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The Journal of Neuroscience, July 15, 2000, 20(14):5461-5467
Synaptic Interactions between Thalamic Inputs to Simple Cells in
Cat Visual Cortex
W. Martin
Usrey1, 2,
Jose-Manuel
Alonso1, 3, and
R.
Clay
Reid1, 2
1 Laboratory of Neurobiology, The Rockefeller
University, New York, New York 10021, 2 Department of
Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, and
3 Department of Psychology, University of Connecticut,
Storrs Mansfield, Connecticut 06269
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ABSTRACT |
We performed experiments in the cat geniculocortical pathway,
in vivo, to examine how presynaptic spikes interact to
influence the firing of postsynaptic targets. In particular, we asked
(1) how do multiple spikes from a single presynaptic neuron interact to
influence the firing of a postsynaptic target (homosynaptic interactions), (2) how do spikes from two different presynaptic neurons interact (heterosynaptic interactions), and (3) what
is the time course of homosynaptic and heterosynaptic interactions? We
found that both homosynaptic and heterosynaptic interactions increase
the likelihood of driving a postsynaptic spike, although with different
time courses. For two spikes traveling down a single geniculate axon,
the second spike is more effective than the first for ~15 msec. For
two spikes on separate axons, the interaction is faster (~7 msec
duration, ~2.5 msec time constant). Thus changes in firing rate are
perhaps best relayed by homosynaptic interactions, whereas
heterosynaptic interactions may help detect coincident spikes from
different thalamic inputs.
Key words:
Key words: lateral geniculate nucleus; thalamus; Area 17; geniculocortical; coincidence detection
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INTRODUCTION |
From intracellular studies, in
vitro, much is known about how the timing of presynaptic impulses
can facilitate and/or depress the EPSPS evoked in the postsynaptic cell
(Magleby, 1987 ; Zucker, 1989). Little is known, however, about the role
of presynaptic timing at the level of the postsynaptic cell's spike
train during sensory processing. In the visual pathway of the cat,
simple cells in layer 4 of visual cortex receive convergent input from
multiple geniculate cells (Hubel and Wiesel, 1962; Tanaka, 1983; 1985; Reid and Alonso, 1995). This raises the question of how geniculate action potentials interact to drive simple-cell responses. Two broad
categories of potential interaction include (1) heterosynaptic interactions interactions between action potentials traveling down different geniculate axons, and (2) homosynaptic
interactionsinteractions between action potentials traveling
down single geniculate axons.
Several lines of evidence indicate that geniculate impulses must
interact at some level to drive simple-cell responses. First, the
transfer of presynaptic spikes to postsynaptic spikes is not one to
one. Approximately 30 geniculate cells provide synaptic input to an
individual simple cell (for review, see Reid et al., 2000), and each of
these geniculate cells is considerably more active than their
simple-cell target (Reid and Alonso, 1995; Alonso, et al., 1996).
Second, there is a dramatic transformation in receptive-field structure
between geniculate cells and their target simple cells. Geniculate
cells have receptive fields with circular centers (`on' or
`off') and antagonistic surrounds (Hubel and
Wiesel, 1961). In contrast, simple cells have elongated receptive
fields with adjacent on and off subregions (Hubel
and Wiesel, 1962). Several studies have shown that the elongated,
on and off subregions of the simple cell result
from convergent input from multiple geniculate cells that have
overlapping receptive fields of matching sign (Hubel and Wiesel, 1962;
Tanaka, 1983, 1985; Reid and Alonso, 1995; Alonso et al., 1996). Third,
previous work from our laboratory has shown that when two presynaptic
geniculate cells fire spikes within 1 msec of each other, the spikes
interact synergistically to drive simple-cell responses (Alonso et al.,
1996). Although this study demonstrated that presynaptic spikes from
two geniculate cells reinforce each other (heterosynaptic
interactions), the study did not examine the time course of the
interaction. Furthermore, it is an open question as to how pairs of
spikes from a single geniculate cell interact (homosynaptic
interactions) to drive simple-cell spikes.
To study the interactions between homosynaptic and heterosynaptic
inputs to cortical simple cells, we simultaneously recorded the
responses of monosynaptically connected geniculate cells and simple
cells in the cat in vivo and examined the interactions between pairs of presynaptic spikes. This approach is similar in style
to a recent study from our laboratory that examined homosynaptic interactions between pairs of spikes from retinal ganglion cells to
geniculate cells [Usrey et al. (1998); also see Mastronarde (1987)].
For the pathway from retina to LGN, we found that homosynaptic interactions between pairs of spikes are reinforcing for ~30 msec. In
the current study, we show that homosynaptic and heterosynaptic interactions at the next stage of processing, between geniculate inputs
to the cortex, are likewise reinforcing, although with shorter time scales.
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MATERIALS AND METHODS |
Fourteen adult cats were used in this study. All surgical and
experimental procedures conformed to National Institutes of Health and
U.S. Department of Agriculture guidelines. These procedures have been
reported previously (Alonso et al., 1996; Usrey et al., 1998, 1999).
Surgical anesthesia was induced with ketamine (10 mg/kg, i.m.),
followed by thiopental sodium (20 mg/kg, i.v., supplemented as needed).
Once all surgical procedures were complete, anesthesia was
maintained with thiopental sodium (2 mg · kg 1 · h1, i.v.,
supplemented as needed). Animals were then paralyzed with vecuronium
bromide (0.2 mg · kg1 · h1, i.v.)
and ventilated mechanically. Proper depth of anesthesia was ensured
throughout the experiment by (1) monitoring the EEG for changes in
slow-wave/spindle activity and (2) monitoring the EKG and expired
CO2 for changes associated with a decrease in the depth of anesthesia.
Receptive fields of geniculate cells were mapped quantitatively by
reverse correlation (Citron et al., 1981; Jones and Palmer, 1987) using
pseudorandom spatiotemporal white-noise stimuli (m-sequences) (Sutter,
1992; Reid et al., 1997). The stimulus was a 16 × 16 grid of rapidly
changing black and white squares (pixels). The stimuli were created
with an AT-Vista graphics card (Truevision, Indianapolis, IN) running
at a frame rate of 128 Hz. The stimulus program was developed with
subroutines from a runtime library, YARL, written by Karl Gegenfurtner
(New York University). The mean luminance of the stimulus monitor was
40-50 cd/m2. Pixels were small enough to map
receptive fields with a reasonable amount of detail (~0.4°/pixel).
Once receptive fields were mapped with the white-noise stimulus, large
numbers of spikes were collected for cross-correlation analysis using
an optimally oriented, drifting (4 Hz) sine-wave grating.
Simultaneous recordings were made from geniculate and cortical neurons
that had overlapping receptive fields. Geniculate recordings were made
with the Eckhorn multi-electrode array (Eckhorn and Thomas, 1993).
Cortical recordings were made with individual tungsten electrodes
(Hubel, 1957). Spike isolation was confirmed with off-line waveform
analysis (Datawave Systems, Longmont, CO), presence of a refractory
period as seen in autocorrelations, and observation of analog data
recorded on tape. Significance of correlogram peaks was assessed with
the method of Reid and Alonso (1995) using a bandpass filter of 75-750
Hz to capture the fast peaks but exclude the slower stimulus dependent
correlations. The peak integral was determined from unfiltered
correlograms (3.0 msec range around maximum), minus the shuffle
correlation and/or baseline (taken from 3 msec ranges immediately
before and after the peak range). The efficacy of geniculate spikes was
defined as (peak integral)/(total geniculate spikes). For the analysis
of homosynaptic and heterosynaptic interactions between pairs of
spikes, the efficacy of each spike in a pair was performed in the same
manner. The definition of these pairs of spikes is described in legends
to Figures 3 (homosynaptic) and 5 (heterosynaptic).
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RESULTS |
Comparing receptive fields and assessing connectivity
Simultaneous recordings were made from 224 pairs of geniculate
cells and layer 4 simple cells with overlapping receptive fields. Receptive fields were mapped using a white-noise stimulus (m-sequences) (Sutter, 1992; Reid et al., 1997); connectivity was assessed by cross-correlating geniculate and simple-cell spike trains (see Materials and Methods). The distinguishing feature in a
cross-correlogram indicative of a monosynaptic connection is a rapidly
rising, short-latency (2-4 msec) peak (Tanaka, 1983, 1985; Reid and
Alonso, 1995; Reid, 2000). Of the 224 pairs of cells, 61 were
determined to be monosynaptically connected. Consistent with previous
reports (Tanaka, 1983, 1985; Reid and Alonso, 1995; Alonso et al.,
1996), monosynaptic connections were only seen between cells with
overlapping receptive fields of the same sign (for instance,
on-center geniculate receptive field overlapping the
on-subregion of a simple cell).
The analysis for examining interactions between presynaptic spikes
required a great deal of data. Of the 61 pairs of cells with
monosynaptic connections, 11 had sufficient signal-to-noise to perform
this analysis. These pairs met the criterion that the `monosynpatic
peak' in the bandpass-filtered cross-correlogram (see Materials and
Methods) was at least 6 SDS above the noise. These pairs had > 10,000
geniculate spikes (mean = 52,000) and > 2500 cortical spikes
(mean = 12,000). From this data set, we examined the interactions
between pairs of geniculate spikes traveling down a single presynaptic
axon (homosynaptic interactions). Receptive fields and
cross-correlograms for each of these 11 pairs of cells are shown in
Figure 1.
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Figure 1.
Simultaneous recordings from geniculate cells
and simple cells with overlapping receptive fields. Top,
Illustration of the experiment. A single electrode was inserted into
layer 4 of visual cortex; up to seven electrodes were inserted into the
LGN. Visual responses to a white-noise stimulus (shown) and drifting
sine-wave grating were recorded. Bottom, Receptive fields
and cross-correlograms for each pair of cells (n = 11)
that were monosynaptically connected and studied for interactions
between geniculate spikes. Regions of a cell's receptive field excited
by the bright phase of the white-noise stimulus (see Materials and
Methods) are shown in white; regions excited by the dark
phase are shown in black. The two panels for each pair of
receptive fields correspond to the same stimulus window.
Circles represent a Gaussian fit to the geniculate receptive
field (radius: 2.5 ). Stimulus pixel size was 0.4°. The
cross-correlograms shown to the right of the receptive
fields each have a short-latency peak (above the stimulus-dependent
shuffle correlogram, shown in gray), indicating a
monosynaptic connection between the geniculate cell and the simple
cell.
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Homosynaptic interactions
To determine whether spike history influences the efficacy of
geniculate spikes in driving simple-cell spikes, we looked at pairs of
spikes traveling down a single geniculate axon and asked whether the
first or second spike was more likely to lead to a simple-cell spike.
An example illustrating the difference in first and second spike
efficacy is shown in Figure 2. In this example, we
recorded the responses of an off-center geniculate cell
whose receptive field overlapped the off-subregion of a
simultaneously recorded simple cell (Fig. 2A,B).
Simple cross-correlation analysis indicated that the simple cell often
fired in response to a geniculate spike (Fig. 2C,D). To
examine potential interactions between spikes from the geniculate cell
in driving the simple cell, we extracted pairs of spikes (with 5 msec
interspike intervals) out of the original geniculate spike train and
looked at the efficacy of first and second spikes (Usrey et al., 1998).
These interactions are shown in two ways: as a raster plot of cortical
firing with respect to paired geniculate spikes (Fig.
2E)and also as a paired-spike cross-correlogram (Fig. 2F), which is the
vertical sum of the raster plot. As can be seen particularly in the
paired-spike correlogram, the second spike is more likely than the
first to contribute to a simple-cell response.
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Figure 2.
Comparison of the effectiveness of two geniculate
spikes (interspike interval = 5.0 ± 0.2 msec) from the same
geniculate cell. A, B, Receptive fields of a geniculate
off-cell and cortical simple cell mapped with white noise
(details as in Fig. 1). C, Raster plot of simple-cell spikes
relative to 1000 geniculate spikes. The simple cell often fired ~2
msec after a geniculate spike. D, Cross-correlogram, which
is equivalent to the sum of all rows of the raster plot
(C); units are simple-cell spikes per second after the
average geniculate spike. The narrow, short-latency peak [above the
stimulus-dependent shuffle correlogram (gray line);
Perkel et al. (1967)] indicates that the geniculate cell provided
monosynaptic input to the simple cell (Tanaka, 1983, 1985; Reid and
Alonso, 1995). Visual stimulus: drifting sine-wave grating of optimal
orientation. Total time: 2062 sec. Geniculate spikes: 64,779;
simple-cell spikes: 8635. Efficacy of geniculate input: 2.1% (see
Materials and Methods). E, Raster plot of simple-cell firing
relative to 1000 pairs of geniculate spikes, each separated by
5.0 ± 0.5 msec and preceded by > 5.0 msec dead time. More
simple-cell spikes followed second geniculate spikes than followed
first geniculate spikes. F, Cross-correlogram between paired
geniculate spikes and simple-cell spikes. Geniculate paired
spikes: 5450. Efficacy of first spikes (peak 1): 1.2%. Efficacy of
second spikes (peak 2): 5.1%.
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Geniculate cells generate action potentials with a broad range of
interspike intervals. This raises the question, over what range of
interspike intervals are second spikes more effective than first spikes
at driving a simple-cell response? To address this question, we
measured the efficacy (efficacy = % presynaptic spikes that lead to
a postsynaptic spike) of first and second geniculate spikes when they
occurred at interspike intervals ranging from ~3 msec to 30 msec. The
shortest interspike intervals were set by the refractory period of the
geniculate cell. In comparing the efficacy of two geniculate spikes,
the interspike interval between them should be shorter than the
interspike interval before the first spike; otherwise, the first spike
will undergo similar interactions (from a previous spike) as the second
spike. We therefore examined the efficacy of first and second
geniculate spikes when the first spike followed a previous spike by at
least 10 or 20 msec (dead time). Note that interspike intervals greater
than the dead time are difficult to interpret, because the first spike might in fact be preceded by a shorter interspike interval than the
second. With interspike intervals between 4 and 10 msec, we found that
second spikes were approximately twice as likely as first spikes to
drive simple-cell spikes (Fig. 3). At interspike intervals > 10 msec, the enhanced efficacy of second spikes
diminished; at interspike intervals > 15 msec, first and second
spikes had similar efficacies.
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Figure 3.
Time course and magnitude of homosynaptic
paired-spike enhancement. A, Illustration of analysis
showing the temporal relationships between dead time and two successive
LGN spikes. Pairs of spikes with a given interspike interval
(ISI) were included in the analysis if there were no
spikes before spike 1 within the dead time (10 or 20 msec). B,
C, Efficacy of pairs of geniculate spikes (percentage that evoked
a simple-cell spike) that occurred at different ISIs after a dead time
> 10 msec and > 20 msec; these dead times were selected because
they are shorter (> 10 msec) and longer (> 20 msec) than the
duration of homosynaptic reinforcement (~15 msec; see Results for
reasoning). Curves in B and C are from the same
geniculate cell and simple cell. Gray lines: efficacy of
first geniculate spikes; black lines: efficacy of second
geniculate spikes. Efficacy at each geniculate ISI was calculated as in
Figure 2, then smoothed with 4 msec boxcar average. D, E,
Average efficacy profiles for all 11 pairs of cells after a dead time
> 10 msec and > 20 msec.
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The effect of paired-spike enhanced efficacysecond spikes
are more effective than first spikes when they occur within ~15 msec
of the first spikewas seen in 10 of 11 pairs of cells that we
studied. The scatter plot in Figure 4 shows the
relationship between the efficacy of first and second spikes for each
of the cell pairs studied. The two points that fall below the line of unit slope represent values from the same pair of cells when examined with two different dead times (> 10 and > 20 msec). All of the pairs of cells (11/11) displayed enhanced efficacy of second spikes when the cells were excited with the white-noise stimulus (data not
shown).
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Figure 4.
Scatter plot of efficacies of second versus first
geniculate spikes; all but one pair of cells showed homosynaptic
enhancement of second spikes. Efficacies were averaged over ISI range
4-10 msec, weighted by number of occurrences of each ISI. The visual
stimulus was a drifting (4 Hz) sine-wave grating. Dead time
(DT) was either > 10 msec (white
circles) or > 20 msec (gray circles). Points
on either axis are for efficacies < 0.1%.
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Heterosynaptic interactions
Out of 224 pairs of geniculate cells and simple cells in our data
set, we recorded 13 `triplets' in which two geniculate cells (Fig.
5A, LGN A and LGN B) were
connected to a simultaneously recorded simple cell. Two of these cases
met our strict criterion for homosynaptic analysis (described above;
pairs 215/217, 223/224). These two cases, along with two additional
cases (for which the stronger geniculate input was just below our
criterion for the homosynaptic analysis), were examined for
heterosynaptic interactions between spikes that converge onto a simple
cell from different geniculate axons. Previously, we have shown that
synchronous geniculate spikes (< 1 msec) from two geniculate
cells reinforce each other and are synergistic in driving simple-cell
responses (Alonso et al., 1996). In the present analysis, we examined
the time course of this heterosynaptic reinforcement (Fig.
5A).
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Figure 5.
Time course and magnitude of heterosynaptic
paired-spike enhancement. A, Illustration of analysis
showing the temporal relationships between spikes from two LGN cells
(LGN A and B). Spike 1 was from cell
A; spike 2 was from cell B. For various ISIs
between spike 1 and spike 2, it was required that cell A fire no spikes
during a lockout period, which included the ISI plus 4 msec. The
additional 4 msec insured that a second spike from cell A did not sum
with spike 2 (from cell B). In addition, the analysis required that
cell B produced no spikes during a dead time of 15 msec (the
approximate duration of homosynaptic interactions) before
spike 2. B, Time course of heterosynaptic interactions
(effect of cell A on cell B) versus homosynaptic interactions (effect
of B on B) for a single cell. C, Averaged heterosynaptic
interactions for the 4 `triplets' in our data set. For each triplet,
the effect was more pronounced when the strong input preceded the weak
input. D, Comparison of average heterosynaptic interactions
(strong input preceding weak) versus average homosynaptic interactions
for same cells (as in B).
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As with homosynaptic interactions, we found that a pair of spikes (as
defined in Fig. 5A) from different geniculate cells reinforce each other to increase the probability that the second spike
evokes a simple-cell spike. At the shortest interspike intervals studied (2 msec), cell A strongly reinforced the efficacy of cell B. In
contrast to homosynaptic reinforcement, which was often constant in
strength for ~10 msec and then decayed to baseline values at ~15
msec, heterosynaptic reinforcement was much briefer (Fig.
5B,D). Reinforcement decreased to ~1/e with a time
constant of ~2.5 msec for the single example (Fig. 5B) as
well as for the average (Fig. 5C). Finally, reinforcement
could not be detected at intervals > 7 msec. Because either of the
two LGN cells could be `cell A,' for each triplet we could examine
the effect of the stronger geniculate input on the weaker, and vice
versa. In our four examples, the heterosynaptic influence was
reciprocal, but the stronger input affected the weaker more
dramatically (Fig. 5C).
We wished to examine whether the fast heterosynaptic interactions were
attributable to linear summation between the two geniculate inputs.
That is, we asked whether the tail of the correlation between cell A
and the cortical cell simply added with the peak of the correlation
between cell B and the cortical cell. In all cases, the tail of cell
A's correlation alone was much smaller than the heterosynaptic
interaction between cells A and B; that is, the heterosynaptic
interaction between cell A and cell B was supralinear [analysis not
shown; see Alonso et al. (1996)].
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DISCUSSION |
In our examination of homosynaptic and heterosynaptic interactions
between geniculate inputs to simple cells in cat visual cortex, we
found that pairs of geniculate spikes reinforce each other so that the
second spike is more likely to drive simple-cell action potentials. For
pairs of spikes travelling down a single geniculate axon, the window
for reinforcement was ~15 msec. For pairs of spikes traveling down
separate geniculate axons, the window for reinforcement was shorter,
~7 msec. With these heterosynaptic interactions, maximal
reinforcement occurred at the shortest intervals examined and decayed
with a time-constant ~2.5 msec. In the following sections, we discuss
the potential mechanisms of homosynaptic and heterosynaptic
reinforcement and the functional implications of these two phenomena.
Potential mechanisms of homosynaptic and
heterosynaptic reinforcement
For homosynaptic interactions between two spikes traveling down a
single geniculate axon, reinforcement could occur by presynaptic mechanisms, postsynaptic mechanisms, or both. The most likely candidate
for a presynaptic mechanism is the accumulation of calcium in the
presynaptic terminal after the occurrence of a previous spike (Magleby,
1987; Zucker, 1989). Potential postsynaptic mechanisms include
involvement of the membrane time constant of the postsynaptic cell (for
review, see Koch et al., 1996), active dendritic conductances (Hirsch
et al., 1995), and voltage-gated currents that underlie action
potential generation (Azouz and Gray, 2000; see also Mainen and
Sejnowski, 1995; Carandini et al., 1996; Nowak et al., 1997; Volgushev
et al., 1998).
A comparison of the time course of homosynaptic reinforcement with the
time course of heterosynaptic reinforcement should shed some light on
whether homosynaptic reinforcement occurs presynaptically or
postsynaptically. Although homosynaptic inputs have potential access to
both presynaptic and postsynaptic mechanisms, heterosynaptic inputs
have access only to postsynaptic mechanisms. Because the time course of
reinforcement was longer (approximately two times) for homosynaptic
inputs compared with heterosynaptic inputs, it seems likely that at
least some of the homosynaptic effect is presynaptic.
It should be noted, however, that postsynaptic mechanisms could have
caused this difference in time course between heterosynaptic and
homosynaptic interactions. The most likely scenario would be if inputs
from two different cells tended to be farther apart than inputs from a
single cell (trivially true if each afferent only provided a single
synapse). In this case, however, homosynaptic inputs would, if
anything, be faster than heterosynaptic. If there were passive
dendritic summation and somatic spike initiation, then there would be
no difference between nearby and distant inputs. If, however, there
were local nonlinear mechanismseither active conductances (Hirsch et
al., 1995; Schiller et al., 1997; Sabatini and Regehr, 1999) or a shunt
caused by strong synaptic input (Reid et al., 1992)these mechanisms
would speed up integration at local sites compared with distant sites.
Because we find that homosynaptic interactions are, in fact, slower
than heterosynaptic interactions, it seems likely that even if
postsynaptic mechanisms play a role, presynaptic mechanisms must be
present as well.
If there is a presynaptic component to homosynaptic reinforcement, it
almost certainly involves a dynamic interplay between facilitation and
depression. In the past, studies performed in vitro
examining facilitation and depression usually relied on protocols in
which pairs of stimuli were delivered on a relatively quiescent
baseline, or trains of spikes were elicited at constant rates (Magleby,
1987; Zucker, 1989). More recently, studies in vitro
(Markram and Tsodyks, 1996; Abbott et al., 1997; Dobrunz et al., 1997;
Tsodyks and Markram, 1997; Varela et al., 1997; Dobrunz and Stevens,
1999; Varela et al., 1999) have begun to use more naturalistic
presynaptic spike trains, similar to those measured in vivo.
Under these conditions, synaptic efficacy appears to depend in a
complex fashion on the local temporal structure of the input.
Although the temporal structure of the presynaptic spike train
certainly is important in determining the extent of synaptic modulation, the local environment surrounding a cell, which can be
quite different in vitro as compared with in
vivo, also appears to play a significant role. Initial experiments
performed in vitro on slices of cat visual cortex indicated
that geniculate inputs undergo paired-pulse depression (Stratford et
al., 1996; see also Gil et al., 1999). More recent work, however,
indicates that when neuromodulators are added and the ionic environment
is changed to mimic conditions present in vivo, the
paired-pulse depression of inputs to visual cortical neurons can
decrease and, in some cases, change to facilitation (Sanchez-Vives et
al., 1999).
The time course of homosynaptic reinforcement that we recorded in
vivo (~15 msec) was relatively short compared with the time course of paired-pulse facilitation that has been measured in other
brain regions in vitro (Magleby, 1987; Zucker, 1989). In a
recent study, we examined homosynaptic interactions between spikes from
retinal ganglion cells to geniculate cells in the cat (Usrey et al.,
1998). Results from this study showed that retinal spikes also undergo
strong, paired-spike reinforcement for interspike intervals up to ~30
msec. Although the retinogeniculate window for reinforcement is
somewhat longer than that measured in the current study of
geniculocortical inputs, both windows are still relatively short
compared with results obtained in vitro. This finding is
consistent with other observations that many cellular properties/reactions become faster when they occur in the in
vivo environment (Sabatini and Regehr, 1996, 1999).
Functional implications of homosynaptic and
heterosynaptic reinforcement
A comparison between the time courses of homosynaptic versus
heterosynaptic interactions demonstrates that not all geniculate spikes
are equal. For a pair of spikes traveling down a single geniculate
axon, the second spike is more effective than the first at driving a
target simple cell for ~15 msec. For two spikes traveling down
separate geniculate axons, spikes interact for a shorter period of
time; reinforcement is strongest at the shortest interspike intervals
and drops rapidly to undetectable levels by ~7 msec. Furthermore, we
have shown that when these geniculate spikes arrive within 1 msec of
each other, they interact synergistically to drive simple-cell
responses (Alonso et al., 1996). These results suggest that information
encoded in firing rate (or bursts) (Sherman, 1996; Reinagel et al.,
1999; Martinez-Conde et al., 2000) is best detected by homosynaptic
interactions, whereas information encoded in coincident firing (Sillito
et al., 1994; Konig et al., 1996; Dan et al., 1998) is best detected by
heterosynaptic interactions.
Recently, we have also shown that geniculate cells that receive common
input from a retinal ganglion cell fire up to 40% of their spikes
within 1 msec of each other (Cleland, 1986; Sillito, et al., 1994;
Alonso et al., 1996; Castelo-Branco, et al., 1996; Usrey et al., 1998).
These synchronous spikes in the LGN are preferentially driven by
retinal spikes during periods of high retinal firing (Usrey et al.,
1998). Therefore, it is possible that the primary benefit of such a
mechanism would be to selectively amplify signals from retinal ganglion
cells that are being driven very strongly (as distinct from any
mechanism that might alter the receptive-field properties of cortical
neurons) (Sillito et al., 1994). Furthermore, additional information
could be potentially encoded if these highly synchronous spikes could
be detected independently (Dan et al., 1998). Although coincidence
detection has been the subject of much debate and may not occur at all
cortical synapses (for review, see König et al., 1996; Usrey and
Reid, 1999), it may be important in the pathway from LGN to cortex,
where there is (1) a mechanism for generating coincident geniculate
spikes, (2) additional information embedded in coincident spikes, and
(3) a mechanism for reading off coincident spikes.
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FOOTNOTES |
Received Jan. 31, 2000; revised April 19, 2000; accepted April 20, 2000.
This work was supported by National Institutes of Health Grants
EY06604, EY10115, EY05253, and EY12196, the Klingenstein Fund, the
Fulbright/MEC, the Charles H. Revson Foundation, and the Harvard Mahoney Neuroscience Institute. Expert technical assistance was provided by Kathleen McGowan, Christine Gallagher, and David Landsberger.
Correspondence should be addressed to R. Clay Reid, Department of
Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, MA
02115. E-mail: clay_reid{at}hms.harvard.edu.
Dr. Usrey's current address: Center for Neuroscience, University of
California, Davis, Davis, CA 95616.
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REFERENCES |
-
Abbott LF,
Varela JA,
Sen K,
Nelson SB
(1997)
Synaptic depression and cortical gain control.
Science
275:220-224.
-
Alonso JM,
Usrey WM,
Reid RC
(1996)
Precisely correlated firing in cells of the lateral geniculate nucleus.
Nature
383:815-819[Medline].
-
Azouz R, Gray CM (2000) Dynamic spike threshold reveals
synaptic coincidence detection in cortical cells in vivo. Proc Natl
Acad Sci USA, in press.
-
Carandini M,
Mechler F,
Leonard CS,
Movshon JA
(1996)
Spike train encoding by regular-spiking cells of the visual cortex.
J Neurophysiol
76:3425-3441[Abstract/Free Full Text].
-
Castelo-Branco M,
Neuenschwander S,
Herculano S,
Singer W
(1996)
Synchronization of visual responses between the cortex, LGN and retina in the anesthetized cat.
Soc Neurosci Abstr
22:643.
-
Citron MC,
Emerson RC,
Ide LS
(1981)
Spatial and temporal receptive-field analysis of the cat's geniculocortical pathway.
Vision Res
21:385-396[Web of Science][Medline].
-
Cleland BG
(1986)
The dorsal lateral geniculate nucleus of the cat.
In: Visual neuroscience (Pettigrew JD,
Sanderson KS,
Levick WR,
eds), pp 111-120. London: Cambridge UP.
-
Dan Y,
Alonso JM,
Usrey WM,
Reid RC
(1998)
Coding of visual information by precisely correlated spikes in the lateral geniculate nucleus.
Nat Neurosci
1:501-507[Web of Science][Medline].
-
Dobrunz LE,
Stevens CF
(1999)
Response of hippocampal synapses to natural stimulation patterns.
Neuron
22:157-166[Web of Science][Medline].
-
Dobrunz LE,
Huang EP,
Stevens CF
(1997)
Very short-term plasticity in hippocampal synapses.
Proc Natl Acad Sci USA
94:14843-14847[Abstract/Free Full Text].
-
Eckhorn R,
Thomas U
(1993)
A new method for the insertion of multiple microprobes into neural and muscular tissue, including fiber electrodes, fine wires, needles and microsensors.
J Neurosci Methods
49:175-179[Web of Science][Medline].
-
Gil Z,
Connors BW,
Amitai Y
(1999)
Efficacy of thalamocortical and intracortical synaptic connections: quanta, innervation, and reliability.
Neuron
23:385-397[Web of Science][Medline].
-
Hirsch JA,
Alonso JM,
Reid RC
(1995)
Visually evoked calcium action potentials in cat striate cortex.
Nature
378:612-616[Medline].
-
Hubel DH
(1957)
Tungsten microelectrode for recording from single units.
Science
125:549-550[Free Full Text].
-
Hubel DH,
Wiesel TN
(1961)
Integrative action in the cat's lateral geniculate body.
J Physiol (Lond)
155:385-398.
-
Hubel DH,
Wiesel TN
(1962)
Receptive fields, binocular interaction and functional architecture in the cat's visual cortex.
J Physiol (Lond)
160:106-154.
-
Jones JP,
Palmer LA
(1987)
The two-dimensional spatial structure of simple receptive fields in cat striate cortex.
J Neurophysiol
58:1187-1211[Abstract/Free Full Text].
-
Koch C,
Rapp M,
Segev I
(1996)
A brief history of time (constants).
Cereb Cortex
6:93-101[Abstract/Free Full Text].
-
König P,
Engel AK,
Singer W
(1996)
Integrator or coincidence detector? The role of the cortical neuron revisited.
Trends Neurosci
19:130-137[Web of Science][Medline].
-
Magleby KL
(1987)
Short-term changes in synaptic efficacy.
In: Synaptic function (Edelman GM,
Gall WE,
Cowan WM,
eds), pp 21-56. New York: Wiley.
-
Mainen ZF,
Sejnowski TJ
(1995)
Reliability of spike timing in neocortical neurons.
Science
268:1503-1506[Abstract/Free Full Text].
-
Markram H,
Tsodyks M
(1996)
Redistribution of synaptic efficacy between neocortical pyramidal neurons.
Nature
382:807-810[Medline].
-
Martinez-Conde S,
Macknik SL,
Hubel DH
(2000)
Microsaccadic eye movements and firing of single cells in the striate cortex of macaque monkeys.
Nat Neurosci
3:251-258[Web of Science][Medline].
-
Mastronarde DN
(1987)
Two classes of single-input X-cells in cat lateral geniculate nucleus. II. Retinal inputs and the generation of receptive-field properties.
J Neurophysiol
57:381-413[Abstract/Free Full Text].
-
Nowak LG,
Sanchez-Vives MV,
McCormick DA
(1997)
Influence of low and high frequency inputs on spike timing in visual cortical neurons.
Cereb Cortex
7:487-501[Abstract/Free Full Text].
-
Perkel DH,
Gerstein GL,
Moore GP
(1967)
Neuronal spike trains and stochastic point processes. II. Simultaneous spike trains.
Biophys J
7:419-440.
-
Reid RC
(2000)
In: Divergence and reconvergence: multielectrode analysis of feedforward connections in the visual system (Nicolelis MAL, ed). New York: Springer Verlag, in press.
-
Reid RC,
Alonso JM
(1995)
Specificity of monosynaptic connections from thalamus to visual cortex.
Nature
378:281-284[Medline].
-
Reid RC,
Victor JD,
Shapley RM
(1992)
Broadband temporal stimuli decrease the integration time of neurons in cat striate cortex.
Vis Neurosci
9:39-45[Web of Science][Medline].
-
Reid RC,
Victor JD,
Shapley RM
(1997)
The use of m-sequences in the analysis of visual neurons: linear receptive field properties.
Vis Neurosci
14:1015-1027[Web of Science][Medline].
-
Reid RC,
Alonso JM,
Usrey WM
(2000)
Integration of thalamic inputs to cat primary visual cortex.
In: Cerebral cortex (13): cat visual cortex (Payne BR,
Peters A,
eds). New York: Plenum, in press.
-
Reinagel P,
Godwin D,
Sherman SM,
Koch C
(1999)
Encoding of visual information by LGN bursts.
J Neurophysiol
81:2558-2569[Abstract/Free Full Text].
-
Sabatini BL,
Regehr WG
(1996)
Timing of neurotransmission at fast synapses in the mammalian brain.
Nature
384:170-172[Medline].
-
Sabatini BL,
Regehr WG
(1999)
Timing of synaptic transmission.
Annu Rev Physiol
61:521-542[Web of Science][Medline].
-
Sanchez-Vives MV,
Nowak LG,
McCormick DA
(1999)
Why might synaptic depression be lesser in vivo than in vitro?
Soc Neurosci Abstr
25:2191.
-
Schiller J,
Schiller Y,
Stuart G,
Sakmann B
(1997)
Calcium action potentials restricted to distal apical dendrites of rat neocortical pyramidal neurons.
J Physiol (Lond)
505:605-616[Abstract/Free Full Text].
-
Sherman SM
(1996)
Dual response modes in lateral geniculate neurons: mechanisms and functions.
Vis Neurosci
13:205-213[Web of Science][Medline].
-
Sillito AM,
Jones HE,
Gerstein GL,
West DC
(1994)
Feature-linked synchronization of thalamic relay cell firing induced by feedback from the visual cortex.
Nature
369:479-482[Medline].
-
Stratford KJ,
Tarczy-Hornoch K,
Martin KA,
Bannister NJ,
Jack JJ
(1996)
Excitatory synaptic inputs to spiny stellate cells in cat visual cortex.
Nature
382:258-261[Medline].
-
Sutter EE
(1992)
A deterministic approach to nonlinear systems analysis.
In: Nonlinear vision: determination of neural receptive fields, function and networks (Pinter R,
Nabet B,
eds), pp 171-220. Cleveland: CRC.
-
Tanaka K
(1983)
Cross-correlation analysis of geniculostriate neuronal relationships in cats.
J Neurophysiol
49:1303-1318[Abstract/Free Full Text].
-
Tanaka K
(1985)
Organization of geniculate inputs to visual cortical cells in the cat.
Vision Res
25:357-364[Web of Science][Medline].
-
Tsodyks MV,
Markram H
(1997)
The neural code between neocortical pyramidal neurons depends on neurotransmitter release probability.
Proc Natl Acad USA
94:719-723[Abstract/Free Full Text].
-
Usrey WM,
Reid RC
(1999)
Synchronous activity in the visual system.
Annu Rev Physiol
61:435-456[Web of Science][Medline].
-
Usrey WM,
Reppas JB,
Reid RC
(1998)
Paired-spike interactions and synaptic efficacy of retinal inputs to the thalamus.
Nature
395:384-387[Medline].
-
Usrey WM,
Reppas JB,
Reid RC
(1999)
Specificity and strength of retinogeniculate connections.
J Neurophysiol
82:3527-3540[Abstract/Free Full Text].
-
Varela JA,
Sen K,
Gibson J,
Fost J,
Abbott LF,
Nelson SB
(1997)
A quantitative description of short-term plasticity at excitatory synapses in layer 2/3 of rat primary visual cortex.
J Neurosci
17:7926-7940[Abstract/Free Full Text].
-
Varela JA,
Song S,
Turrigiano GG,
Nelson SB
(1999)
Differential depression at excitatory and inhibitory synapses in visual cortex.
J Neurosci
19:4293-4304[Abstract/Free Full Text].
-
Volgushev M,
Chistiakova M,
Singer W
(1998)
Modification of discharge patterns of neocortical neurons by induced oscillations of the membrane potential.
Neuroscience
83:15-25[Web of Science][Medline].
-
Zucker RS
(1989)
Short-term synaptic plasticity.
Annu Rev Neurosci
12:13-31[Web of Science][Medline].
Copyright © 2000 Society for Neuroscience 0270-6474/00/20145461-07$05.00/0
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ABSTRACT
INTRODUCTION
