
dendritic spines (Yuste and Denk, 1995; Hoffman et al., 1997; Magee and
Johnston, 1997). Finally, the SPW-associated dendritic depolarization
and postsynaptic spiking together or separately may facilitate opening
of NMDA channels, thus providing another route for
Ca2+ influx. It has yet to be established whether
these various mechanisms are present simultaneously during SPWs, and
future research will disclose the mechanism of their
cooperativeness.
Fast action potentials may be generated in dendrites
One of the most intriguing and controversial issues regarding
dendritic function is whether action potentials have a fixed site of
generation in the axon initial segment or whether they can be initiated
at multiple locations (Shepherd and Brayton, 1987; Llinás and
Nicholson, 1971; Segev and Rall, 1988; Jaslove, 1992; Softky, 1994;
Traub et al., 1994). The initiation of Na+ action
potentials in the axon initial segment or the axon and their active
back propagation to the dendritic tree have been directly verified
under some conditions. The initiation of Na+ action
potentials in dendrites is more controversial (Stuart et al., 1997).
Dendritically generated spikes in cortical pyramidal cells have been
observed by extracellular field recordings and by intracellular
recordings with sharp electrodes and patch pipettes (Spencer and
Kandel, 1961; Wong et al., 1979; Herreras, 1990; Turner et al., 1991;
Wong and Stuart, 1992; Regehr et al., 1993). An important argument
against the physiological relevance of these observations is that all
experiments used an excessive synchrony of presynaptic fibers induced
by electrical stimulation (Mainen et al., 1995; Stuart et al., 1997).
Although many of the action potentials recorded in dendrites in
vivo likely reflect action potentials initiated in the soma and
back-propagating into the dendrites, two observations indicate that
action potentials can also be initiated at dendritic locations. First,
more spikes were observed during SPW bursts in dendritic recordings
than in somatic recordings. The additional dendritic spikes must be
generated in the dendrites but must not propagate reliably enough to
trigger action potentials at the soma. Second, when small- and
large-amplitude spikes were considered, the interspike intervals in
dendritic recordings were shorter than expected on the basis of spike
refractoriness. The refractory period for dendritically initiated
spikes likely extends to some distance over which the spike propagates
actively, but spikes may be generated at other dendritic locations
while one dendritic spike initiation zone is refractory. The most
parsimonious explanation of our findings is that action potentials
emanated from multiple sites. In support of our in vivo
observations, simultaneous recordings from the soma and dendrites of
CA1 pyramidal cells in vitro indicate that focally triggered
spikes in dendrites often fail to invade the soma (N. L. Golding
and N. Spruston, personal communication). These findings therefore
indicate that the function of action potentials confined to the
dendrites is fundamentally different from somatic action potentials
that signal via the axon. One of these functions may be to trigger
local Ca2+ spikes and modify synaptic strength.
| |
FOOTNOTES |
Received Sept. 22, 1997; revised Feb. 27, 1998; accepted March 4, 1998.
This work was supported by National Institute of Neurological Diseases
and Stroke Grant NS34994, the Human Frontier Science Program, the
Whitehall Foundation, and the Soros Foundation. We thank B. Christie,
J. Csicsvari, N. L. Golding, D. Johnston, T. Sejnowski, N. Spruston, M. Steriade, K. Svoboda, D. W. Tank, and J. Zackheim for
their comments on an earlier version of this manuscript.
Correspondence should be addressed to György Buzsáki,
Center for Molecular and Behavioral Neuroscience, Rutgers University, 197 University Avenue, Newark, NJ 07102.
| |
REFERENCES |
-
Andersen P,
Bliss TVP,
Skrede KK
(1971)
Lamellar organization of hippocampal excitatory pathways.
Exp Brain Res
13:222-238[Web of Science][Medline].
-
Bliss TVP,
Collingridge GL
(1993)
A synaptic model of memory: long-term potentiation in the hippocampus.
Nature
361:31-39[Medline].
-
Buzsáki G
(1986)
Hippocampal sharp waves: their origin and significance.
Brain Res
398:242-252[Web of Science][Medline].
-
Buzsáki G
(1989)
Two-stage model of memory trace formation: a role for "noisy" brain states.
Neuroscience
31:551-570[Web of Science][Medline].
-
Buzsáki G,
Leung LS,
Vanderwolf CH
(1983)
Cellular basis of hippocampal EEG in the behaving rat.
Brain Res
6:139-171[Web of Science].
-
Buzsáki G,
Horvath Z,
Urioste R,
Hetke J,
Wise K
(1992)
High frequency network oscillation in the hippocampus.
Science
256:1025-1027[Abstract/Free Full Text].
-
Buzsáki G,
Penttonen M,
Nádasdy Z,
Bragin A
(1996)
Pattern and inhibition-dependent invasion of pyramidal cell dendrites by fast spikes in the hippocampus in vivo.
Proc Natl Acad Sci USA
93:9921-9925[Abstract/Free Full Text].
-
Callaway JC,
Ross WN
(1995)
Frequency-dependent propagation of sodium action potentials in dendrites of hippocampal CA1 pyramidal neurons.
J Neurophysiol
74:1-9[Abstract/Free Full Text].
-
Christie BR,
Eliot LS,
Ito K-I,
Miyakawa H,
Johnston D
(1995)
Different Ca2+ channels in soma and dendrites of hippocampal pyramidal neurons mediate spike-induced Ca2+ influx.
J Neurophysiol
93:2553-2557.
-
Christie BR,
Magee JC,
Johnston D
(1996)
The role of dendritic action potentials and Ca2+ influx in the induction of homosynaptic long-term depression in hippocampal CA1 pyramidal neurons.
Neurobiol Learn Mem
3:160-169.
-
Chrobak JJ,
Buzsáki G
(1996)
High-frequency oscillations in the output networks of the hippocampal-entorhinal axis of the freely behaving rat.
J Neurosci
16:3056-3066[Abstract/Free Full Text].
-
Csicsvari J,
Hirase H,
Moore K,
Penttonen M,
Buzsáki G
(1997)
Monosynaptic interactions between CA1 pyramidal cells and interneurons in the behaving rat.
Soc Neurosci Absr
23:483.
-
Fox SE
(1989)
Membrane potential and impedance changes in hippocampal pyramidal cells during theta rhythm.
Exp Brain Res
77:283-294[Web of Science][Medline].
-
Herreras O
(1990)
Propagation of dendritic action potential mediates synaptic transmission in CA1 pyramidal cells in situ.
J Neurophysiol
64:1429-1441[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].
-
Hotson JR,
Prince DA
(1980)
A calcium-activated hyperpolarization follows repetitive firing in hippocampal neurons.
J Neurophysiol
43:409-419[Abstract/Free Full Text].
-
Ishizuka N,
Cowan WM,
Amaral DG
(1995)
A quantitative analysis of the dendritic organization of the pyramidal cells in the rat hippocampus.
J Comp Neurol
362:17-45[Web of Science][Medline].
-
Jaffe DB,
Johnston D,
Lasser-Ross N,
Lisman JE,
Miyakawa H,
Ross WN
(1992)
The spread of Na+ spikes determines the pattern of dendritic Ca2+ entry into hippocampal neurones.
Nature
357:244-246[Medline].
-
Jaslove SW
(1992)
The integrative properties of spiny distal dendrites.
Neuroscience
47:495-519[Web of Science][Medline].
-
Jester J,
Campbell L,
Sejnowski T
(1996)
Associative EPSP-spike potentiation induced by pairing orthodromic and antidromoc stimulation in rat hippocampal slices.
J Physiol (Lond)
484:689-705[Abstract/Free Full Text].
-
Johnston D,
Magee JC,
Colbert CM,
Christie BR
(1996)
Active properties of neuronal dendrites.
Annu Rev Neurosci
19:165-186[Web of Science][Medline].
-
Jung HY,
Mickus T,
Spruston N
(1997)
Prolonged sodium channel inactivation contributes to dendritic action potential attenuation in hippocampal pyramidal neurons.
J Neurosci
17:6639-6646[Abstract/Free Full Text].
-
Kim HG,
Beierlein M,
Connors BW
(1995)
Inhibitory control of excitable dendrites in neocortex.
J Neurophysiol
74:1810-1814[Abstract/Free Full Text].
-
Leung LS,
Yim CY
(1986)
Intracellular records of theta rhythm in hippocampal CA1 cells of the rat.
Brain Res
367:323-327[Web of Science][Medline].
-
Llinás R,
Nicholson C
(1971)
Electroresponsive properties of dendrites and somata in alligator Purkinje cells.
J Neurophysiol
34:532-551[Free Full Text].
-
Magee JC,
Johnston D
(1995)
Synaptic activation of voltage-gated channels in the dendrites of hippocampal pyramidal neurons.
Science
268:301-304[Abstract/Free Full Text].
-
Magee JC,
Johnston D
(1997)
A synaptically controlled, associative signal for Hebbian plasticity in hippocampal neurons.
Science
275:209-213[Abstract/Free Full Text].
-
Mainen ZF,
Joerges J,
Huguenard JR,
Sejnowski TJ
(1995)
A model of spike initiation in neocortical pyramidal cells.
Neuron
15:1427-1439[Web of Science][Medline].
-
Markram H,
Lübke J,
Frotscher M,
Sakmann B
(1997)
Regulation of synaptic efficacy by coincidence of postsynaptic APs and EPSPs.
Science
275:213-215[Abstract/Free Full Text].
-
Miles R,
Tóth K,
Gulyás AI,
Hájos N,
Freund TF
(1996)
Differences between somatic and dendritic inhibition in the hippocampus.
Neuron
16:815-823[Web of Science][Medline].
-
Miyakawa H,
Ross WN,
Jaffe D,
Callaway JC,
Lasser-Ross N,
Lisman JE,
Johnston D
(1992)
Synaptically activated increases in Ca2+ concentration in hippocampal CA1 pyramidal cells are primarily due to voltage-gated Ca2+ channels.
Neuron
9:1163-1173[Web of Science][Medline].
-
Ranck Jr JB
(1973)
Studies on single neurons in dorsal hippocampal formation and septum in unrestrained rats. I. Behavioral correlates and firing repertoires.
Exp Neurol
42:461-531.
-
Regehr W,
Tank DW
(1992)
Calcium concentration dynamics produced by synaptic activation of CA1 pyramidal cell.
J Neurosci
12:4202-4223[Abstract].
-
Regehr W,
Kehoe J,
Ascher P,
Amstrong C
(1993)
Synaptically triggered action potentials in dendrites.
Neuron
11:145-151[Web of Science][Medline].
-
Schwartzkroin PA,
Stafstrom CE
(1980)
Effect of EGTA on the calcium activated afterhyperpolarization in CA3 pyramidal cells.
Science
210:1125-1126[Abstract/Free Full Text].
-
Segev I,
Rall W
(1988)
Computational study of an excitable dendritic spine.
J Neurophysiol
60:499-523[Abstract/Free Full Text].
-
Shepherd GM,
Brayton RK
(1987)
Logic operations are properties of computer-simulated interactions between excitable dendritic spines.
Neuroscience
21:151-166[Web of Science][Medline].
-
Sik A,
Penttonen M,
Ylinen A,
Buzsáki G
(1995)
Hippocampal CA1 interneurons: an in vivo intracellular labeling study.
J Neurosci
15:6651-6665[Abstract/Free Full Text].
-
Softky W
(1994)
Sub-millisecond coincidence detection in active dendritic trees.
Neuroscience
58:13-41[Web of Science][Medline].
-
Soltész I,
Deschénes M
(1993)
Low- and high-frequency membrane potential oscillations during theta activity in CA1 and CA3 pyramidal neurons of the rat hippocampus under ketamine-xylazine anesthesia.
J Neurophysiol
70:97-116[Abstract/Free Full Text].
-
Spencer WA,
Kandel ER
(1961)
Electrophysiology of hippocampal neurons. IV. Fast prepotentials.
J Neurophysiol
24:272-285[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].
-
Stuart G,
Sakmann B
(1994)
Active propagation of somatic action potentials into neocortical pyramidal cell dendrites.
Nature
367:69-72[Medline].
-
Stuart G,
Spruston N,
Sakmann B,
Häuser M
(1997)
Action potential initiation and backpropagation in neurons of the mammalian CNS.
Trends Neurosci
20:125-131[Web of Science][Medline].
-
Suzuki SS,
Smith GK
(1987)
Spontaneous EEG spikes in the normal hippocampus. I. Behavioral correlates, laminar profiles and bilateral synchrony.
Electroencephalogr Clin Neurophysiol
67:438-459.
-
Svoboda K,
Denk W,
Kleinfleld D,
Tank DW
(1997)
In vivo dendritic calcium dynamics in neocortical pyramidal neurons.
Nature
385:161-165[Medline].
-
Traub RD,
Jefferys J,
Miles R,
Whittington M,
Tóth K
(1994)
A branching dendritic model of a rodent CA3 pyramidal neurone.
J Physiol (Lond)
481:79-95[Abstract/Free Full Text].
-
Tsubokawa H,
Ross W
(1996)
IPSPs modulate spike backpropagation and associated (Ca2+)i changes in the dendrites of hippocampal CA1 pyramidal neurons.
J Neurophysiol
76:2896-2906[Abstract/Free Full Text].
-
Turner RW,
Meyers ER,
Richardson TL,
Barker JLJ
(1991)
The site for initiation of action potential discharge over the somatosensory axis of rat hippocampal CA1 neurons.
J Neurosci
11:2270-2280[Abstract].
-
Wong RKS,
Stuart MJ
(1992)
Different firing patterns generated in dendrites and somata of CA1 pyramidal neurons in the guinea-pig hippocampus.
J Physiol (Lond)
457:675-687[Abstract/Free Full Text].
-
Wong RKS,
Prince DA,
Basbaum AI
(1979)
Intradendritic recordings from hippocampal neurons.
Proc Natl Acad Sci USA
76:986-990[Abstract/Free Full Text].
-
Ylinen A,
Bragin A,
Nádasdy Z,
Jandó G,
Szabó I,
Sik A,
Buzsáki G
(1995a)
Sharp wave associated high frequency oscillation (200 Hz) in the intact hippocampus: network and intracellular mechanisms.
J Neurosci
15:30-46[Abstract].
-
Ylinen A,
Soltész I,
Bragin A,
Penttonen M,
Sik A,
Buzsáki G
(1995b)
Intracellular correlates of hippocampal theta rhythm in identified pyramidal cells, granule cells and basket cells.
Hippocampus
5:78-90[Web of Science][Medline].
-
Yuste R,
Denk W
(1995)
Dendritic spines as a basic unit of synaptic integration.
Nature
375:682-684[Medline].
-
Yuste R,
Tank D
(1996)
Dendritic integration in mammalian neurons, a century after Cajal.
Neuron
16:701-716[Web of Science][Medline].
Copyright © 1998 Society for Neuroscience 0270-6474/98/18103919-10$05.00/0
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E. S. Fortune and G. J. Rose
Voltage-Gated Na+ Channels Enhance the Temporal Filtering Properties of Electrosensory Neurons in the Torus
J Neurophysiol,
August 1, 2003;
90(2):
924 - 929.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Takahashi, Y. Anzai, and Y. Sakurai
Automatic Sorting for Multi-Neuronal Activity Recorded With Tetrodes in the Presence of Overlapping Spikes
J Neurophysiol,
April 1, 2003;
89(4):
2245 - 2258.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. C. Stacey and D. M. Durand
Noise and Coupling Affect Signal Detection and Bursting in a Simulated Physiological Neural Network
J Neurophysiol,
November 1, 2002;
88(5):
2598 - 2611.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Lopez-Aguado, J. M. Ibarz, P. Varona, and O. Herreras
Structural Inhomogeneities Differentially Modulate Action Currents and Population Spikes Initiated in the Axon or Dendrites
J Neurophysiol,
November 1, 2002;
88(5):
2809 - 2820.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M J Gillies, R D Traub, F E N LeBeau, C H Davies, T Gloveli, E H Buhl, and M A Whittington
A model of atropine-resistant theta oscillations in rat hippocampal area CA1
J. Physiol.,
September 15, 2002;
543(3):
779 - 793.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Buzsaki, J. Csicsvari, G. Dragoi, K. Harris, D. Henze, and H. Hirase
Homeostatic Maintenance of Neuronal Excitability by Burst Discharges In Vivo
Cereb Cortex,
September 1, 2002;
12(9):
893 - 899.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. E. Larkum and J. J. Zhu
Signaling of Layer 1 and Whisker-Evoked Ca2+ and Na+ Action Potentials in Distal and Terminal Dendrites of Rat Neocortical Pyramidal Neurons In Vitro and In Vivo
J. Neurosci.,
August 15, 2002;
22(16):
6991 - 7005.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Maccaferri and R. Dingledine
Control of Feedforward Dendritic Inhibition by NMDA Receptor-Dependent Spike Timing in Hippocampal Interneurons
J. Neurosci.,
July 1, 2002;
22(13):
5462 - 5472.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. L. Golding, W. L. Kath, and N. Spruston
Dichotomy of Action-Potential Backpropagation in CA1 Pyramidal Neuron Dendrites
J Neurophysiol,
December 1, 2001;
86(6):
2998 - 3010.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Kloosterman, P. Peloquin, and L. S. Leung
Apical and Basal Orthodromic Population Spikes in Hippocampal CA1 In Vivo Show Different Origins and Patterns of Propagation
J Neurophysiol,
November 1, 2001;
86(5):
2435 - 2444.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
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]
|
|
|
|
|
|
|
W. C. Stacey and D. M. Durand
Synaptic Noise Improves Detection of Subthreshold Signals in Hippocampal CA1 Neurons
J Neurophysiol,
September 1, 2001;
86(3):
1104 - 1112.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Steriade
Impact of Network Activities on Neuronal Properties in Corticothalamic Systems
J Neurophysiol,
July 1, 2001;
86(1):
1 - 39.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Su, G. Alroy, E. D. Kirson, and Y. Yaari
Extracellular Calcium Modulates Persistent Sodium Current-Dependent Burst-Firing in Hippocampal Pyramidal Neurons
J. Neurosci.,
June 15, 2001;
21(12):
4173 - 4182.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M E Larkum, J J Zhu, and B Sakmann
Dendritic mechanisms underlying the coupling of the dendritic with the axonal action potential initiation zone of adult rat layer 5 pyramidal neurons
J. Physiol.,
June 1, 2001;
533(2):
447 - 466.
[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]
|
|
|
|
|
|
|
N. P. Staff, H.-Y. Jung, T. Thiagarajan, M. Yao, and N. Spruston
Resting and Active Properties of Pyramidal Neurons in Subiculum and CA1 of Rat Hippocampus
J Neurophysiol,
November 1, 2000;
84(5):
2398 - 2408.
[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]
|
|
|
|
|
|
|
I. Segev and M. London
Untangling Dendrites with Quantitative Models
Science,
October 27, 2000;
290(5492):
744 - 750.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
D. A. Henze, Z. Borhegyi, J. Csicsvari, A. Mamiya, K. D. Harris, and G. Buzsaki
Intracellular Features Predicted by Extracellular Recordings in the Hippocampus In Vivo
J Neurophysiol,
July 1, 2000;
84(1):
390 - 400.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. D. Harris, D. A. Henze, J. Csicsvari, H. Hirase, and G. Buzsaki
Accuracy of Tetrode Spike Separation as Determined by Simultaneous Intracellular and Extracellular Measurements
J Neurophysiol,
July 1, 2000;
84(1):
401 - 414.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Tsubokawa, S. Offermanns, M. Simon, and M. Kano
Calcium-Dependent Persistent Facilitation of Spike Backpropagation in the CA1 Pyramidal Neurons
J. Neurosci.,
July 1, 2000;
20(13):
4878 - 4884.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Maccaferri, J David, B Roberts, P. Szucs, C. A Cottingham, and P. Somogyi
Cell surface domain specific postsynaptic currents evoked by identified GABAergic neurones in rat hippocampus in vitro
J. Physiol.,
April 1, 2000;
524(1):
91 - 116.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. C. Stacey and D. M. Durand
Stochastic Resonance Improves Signal Detection in Hippocampal CA1 Neurons
J Neurophysiol,
March 1, 2000;
83(3):
1394 - 1402.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. E. Larkum, K. M. M. Kaiser, and B. Sakmann
Calcium electrogenesis in distal apical dendrites of layer 5 pyramidal cells at a critical frequency of back-propagating action potentials
PNAS,
December 7, 1999;
96(25):
14600 - 14604.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. King, D. A Henze, X. Leinekugel, and G. Buzsaki
Hebbian modification of a hippocampal population pattern in the rat
J. Physiol.,
November 15, 1999;
521(1):
159 - 167.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. L. Golding, H.-y. Jung, T. Mickus, and N. Spruston
Dendritic Calcium Spike Initiation and Repolarization Are Controlled by Distinct Potassium Channel Subtypes in CA1 Pyramidal Neurons
J. Neurosci.,
October 15, 1999;
19(20):
8789 - 8798.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. C. Magee and M. Carruth
Dendritic Voltage-Gated Ion Channels Regulate the Action Potential Firing Mode of Hippocampal CA1 Pyramidal Neurons
J Neurophysiol,
October 1, 1999;
82(4):
1895 - 1901.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Gur, A. Beylin, and D. M. Snodderly
Physiological Properties of Macaque V1 Neurons are Correlated With Extracellular Spike Amplitude, Duration, and Polarity
J Neurophysiol,
September 1, 1999;
82(3):
1451 - 1464.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Kocsis, A. Bragin, and G. Buzsaki
Interdependence of Multiple Theta Generators in the Hippocampus: a Partial Coherence Analysis
J. Neurosci.,
July 15, 1999;
19(14):
6200 - 6212.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. A. Hoffman and D. Johnston
Neuromodulation of Dendritic Action Potentials
J Neurophysiol,
January 1, 1999;
81(1):
408 - 411.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Csicsvari, H. Hirase, A. Czurko, A. Mamiya, and G. Buzsaki
Oscillatory Coupling of Hippocampal Pyramidal Cells and Interneurons in the Behaving Rat
J. Neurosci.,
January 1, 1999;
19(1):
274 - 287.
[Abstract]
[Full Text]
[PDF]
|
|
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Top
Abstract
Introduction
