Download Striate cortex increases contrast gain of macaque LGN neurons

Visual Neuroscience (2000), 17, 485–494. Printed in the USA.
Copyright © 2000 Cambridge University Press 0952-5238000 $12.50
Striate cortex increases contrast gain
of macaque LGN neurons
ANDRZEJ W. PRZYBYSZEWSKI, JAMES P. GASKA, WARREN FOOTE,
and DANIEL A. POLLEN
Department of Neurology, University of Massachusetts Medical Center, Worcester
(Received October 5, 1999; Accepted January 28, 2000)
Abstract
Recurrent projections comprise a universal feature of cerebral organization. Here, we show that the corticofugal
projections from the striate cortex (V1) to the lateral geniculate nucleus (LGN) robustly and multiplicatively
enhance the responses of parvocellular neurons, stimulated by gratings restricted to the classical receptive field and
modulated in luminance, by over two-fold in a contrast-independent manner at all but the lowest contrasts. In the
equiluminant plane, wherein stimuli are modulated in chromaticity with luminance held constant, such enhancement
is strongly contrast dependent. These projections also robustly enhance the responses of magnocellular neurons but
contrast independently only at high contrasts. Thus, these results have broad functional significance at both network
and neuronal levels by providing the experimental basis and quantitative constraints for a wide range of models on
recurrent projections and the control of contrast gain.
Keywords: Striate cortex, Contrast gain, LGN, Macaque monkey, Vision
jected forward (Mumford, 1992; Rao & Ballard, 1999). In discussing the latter predictive model with applicability to both
corticofugal and corticocortical recurrent projections, Koch and
Poggio (1999) note that “it will be critical to unravel the precise
function of corticocortical feedback projections and their biophysical model of operation, whether linearly subtractive as in Rao and
Ballard’s model or modulatory multiplicative (or divisive).” Thus,
even some of the most basic issues concerning the functional role
of the corticofugal visual system in the primate remain unresolved.
In our attempt to determine the most general function of the
corticofugal pathways from the striate cortex, V1, to the LGN, we
first determined the contrast–response functions for parvocellular
and magnocellular neurons and then reversibly inactivated V1 by
cooling. The corticofugal pathways originate in layer 6 of V1
(Fitzpatrick et al., 1994). Based upon the similar results by others
studying corticocortical feedback under sufentanil anesthesia (Nothdurft et al., 1999) and in awake animals (Knierim & Van Essen,
1992; see also Discussion), we assume that the corticofugal pathways are also largely normally active during both the pre- and
post-cooling control periods and are largely inactivated during
cooling of V1. Thus, we infer that the corticofugal pathways normally produce changes in activity that are the converse to those
observed during cooling of V1.
We have attempted to circumvent some of the possibly confounding effects of stimulus design in previous studies. First, we
predetermine the optimal stimulus parameters for stimuli modulated in luminance or chromaticity. We then explore the full range
of Michaelson contrasts to calculate contrast–response functions—a
fundamental neuronal response characteristic—using interleaved
Introduction
Recurrent projections comprise a universal and anatomically prominent feature of cerebral organization in all sensory and motor
systems (Rockland & Pandya, 1978; Pandya & Yeterian, 1985;
Felleman & Van Essen, 1991; Salin & Bullier, 1995). Even so, and
despite strong evidence for specialized functions of corticofugal
pathways in the feline visual system for selectively facilitating the
transmission of signals from binocularly viewed objects that are
near the fixation plane (Schmeliau & Singer, 1977; Tsumoto et al.,
1978), for enhancing length tuning of lateral geniculate nucleus
(LGN) neurons (Murphy & Sillito, 1987), and for improving the
detection of focal orientation discontinuities (Sillito et al., 1995),
an understanding of their general function and significance has
remained controversial and a matter of broad current interest. Indeed, the effects of reversible inactivation of V1 on LGN function
have been so variable with respect to the resultant strength and
consistency of residual evoked responses in the LGN (Kalil &
Chase, 1970; Baker & Malpeli, 1977) that Crick and Koch (1998)
upon reviewing the literature concluded that the visual cortex has
only weak excitatory and modulatory effects on the receptive-field
properties of geniculate cells.
Others, applying principles of predictive coding, have suggested that some feedback projections may suppress predictable
features of the input so that only the unexpected residua are pro-
Address correspondence and reprint requests to: Daniel A. Pollen, Department of Neurology, University of Massachusetts Medical Center, Worcester, MA 01655, USA. E-mail: [email protected]
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stimuli to minimize the distorting effects of random changes in
cortical excitability. In contradistinction to previous studies in the
macaque (Hull, 1968; Marrocco & McClurkin, 1985), we then
limit these stimuli to the classical receptive field (center and surround) to avoid effects induced by stimulation of the extended
surround. This distinction may be important because the effects of
stimulation of the extended or nonclassical surround of LGN neurons on their activity are largely suppressive and are mediated at
least in part by corticofugal activation (Marrocco et al., 1982;
Marrocco & McClurkin, 1985). This is not to minimize the role of
the suppressive surround and its partial control by cortical feedback in the overall function of corticofugal pathways; rather, we
believe that our present studies of the corticofugal projections
subserving the classical center and surround comprise an essential
first step before the subsequent issue of the extended surround can
be addressed.
Methods
Anesthesia and analgesia
Six macaque monkeys (Macaca fascicularis) were maintained under sufentanil anesthesia with arterial pulse and blood pressure
continuously monitored. Animal care was in accordance with institutional guidelines. The dose of sufenta was adjusted, generally
within the 2–8 mg0kg0h range, to eliminate pain as judged by
precluding abnormal increases in pulse or blood pressure either
spontaneously or in response to tail pinch. The animals were paralyzed with Pavulon 0.2 mg0kg0h so as to maintain retinal fixation
and ventilated so as to keep the exhaled CO2 close to 4%.
Optics
After inducing cycloplegia of each eye by topical application of
drops of ophthalmic atropine, we utilized slit retinoscopy to select
contact lenses that would focus each eye on the monitor set at a
distance of 1 m. Additional trial lenses were used when necessary
to adjust the refraction to within 0.25 diopters. When we compared
refractive corrections based on retinoscopy with those obtained by
optimizing the contrast–response function of individual LGN neurons to sine-wave gratings of high spatial frequency, we obtained
comparable results. The positions of the optic discs and foveae
were back-projected using a reversible ophthalmoscope and mapped.
Monitor characteristics
Stimuli were displayed on a 17-inch color monitor (EZIO XTC7S) with D65 white point (CIE standard) and with a spatial
resolution of 640 by 480 pixels and a refresh rate of 160 Hz. A
Minolta CL-100 chroma meter was used to measure the tristimulus
values and intensity response of the R, G, and B phosphors. Monitor gamma was corrected using lookup tables.
The unit vectors along each dimension in color space were
made similar to those used by Lennie et al. (1990). Unit modulation along the luminance axis produced a Michaelson contrast of
1.0. Along the constant RG axis unit modulation produced a contrast of 0.84 to the B cones with the no contrast to other cones.
Along the constant B axis unit modulation produced a contrast of
0.023 to the R cones, a contrast of 0.045 to the G cones and no
modulation to the B cones.
A.W. Przybyszewski et al.
Reversible inactivation of V1 by cooling
We used a silver cooling plate of 17 3 18 mm attached to a Peltier
device to transdurally cool and subsequently rewarm the dorsal
surface of the macaque striate cortex. A 2-mm-diameter hole in the
center of the plate permitted us to insert a microelectrode through
the dura and advance it to reach the layer 6–white matter interface
which was recognized by the depth below which we ceased recording from cortical neurons. We then withdrew the electrode
until we once again recorded from cortical cells in the functionally
identified deepest cortical layer. Using a thermistor at the surface
of the plate, we could monitor temperatures necessary to inactivate
activity in layer 6 in response to a drifting bar or grating. Effective
surface temperatures to inactivate the deep layers ranged from 98C
to 128C. The region of Vl cooled by our probe included a sector of
the inferior visual field out to about 5 deg along both vertical and
horizontal meridia exclusive of the more laterally located central
1–2 deg. Consequently, we searched for retinotopically corresponding recording sites within the LGN.
Confirming previous results (Hull, 1968; Kalil & Chase, 1970;
Baker & Malpeli, 1977; Marrocco & McClurkin, 1985), we found
no effects on the activity of LGN neurons unless such neurons
were retinotopically related to the region of Vl that was cooled.
Moreover, Hull (1968) and Kalil and Chase (1970) have already
confirmed that cooling of V1 does not alter LGN temperature. The
latter group also confirmed that cortical cooling did not produce
either local vascular changes within the LGN or changes in systemic blood pressures. Thus, they conclude that local cooling of
V1 does not produce any significant nonspecific effects in the
LGN.
Moreover, we carried out controls on the viability of activity in
the superficial layers of V1 in order to see if such activity returned
to baseline after a single cooling cycle. We selected superficial
cells for this test because these neurons are physically closest to
the cooling probe and thus likely to be subjected to the most
extreme effects of cooling. Responses of superficial cells in Vl,
tested for spatial-frequency selectivity, ceased during cooling and
spatial-frequency selectivity curves subsequently returned to baseline during recovery. These studies also showed that although the
action potentials and the hyperpolarizing afterpotentials slowed
progressively during cooling, they returned to control levels during
recovery. This suggests that cooling of V1 to temperatures such as
we have employed for relatively short periods of 3– 6 min does not
necessarily produce irreversible damage to the striate cortex—at
least as long as enough time is allowed between successive coolings for recovery. Even so, we typically carried out only four to
five cooling cycles in a given hemisphere before switching to the
other side.
Identification of LGN neurons
We initially searched for the parafoveal representation (i.e. central 2–5 deg) of the contralateral inferior visual field of the LGN
studied so that we could selectively inactivate the retinotopically
corresponding exposed surface of V1. We directed a tungsten
microelectrode vertically through the cortex towards the LGN at
coordinates 11 mm lateral to the midline and 3 mm posterior to
the central sulcus (R. Shapley, personal communication). Along
the way to the LGN, we encountered neurons with very large
binocularly driven receptive fields and with response properties
typical of those of cells of the perigeniculate nucleus (Funke &
Eysel, 1998) at depths of 18–20 mm below the cortical surface
Striate control of LGN contrast gain
before the microelectrode entered the upper layers of the LGN
wherein response characteristics changed abruptly.
The first such neurons then encountered had ON-Center welllocalized receptive fields, exhibited pronounced chromatic opponency in three-dimensional (3D) color space (Derrington et al.,
1984) and were selectively driven by the contralateral eye. With
further advance of the microelectrode; we encountered ON-Center
chromatically opponent cells driven by the ipsilateral eye. With
still deeper penetration of the microelectrode, we recorded in the
anticipated sequence from the two predominantly OFF-center parvocellular layers before the microelectrode reached the two magnocellular layers. When we did not reach populations of LGN cells
in retinotopic correspondence to cells on the exposed surface of
V1, we re-positioned the microelectrode in accordance with the
topographic mapping of the macaque LGN by Malpeli and Baker
(1975). In all studies, the ineffective eye was covered during stimulation of the effective eye.
In some experiments, we initially studied parvocellular neurons. In others, we first sought out and studied magnocellular
neurons so as to even up the numbers of such cells studied and to
eliminate any bias that magnocellular neurons might otherwise be
selective studied late in the course of the experiments and only
after several cooling cycles of the striate cortex. Thus, differences
in corticofugal effects on these cell types reflect genuine functional
differences which are not related to the order in which cells were
studied.
At the end of each experiment, the animal was euthanized by
intravenous injection of sodium pentobarbital 100 mg0kg and the
brain was fixed in 10% formalin. Tracts through the LGN were
confirmed histologically in the first three experiments. Thereafter,
we relied on functional identification. We chose not to make electrolytic lesions within the main body of the LGN because such
lesions might destroy corticofugal fibers projecting to deeper LGN
cells that we might wish to study.
Determination of chromatic opponency
Responses of LGN cells to a set of gratings spaced 45 deg apart in
the three principal planes in the color space were fit to a model that
assumes linear summation of cone signals by LGN cells. The
direction of the vector yielding maximum response was used to
characterize the chromatic sensitivity of the cell. Following Lennie
et al. (1990), we use u to denote the elevation above the equiluminant plane and f to denote the azimuth in the equiluminant plane
with f 5 u along the constant B axis.
Functional identification of LGN neurons
Magnocellular neurons can be distinguished from parvocellular
neurons by their poor sensitivity to modulation in the equiluminant
plane. In this study, a cell was classified as color sensitive if the
elevation of its maximum response was less than 60 deg. Examination of the LGN data presented by Derrington et al. (1984)
shows that no magnocellular cells in their sample would be classified as color sensitive using this criterion. Color-sensitive cells
were tentatively identified as parvocellular neurons. Noncolorselective neurons with low contrast sensitivity (i.e. with thresholds
at contrasts of close to 0.03) were tentatively identified as magnocellular neurons (Derrington & Lennie, 1984; Kaplan & Shapley, 1986). These tentative identifications of cell types were accepted
only when they correlated well with the laminar localization of cell
487
types predicted from the expected alternation of eye preferences as
the microelectrode vertically traversed the LGN.
Selection of stimulus parameters
The approximate extent of the diameter of the classical center and
surround of each receptive field was calculated using a differenceof-Gaussian model to best fit the spatial-frequency selectivity curve.
The contrast–response functions for both magnocellular and parvocellular neurons were then tested with drifting sine-wave gratings modulated in luminance over a range of contrasts at a temporal
frequency of generally 8 Hz (range 4–12 Hz) over the predetermined classical center and surround at a spatial frequency close to
the highest spatial frequency before responses began to fall off on
the high spatial frequency side. Magnocellular neurons were studied at spatial frequencies from 0.5–2 cycles0deg with a median
value of 0.5 cycle0deg and parvocellular neurons were studied at
spatial frequencies of 0.25–8 cycles0deg with a median value of
0.5 cycle0deg. Aperture widths for magnocellular neurons ranged
from 1– 4 deg with a median value of 2 deg; aperture widths for
parvocellular neurons also ranged from 1– 4 deg but with a median
value of 1.5 deg.
Results
Contrast–response functions for 25 LGN neurons on which we
were able to complete the full cycle of tests were determined for
drifting sine-wave gratings modulated in luminance before, during, and after reversible cooling of the ipsilateral striate cortex.
In addition, we were also able to hold a subset of five parvocellular neurons long enough after the luminance studies were
completed to carry out a second cooling cycle while testing
contrast–response functions using chromatically opponent gratings of very low spatial frequency modulated along the neuron’s
preferred azimuth in the equiluminant plane (Derrington et al.,
1984; Lennie et al., 1990). In almost all cases, the contrast gain,
which we define as the amplitude of the first harmonic of a
cell’s response to drifting gratings, divided by contrast, was substantially reduced for both magnocellular and parvocellular neurons usually within 2–5 min after cooling had begun. Recovery
to baseline values after cooling generally took 10–15 min but
sometimes longer. On average, pre-cooling and recovery control
values were similar (Fig. 1a) and responses observed during
cooling were substantially lower (Fig. 1b).
The amplitudes R of the first harmonic of each cell’s responses
to drifting sine-wave gratings as a function of the Michaelson
contrast c were fitted to both the Michaelis–Menten equation as
applied to visual physiology by Naka and Rushton (1966) and
power functions; see also Hering (1874). In the former equation,
R 5 Rmaxc n0~c n 1 b n ), where Rmax represents the derived maximum value and b the semisaturation contrast, that is, the contrast
required to evoke a response equal to one-half the derived maximum value. In the latter case, the power function R 5 10 a c b is
represented as a straight line in the log–log plot log(R) 5 a 1 b
log(c). We have chosen those functions that fit the data by minimizing the RMS (root mean square) error and which were then
plotted on both log–log and linear–linear scales with b in the
former instance representing the slope on the log–log plot.
We have chosen to fit the contrast–response functions of parvocellular neurons by power functions rather than by the Michaelis–
Menten equation. The responses of such cells do not show saturation
at high contrasts and their responses in log–log coordinates look
488
A.W. Przybyszewski et al.
Fig. 1. Modulated responses of LGN cells to drifting gratings of optimal spatial frequency measured at the drift frequency before,
during, and after V1 cooling. Averaged responses at different contrasts were plotted as single points for magnocellular neurons (open
circles) for parvocellular neurons (open triangles) with coordinate value before cooling against value after cooling in (a) or against
response during cooling in (b).
linear (Fig. 2a) confirming Derrington and Lennie (1984). Such
fits by power functions requires only two free variables compared
to the three required by the Michaelis–Menten equation and avoids
the implausible generation of semisaturation contrasts (b) substantially greater than 1.0 that invariably follows when we try to fit the
data to the Michaelis–Menten equation.
When response versus contrast was plotted on a log–log scale
for gratings modulated in luminance before, during, and after cooling, parvocellular neurons, on average, underwent a largely uniform decline in responsivity of just over an octave spanning most
of the contrast range as shown for the combined responses of ten
such neurons (Fig. 2a). Because responses before and after cooling
were so similar (Fig. 1), we could have combined these responses
and obtained even smaller standard errors of the means than are
shown in Fig. 2. However, because the differences in the curves for
the population before and during cooling are statistically significant anyway (see below) and because we would prefer to display
data for comparable members of trials, we chose not to average the
pre- and post-cooling control results.
The shift of the contrast–response functions of ten parvocellular neurons (seven ON-center and three OFF-center) cells to the
right (or down) following inactivation of V1 is statistically significant and occurs without a statistically significant change in slope
(Table 1). The near-uniform response suppression in the log–log
plot over most of the contrast range suggests that inactivation of
V1 divisively decreases the activity of LGN neurons. Conversely,
in the absence of such inactivation, that is, with V1 normally
active, the effect of V1 on parvocellular neurons is to multiplicatively enhance the contrast gain of these cells on average by just
over two-fold or equivalently by just over an octave (Fig. 2a). This
suggests that feedback from V1 becomes independent of stimulus
contrast. This independence could be related to selective neurons
in V1 that saturate at low contrasts (0.1) (Sclar et al., 1990; Albrecht & Hamilton, 1992). These effects hold over the entire range
of observed preferred spatial frequencies from 1–8 cycles0deg.
The suppressive effects of cooling on ten magnocellular neurons (six ON-center and four OFF-center cells) (Fig. 2b) were on
average similar to those observed in parvocellular neurons (Fig. 2a)
at high contrast but had different characteristics at lower contrast.
At higher contrasts there is an almost parallel downward shift in
magnocellular responses as a consequence of inactivation of V1.
At these higher contrasts, the effect of cooling V1 on magnocellular neurons looks similar to those of parvocellular cells (Fig. 2a),
that is, a multiplicative contrast–independent shift. This effect could
be related to V1 cells that saturate at contrasts above 0.2 (Sclar
et al., 1990; Albrecht & Hamilton, 1992). At these contrasts or
higher, the responses of magnocellular neurons are more than twofold greater when the corticofugal pathways are operant. At lower
contrasts, however, the effect of cooling of V1 on magnocellular
neurons is strongly contrast dependent (Fig. 2b). This effect could
be related to the frequency-dependent increase in the amplitude of
excitatory postsynaptic potentials (EPSPs) of LGN cells by corticofugal excitation (Lindstrom & Wrobel, 1990). The shift of the
contrast–response function to the right (or down) after inactivation
of V1 (Fig. 2b) is statistically significant as is the decrease in the
slope of the response function (Table 1).
The differential effects of cooling on magnocellular and parvocellular neurons at low contrasts is not likely due to a difference
in stimulus parameters used to test these two populations. These
parameters were rather similar (see Methods).
Cooling also depressed the contrast–response function measured using chromatically opponent equiluminant stimuli for parvocellular neurons that were strongly tuned along either the
red–green (four cells) or blue–yellow axes (one cell). Stimuli were
also limited to the classical receptive field and presented at very
low spatial frequencies because such frequencies optimize responses of parvocellular LGN cells for equiluminant stimuli (Derrington et al., 1984). A subset of five such neurons were held long
enough to be tested over the contrast range to both gratings modulated in luminance (Fig. 2c) and gratings of very low spatialfrequency selectivity modulated in chromaticity in the equiluminant
plane (Fig. 2d). Cooling suppressed the responses to chromatically
opponent stimuli even more strongly than those to gratings modulated in luminance especially at high contrasts. The extent of the
Striate control of LGN contrast gain
489
Fig. 2. Averaged responses 6 SEM of ten parvocellular neurons (a), ten magnocellular neurons (b), and five parvocellular neurons
(c, d) plotted as a function of luminance contrast (a–c) or chromatic contrast (d) before (circles) and during (squares) cooling of V1.
The mean values for each population were obtained by summation of average responses of each individual cell at each stimulus
contrast. Parvocellular responses were fitted with power functions. Magnocellular responses before cooling (b) were fitted with two
power functions related to two different ranges of responses (interrupted lines) and also with the Michaelis–Menten function (solid
line). Coefficients a, b, and RMS (root mean square error) are noted above each curve. Parvocellular neurons in (c) and (d) show no
differences in their responses for stimulus contrasts below 0.1 and only responses to stimuli with contrasts above 0.1 were fitted with
power functions. The responses before cooling for all contrasts were fitted with the power functions. During cooling, responses to the
lowest contrast were not different from responses to two-fold higher contrast and this point was not fitted.
suppression decreased logarithmically with lower contrast which
can be approximated as the change of the line slope in the log–log
plot (Fig. 2d) resembling that of magnocellular neurons at lower
contrasts (Fig. 2b).
Because inactivation of V1 has a stronger effect on the responses of parvocellular neurons to changes in chromatic contrast
than to changes in luminance contrast, we could show that the
changes in the intercept and slope of response functions to changes
in chromatic contrast by inactivation of V1 (Fig. 2d) are statistically significant even for a population of five cells (Table 1). The
mean slope calculated from slopes of individual cells for the chromatic contrast–response function was 0.835 in the control and
0.404 during cooling; this difference was highly significant in a
t-pair Student test (t 5 5.62, P , 0.0025). Conversely, the
mean slope for the luminance contrast–response function for the
same cells (Table 1) was 0.609 in the control and 0.649 during
inactivation of V1; this difference is not significant in a t-pair test
(P . 0.5).
We have confirmed the above differences by also applying a
nonparametric test. We have evaluated the responses of these same
cells to contrast changes in luminance and in the equiluminant
plane using the sign test. We have first tested the null hypothesis
that intercept values (parameter a in the power function R 5 10 a c b !
during control and cooling are from the same populations for luminance and for color stimuli. We have rejected this null hypothesis and shown with a probability (P , 0.05) that parameter a is
from different populations before and during cooling. We then
tested the null hypothesis that the slope values (parameter b) are
from the same populations before and during cooling for color and
for luminance. We also rejected this null hypothesis and showed
490
A.W. Przybyszewski et al.
Table 1. Summary of the statistical analysis for either cell populations or means of individual cell values—the latter
indicated by “mean ind” a
Cell type
ec
N
par
mean
95% conf int
sig
Statistical test
Control
Cool
Control
Cool
Control
Cool
Control
Cool
Control
Cool
Cool
Control
Cool
Cool
Control
Cool
Cool
Control
Cool
Cool
10
10
10
10
10
10
10
10
5
5
5
5
5
5
5
5
5
5
5
5
a
a
b
b
a
a
b
b
a
a
a
b
b
b
a
a
a
b
b
b
1.449
1.062
0.721
0.610
1.407
0.998
0.561
0.337
1.201
0.903
(1.394, 1.504)
(0.896, 1.227)
(0.662, 0.780)
(0.431, 0.788)
(1.307, 1.507)
(0.961, 1.034)
(0.452, 0.669)
(0.297, 0.376)
(1.008, 1.394)
(0.643, 1.162)
t-pair Student
(0.400, 0.817)
(0.368, 0.929)
t-pair Student
(0.955, 1.623)
(0.449, 0.807)
t-pair Student
(0.474, 1.115)
(0.210, 0.597)
t-pair Student
—
P , 0.05
—
n.s.
—
P , 0.05
—
P , 0.05
—
P , 0.05
n.s.
—
n.s.
n.s.
—
P , 0.05
P , 0.002
—
P , 0.05
P , 0.0025
—
t-test population
—
t-test population
—
t-test population
—
t-test population
—
Sign test population
mean ind
—
sign test population
mean ind
—
Sign test population
mean ind
—
Sign test population
mean ind
Parvo lum.
Magno lum.
Parvo lum.
Parvo equilum.
0.609
0.649
1.289
0.628
0.835
0.404
a
In left column cells types are specified as magnocellular by “Magno” or parvocellular by “ Parvo.” Studies in which contrast is
modulated in luminance indicated by “lum” and in equiluminance indicated by “equilum.” Experimental condition “ec” specific for
either “control” or during cooling of V1 by “cool.” Number of cells signified by “N.” The parameter analyzed signified by “par” for
either (a)—intercept or (b)—the slope. The 95% confidence interval for parameters of the linear regression after logarithmic data
transformation signified by “95% conf int.” Part of the data was also analyzed using the t-pair Student test and sign test for intercept
or slope differences related to the individual cells. The probability of the statistical significance “sig” of the changes in the (a) or (b)
parameter as an effect of V1 cooling is indicated by the (P ) values; “n.s.” indicates not statistically significant. In statistical t-tests for
cell populations, the responses of the individual cells to each contrast were averaged and logarithmically transformed. The confidence
intervals of the linear regression parameters were then compared before and after cooling. In the tests for the means of individual values
(mean ind), the contrast responses of each individual cell were also logarithmically transformed and the coefficients of the linear
regression were compared before and during cooling. The t-pair Student test was performed on the population of these parameters
before and during cooling.
with the probability (P , 0.05) that b is from different populations
before and during cooling for color but not for luminance. Thus, in
the absence of cortical inactivation, corticofugal activity produces
a contrast-dependent change of the contrast gain of parvocellular
neurons responding to full-field chromatic stimuli.
Recurrent projections enhance different parvocellular neurons
to different extents inasmuch as some cells produced responses
scarcely greater than zero to low contrast stimuli modulated in
luminance (Fig. 3a) or chromaticity (Fig. 3c). This result suggests
that the output of some LGN cells—at least in anesthetized
animals—may be substantially dependent on corticofugal activity
as well as upon retinal input and that the corticofugal projections
are nonuniform with respect to the strength of their input on target
cells.
Averaged responses of magnocellular and parvocellular individual neurons were also analyzed by comparing averaged coefficients of Michaelis–Menten or power functions before and during
cooling of V1. We did not find statistically significant differences
in these results for magnocellular and parvocellular ON- or OFFcenter cells. Our control contrast-response functions were generally consistent with those of others (Sclar et al., 1990).
Averaged responses of individual magnocellular neurons were
fitted with the Michaelis–Menten equation yielding a mean Rmax of
43.1 6 8.1 (SEM—standard error of the mean) spikes0s in control
conditions and 24.5 6 4.9 spikes0s during cooling. The difference
of 18.2 6 4.3 spikes0s is statistically significant (P , 0.01, t-pair
Student test). The semisaturation contrast b and exponent n coefficients did not change significantly during cooling. Responses of
individual parvocellular neurons were fitted before and during cooling using the Michaelis–Menten equation and a power function. In
the control conditions, Rmax was 70.8 6 14.4 spikes0s, during
cooling Rmax was 27.7 6 3.9 spikes0s which means that V1 inactivation decreased Rmax in a statistical significance way (P , 0.04),
whereas the semisaturation contrast and n did not differ before and
during cooling. Using the power function, we obtained the mean
intercept a which is related to log Rmax 0b n and was 1.34 6 0.08
spikes0s in controls and 0.93 6 0.10 spikes0s during cooling. The
difference 0.42 6 0.08 spikes0s was statistically significant (P ,
0.002, t-pair Student test). Cooling did not significantly change the
mean slope which was 0.73 6 0.07 in the control and 0.74 6 0.007
during cooling. This slope equals the exponent n of the Michaelis–
Menten equation for contrasts much less than the semisaturation
contrast.
Inactivation of V1 did not significantly modify the spontaneous
mean level of LGN activity. For example, for the ten parvocellular
neurons of Fig. 2a, the mean value of spontaneous activity dropped
from 42.3 6 11.58 to 37.2 6 10.31 spikes0s after cooling of V1.
The difference of 5.1 6 6.75 did not attain statistical significance
(t-pair Student test). For the magnocellular neurons of Fig. 2b,
there was a statistically nonsignificant increase in average spon-
Striate control of LGN contrast gain
491
Fig. 3. An example of averaged responses 6 SEM of two parvocellular (a, c) and magnocellular (b, d) LGN neurons to drifting gratings
at different contrasts before (circle) and during (squares) cooling of V1. Responses of parvocellular neurons were fitted to power
functions, and responses of magnocellular were fitted to the Michaelis–Menten equation.
taneous activity after inactivation of V1 from 8.25 6 1.33 to 10.l 6
2.63 spikes0s. Even so, the modulated levels of evoked activity
were markedly suppressed during cooling (Fig. 2b).
Contrast–response functions plotted on a linear–linear scale for
individual parvocellular (Figs. 3a and 3c) and magnocellular neurons (Figs. 3b and 3d) are also of interest because the linear–linear
plots well illustrate the saturation of the responses of magnocellular neurons at high contrast in contradistinction to those of parvocellular neurons. These examples, especially those in Figs. 3a
and 3c, represent some of the strongest effects of cortical inactivation on LGN evoked activity that we have observed. However,
they fall within a continuous range for such effects on individual
cells across the population at different contrasts as shown in Fig. 1b.
Contrast–response functions during cooling for some neurons, see for example (Fig. 3d), resemble those of retinal ganglion cells insofar as the semisaturation contrast b and exponent
n fitting the Michaelis–Menten equations approximate those for
retinal M-ganglion cells (Croner & Kaplan, 1995) and population averages for the retinal inputs to magnocellular neurons
(Kaplan & Shapley, 1986). In the latter study, b was 0.13 for
n 5 1 (used as constant) for an average of 36 retinal cells. Such
values are similar to our example of b 5 0.1 and n 5 1.1 for the
magnocellular neuron of Fig. 3d during cortical inactivation.
Cortical inactivation may also decrease a cell’s maximum response without changing the “nonlinearity” as measured by the
exponent n in the Michaelis–Menten equation. For example, the
value of n remained 1.2 for the magnocellular neuron of Fig. 3b
despite a two-fold decrease in derived Rmax during cortical inactivation. For this cell, cooling caused a significant increase in the
semisaturation contrast b which extends the linear range of the
cell’s responses to stimuli at different contrasts. However, for other
magnocellular neurons (Fig. 3d), the linear response range decreases during cooling even if n decreases and approximates 1, but
the semisaturation contrast decreases two-fold. Moreover, the slope
b in the power function equation (analogous to n in the Michaelis–
Menten equation) for the parvocellular neurons can increase (Fig. 3a)
or decrease (Fig. 3c) following cortical inactivation, but its mean
value for the population does not change significantly.
Discussion
Because these experiments were carried out under anesthetic doses
of sufentanil up to 8 mg0kg0h, we first consider whether such
anesthesia may have altered the response properties tested. A
number of long latency contextual effects believed to depend at
least in part upon corticocortical recurrent projections have been
492
demonstrated in V1 of the alert behaving monkey (Lamme, 1995;
Zipser et al., 1996). Certain contextual effects studied by the
same group are selectively suppressed by isoflurane anesthesia
(Lamme et al., 1998). However, when Nothdurft et al. (1999)
compared the effects of sufentanil anesthesia (5–8 mg0kg0h) on
the responses of V1 neurons to contextual modulations, they
found results similar to those that the same laboratory had found
earlier in alert behaving animals (Knierim & Van Essen, 1992).
Thus, feedback-dependent contextual modulations in V1 are largely
preserved under sufentanil anesthesia. It would seem likely, although not yet proved, that the more proximal corticofugal loop
would be no more severely affected than the recurrent projections to V1.
Even under sufentanil anesthesia, the corticothalamic projections enhance the contrast gain of both parvocellular and magnocellular neurons to stimuli modulated in luminance as well as to
stimuli modulated in color in the equiluminant plane for parvocellular neurons. The corticofugal projections normally express a general and often robust effect on the contrast gain of LGN neurons,
taking the term robust to indicate a gain in neural responsivity of
at least two-fold, when the corticofugal pathways are operant. The
responses of parvocellular LGN neurons are multiplicatively enhanced (as predicted by Grossberg, 1980; Koch, 1187) by descending pathways from striate cortex in a contrast-independent manner
over all but the very lowest range of contrasts. The responses of
magnocellular neurons are also multiplicatively enhanced by such
feedback and the enhancement is largely contrast independent at
contrasts above 0.2 and highly contrast dependent at lower contrasts (Fig. 2b).
What mechanisms might underlie the contrast-independent multiplicative enhancement of the responses of LGN neurons by corticofugal activity over a wide contrast range? It is necessary to
explain both why the enhancement becomes largely contrast independent above certain low values of contrast and is multiplicative. We suggest that the former property may reflect the response
characteristics of corticofugal neurons that project to parvocellular
and magnocellular neurons and may saturate at different contrasts
(Sclar et al., 1990; Albrecht & Hamilton, 1992).
If this were the case, then the corticofugal drive upon LGN
neurons becomes constant above a certain contrast and the explanation for the multiplicative effect must be subcortical. In theory,
a multiplicative effect can result from either a direct effect of one
type of excitatory synaptic activity upon another or by withdrawal
of a constant divisive effect upon target LGN neurons. We cannot
exclude the possibility that corticofugal activation normally produces a disinhibitory effect (Wörgötter et al., 1998) on relay neurons by reducing shunting, that is, divisive, inhibition from inhibitory
interneurons within the LGN. However, we cannot ignore the possibility of multiplicative effects on the basis of excitatory inputs
especially in view of pertinent anatomic results. For example, the
retinal afferents to LGN relay cells terminate on proximal dendrites, whereas the vastly more numerous corticofugal afferents
terminate on distal dendrites (Sherman & Koch, 1986). Moreover,
although both afferent pathways to LGN relay cells use glutamate
as neurotransmitter, the retinal afferents activate only ionotropic
receptors, whereas the corticofugal afferents activate both ionotropic and metabotropic receptors (McCormick & von Krosigk,
1992; Sherman & Guillery, 1998).
Activation of metabotropic receptors, as would occur when V1
is active, produces a marked decrease in apparent input conductance and a corresponding increase in input resistance by reducing
a K 1 current in the LGN of the guinea pig (McCormick & von
A.W. Przybyszewski et al.
Krosigk, 1992). There would also be a converse lowering of input
impedance of LGN cells by corticofugal activation of ionotropic
receptors. However, based on the work in the guinea pig, we would
expect this effect to be smaller than that due to activation of
metabotropic receptors. A corresponding net increase in input impedance would be expected to increase the voltage of EPSPs generated by retinal afferents although the magnitude of this effect in
the primate remains unknown. Thus, it is tempting to wonder
whether activation of metabotropic receptors by corticofugal activity leads to some of the multiplicative enhancement of the contrast gain of LGN relay cells.
The corticofugal pathways also project to the perigeniculate
nucleus (PGN), a thin shell of inhibitory interneurons surrounding
part of the LGN, which projects both to relay cells and inhibitory
interneurons within the LGN (Montero & Singer, 1985; Steriade
et al., 1986). However, it is unlikely that the spatially restricted
stimuli that we used to excite the classical receptive fields (RF) of
LGN neurons were sufficiently large to activate PGN neurons
which generally require stimulation over an area greater than the
classical RF of LGN cells at common retinal eccentricities for
more than minimal activation (Funke & Eysel, 1998). Moreover,
the firing patterns of PGN and LGN neurons inversely correlate
with each other (Funke & Eysel, 1998) suggesting a dominant role
for the direct inhibitory pathway from PGN to LGN relay cells and
a minimal role for a disinhibitory pathway to relay cells. Thus,
inactivation of the V1 r PGN pathway would be expected to
produce an increase in LGN activity, an effect we rarely observed
and even then only minimally (Fig. 1b). Thus, it is more likely that
the effects on LGN neurons we observed after inactivation of V1
were mediated by either the direct corticofugal pathway onto LGN
relay cells or by disinhibitory effects onto relay cells via interneurons (Wörgötter et al., 1998).
The fact that our results imply exclusively excitatory modulatory effects of the corticofugal projections in our experimental
situation requires comment. This preponderance of corticofugal
excitation may depend upon both spatial and temporal factors.
With respect to spatial factors, we know that direct activation of
layer 6 cells in the cat by electrophoretic application of glutamate
excites LGN cells with receptive-field centers in close retinotopic
correspondence to those of striate neurons at the site of activation
and inhibits LGN cells with field centers that are not in such close
retinotopic correspondence (Tsumoto et al., 1978). Thus, it is not
surprising that we found predominantly excitatory effects inasmuch as our stimuli were targeted to the classical receptive field
for each LGN cell under study and thus preferentially excited
corticofugal cells with receptive fields necessarily in retinotopic
correspondence to those of LGN neurons.
Tsumoto et al. (1978) further interpret their results to imply a
center-surround organization of the corticofugal system, perhaps
both within the cortex and the LGN, such that excitation of a
restricted region of the cortex preferentially facilitates afferent
activity in the retinotopically corresponding region of the LGN
while suppressing activity outside this region. If so, our results
confirm the central excitatory mechanism and identify a role for it
within the context of the control of contrast gain of LGN neurons
but do not address the issue of corticofugal inhibition when activation of cortical and geniculate neurons are retinotopically mismatched. With respect to temporal issues, we again note that our
stimuli were generally tested at 8 Hz (range 4–12 Hz), but we
acknowledge that we cannot exclude the possibility that the employment of temporal frequencies outside this range might have
revealed different effects.
Striate control of LGN contrast gain
The modulatory effects of corticofugal activity that we have
inferred by selectively stimulating the classical RF while reversibly inactivating the striate cortex are strong and invite comparisons to analogous studies in other sensory systems. Comparable
reductions in the responses of neurons in the medial geniculate
nucleus and inferior colliculus of the mustached bat to optimally
tuned auditory frequencies have been observed when the auditory
cortex is inactivated (Zhang et al., 1997). Thus, strong, that is,
more than two-fold, enhancement of responses to optimally tuned
activity within thalamic relay nuclei by corticofugal feedback may
be a general feature across sensory systems. Moreover, the recurrent projections from V2 back to V1 (Payne et al., 1996) and from
MT0V5 back to V3, V2 and V1 (Hupé et al., 1998) produce similarly strong effects.
Finally, our results provide a quantitative experimental basis for
broad classes of models that suggest that recurrent projections
from higher cortical areas can selectively enhance afferent activity
arising from lower levels so that a mutually consistent description
of sensory data is iteratively achieved across successive subcortical and cortical areas (Pribram, 1974; Milner, 1974; Harth, 1976;
Grossberg, 1976, 1980; Edelman, 1978; Koch, 1987; Damasio,
1989; Mumford, 1991, 1992, 1994; Ullman, 1995; Przybyszewski,
1998; for review, see Pollen, 1999).
Acknowledgments
We thank Peter Schiller for loaning us his cooling plate and Peltier device
and Mark Rubin for constructive criticisms. We thank Murray Sherman for
suggesting a possible explanation at the receptor level for the multiplicative
effect of corticofugal activity on the contrast gain of LGN cells. This work
was supported by Grant EY05156 from the NEI and a Grant from the
Whitehall Foundation (to D.A.P.).
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