Department of Physiology and Clinical Neurological Sciences, University of Western Ontario, London, Ontario N6A 5A5, Canada
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ABSTRACT |
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Kloosterman, Fabian, Pascal Peloquin, and L. Stan Leung. Apical and Basal Orthodromic Population Spikes in Hippocampal CA1 In Vivo Show Different Origins and Patterns of Propagation. J. Neurophysiol. 86: 2435-2444, 2001. There is controversy concerning whether orthodromic action potentials originate from the apical or basal dendrites of CA1 pyramidal cells in vivo. The participation of the dendrites in the initialization and propagation of population spikes in CA1 of urethan-anesthetized rats in vivo was studied using simultaneously recorded field potentials and current source density (CSD) analysis. CSD analysis revealed that the antidromic population spike, evoked by stimulation of the alveus, invaded in succession, the axon initial segment (stratum oriens), cell body and ~200 µm of the proximal apical dendrites. Excitation of the basal dendrites of CA1, following stimulation of CA3 stratum oriens, evoked an orthodromic spike that started near the cell body or initial segment and then propagated ~200 µm into the proximal apical dendrites. In contrast, the population spike that followed excitation of the apical dendrites of CA1 initiated at the proximal apical dendrites, 50-100 µm distal to the cell body layer, and then propagated centripetally to the cell body and the proximal basal dendrites. A late apical dendritic spike may arise in the mid-apical dendrites (250-300 µm from the cell layer) and propagated distally. The origin or the pattern of propagation of each population spike type was similar for near-threshold to supramaximal stimulus intensities. In summary, population spikes following apical dendritic and basal dendritic excitation in vivo appeared to originate from different locations. Apical dendritic excitation evoked a population spike that initiated in the proximal apical dendrites while basal dendritic excitation evoked a spike that started near the initial segment or cell body. An original finding of this study is the propagation of the population spike from basal to apical dendrites in vivo or vice versa. This backpropagation from one dendritic tree to the other may play an important role in the synaptic plasticity among a network of CA3 to CA1 neurons.
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INTRODUCTION |
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Recent studies revealed that the
dendrites of neurons are not passive structures that merely provide
electrotonic spread of postsynaptic potentials. Instead, the dendrites
may generate spikes or otherwise amplify postsynaptic signals by means
of voltage-sensitive Na+ and
Ca2+ channels (Buzsáki et al.
1996; Magee and Johnston 1995a
,b
; Spencer and Kandel 1968
; Spruston et al. 1995
;
Wong et al. 1979
). A model of dendritic function that
emerged from in vitro patch-clamp studies is that during weak
orthodromic activation, a cortical pyramidal cell fires near the cell
body and this spike backpropagates down the dendrites (Jaffe et
al. 1992
; Spruston et al. 1995
).
Conflicting results showed that spikes start at the apical dendrites of
hippocampal CA1 pyramidal cells in vivo. Field potential profiles
suggested that orthodromic spikes started at the proximal apical
dendrites of CA1 pyramidal cells in anesthetized rabbits and cats,
following excitation of the apical dendrites by the Schaffer
collaterals (Andersen and Lomo 1966; Fujita and
Sakata 1962
). Current source density (CSD) analysis in
anesthetized rats confirmed that the orthodromic population spike
started at the proximal apical dendrites of CA1 (Herreras
1990
). Apical dendritic spikes were found using extracellular
recordings in vitro (Taube and Schwartzkroin 1988
;
Turner et al. 1989
; Vida et al. 1995
), but the predominant view is that an apical dendritic spike was only
generated by high-intensity stimulation of the Schaffer collaterals (Golding and Spruston 1998
; Turner et al.
1991
, 1993
). Furthermore, CSD studies of
orthodromic population spikes in CA1 in vitro consistently showed that
spikes originated near the cell body layer and not at the dendrites
(Miyakawa and Kato 1986
; Richardson et al.
1987
).
It is possible that the afferent stimulus intensity was a confounding
variable in the origin of the population spike, but this issue has not
been investigated. The in vivo study of Herreras (1990)
relied mostly on supramaximal stimulation and the in vitro studies
(Miyakawa and Kato 1986
; Richardson et al.
1987
) likely used high stimulus intensities as well, although
it is difficult to compare the stimulus intensities in vivo and in
vitro. Richardson et al. (1987)
concluded that the
orthodromic population spike originated near the cell layer in vitro,
irrespective of whether the basal or apical dendrites were excited. The
origin of basal dendritic spikes in vivo has not been studied. Thus our
objective was to study orthodromic population spikes in CA1 of
urethan-anesthetized rats in vivo, following basal or apical dendritic
excitation of near-threshold to supramaximal stimulus intensities.
In distinction to previous studies, we analyzed CSDs derived from
simultaneous recordings at multiple sites. The alternate technique of
deriving CSDs from sequentially acquired evoked potentials assumes that
the responses are stationary in time, which may be violated by the
notorious variability of orthodromic spikes. In theory, a potential
field is generated instantaneously (Plonsey 1969) and
extracellular potentials at different sites should be acquired
simultaneously. We used silicon probes fabricated with precise
interelectrode distances (Bement et al. 1986
;
Ylinen et al. 1995
); the accurate spatial interval
reduces the error in the CSD estimates.
We found different origins and patterns of propagation for the
orthodromic population spike following apical dendritic excitation, as
compared with that following basal dendritic excitation or that
following antidromic stimulation. Part of the study was presented as an
abstract (Leung et al. 2000).
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METHODS |
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Rats (220-450 g) were anesthetized with urethan (1.2-1.5 g/kg ip). The recording probes were positioned in CA1 area at P3.6-4.5, L2.4-3 (with respect to bregma). Stimulating electrodes were placed in 1) alveus in CA1 at 0.5-1.5 mm posterior and slightly lateral to the recording site; 2) stratum oriens of CA3a or CA3b, at P3.2, L3.3, 2.9-3.1 mm below the skull surface, to activate the basal dendritic synapses of CA1; and 3) stratum radiatum of CA3b to activate the apical dendritic synapses of CA1. Stimulation rate was <0.1 Hz.
Silicon recording probes were provided by the National Institutes
of Health Center of Neural Communication Technology, University of
Michigan. The typical probe used had 16 recording sites spaced 50 µm
apart on a vertical shank ("16 channel"). Preliminary data were
collected in 12 rats using a 16-channel probe of 100-µm interval; these data are consistent with the conclusions of the present study but
are not included in RESULTS. Another probe had two shanks separated by 300 µm and 6 recording sites at 25-µm intervals on each shank ("2 × 6 channel"). In some experiments, the 2 × 6-channel probe was moved 100 µm deeper after a set of
recordings, to obtain more depth coverage. The stability of the
response was determined by superposition of records at the same
absolute depth after repositioning. The signals were amplified
200-1,000 times by preamplifier and amplifier and passed through a
high-pass filter with 0.08-Hz corner frequency. Sixteen sample-and-hold
circuits maintained the simultaneity of the signals during digitization
by a 16-bit A/D converter at 20-40 kHz. Single or average
(n = 4) sweeps were stored by a custom program.
One-dimensional CSD(z, t) as a function of
depth z and time t was calculated by a
second-order differencing formula (Freeman and Nicholson
1975; Leung 1990
)
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(1) |
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(2) |
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CSD events related to the population spike were isolated by subtracting
the CSDs associated with the field excitatory postsynaptic potentials
(fEPSPs). At a high stimulus intensity, a set of CSD1(z, t)
was assumed to consist of a population spike superimposed on the fEPSP.
At each depth, a template for the fEPSP was provided by the response
CSD2(z, t) evoked by a low stimulus intensity below the population spike threshold. A new response CSD3(z,
t) = Amp * CSD2(z, t
t), was the fEPSP template scaled by an amplification factor (Amp) and time-shifted by
t. The time shift was
necessary to optimize responses across a range of stimulus intensity.
Intracellular EPSPs recorded in vitro showed an earlier onset latency
for high than low stimulus intensity (data not shown). Different values for Amp and
t were iterated by a microcomputer to
minimize the sum square error,
[CSD3(z,
t)
CSD1(z,
t)]2, over all channels and for the
duration of the rising phase of the fEPSPs before the spike.
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RESULTS |
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The data from 25 rats were reported in this study: 22 using the
50-µm 16-channel probe and 3 using the 2 × 6-channel probe. Small dye injections (data not shown, but see technique in Leung et al. 1995) at the depth of the maximal sink of the antidromic population spike was found within the CA1 pyramidal cell layer, confirming previous results (Leung 1979b
;
Lopez-Aguado et al. 2000
). Thus the maximal antidromic
spike sink was assumed to mark the middle of the pyramidal cell layer.
The error of this assumption was estimated at ~25 µm, half the
width of the cell layer. A lesion made by the deepest electrode of the
silicon probe (not shown) was also consistent with the cell layer depth
estimate. The pyramidal cell layer was assigned a depth of 0 µm, and
"positive" depth was defined to be toward apical dendrites.
CSD profiles of an antidromic population spike
An antidromic population spike was evoked by stimulation of the
alveus, with a threshold of about 29 ± 4 µA (mean ± SE,
n = 21 rats). Alvear stimulation first activated a
compound action potential generated by the axonal fibers in the alveus,
many of which were axon collaterals of CA1 pyramidal cells
(Leung 1979a). Depth recordings of the field potentials
showed a fast negative transient traveling from the alveus to the
stratum oriens and then the cell layer (Fig.
1A) (Leung
1979a
,b
; Richardson et al. 1987
).
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CSD analysis of the depth potentials revealed an early but small sink
in stratum oriens, which was interpreted as a current sink at the axon
initial segments (IS at 100 µm in Figs. 1C and 2A). The
IS sink was followed by a much larger somatic spike sink (SS) at the
cell body layer (0 µm). After a short delay, the cell body sink was
followed by an apical dendritic sink (AS at 100-150 µm in Figs.
1C and 2A). Depth profiles of the CSD at fixed
time instants show that the first detectable dipole field at ~1 ms latency was a sink maximal at
100 µm (Fig.
3A) accompanied by sources at
the proximal apical dendrites (50-150 µm). At 1.4-s latency, the
peak sink invaded the cell layer (0 µm) before propagating into the
proximal apical dendrites (2- and 2.2-ms latency in Fig. 3A).
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Patterns of origin and propagation of apical orthodromic population spike
Apical dendritic excitation of CA1 was evoked by stimulation of
CA3b stratum radiatum, with a stimulus threshold of 20 ± 1.6 µA
(n = 17). The field potential was negative at the
apical dendrites and positive at the basal dendrites (Fig.
1B). CSDs showed a maximal fEPSP sink at the apical
dendrites (50-200 µm) and sources elsewhere in CA1 (Fig.
1D). The threshold for evoking a population spike at the
cell body layer was 105 ± 13 µA (n = 17). The
population spike was superimposed on the slower fEPSP (Figs.
1D and 2C). As described in METHODS,
the high-intensity stimulus response (dark trace) at each depth was
fitted by an amplified and time-shifted response evoked by a
low-intensity stimulus (light trace in Fig. 1D and red trace
in Fig. 2C). The difference between the high- and
low-intensity traces revealed a sharp sink at 50 µm in the apical
dendrites (labeled AS in Figs. 1D, 2C, and
2F). The latter sharp sink peaked at ~5-ms latency in Fig.
2F and was interpreted as an apical dendritic (AS) spike.
The AS then propagated to the cell body and basal dendrites (BS in
Figs. 1D, 2C, and 2F). The latency of
the spike sink progressively increased from 100 µm to 150 µm
(stratum oriens), with the largest spike sink typically in the stratum
oriens (Fig. 2F).
In all rats studied after apical dendritic excitation, the population
spike was found to start at the proximal apical dendrites, at a depth
between the maximal EPSP sink and the cell body (AS at 50-100 µm in
Figs. 1D and 2C). The proximal apical population spike propagated centripetally toward the cell body layer, and then the
basal dendrites. In most (6 of 8) rats in which the distal apical
dendritic layer was mapped, a distal (>250 µm) apical dendritic spike was observed to start at a relatively late latency (~5 ms) at
the distal border of the postsynaptic sink (AS at 200-300 µm in Fig.
2F). The latter spike propagated centrifugally up to
300-400 µm distal from the cell body layer; the deepest extent of
propagation was not revealed in the example shown in Fig.
2F. Late CSDs after the spike were not interpreted. In one
example shown, some of the late CSDs resulting from subtracting the
low- from the high-intensity responses (open arrowhead in Fig. 2,
C and F) could be generated by polysynaptic
apical dendritic excitation of CA1, with minor contribution by
afterpotentials and inhibition (Leung 1979a,b
; Roth and Leung 1995
).
The generation and propagation of the apical dendritic population spike
are illustrated further by the CSD spatial profiles (Fig.
3C). At 3.9-ms latency, the depth profiles of the two sets of CSDs, evoked at low and high intensity, were almost identical. At
4.4-ms latency (Fig. 3C), small differences in the CSDs
emerged, which were interpreted as early spike sinks at the proximal
dendritic locations of 100-150 µm. At 4.9-ms latency, a clear
dendritic spike sink was found at 50-100 µm (Fig.
3C), and it was accompanied by a source at >150 µm. The
spike sink progressively became maximal at 0 µm (5.4-ms latency) and
50 µm (5.9- and 6.4-ms latency). A minor distal dendritic sink also
developed at 200-250 µm at 6.4- to 6.9-ms latency. The CSD profiles
of the isolated population spike (resulting from subtracting the low-
from the high-intensity response) are shown in Fig.
4B. At 4.9 and 5.4 ms, a
single spike sink is surrounded by sources (Fig. 4B). At
>5.9 ms, an additional distal dendritic spike sink is shown at
200-300 µm.
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CSDs following apical dendritic excitation of various stimulus
intensities were studied in 10 rats. As shown in Fig.
5, A and D, a
stimulus intensity of 180 µA evoked CSDs corresponding to a
near-threshold population spike of amplitude ~0.3 mV (measured at
50 µm). The population spike potential increased progressively with
stimulus intensity until saturation at ~350 µA (Fig.
5F). Irrespective of stimulus intensity, all CSD profiles
show that the population spike started at the proximal apical dendrites (50-100 µm) and then propagated centripetally toward the soma and
basal dendrites. The involvement of the proximal apical dendritic location of 100 µm during the onset of the population spike (*, Fig.
5) was more apparent at stimulus intensities that were above threshold
(Fig. 5, B, C, and E) than at
near-threshold (Figs. 5, A and D). However,
instantaneous spatial CSD profiles (plots similar to Fig. 3; not shown)
did not reveal a difference between the onset of a population spike
evoked at near-threshold and suprathreshold stimulus intensities. The
propagation of the spike to the basal dendrites (BS at
50 and
100
µm in Fig. 5, A-E) was found at all stimulus intensities,
although small at near-threshold intensity (Fig. 5D). Fewer
and more temporally dispersed unitary spikes (Andersen et al.
1971
) may account for the small and wide population spike at
near-threshold intensity, especially at onset and long latencies.
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Basal dendritic evoked population spikes starting near the cell body layer
Stimulation of CA3b stratum oriens evoked fEPSPs that were
negative at the basal dendrites and positive at the cell layer and
apical dendrites. The stimulus threshold for the basal fEPSPs was
30 ± 6.5 µA (n = 10). CSD analysis revealed
maximal sink for the fEPSPs at stratum oriens (100 µm in Fig.
2A) and maximal source at the cell layer, confirming
excitation of CA1 at the basal dendrites (Roth and Leung
1995
).
The stimulus threshold for a population spike following basal dendritic
excitation was 119 ± 15 µA (n = 10). Again, the
population spike was shown by subtracting the CSD transients following
low-intensity stimulation (red traces in Fig. 2B) from those
following high-intensity stimulation (black traces), yielding traces in
Fig. 2E. The low- and high-intensity responses overlapped
each other before the onset of the population spike, as is expected for
an optimal curve fit of the fEPSP. The earliest deviation of the high-
from the low-intensity stimulus-evoked CSDs occurred at about 4-ms
latency, with the onset of a sink occupying 50 to 50 µm (Figs.
3B and 4A). This was interpreted as the onset of
the population spike sink. Among a group of 10 rats, the earliest
population spike showed a maximal sink from
50 to 50 µm, i.e., near
the cell layer. In the example shown, the earliest population spike
sink peaked in 4-ms latency at
50 µm, but the sink was spread over
150 µm. Within ~0.5 ms, the maximal sink shifted to 0 µm (Figs.
3B and 4A). At 5- to 6.5-ms latency, the spike
sink was seen to progressively invade the proximal apical dendrites, up
to about 200 µm (Figs. 2E, 3B, and
4A). This pattern of onset of the population spike near the
soma, followed by propagation of the spike into the proximal apical
dendrites, was found in all 10 rats after basal dendritic excitation.
The progressive shift of a spatial pattern of "source-sink-source" to increasing depth (basal to apical direction in Fig. 4A)
illustrates this propagation.
Latency and amplitude of peak population spike sinks
The plot of antidromic spike peak latency as a function of depth
(Fig. 6A) reveals that the
spike peak was progressively delayed from stratum oriens (150 µm)
to the proximal apical dendrites (200 µm). The conduction velocity of
the peak sink from
150 to 0 µm was estimated at 0.31 ± 0.03 mm/ms (by linear regression analysis), higher than the conduction
velocity in the proximal apical dendrites (from 50 to 200 µm), which
was estimated at 0.14 ± 0.01 (Fig. 6A). The most
distal propagation of a fast antidromic spike sink was found at
157 ± 8 µm (n = 21; range 100-200 µm). However, the peak amplitude of the antidromic spike sink progressively decreased from 0 to 200 µm (Fig. 6B).
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The orthodromic population spike following basal dendritic excitation
shows a progressive delay similar to the antidromic spike, i.e., the
delay increased from 100 to 200 µm (Fig. 2E and Fig.
6A). The average conduction velocity was 0.17 ± 0.01 mm/ms, and not statistically different between proximal basal and
apical dendrites. In contrast, the delay in peak spike latency was
reversed for the population spike following apical dendritic excitation. The progressive delay of the spike peak from apical to
basal dendrites gave an estimate of the average conduction velocity of
0.15 ± 0.01 mm/ms (Figs. 2F and 6A).
The maximal sink of all types of population spikes peaked near the cell body layer and declined distally (Fig. 6B). The population spike following basal dendritic excitation tends to peak near the proximal basal dendrites (Fig. 6B) or the cell layer (Fig. 2E).
Spatial smoothing and conductivity
The CSD waveforms derived with (n = 2 in Eq. 1, METHODS) and without spatial smoothing (n = 1 in Eq. 1) are shown in Fig. 7, A and B, respectively. These CSD profiles, assuming uniform conductivity, are similar except for a difference in absolute amplitudes. The CSDs were then derived using nonuniform, layer-by-layer conductivity values (Eq. 2, METHODS). The main assumption was a lower conductivity at the CA1 pyramidal cell layer and the alveus, and it resulted in smaller CSD amplitudes near the soma (including the somatic spike sink; Fig. 7C). However, the conclusions about the onset or pattern of propagation of the population spikes remain the same with nonuniform conductivity (Fig. 7).
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DISCUSSION |
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Different spike origins for orthodromic basal or apical spikes
One main finding of this study is that apical and basal dendritic excitation resulted in action potentials that initiated at different locations of the CA1 pyramidal cells. Basal dendritic excitation evoked a spike that started near the cell body or initial segment and then invaded the proximal apical dendrites. The latter sequence is similar to that of an antidromic spike. In contrast, apical dendritic excitation resulted in an orthodromic spike that started at the proximal apical dendrites and propagated to the cell body and basal dendrites.
The origin of the spike following apical dendritic (stratum radiatum)
excitation was located at the proximal apical dendrites, 50-150 µm
from the cell body. This initiation site was found following low- or
high-intensity stimulation of CA3. This spike initiation site
corresponds to the first- or second-order apical dendritic branches of
the CA1 pyramidal cells. At the time of its onset, the spike sink was
at a mid-apical-dendritic location of 100-150 µm, although
relatively small in amplitude. The sink then increased severalfold in
amplitude, while it invaded the more proximal dendrites (50 µm).
Based on its fast time course, it may be inferred that the spike sinks
were mediated by voltage-dependent Na+ currents
(Miyakawa and Kato 1986; Turner et al.
1989
), and not by the long-duration (>5 ms)
Ca2+ currents (see, e.g., Golding et al.
1999
; Kamondi et al. 1998
).
The decline in amplitude of the fast spike sink from soma to apical
dendrites (Fig. 6B) is consistent with the decrease in amplitude of the intradendritically recorded fast spike (Kamondi et al. 1998; Magee and Johnston 1995a
,b
;
Turner et al. 1991
). The decline of the spike height in
the dendrites may be primarily caused by an increase in the density of
dendritic K+ channels (Hoffman et al.
1997
), since Na+ channel density was
relatively uniform through the proximal dendrites of adult animals
(Magee and Johnston 1995a
,b
). The ratio of
Na+ to K+ permeability may
be the most important parameter that determines the amplitude of the
spike sink in the dendrites (Varona et al. 2000
). In
addition, the small amplitude of the spike sink at its onset in the
proximal apical dendrites may be due to the small diameter of the
dendritic branches and the relatively large synaptic depolarization and
conductance at the apical dendrites.
A voltage-sensitive prepotential may contribute to the early onset of a
proximal apical dendritic sink. Spike prepotentials may be mediated by
noninactivating Na+ currents (MacVicar
1985; Turner et al. 1989
), and contributed partly by a decreasing K+ current (Storm
1988
). We suggest that a slow prepotential did not generate the
early AS sink because 1) the onset of the dendritic sink was
sharp and uncharacteristic of slow prepotentials, and 2) the
spike sink at the proximal apical dendrites appeared to travel
proximally at 0.15 mm/ms (Fig. 6A), similar to the
conduction velocity of a distally backpropagating antidromic population spike.
Basal dendritic excitation of CA1 pyramidal cells evoked a population
spike sink that started at a depth typically ranging from 50 to +50
µm, with the sink typically maximal at the cell body layer (0 µm)
at spike onset. It is possible that proximal basal and apical dendrites
were involved in spike initiation. However, a distinct and independent
spike sink generated only by the dendrites is not typically revealed.
At the onset of the basal population spike (4 and 4.5 ms in Figs.
3B and 4A), the sink extending from
50 to +50
µm may be caused partly by proximal dendritic sinks, or by sinks at
the IS and cell bodies.
The initiation of an action potential at the proximal apical dendrites,
even at low stimulus intensities, appears to be at odds with the in
vitro results. A low-threshold stimulus in vitro was found to initiate
an action potential at the initial segment (Spruston et al.
1995; Stuart et al. 1997
) or the axon
(Colbert and Johnston 1996
), and only high-intensity
orthodromic stimulation initiated an action potential starting at the
apical dendrites (Stuart et al. 1997
; Turner et
al. 1991
, 1993
). However, a stimulus that evoked
a detectable orthodromic population spike in vivo (the smallest
population spike was of ~0.3 mV) may be sufficiently strong to
depolarize the apical dendrites and induce dendritic spiking. Even
lower stimulus intensities may induce action potentials from the axon
initial segments of single neurons, but these action potentials may be
too temporally dispersed to result in a population spike
(Andersen et al. 1971
).
The origin of an orthodromic spike from the proximal apical
dendrites following apical dendritic excitation confirmed the result of
Herreras (1990), who used supramaximal stimulation of the CA3 region. By using simultaneous field recordings, we have extended Herreras' result to population spikes evoked by
near-threshold orthodromic stimulation. Vida et al.
(1995)
also inferred the presence of an orthodromically evoked
voltage-dependent event in the proximal dendrites in vitro, in
particular after long-term potentiation. However, other CSD studies in
vitro reported that the orthodromic spike originated near the cell body
(Miyakawa and Kato 1986
; Richardson et al.
1987
). Accurate extracellular determination of the spike origin
in vitro may require simultaneous recordings, which has not been done.
Herreras (1990) reported a late, proximal apical
dendritic sink (LS) that was not apparent in our study, although we
deliberately studied stimulus intensities near the population spike
threshold. There are differences in the synaptic activation in
Herreras' study and ours that may account for the presence of LS. Our
CA3 stimulation typically evoked a maximal stratum radiatum synaptic sink at 200 µm, accompanied by a smooth spatial decay of the passive source that was contiguous with the synaptic sink. In contrast, Herreras (1990)
evoked a synaptic sink at 100 µm that
was spatially separated from a passive soma source. Although a
noninactivating Na+ current (Turner et al.
1989
) may contribute to the slow LS (and initiation of a fast
spike), we would also suggest a contribution by synaptic currents at
the proximal dendrites.
Pattern of spike propagation
We confirmed the propagation of the antidromic spike from the
inferred initial segment (stratum oriens) to the cell body. The main
evidence is based on instantaneous snapshots of the CSD profiles (Fig.
3A) that showed a spike sink at 50 and
100 µm in the
stratum oriens preceding the larger spike sink at the cell body layer
(0 µm). Varona et al. (2000)
inferred that a negative potential transient recorded in stratum oriens was generated by spikes
at the nodes of Ranvier, but their experimental CSD data showed no
stratum oriens (spike) sink preceding the somatic population spike sink.
The propagation of the antidromic population spike into the basal and
apical dendrites of CA1 pyramidal cells has been shown before
(Leung 1979b; Lopez-Aguado et al. 2000
).
Similar propagation of the orthodromic population spike into the basal
dendrites has been reported in vitro (Richardson et al.
1987
; Turner et al. 1989
) but not in vivo. A
previous in vivo study showed that the apical dendritic population
spike stopped at the cell body and failed to invade the basal dendrites
(Herreras 1990
).
In this study, the population spike appeared to originate from
the "penumbra" region of depolarization, near but removed from the
site of the maximal postsynaptic depolarization. It is possible that
the large synaptic sink and the passive source corresponding to the
somatic spike may obscure a possible spike sink at 100-150 µm (Fig.
2F). We may also suggest that the mid-dendritic
depolarization of pyramidal cells near the excitatory synapses is large
enough to inactivate action potentials in vivo. Thus a population spike originating from the proximal apical dendrites may have difficulty traveling across the site of maximal postsynaptic depolarization, but
it travels to the cell body and basal dendrites and peaked at 50 µm
(Fig. 6B). Similarly, the population spike arising from basal dendritic excitation did not appear to invade the basal dendrites, but propagated toward the apical dendrites, where it peaked
at 50 µm (Fig. 6B). Other factors, such as a higher ratio of voltage-dependent Na+ to
K+ channel in the proximal than distal dendrites
(Hoffman et al. 1997
; Magee and Johnston
1995a
,b
; Varona et al. 2000
) may determine spike
initiation at the proximal apical dendrites, and the extent of
propagation into the distal dendrites. The penumbra theory of spike
onset also accounts for the late (~5-ms latency) apical dendritic
spike that propagated distally from the distal border of the
postsynaptic EPSP sink (AS at 250-300 µm in Fig. 2F).
The propagation of a dendritic spike from the apical dendrites to the
basal dendrites, or vice versa, may have important functional consequences. It has been suggested that spike backpropagation may open
N-methyl-D-aspartate or voltage-sensitive
Ca2+ channels and thus mediate long-term
potentiation (LTP) (Jaffe et al. 1992; Magee and
Johnston 1995a
; Stuart et al. 1997
;
Tsubokawa and Ross 1996
). Backpropagation of the
dendritic spike from one dendritic tree to the other may facilitate
synaptic plasticity across basal and apical dendrites of the same CA1
pyramidal cell. Heterosynaptic LTP has indeed been observed in CA1 in
vivo (Leung and Shen 1995
). If a single CA1 pyramidal
cell was induced to fire repetitively by basal dendritic excitation,
backpropagation of the spikes to the apical dendritic synapse may
induce apical LTP if there was coincident presynaptic apical dendritic
afferent activity. The basal and apical dendritic trees of CA1
pyramidal cells receive inputs primarily from different sets of CA3
neurons (Ishizuka et al. 1990
; Li et al.
1993
). Heterosynaptic plasticity may then reinforce the
functional connections from CA3 to CA1 for a small number of CA1
neurons that receive basal and apical excitation at a particular time delay.
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ACKNOWLEDGMENTS |
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We thank B. Shen and K. Wu for technical assistance.
This work was supported by grants from the Medical Research Council of Canada (MOP-36421) and Natural Sciences and Engineering Research Council to L. S. Leung. Silicon probes were provided by the University of Michigan, supported by National Center for Research Resources Grant P41 RR-09754. F. Kloosterman was funded by several Dutch organizations: Stichting Dr Hendrik Muller's Vaderlandsch Fonds, The Hague; Amsterdam University Society, Amsterdam; Dutch National Epilepsy Fund, Houten; Dutch Brain Foundation, The Hague; and Stichting Bekker-La Bastide-Fonds, Rotterdam.
Present address of F. Kloosterman: Swammerdam Institute for Life Sciences, Section Neurobiology, University of Amsterdam, Kruislaan 320, 1098 SM Amsterdam, The Netherlands.
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FOOTNOTES |
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Address for reprint requests: L. S. Leung, Dept. of Clinical Neurological Sciences, University Campus, LHSC, University of Western Ontario, London, Ontario N6A 5A5, Canada (E-mail: sleung{at}uwo.ca).
Received 15 December 2000; accepted in final form 16 May 2001.
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REFERENCES |
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