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Volume 17, Number 10,
Issue of May 15, 1997
pp. 3684-3709
Copyright ©1997 Society for Neuroscience
Timing of the Critical Period for Plasticity of Ocular Dominance
Columns in Macaque Striate Cortex
Jonathan C. Horton and
Davina R. Hocking
Beckman Vision Center, University of California, San Francisco, San
Francisco, California 94143-0730
ABSTRACT
- INTRODUCTION
- MATERIALS AND METHODS
- RESULTS
- DISCUSSION
- FOOTNOTES
- REFERENCES
ABSTRACT 
Visual deprivation induced by monocular eyelid suture, a
laboratory model for congenital cataract, results in shrinkage of ocular dominance columns serving the closed eye. We performed monocular
suture in macaques at ages 1, 3, 5, 7, and 12 weeks to define the
critical period for plasticity of ocular dominance columns. After a
minimum survival of 8 months, complete montages of
[3H]proline-labeled columns were reconstructed from
flat-mounts of striate cortex in both hemispheres. In any given monkey,
visual deprivation induced the columns throughout striate cortex (V1) to retract the same distance from their original borders in layer IVc
. After deprivation, the widest columns remained in the foveal representation and along the V1/V2 border, where columns are widest in
control animals. The narrowest deprived columns belonged to the
ipsilateral eye, especially along the horizontal meridian and in the
periphery, where columns are narrowest in control animals. At the
earliest age that we tested (1 week), visual deprivation reduced the
columns to fragments. These fragments always coincided with a
cytochrome oxidase patch, or a short string of patches, in the upper
layers. More severe column shrinkage occurred in layer IVc (parvo)
than layer IVc
(magno). The geniculate input to the patches in layer
III (konio) appeared normal after deprivation, despite loss of CO
activity. Surprisingly, the blind spot representation of the open eye
was shrunken by monocular deprivation, although binocular competition
is absent in this region. Our principal finding was that eyelid suture
at age 1 week caused the most severe column shrinkage. With suture at
later ages, the degree of column shrinkage showed a progressive
decline. Deprivation commencing at age 12 weeks caused no column
shrinkage. These results imply that primate visual cortex is most
vulnerable to deprivation during the first weeks of life. Our
experiments should provide further impetus for the treatment of
children with congenital cataract at the earliest possible age.
Key words:
Key Words: ocular dominance column;
critical period;
amblyopia;
visual deprivation;
cytochrome oxidase patch;
flat-mount;
striate
cortex
INTRODUCTION
The most severe form of amblyopia develops when a
newborn child is deprived of vision in one eye by a dense unilateral
cataract (Boothe et al., 1985
). In a series of landmark experiments,
Wiesel and Hubel (1963, 1965) raised kittens with the lids of one eye sutured to simulate congenital monocular cataract. Electrophysiological recordings from striate cortex (V1) revealed that few cells could be
driven via the deprived eye. Later, the anatomical correlate of this
shift in ocular dominance was shown in cats and monkeys by intraocular
injection of [3H]proline (Hubel et al., 1977; Shatz and
Stryker, 1978; Swindale et al., 1981). The ocular dominance columns
serving the deprived eye appeared severely shrunken because of
contraction of their geniculocortical terminal arbors. Wiesel and Hubel
(see Wiesel, 1982) proposed that visual deprivation produces amblyopia
by causing the deprived eye to become disconnected from the cortical
circuits required for the normal processing of retinal input.
Ocular dominance columns are vulnerable to shrinkage for only a short
time after birth, called the "critical period" (Hubel and Wiesel,
1970). Once neonates develop beyond the critical period, the width of
their ocular dominance columns becomes immutable. To define the
beginning and the end of the critical period, LeVay et al. (1980)
performed monocular suture in a series of 10 macaques at successively
later ages, ranging from 2 d to adult. To their surprise, the age
at eyelid suture seemed to make no difference for the first 6 weeks of
life. The same degree of column shrinkage was found in all animals
sutured during this interval. The critical period did not appear to
wane until ~10 weeks, when eyelid closure caused only mild column
shrinkage. The end of the critical period was not defined exactly, but
eyelid suture at 7 months had no effect.
Results obtained from these animal experiments have altered the
management of congenital cataract in children. Before 1980, the
prognosis for monocular congenital cataract was considered dismal and
successful visual rehabilitation was virtually unknown (Cordes, 1957;
Costenbader and Albert, 1957; Ryan et al., 1965; Parkes and Hiles,
1967; Francois, 1979). After the discovery of the critical period for
plasticity of ocular dominance columns, a few innovative clinicians
showed that good vision could be obtained in children if cataract
surgery were performed at an early age, followed by immediate optical
correction and vigorous patching therapy (Enoch and Rabinowicz, 1976;
Beller et al., 1981; Pratt-Johnson and Tillson, 1981). It has now
become accepted practice that dense, monocular cataract should be
removed before age 4 months (Vaegan and Taylor, 1979; Rogers et al.,
1981; Birch and Stager, 1988; Drummond et al., 1989; Cheng et al.,
1991; Wright et al., 1992; Birch et al., 1993). However, there is still
no consensus about the urgency of cataract surgery within this time
frame (Birch and Stager, 1996). Hoyt removed a dense, monocular
cataract from a baby 7 hr after birth, and the child attained an acuity
of 20/20 (Beller et al., 1981). Is such early action warranted, or does surgery anytime during a "grace period" of a few weeks or months after birth produce comparable results?
To furnish anatomical data pertinent to this issue, we repeated the
experiments of LeVay et al. (1980) by performing monocular eyelid
suture in a series of baby macaques at successively later ages. After
the monkeys were at least 8 months old, flat-mounts of striate cortex
were prepared from each animal to measure the amount of column
shrinkage. In most animals, we reconstructed the entire pattern of
ocular dominance columns to avoid sampling bias that might arise from
examining only a small area. Preparing flat-mounts also allowed us to
determine whether columns vary in their susceptibility to shrinkage
according to their location within the overall mosaic (e.g., we
measured shrinkage of foveal columns vs peripheral columns, ipsilateral
columns vs contralateral columns, etc.). We also compared how the three
major projections from the lateral geniculate body (parvo 
layer
IVc; magno layer IVc; konio layers II and III) are
affected by visual deprivation. Finally, we examined the relationship
between the cytochrome oxidase (CO) patches ("puffs" or
"blobs") and the shrunken islands of ocular dominance columns that
survive in layer IVc after early monocular suture. The main finding
emerging from this study is that the shrinkage of ocular dominance
columns is greatest when visual deprivation begins right after birth,
modifying the original conclusion reached by LeVay et al. (1980).
MATERIALS AND METHODS
Experimental animals and surgical procedures. The
first experiment was performed on a single male Macaca
fascicularis (Monkey 0) born at the New England Regional Primate
Center. The right eyelids were sutured under general anesthesia with
ketamine HCl (10 mg/kg, i.m.) at age 1 week. At age 11 months, the animal was transferred to the University of California, San
Francisco (UCSF) for injection of [3H]proline into the
lateral geniculate body, following a protocol approved by the UCSF
Committee on Animal Research. Our procedures for making tracer
injections and for preparing histological sections have been described
elsewhere (Horton and Stryker, 1993a). In brief, 0.5 mCi of
[3H]proline in 2.5 µl was deposited by pressure
injection at the border between laminae 3 and 4 of the right lateral
geniculate body. After a survival time of 2 d, the monkey was
given a lethal intravenous dose of thiopental and perfused with
fixative. The right occipital lobe was sectioned parallel to the
opercular surface (without unfolding and flat-mounting), and alternate
sections were prepared for CO and autoradiography.
The remaining experiments were performed in eight unrelated macaques
(Monkeys 1-8) bred by timed matings at the California Regional Primate
Research Center (Davis, CA). For the 1994 season, when most of these
animals were born, mean gestation in the colony was 165 d (SD,
±8.9 d, n = 61). This wide variability represented a
potential confounding factor, because two animals sutured the same time
after birth might easily differ by several weeks in their gestational
age and, therefore, in their susceptibility to visual deprivation. To
minimize this problem, the veterinary staff allowed us to select babies
from the colony born naturally within 2 d of full gestation
[embryonic day 163 (E163) to E167].
All experimental procedures were approved by the Committees on Animal
Research at the University of California, Davis and UCSF. To induce
amblyopia, the lids of the right eye were sutured at exactly 1, 3, 5, 7, or 12 weeks after birth (Table 1). Tarsorrhaphy was
performed under anesthesia with ketamine HCl (10 mg/kg,
i.m.). After the eyelids were infiltrated with 0.5% lidocaine plus
epinephrine (1:200,000), they were trimmed to expose the tarsal plates
and fused with 6-0 Vicryl interrupted horizontal mattress sutures. The
babies were examined daily for a week to verify that the eyelids were
sealed. The eyelids healed completely in every animal within 1 week.
Table 1.
Experimental animals
|
Monkey 1 |
Monkey 2 |
Monkey 3 |
Monkey
4 |
Monkey 5 |
Monkey 6 |
Monkey 7 |
Monkey
8 |
|
| Sex |
male |
male |
male |
male |
female |
male |
male |
male |
| Length
of gestation
(d) |
E167 |
E166 |
E167 |
E164 |
E167 |
E164 |
E165 |
E165 |
| Macaque
species |
fascicularis |
fascicularis |
mulatta |
mulatta |
mulatta |
mulatta |
mulatta |
mulatta |
| Age
at suture |
7 d |
7 d |
7 d |
21 d |
35 d |
35 d |
49 d |
84
d |
| Eye
sutured |
right |
right |
right |
right |
right |
right |
right |
right |
| Eye
injected |
right |
right |
left |
left |
left |
left |
left |
left |
| Eye
enucleated |
right |
- |
right |
right |
- |
right |
right |
- |
| Survival
time after enucleation |
10 d |
- |
58 d |
24 d |
- |
42
d |
20 d |
- |
| Age at perfusion |
11 months |
14 months |
11
months |
8 months |
26 months |
15 months |
8 months |
15
months |
| Weight at Perfusion |
1.47 kg |
1.87 kg |
1.53 kg |
1.38
kg |
3.14 kg |
1.93 kg |
1.64 kg |
2.21 kg |
|
|
|
|
When the animals were at least 7 months old, they were transferred to
UCSF to label their ocular dominance columns with
[3H]proline. The tracer was prepared by reconstituting 2 mCi of L-[2,3,4,5-3H]proline (specific
activity 102-106 Ci/mmol; Amersham, Arlington Heights, I)L in 20 µl
of sterile balanced salt solution. It was injected into the
mid-vitreous of either the amblyopic right eye or the normal left eye
(Table 1) under anesthesia with ketamine HCl (10 mg/kg,
i.m.) and topical proparacaine HCl. Immediately after, the fundus was
examined with an indirect ophthalmoscope to verify that no injury had
occurred. For tracer injection into the amblyopic eye (Monkeys 1 and
2), the eyelids were opened briefly and then resutured. Survival times
after eye injection were 7-9 d, except for Monkey 1, whose survival
time was 17 d.
In five monkeys, the ocular dominance columns were double-labeled by
enucleating the amblyopic right eye and staining the cortex for CO
(Table 1). Enucleation was performed using sterile technique under
anesthesia with ketamine HCl (20 mg/kg, i.m.) and a
retrobulbar injection of 2 ml of 1% lidocaine plus epinephrine (1:100,000). After surgery, buprenorphine HCl (0.02 mg/kg, i.m.) was administered every 8 hr for 2 d to
ensure analgesia. Survival times ranged between 10 and 58 d (Table
1). Enucleation was done no earlier than age 7 months (well after the
critical period) so that it would have no confounding effect on the
width of the ocular dominance columns (LeVay et al., 1980).
We enucleated one eye to have CO available as a "back-up" label in
case the autoradiography failed. In the end, the autoradiography succeeded in each animal, so it was not necessary to reconstruct the
ocular dominance columns from the CO sections. However, for the sake of
comparison we reconstructed the ocular dominance columns using both
methods in Monkey 1.
Histological procedures. Before perfusion, the eye injected
with [3H]proline was examined again under ketamine
anesthesia (20 mg/kg, i.m.) with an indirect
ophthalmoscope to verify that no injury had resulted from the tracer
injection. In every case, the injected eye appeared undamaged (in
Monkey 1, this procedure was done before enucleation of the right eye,
rather than before perfusion). After receiving a lethal injection of
sodium pentobarbital into the peritoneal cavity, each monkey was
perfused through the left ventricle with 1 l of normal saline
followed by 1 l of 2% paraformaldehyde in 0.1 M
phosphate buffer. Striate cortex from each occipital lobe was unfolded,
flattened, and sectioned at 30 µm. Alternate sections were reacted
for CO (Wong-Riley, 1979) or coated with emulsion for autoradiography
(Wiesel et al., 1974). Our methods for preparing flat-mounts and
processing sections have been described in detail previously (Horton
and Hocking, 1996b,c).
Data analysis. The autoradiographs were photographed in
dark-field illumination using Technical Pan film (Eastman Kodak,
Rochester, NY) and developed with Technidol developer (Eastman Kodak).
CO sections were photographed in bright-field using Plus-X Pan film (Eastman Kodak) and developed with Microdol-X (Eastman Kodak). Negatives were scanned into the computer and montages were prepared using Photoshop 3.0 (Adobe Systems) (Horton and Hocking, 1996b,c). To
prepare black and white drawings, we created a transparent layer
overlying the completed montage, traced the borders of the dark columns
at high magnification on the monitor using the "pencil" function at
a 1 pixel setting, and then flood-filled them with black. For
quantification of column areas, the drawings were analyzed with Mocha
(Jandel Scientific, San Rafael, CA). This program uses a thresholding
function to assign pixels to black (level of gray = 1) or white
(level of gray = 256). Pixels were converted to mm2 by
calibration with the scale bar. Intermediate levels of gray were used
to measure the unreconstructable areas, blind spots, and monocular
crescents. To facilitate comparison between experiments, all montages
in this paper were reproduced at identical scale.
RESULTS
Monkey 0 (deprived at age 1 week)
The goal of this experiment was to fill the thalamic projection to
the CO patches in the upper layers of striate cortex by depositing a
massive quantity (0.5 mCi) of [3H]proline into the middle
of the right lateral geniculate body. After injection, layer IVc was
densely labeled throughout the entire flat, exposed lateral convexity
of the right occipital lobe. This region, called the operculum,
represents the central 0°-8° of the contralateral visual hemifield
(see Fig. 7 for retinotopic coordinates of V1). The upper layers were
labeled only in the medial half of the operculum, from ~2.5°-8°
(Fig. 1A). Autoradiographs revealed
rows of patches in layer III, merging together like pearls on a string.
An adjacent CO section showed alternating rows of light and dark
patches (Fig. 1B), as reported previously after visual deprivation at age 1 week (Horton and Stryker, 1993a). The
adjacent sections matched: every row of CO patches coincided with a row
of proline label. Despite shrinkage of the right eye's ocular
dominance columns in layer IVc (which was not well seen, because the
geniculocortical afferents serving both eyes were flooded with
[3H]proline), the projection to the upper layers seemed
normal. In fact, without referring to the adjacent CO section, we could not tell which rows of proline patches belonged to the deprived eye.
This result implied that the koniocellular projection to the upper
layers was less susceptible to visual deprivation than the
parvocellular projection to layer IVc.
Fig. 7.
Monkey 2. Schematic drawing showing the
retinotopic coordinates in unfolded, flattened macaque V1, to aid in
interpretation of our flat-mount montages. The shaded
area in the lateral portion of each cortex is the exposed, flat
operculum of the occipital lobe, which represents the central
~0°-8° (Fig. 4A,B).
The shaded areas in the upper, medial portion of the
left and right V1 are illustrated in Figures 6 and 8, respectively.
BS, Blind spot; MC, monocular
crescent.
[View Larger Version of this Image (23K GIF file)]
Fig. 1.
Monkey 0 (1 week suture). A,
Autoradiograph of a single section passing through layer III in the
medial half of the right operculum. The radioactive tracer appears
bright in dark-field illumination. The section just grazed the
honeycomb in layer IVa at its deepest point (curved
arrow). Parallel rows of patches were labeled by saturating the
lateral geniculate body with a huge injection of
[3H]proline. The arrows indicate five rows
of patches serving the normal left eye. Blood vessels used for section
alignment are marked with arrowheads. B,
Adjacent section showing the array of CO patches. The staining was
poor, but one can detect alternating light and dark rows. The
arrows mark five dark rows (left eye) that match the
arrows in A. Comparison of
A and B indicated that every row of CO
patches was well labeled by [3H]proline; deprivation of
the right eye caused no obvious attenuation of the koniocellular
projection to its rows of CO patches. Scale bar, 2 mm.
[View Larger Version of this Image (116K GIF file)]
Monkey 1 (deprived at age 1 week)
This animal received an injection of [3H]proline
into the deprived right eye. Autoradiographs showed severe shrinkage of
the ocular dominance columns on the opercula (Fig.
2A,B). Only 16% of layer IVc in
each hemisphere was occupied by geniculate afferents serving the
amblyopic right eye (Table 2). The pattern of column shrinkage showed two gradients: the columns became smaller and more
fragmented moving (1) from the fovea to the periphery and (2) from the
vertical meridian to the horizontal meridian. Together, these two
gradients reduced the deprived eye's columns to scattered islands
along the horizontal meridian at 8°. By contrast, the deprived eye's
columns remained relatively intact within the foveal representation
(Fig. 2E,F).
Fig. 2.
Monkey 1 (1 week suture). A,
B, Montages of autoradiographs showing severe shrinkage
of ocular dominance columns in layer IVc. The deprived right eye was
injected with [3H]proline at age 11 months and enucleated
1 week later. Tissues were processed after an additional 10 d
survival period. The region within the box is shown in
Figure 3A at higher power. C,
D, Montages of adjacent CO sections, showing a labeling
pattern in layer IVc matching the autoradiographs above. The
boxed region in C is shown in Figure
3B. E, F, Drawing of the
autoradiographs in A and B showing how
the deprived columns become gradually more fragmented moving from the
fovea to the periphery (curved arrows) and from the
vertical meridian to the horizontal meridian (straight
arrows). The latter effect is less striking. See Figure 7 for
the retinotopic coordinates of V1. Areas shaded with
gray could not be reconstructed.
[View Larger Version of this Image (128K GIF file)]
In this monkey, we double-labeled the ocular dominance columns with CO
by enucleating the amblyopic right eye 1 week after injecting it with
[3H]proline. After waiting an additional 10 d, to
allow cortical CO levels to drop after enucleation, we prepared
alternate sections for autoradiography and CO (compare Fig.
2A,B with 2C,D). In Figure 3, A and B, a small region of
layer IVc from an autoradiograph and an adjacent CO section is shown
at higher power. The two labels appeared nearly identical, but small
differences were evident on close scrutiny. We attributed these subtle
discrepancies to the fact that the sections were adjacent, not the
same, and therefore passed through layer IVc at slightly different
depths. In addition, the columns were labeled more intensely by
[3H]proline than CO in this animal, causing the
boundaries of the proline columns to appear slightly expanded. The
match between the CO columns and the proline columns confirmed a
previous study showing that CO accurately labels the ocular dominance
columns in deprived animals (Horton and Stryker, 1993a).
Fig. 3.
Monkey 1 (1 week suture). A,
Autoradiograph from the box in Figure 2A, showing
shrunken column fragments (arrows) in layer IVc.
B, Adjacent CO section, from the box in Figure
2C, showing pale, shrunken columns
(arrows) in layer IVc after enucleation of the
deprived right eye. The match between the columns labeled by
autoradiography and CO is excellent. C, Array of CO
patches in layer III from the same region of cortex shown in the
preceding panel. The patches are organized into dark (large
arrows) and light (small arrows) rows.
D, Tracing of the column fragments in B
onto the CO patches in C. The column remnants coincide
with the CO patches, always encircling individual patches or clusters of patches. Blood vessels used to align sections in
B-D are marked by
arrowheads. Scale bar, 1 mm (all panels to
scale).
[View Larger Version of this Image (151K GIF file)]
In Monkey 1, CO staining showed alternating rows of light and dark
patches in the upper layers. The shrunken fragments of ocular dominance
columns in layer IVc (Fig. 3B) were traced onto the array
of CO patches (Fig. 3C) to test their relationship (Fig. 3D). The remnants of ocular dominance columns were always
centered on CO patches. For example, where the ocular dominance columns were reduced to small islands, they encircled a single CO patch. Where
longer column fragments survived, they encompassed a short string of CO
patches. In these cases, the boundary of the shrunken column never
ended on a CO patch but, instead, passed between two adjacent patches.
These findings were verified by examining three regions at high power
from each operculum, containing a total of 78 column fragments in layer
IVc.
Monkey 2 (deprived at age 1 week)
The opercula of this animal showed severe shrinkage of the
deprived right eye's columns in layer IVc (Fig.
4A,B,E,F). The effect was even
more striking than in Monkey 1 (compare Figs. 2E,F
and 4E,F). This difference illustrates that
two animals deprived in an identical manner can vary in their degree of
column shrinkage. In Monkey 2, unlike Monkey 1, the deprivation effect
was asymmetric (compare Fig. 4A,B).
The right eye's columns occupied 12% of the ipsilateral operculum,
but only 8% of the contralateral operculum (Table 2).
Fig. 4.
Monkey 2 (1 week suture). A,
B, Montages of autoradiographs showing severe shrinkage
of the right eye's columns labeled by [3H]proline. The
columns were slightly more shrunken in the cortex contralateral (left
V1) to the deprived eye, as one can appreciate by comparing the foveal
regions in both hemispheres. The area within the box in
B appears in Figure 5. C, Montage of
layer IVc (magno) in the left operculum, showing less severe
fragmentation of the ocular dominance columns, compared with the
columns in layer IVc (parvo) in the panel above. D,
CO-stained section showing rows of patches in the upper layers of the
right operculum. Despite dramatic column shrinkage in layer IVc
(B), CO staining in the deprived eye's rows of patches
was only mildly reduced. E, F, Drawing of
the montages in A and B.
[View Larger Version of this Image (124K GIF file)]
It is difficult to compare [3H]proline columns in
different sublayers of IVc, because they are more crisp and intense in
layer IVc than in layer IVc (see Fig. 30 in Horton, 1984).
Nonetheless, we observed an obvious difference in the shrinkage of
layers IVc and IVc (compare Fig.
4A,C). Rather than breaking into
fragments, the columns in layer IVc appeared relatively intact,
preserving their original stripe-like configuration. In all animals
sutured at age 5 weeks or younger, there was less column shrinkage in layer IVc than in layer IVc. This finding implies that the
magnocellular projection (layer IVc) is less vulnerable than the
parvocellular projection (layer IVc) to the effects of visual
deprivation.
In layer IVc, the CO activity was homogeneous (Horton and Stryker,
1993a). In layers II and III, there were alternating dark and pale rows
of CO patches (Fig. 4D). We examined the relationship between the shrunken ocular dominance columns in layer IVc and the
CO patches in layer III, seeking to corroborate our findings in Monkey
1. Figure 5A shows an autoradiograph from the
right operculum of Monkey 2. Approximately 10 shrunken islands were labeled in layer IVc. The perimeter of each column fragment
encircled a single CO patch, or a cluster of patches, in the upper
layers (Fig. 5B,C). This finding
was confirmed by testing three regions from each operculum containing a
total of 62 column fragments.
Fig. 5.
Monkey 2 (1 week suture). A, Single
autoradiograph from the region enclosed by the box in Figure
4B, showing fragments of deprived right eye
columns. B, CO section from the corresponding area in
Figure 4D, showing the patches in the upper
layers. C, Tracing of the column fragments in
A onto the CO patches in B, demonstrating
that column remnants in layer IVc always encircle a CO patch or a
short string of CO patches. Note that the CO patches circled in this figure are no more pale than other CO
patches in deprived rows. Blood vessels used for section alignment are marked by arrowheads. Scale bar, 1 mm for all three
panels.
[View Larger Version of this Image (83K GIF file)]
In Monkey 2, the shrinkage of ocular dominance columns was so severe
that many CO patches in deprived rows came to be situated over regions
of layer IVc taken over by the normal eye. These patches were not
spared the loss of CO activity suffered by fellow patches remaining in
territory held by the deprived eye: CO activity was reduced in all
patches located within a deprived row (Figs. 4D,
5B). This finding suggests that, although layer IVc was
taken over by the open eye, functional connections serving the open eye
were not established to the deprived eye's patches, leaving them with
reduced metabolic activity.
In Monkeys 1 and 2, the ocular dominance columns of the deprived eye
were best preserved in the foveal representation. This finding, also
observed in a third monkey (Horton and Stryker, 1993a), led us to
suggest in a preliminary report that ocular dominance columns within
the foveal representation are less susceptible to shrinkage induced by
early monocular deprivation (Horton and Stryker, 1993b). However, our
view has changed after examining peripheral regions of striate cortex
hidden within the calcarine fissure. Figure
6A shows layer IVc from the
peripheral left cortex of Monkey 2, contralateral to the deprived eye.
The location of this tissue segment within striate cortex is shown
schematically in Figure 7 (left). The labeled
columns of the deprived right eye were shrunken, but they still
occupied 19% of layer IVc. They were no more shrunken than the
columns located within the foveal representation (compare Figs.
6A and 4A). This finding invalidated our original notion, namely, that column shrinkage becomes
increasingly severe across the cortex from the representation of the
fovea to the periphery.
Fig. 6.
Monkey 2 (1 week suture). A, View
of [3H]proline-labeled columns in the left peripheral
cortex after injection of the deprived right eye. The columns are
shrunken, but no more than on the operculum (compare with Fig.
4A). The labeled columns are more attenuated along the vertical meridian than the horizontal meridian. For retinotopic coordinates and orientation of this tissue segment within
V1, see Figure 7. MC, Monocular crescent.
B, Section from the upper layers of the same tissue
block, showing the CO patches. C, Montage of the
koniocellular projection to the CO patches in layer III, labeled by
[3H]proline injection into the deprived right eye. At
higher power, we verified that every CO patch in rows corresponding to
the deprived columns in layer IVc received a puff of
[3H]proline label. Curiously, no puffs of proline label
were seen in the monocular crescent representation, indicating that CO
patches in this area receive no (or only a weak) thalamic
projection.
[View Larger Version of this Image (90K GIF file)]
Figure 6B shows the CO patches in the upper layers
from the same block. In the monocular crescent, the CO patches were
larger and more widely spaced (Horton, 1984). A montage of
autoradiographs through layer III showed the projection to the patches
of the injected right eye (Fig. 6C). Despite visual
deprivation, all of the right eye's patches were well labeled, except
in the monocular crescent. The absence of patch labeling in the
monocular crescent was unexpected. We have since reviewed
autoradiographs from previous experiments in four normal baby macaques
that showed strong patch labeling after [3H]proline eye
injection (Horton and Hocking, 1996a). In every animal, label in
patches within the contralateral monocular crescent and the ipsilateral
blind spot was absent or was much weaker than in nearby binocular
cortex. We have no explanation for this observation.
For comparison, Figure 8 shows the matching piece of V1
from the right peripheral cortex, ipsilateral to the deprived eye (see
Fig. 7 for orientation). In layer IVc, the ocular dominance columns
of the right eye were obliterated, except for a few islands near the
vertical meridian (Fig. 8A). The deprivation effect
was more striking than in the left peripheral cortex (compare Figs. 8A and 6A). It was also more
striking in layer IVc than IVc (compare Fig. 8A
and 8B), confirming our observation from the operculum of the same animal (Fig. 4C). In the upper layers,
the projection to the right eye's rows of patches (Fig. 8C)
appeared intact. The labeling was indistinguishable from the pattern
seen in normal macaques (see Fig. 5 in Horton and Hocking, 1996a). This
result confirmed our findings in Monkey 0 (Fig. 1). Because the right
eye's afferents to layer IVc were decimated, preserved input to
right eye patches was often situated over regions of layer IVc
surrendered to the left eye. This contrast in the laminar pattern of
labeling within the same tissue block provided the most direct evidence
that visual deprivation had affected the parvocellular projection more
than the koniocellular projection.
Fig. 8.
Monkey 2 (1 week suture). A,
Montage of the right peripheral cortex, ipsilateral to the injected,
deprived right eye (see Fig. 7 for location of this region). The
labeled parvo columns were wiped out completely, except for a few
remnants near the vertical meridian. MC, Monocular
crescent. B, Montage of magno columns, showing much less
shrinkage and fragmentation. In the monocular crescent, no columns were
seen, because this area receives no projection from the ipsilateral
eye. C, The patches in layer III situated within right
eye columns (determined by alignment with panel B)
received strong [3H]proline label from the right eye,
despite virtual elimination of the projection to layer IVc (compare
A, C). This finding indicates that
the koniocellular projection to the upper layers is more resistant to
the effects of visual deprivation than the parvo projection to layer
IVc.
[View Larger Version of this Image (82K GIF file)]
Monkey 3 (deprived at age 1 week)
V1 was flat-mounted as a single piece of tissue to compare column
shrinkage in the operculum and periphery in the same sections. The
normal left eye was injected with [3H]proline, resulting
in expanded columns of label interrupted by dark gaps belonging to the
amblyopic right eye (Fig. 9). The labeling in the
opercula was complementary to the pattern illustrated in Monkeys 1 and
2. Again, a gradient in apparent column shrinkage occurred from the
fovea to the periphery and from the vertical meridian to the horizontal
meridian. The right eye's columns were slightly more shrunken in the
ipsilateral cortex (8% of surface area) than the contralateral cortex
(12% of surface area; Table 2). Overall, the degree of column
shrinkage in Monkeys 1, 2, and 3 was comparable.
Fig. 9.
Monkey 3 (1 week suture). A,
B, Autoradiographic montage of layer IVc after
deprivation of the right eye. The normal left eye was injected with
[3H]proline. The deprivation effect was severe and
complemented the findings obtained in Monkeys 1 and 2 after injection
the deprived eye. C, D, Drawing of the
columns in A and B. This cortex was unusually large and did not flatten well. Despite the blemishes, one
can appreciate that more unlabeled (right eye) columns survived in the
left periphery than in the right periphery. The border of the monocular
crescent could not be discerned in the right cortex, because the ocular
dominance columns of the right eye were extinguished completely in the
periphery. In the left cortex, the boundary of the blind spot
representation of the right eye was uncertain, for the same reason. In
the right cortex, the blind spot (BS) representation of
the left eye was shrunken. MC, Monocular crescent.
[View Larger Versions of these Images (107 + 97K GIF file)]
Although the right and left opercula looked quite similar in Monkey 3, in the periphery the pattern of labeling was quite different on the two
sides. In the right hemisphere, the right eye's columns were nearly
absent in the periphery, except near the vertical meridian (Fig.
9B,D). By contrast, in the left hemisphere the right eye's
columns experienced a renaissance as they approached the monocular
crescent (Figs. 9A,C). They were also larger near the
horizontal meridian than the vertical meridian (the opposite of the
pattern in the right hemisphere). These findings confirmed observations
made in the peripheral fragments from Monkey 2 (Figs. 6, 8). They also
confirmed a report by Hubel et al. (1977) that in peripheral calcarine
cortex the ocular dominance columns appear more shrunken ipsilateral to
the sutured eye (see their Fig.
21A,B).
We believe the key to this ipsi/contra discrepancy in column shrinkage
lies with an observation by LeVay et al. (1985). They discovered that
the columns of the ipsilateral eye become fragmented between the
representation of the blind spot and the monocular crescent in
peripheral cortex, especially along the horizontal meridian. We have
confirmed this finding (Fig.
10A,B). In a
complementary manner, the columns of the contralateral eye become
larger and more confluent in this region. To determine how this
asymmetry might be reflected in the appearance of the columns after
visual deprivation, we simulated column shrinkage using a binary filter provided with the Mocha image analysis software (Jandel Scientific). This filter dilates a white object by converting a monolayer of pixels
surrounding it from black to white. After applying three iterations of
this filter to a normal mosaic of columns, the resultant pattern bore a
close resemblance to the columns in our monkeys deprived at age 1 week
(compare Figs. 9C,D and 10C,D).
In the peripheral right cortex, the right eye's columns (which were
small to begin with) were extinguished, except along the vertical
meridian. In the peripheral left cortex, the right eye's columns
(which were big to begin with) fared much better, especially along the
horizontal meridian.
Fig. 10.
A, B, Pattern of
ocular dominance columns from a normal monkey (reproduced from Fig. 3,
B and E, in Horton and Hocking, 1996c). Between the blind spot and the monocular crescent, the ipsilateral eye's columns become relatively small and fragmented, especially along
the horizontal meridian [e.g., note the diminutive black columns of
the right eye in B near the monocular crescent
(arrow)]. The converse occurs to the contralateral
eye's columns: they become large and confluent, engulfing the
ipsilateral eye's columns. C, D,
Shrinkage of the black columns, modeled using Mocha image analysis
software, by switching the sign of pixels along the borders of the
white columns from black to white. For this simulation, 1 pixel = 58 µm; the average width of ocular dominance columns before
application of the dilation filter was ~8 pixels. After three
iterations of the filter, the columns resembled closely the pattern of
shrinkage seen after visual deprivation at age 1 week (see Fig.
9).
[View Larger Version of this Image (66K GIF file)]
The correlation between the computer model of column shrinkage and our
anatomical data suggests that visual deprivation induces geniculocortical afferents to retract the same distance from the borders of the ocular dominance columns throughout primary visual cortex. The impression of greater shrinkage in the peripheral cortex
ipsilateral to the deprived eye arises because there exists a normal,
preexisting inequality in column widths in this region. There is no
need to invoke a greater sensitivity of the ipsilateral eye to the
effects of visual deprivation to explain why its columns appear smaller
in the periphery after monocular suture.
In monkey 3, the blind spot representation of the left eye in the right
visual cortex was shrunken (Fig.
9B,D). It measured only 4 mm2, compared with an average value of 10 mm2
in normal macaques (Horton and Hocking, 1996c). In this special region,
geniculate afferents serving the right eye face no direct competition
from the left eye because the left eye contributes no input. We
expected this lack of competition to protect the blind spot
representation from shrinkage. Nevertheless, it appears that the left
eye's afferents, presumably serving retina surrounding the optic disk,
invaded the disk's cortical representation. This puzzling result will
be considered further in Discussion.
Monkey 4 (deprived at age 3 weeks)
Figure 11 shows flat-mounts prepared from Monkey
4, after [3H]proline injection into the the normal left
eye. The intensity of autoradiographic labeling was greater in
peripheral calcarine cortex than on the operculum (Kaas et al., 1976;
Hendrickson et al., 1978; LeVay et al., 1978; Spatz, 1979). This
tendency was observed in all of the flat-mounts, although it was more
striking in some than in others. The reason is unclear, but it may
reflect better tracer uptake by ganglion cells in peripheral retina. In addition, the contrast of the autoradiographic label was greater in the
cortex ipsilateral to the injected eye in all animals (Shatz et al.,
1977). In cats, this effect has been attributed to greater tracer
spillover in the lateral geniculate body on the contralateral side
(LeVay et al., 1978). However, in macaques it may indicate more
complete segregation of the geniculate afferents serving the
ipsilateral eye (Horton and Hocking, 1996a).
Fig. 11.
Monkey 4 (3 week suture). A,
B, Autoradiographic montage of layer IVc, showing
shrinkage of the unlabeled columns of the deprived right eye. There was
less column shrinkage than after deprivation starting at age 1 week
(compare with Fig. 9). As in all autoradiographs, the columns were
labeled more intensely in the peripheral cortex than on the operculum
and were labeled more crisply in the cortex ipsilateral to the injected
eye. C, D, Drawings of the columns
showing that after deprivation the columns appeared widest in the
foveal region and along the V1/V2 border (dashed line)
on the operculum. In the right cortex, the blind spot representation was shrunken, as in Figure 9D. Note also that in the
right periphery, the shrunken black columns got progressively thinner
moving from the vertical meridian to the horizontal meridian. In the
left periphery, the opposite occurred: the black columns got wider moving from the vertical meridian to the horizontal meridian, and they
were less shrunken overall. These differences, also seen in Monkeys 2 and 3, occur because in normal monkeys the columns of the ipsilateral
eye become attenuated along the horizontal meridian in the periphery
(see Fig. 10).
[View Larger Versions of these Images (128 + 124K GIF file)]
Eyelid suture at 3 weeks in Monkey 4 caused much less shrinkage of
ocular dominance columns than eyelid suture at age 1 week in Monkeys 1, 2, and 3 (Table 2). On the opercula, the deprived columns remained
coherent stripes rather than breaking into isolated fragments. The
deprived right eye's columns occupied 9% less surface area on the
ipsilateral operculum compared with the contralateral operculum. This
imbalance was also marked in peripheral cortex. On both opercula, the
deprived columns were slightly wider in the foveal region and along the
V1/V2 border, echoing the tendency seen in Monkeys 1, 2, and 3. The
blind spot was also shrunken in the ipsilateral cortex (Fig.
11B), replicating the finding in the ipsilateral
cortex of Monkey 3.
Monkey 5 (deprived at age 5 weeks)
This monkey was the oldest and largest of our cohort but,
ironically, it had the smallest V1 (Table 2). On the left side, the
calcarine fissure did not unfold completely, leaving ~100 mm2 buried (Fig. 12). However, on the right
side we obtained a complete reconstruction, and the surface area of
striate cortex was barely 1000 mm2. The shrunken columns of
the deprived right eye were unlabeled, because
[3H]proline was injected into the normal left eye. In the
left operculum, the column shrinkage was equal to the degree seen in
the left operculum of Monkey 4, sutured at 3 weeks (compare Figs.
12A and 11A). However, in the left
peripheral cortex the column shrinkage in Monkey 5 was less severe than
in the corresponding region of Monkey 4. This point can be appreciated
by observing that more black, unlabeled territory is present between
the blind spot and monocular crescent in Figure 12A
than in Figure 11A. Comparison of Monkeys 4 and 5 illustrates that the relative column shrinkage in central versus
peripheral cortex can vary from animal to animal.
Fig. 12.
Monkey 5 (5 week suture). A,
Montages of layer IVc after injection of the normal left eye. In the
left operculum, the column shrinkage equaled the shrinkage seen in the
left operculum of Monkey 4 (Fig. 11A), despite
starting visual deprivation 2 weeks later. However, in the left
periphery the deprivation effect was less marked. B, The
right operculum showed a comparable deprivation effect, although the
columns were less distinct. The deprivation effect in the right
operculum was less pronounced than in the right operculum of Monkey 4, sutured at 3 weeks. C, D, Drawings of the
montages in A, B. The calcarine fissure
did not open completely in the left cortex.
[View Larger Versions of these Images (118 + 114K GIF file)]
In the right operculum of Monkey 5, the column shrinkage was less than
in the right operculum of Monkey 4 (Table 2). Consequently, for Monkeys
4 and 5 the degree of column shrinkage was equal for the left opercula
and different for the right opercula. This discrepancy is addressed in
Discussion.
Monkey 6 (deprived at age 5 weeks)
Monkey 6 was deprived at age 5 weeks, repeating the
experiment in Monkey 5. Tracer injection into the normal left eye
revealed a more intricate mosaic than in Monkey 5, with a large number of column pairs (145) along the V1/V2 border (Fig. 13).
In Macaca fascicularis we have observed
substantial variability in the periodicity of ocular dominance columns
(Horton and Hocking, 1996c). The results summarized in Table 2 indicate
that a similar degree of variability is present in M. mulatta.
Fig. 13.
Monkey 6 (5 week suture). Montages of layer
IVc after injection of the normal left eye show less shrinkage of
the right eye's columns than in Monkey 4, sutured at 3 weeks. This
animal had small cortices with a large number of column pairs. On the
right operculum, the expanded columns of the left eye merged together, fragmenting the right eye's columns into islands, especially along the
horizontal meridian. This effect did not occur on the left side,
because the columns of the right eye occupied relatively more
territory. Note that the largest column remnants serving the right eye
were found in the foveal regions and in the left periphery.
[View Larger Versions of these Images (136 + 126K GIF file)]
In Monkey 6, the shrunken columns of the right eye occupied
less territory in the right operculum (37%) compared with the left
operculum (43%). In the right operculum, the expanded columns of the
left eye tended to melt together, creating numerous islands of shrunken
black columns (Fig. 13B). In the left operculum,
the left eye's columns did not merge to the same degree
because they occupied relatively less territory. This asymmetry between
hemispheres in column areas belonging to each eye contrasted with the
findings in Monkey 5, also sutured at age 5 weeks. In this animal, the deprived right eye occupied the same territory in the ipsilateral (36%) and the contralateral (35%) opercula.
In Monkey 6 (sutured at 5 weeks), the right eye's columns were
less shrunken than in Monkey 4 (sutured at 3 weeks). This difference held for the opercular and peripheral cortex in both hemispheres (Table 2), supporting the notion that susceptibility to column shrinkage declines with suture at a later age.
Monkey 7 (deprived at age 7 weeks)
The deprivation effect in this monkey was mild (Table 2),
indicating that by age 7 weeks the susceptibility of the ocular dominance columns to shrinkage had declined still further (Fig. 14). The animal had an enormous V1 on each side,
averaging nearly 1600 mm2. Comparison of Figures 12, 13, 14
provides a vivid impression of the range of V1 areas and column
periodicities found in this study. We corroborate Van Essen et al.
(1984), who reported twofold variation in macaque V1 surface area and
no obvious correlation with body weight.
Fig. 14.
Monkey 7 (7 week suture). Montages of layer
IVc showed only mild shrinkage of the unlabeled columns of the right
eye, signifying that the cortex was less vulnerable to the effects of
visual deprivation by age 7 weeks. Note the gargantuan proportions of
V1 and its columns in this animal compared with Monkey 5 (Fig. 12) and
Monkey 6 (Fig. 13).
[View Larger Versions of these Images (140 + 135K GIF file)]
Monkey 8 (deprived at age 12 weeks)
This animal showed no shrinkage of ocular dominance columns after
deprivation of the right eye starting at age 12 weeks (Fig. 15). Column areas for the left and right eye were
nearly equal on the opercula (Table 2). In the periphery, the
ipsilateral eye occupied less territory on each side, as in normal
animals.
Fig. 15.
Monkey 8 (12 week suture). Area measurements in
layer IVc showed normal column areas, indicating that the critical
period for expansion/contraction of columns was over by age 3 months. This animal had prominent widening of its ocular dominance columns within the foveal representation and along the V1/V2 border
(dashed line), an effect seen (to a variable extent) in
all animals.
[View Larger Versions of these Images (133 + 129K GIF file)]
LeVay et al. (1980) reported slight shrinkage of the ocular dominance
columns in a monkey sutured at age 10 weeks, but no shrinkage in
another monkey sutured at age 7 months. The lack of column shrinkage in
Monkey 8 allows one to bracket the end of the critical period more
precisely. In macaques, the susceptibility of ocular dominance columns
to shrinkage induced by monocular suture ends between age 10 and 12 weeks.
DISCUSSION
Timing of the critical period
Hubel, Wiesel, and LeVay's (1977, 1980) images of shrunken
ocular dominance columns provided the first convincing evidence that
anatomical connections in the developing primate brain can be altered
by abnormal sensory stimulation during a critical period after birth.
In their original discussion of this phenomenon, Hubel and Wiesel
(1970) invoked the work of Lorenz (1935) on imprinting behavior
in birds. In ducklings, the "following response" becomes fixed during a brief critical period that peaks at 17 hr after hatching. Ducklings show little interest in following decoys before 12 hr or after 24 hr (Hess, 1973). By analogy, Hubel and Wiesel (1970)
reported in kittens that susceptibility to eyelid closure begins
suddenly near the start of the fourth week and then declines after the
eighth week. From this finding, they concluded that the kitten's
visual system is too immature for monocular deprivation to have much
effect during the first weeks of life. In support of this notion, Olson
and Freeman (1980) found no change in the ocular dominance profiles of
cortical neurons in kittens sutured from day 8 to day 19. Thereafter,
just a few days of monocular deprivation were sufficient to produce a
major shift in ocular preference.
In an initial report concerning macaques, Hubel et al. (1977) suggested
that column shrinkage was more severe after lid suture at age 2 weeks
compared with 3 weeks. In their definitive study, LeVay et al. (1980)
later retracted this observation by concluding: "deprivation begun at
any age from birth to about 6 weeks had approximately the same
effect." This result might be explained if macaques, like cats, were
relatively immune to the effects of monocular deprivation for the first
few weeks after birth. However, LeVay and coworkers found severe column
shrinkage in a monkey sutured at 2 d and examined at 24 d,
nullifying this interpretation.
Repeating the experiments by LeVay and coworkers, we have found greater
shrinkage and fragmentation of ocular dominance columns with lid suture
starting at age 1 week compared with later dates. For example, the
column shrinkage after suture at age 1 week was approximately twice as
severe as the shrinkage after suture at age 5 weeks (Table 2). From
these data, we conclude that macaques are highly sensitive to the
effects of visual deprivation within a week of birth (and probably even
sooner). Unlike kittens, there is no significant delay after birth in
the onset of the critical period.
In making these new observations, we have benefited from information
and methods not available to Hubel et al. when they performed their
classic experiments. As LeVay et al. (1985) discovered only later, the
ocular dominance columns in normal animals show marked regional
variation in width (e.g., the ipsilateral columns become broken and
narrowed in the periphery). To make valid comparisons, it is crucial to
reconstruct wide expanses of cortex to obtain a coherent view of the
shrunken columns or at least to survey the same region in every animal.
LeVay et al. (1980) examined small fragments of tissue, averaging only
~5% of the total V1 surface area, from different regions in each
animal. Improved methods for flat-mounting the cortex and for preparing
computer montages have made it easier to gauge the effects of visual
deprivation more accurately (Horton, 1984; Olavarria and Van Sluyters,
1985; Tootell and Silverman, 1985; Anderson et al., 1988; Rosa et al., 1988; Florence and Kaas, 1992; Hata and Stryker, 1994; Horton and
Hocking, 1996c).
Gradients in column shrinkage
Previous investigators have reported greater shrinkage of
ocular dominance columns ipsilateral to the sutured eye (Hubel et al.,
1977; LeVay et al., 1980) or in peripheral cortex as opposed to
opercular cortex (Swindale et al., 1981). We confirm these tendencies
but attribute them to preexisting inequalities in column widths present
in normal mosaics before the onset of visual deprivation. For example,
the smallest columns are located in the peripheral cortex, serving the
ipsilateral eye. After monocular deprivation, these columns become the
most severely reduced in size. Visual deprivation seems to subtract the
same amount of territory from all of the columns throughout any given
mosaic, at least to a first approximation. This impression was
supported by simulation of column shrinkage using the dilation filter
available with the Mocha image analysis program. Stripping pixels
evenly from one set of columns and adding them to the other set created
a mosaic of artificially shrunken columns that resembled closely those from animals deprived by lid suture (compare Figs. 9 and 10).
The most direct way to prove that visual deprivation reduces columns
everywhere by the same amount would be to compare mosaics in the same
animal, before and after visual deprivation. This is impossible, except
with optical imaging. Unfortunately, this technique cannot image buried
cortex and it renders less distinct columns than
[3H]proline autoradiography. Until a better method
becomes available, we shall be forced to rely on comparisons between
different animals
normal and deprived. This approach is dogged by
marked intrinsic variability from one animal to the next. A few
examples suffice to illustrate how this variability complicated the
interpretation of our data. In normal macaques, we reported recently
that ocular dominance columns are wider in the foveal representation
and along the V1/V2 border (Horton and Hocking, 1996c). In our mosaics,
this tendency accounts for the wider appearance of the columns in these
regions after monocular deprivation (e.g., see Figs. 2, 4, 9, 11, 12, 13, 14, 15).
However, enlargement of the columns in the foveal region and along the
V1/V2 border is quite variable in normal animals and in deprived
animals. This variation makes it difficult to exclude the possibility
that we suggested originally, namely, that columns in these regions are
less susceptible to shrinkage from monocular deprivation (Horton and
Stryker, 1993b).
The second example concerns the degree of column shrinkage ipsilateral
versus contralateral to the deprived eye. In binocular V1 of normal
macaques, the ipsilateral eye's columns occupy less territory overall (43.2 ± SD, 2.4%,
n = 12) than the contralateral eye's columns (56.8%;
calculated from Table 2 in Horton and Hocking, 1996c). Obviously, if
the ipsilateral eye's columns occupy less area in normal animals, they
will appear more shrunken in deprived animals. The predominance of the
contralateral eye is more pronounced in peripheral cortex (mean ratio
63:37) than in opercular cortex (mean ratio 52:48) (Horton and Hocking,
1996c). In normal animals, there is a surprising range in the
contralateral eye/ipsilateral eye ratio of opercular column areas, from
54:46 to 48:52. In peripheral cortex, this variation is even greater.
The ratio can also differ between hemispheres in the same animal. This
fluctuation is sufficient to account for the wide range that we
measured in the ratio of contralateral eye/ipsilateral eye column areas
(Table 2) and for the fact that at least one animal had more shrunken
columns in the operculum contralateral to the deprived eye (e.g.,
Monkey 2, Fig. 4).
Finally, there is real variability in column shrinkage from animal to
animal. Monkey 1 had less shrinkage than Monkey 2, despite suture at
the same age. Monkey 4 (sutured at 3 weeks) had more column shrinkage
in the right operculum than Monkey 5 (sutured at 5 weeks), but the same
shrinkage in the left operculum. This variability can mislead, and it
undoubtedly helped persuade LeVay et al. (1980) that suture at
different dates results in the same degree of column shrinkage. In
principle, variability can be overcome by performing large numbers of
experiments and then subjecting the data to statistical analysis.
However, this approach is not practical for primate studies, which are
inevitably limited to a handful of animals. We reduced variability by
using time-mated animals and sutured enough animals at 1 week and 5 weeks to convince ourselves that a genuine decline occurred in the
susceptibility to column shrinkage over this interval. The study by
LeVay et al. (1980) was limited by their use of newborns of unknown
gestational age and by the fact that they tested only one animal at
each suture date.
Shrunken ocular dominance columns coalesce around CO patches
In the foregoing discussion, we concluded that visual deprivation
attenuates columns equally throughout striate cortex, at least to a
first approximation. We added the proviso because severely deprived
animals exhibit a curious clumping of surviving column remnants that
cannot be explained by equal shrinkage along column frontiers. As
columns become fragmented, they coalesce in layer IVc in register
with CO patches (or short strings of patches) in the
upper layers. We never observed a column remnant in layer IVc
without an associated CO patch. In a sense, this result was not
surprising, because columns shrink by erosion from the edge to the
center, where CO patches are located (Horton and Hubel, 1981; Horton,
1984). Patches also have a tendency to be located at column
bifurcations and excrescences, where ocular dominance columns are wider
to begin with and, therefore, more likely to survive after shrinkage
(Horton, 1984). In peripheral cortex of normal animals, where ocular
dominance columns of the ipsilateral eye become naturally fragmented,
each fragment is aligned with a CO patch (J. Horton and D. Hocking,
unpublished observations). Evidently, in macaques the association
between ocular dominance columns and CO patches remains strong, even
after columns become fragmented by visual deprivation. By contrast, in
normal squirrel monkeys the ocular dominance columns and CO patches are
unrelated (Horton and Hocking, 1996b).
Differing susceptibility of parvo, magno, and
konio projections
The geniculate projection to layer IVc was more shrunken than
the projection to layer IVc (Figs. 4, 8), indicating that the
parvocellular channel conveying fine spatial information to the cortex
is affected more by visual deprivation than the magnocellular channel.
This conclusion supports previous findings in macaques raised with
blurred vision in one eye from atropine (Hendrickson et al., 1987;
Movshon et al., 1987). It is also consistent with the observation in a
reverse-sutured monkey that column plasticity ends first for the
magnocellular projection (LeVay et al., 1980).
The CO patches in the upper layers receive a direct thalamic
projection (Livingstone and Hubel, 1982; Fitzpatrick et al., 1983;
Weber et al., 1983; Horton, 1984; Itaya et al., 1984). Recent evidence
suggests that this projection arises from the koniocellular laminae of
the lateral geniculate body (Hendry and Yoshioka, 1994). In our first
experiment (Fig. 1), this projection appeared normal, despite eyelid
suture at age 1 week. This result might be explained if the open eye's
koniocellular afferents invaded the deprived eye's patches. However,
in another monkey we showed by ocular injection of
[3H]proline that the projection indeed arises from the
deprived eye (Figs.
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