Development of binocular vision

1
Development of binocular vision
Just as with many visual abilities, the newborn
human infant does not exhibit adult levels of
stereopsis, in fact stereopsis is absent in very
young infants. Unlike other visual development,
however, the improvement in stereopsis seems
quite sudden at about 4 months of age.
Streoacuity (arc min)
logMAR acuity
Age (months)
2
Two hypotheses to explain sudden onset of
stereoacuity

• It emerges after the segregation of R and L eye
  inputs in V1, i.e. after ocular dominance columns
  are formed. Rationale is simple prior to
  ocular dominance column formation, the R and L
  eye afferents overlap and it is not clear from
  which eye any signal originates, thus it is not
  possible to construct disparity detectors which
  must respond to specific R and L eye signals.
• Stereo acuity is impossible even for adults if
  the vergence error is a little more than a degree
  or two. Thus, if infant vergence eye movements
  are imprecise or absent, zero measurable
  stereopsis would be expected. However, as soon
  as the eyes converge correctly, stereopsis might
  suddenly appear.

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Anatomy of the binocular visual system
When does this system develop?
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Development of the binocular visual system
In order to attain functional binocular vision,
the two monocular neural images present in the
right and left eyes must converge at the LGN, but
remain in segregated layers, and then project
into interleaved contra and ipsi ocular dominance
banding in layer IVc of V1. When and how does
this happen? This question becomes more
interesting and clinically important when we
realize that normal binocularity in V1 is absent
in some brains.
6
C
5
I
4
C
3
I
I
2
P
P
C
P
1
P
M
M
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What is the timeline?
Pre-natal development
Post-natal development?
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Earlier pathways develop sooner pre-natal
development in the LGN
Shatz Sretevan, 1986
Shape and location of axon terminals at different
embryonic ages
Full-term birth
Laminar segregation of retinal ganglion axon
terminals in the cat LGN
7
Original histological method for observing
ocular dominance banding in layer IVc of V1
involved injection of dye in one eye, with
anterograde transport along axons and
trans-neuronal transport in the LGN
Eye
Chiasm
LGN
V1
Geniculo-cortical projection
8
Using this transneuronal transport technique,
LeVay et al, 1978 examined the emergence of
ocular dominance columns (banding in layer IVc of
monkey V1) in cat .
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Post-natal age (days)
22
Layer IVc
Conclusion Ocular dominance columns emerge
during the early post-natal period when the
visual cortex is sensitive to disruption (the
sensitive period), and thus it was concluded that
the emergence of ocular dominance columns relied
on the same mechanisms responsible for the
disruption of ocular dominance due to monocular
deprivation.
39
92
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Ocular Dominance Histograms
10 days Monocular deprivation at different ages
(cat), Olson and Freeman, 1980).
8
18
28
38
This data set shows that sensitivity to monocular
deprivation climbs soon after birth and declines
after about 1.5 months.
48
58
69
80
109
Normal
91
99
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Data from Olson and Freeman (1978), cat
Sensitive Periods
Banks et al, 1978, human
Mouse
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Hypothesis 1 ocular dominance columns develop
during the sensitive period as a result of
visually activated responses which modify the
ability of the pre-synaptic LGN axons to activate
the post-synaptic V1 neurons.
Axon arbors
Geniculo-cortical axons
Hebbian Model of Synaptic Change
Post-synaptic activity
time
12
More recent experimental data (Crowly and Katz,
1999) rearing Ferrets after eye removal at birth,
ocular dominance columns were observed in V1 via
anterograde transport from LGN to V1 and via
reterograde transport from V1 to LGN. Visual
responses were not required to segregation of R
and L eye signals in V1.
Experiments in cat show ocular dominance columns
present at 2 weeks of age in both normal and
binocularly deprive kittens, again showing that
visual experience was not necessary for ocular
dominance development.
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Development of binocularity in Ferret. Ferret is
used as an experimental model because it is born
far more immature than cats or monkeys.
Crowley and Katz method
LeVay et al method
Newer results show that ocular dominance columns
emerge even before the visual cortex can respond
to visual input, and way before the ocular
dominance can be altered by monocular
deprivation. Explanation of LeVay results dye
leaked out in LGN and spread between layers, thus
being absorbed by both R and L eye projections,
and thus uniform staining was seen in V1
(whoops!).
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Hypothesis 1 can be rejected Ocular dominance
columns emerge in cat and monkey prior to or
immediately after birth and do not require visual
input. It is likely that a similar early
development occurs in humans, and thus the
delayed appearance of stereopsis probably does
not reflect the delayed appearance of ocular
dominance columns in V1. In addition to the
histological evidence showing that ocular
dominance columns develop very early, Chino et al
1997using single unit recordings found that many
neurons in the visual cortex of infant monkeys (6
days post-natal) were disparity selective. Thus
the absence of stereopsis in young monkeys
(cannot be measured prior to 4 weeks), is not due
to an absence of disparity selective cells in
V1. Hypothesis 2 Indeed, vergence eye
movements are very immature and begin to appear
at about 3 months. Thus it is most likely that
the sudden emergence of stereopsis at about 4
months is a direct consequence of the eye
becoming precisely converged. Recall, that, even
in adults, stereopsis is unmeasurable when
targets are far from the Horopter.
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Monocular deprivation paradigm
e.g. deprive LE with occluder, lid suture,
blurring lens, diffuser. Need to reduce contrast
in retinal image
Non-deprived eye
Deprived eye
Reduced retinal image contrast
Reduced neural activity in LGN afferents forming
deprived eye ocular dominance bands
Reduced neural activity in LGN layers responding
to deprived eye
Reduced neural activity in RGC
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Monocular Deprivation (MD)
If MD occurs during the sensitive period, cells
in V1 become completely unresponsive to
stimulation through the deprived eye. How does
this happen?
8
18
28
38
48
58
69
80
10 days Monocular deprivation at different ages
(cat), Olson and Freeman, 1980).
109
Normal
91
99
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LGN
Deprived eye layers
Non-deprived eye layers

• Cell bodies in deprived eye layers are slightly
  smaller.
• Cells respond to visual stimuli normally
• Basically little effect.

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V1 layer IV LGN axon terminals
Notice that equally wide stained (dark) and
unstained (light) bands in the normal cortex
indicating equal representation of R and L eye
neural images
Normal cortex
After prolonged monocular deprivation during the
sensitive period, the LGN afferents no longer
cover 50 of layer IV, but always some afferents
from the deprived eye remain even in cases where
there is no observable physiological response to
the deprived eye.
Monocularly deprived cortex
Thin deprived eye ocular dominance bands (LeVay
et al, 1980)
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V1 anatomical changes following long-term MD
Non-deprived Eye
Examples of LGN axonal arbors in layer IV of V1
from the deprived and non-deprived eyes of a
mouse after long-term MD.
Deprived Eye
20

• After short periods of MD, V1 loses
  responsiveness to deprived eye, but there are no
  changes in the LGN axon arbors. What is the
  cause of this rapid loss of function?
• Loss of pre-synaptic sites on LGN arbors precedes
  shrinkage of arbors.
• post-synaptic changes in V1 neurons.

Silver and Stryker, 1999, using mice found that
complete physiological change to MD occurred
after 2 days, but the number of pre-synaptic
sites was normal as was the level of Synaptic
Vesicle Protein (SVP), thus the rapid changes
following MD likely occur in the post-synaptic V1
cells.
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Experimental Strabismus Use surgical sectioning
of extra-ocular muscles or prisms.
1. Effect on ocular dominance Loss of
binocular neurons in V1. If strabismus is
introduced early enough during the sensitive
period, there can be an almost complete loss of
binocular neurons in V1
Strabismic
Normal
1
2
3
4
5
6
7
1
2
3
4
5
6
7
Strabismic monkeys lack stereopsis
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Rapid physiological changes in V1 following MD
and strabismus are accompanied by rapid changes
in the horizontal connections within the upper
layers of V1.
Example of retrograde labeling within layers 2/3
of V1 which shows the intra-cortical
connectivity. Notice that in the strabismic cat,
RE cells only connect to other RE cells
indicating that the cortex has become monocular.
Strabismic kitten after 2 days
Normal control kitten
Location of retrogradely transported stain
Injection sites
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The mechanisms of plasticity
Hypothesis 1 Hubel and Wiesel, 1970s. Because
monocular deprivation has a much more profound
impact than does binocular deprivation, they
hypothesized that the changes seen in MD were due
to competition between the LGN afferents in layer
IV of V1. Changes occur due to a Hebbian
potentiation of post-synaptic activity. However,
because the effects of MD appear faster and are
more complete in the extra-granular layers of V1,
competition between geniculo-cortical afferents
is not the mechanism. Intra-cortical changes are
the source of the MD effects. Berardi N, et al,
2003, Molecular basis of plasticity in the
visual cortex in Trends in Neuroscience , vol
26, pp 369-376.
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Effect of monocular and binocular deprivation on
visual function
Normals, and non-deprived eyes of MD
Log contrast sensitivity
Congenital cataracts can cause visual deprivation
early in life
Binocular deprivation
Deprived eye of MD
Log spatial frequency
Long-term deprivation during the sensitive period
will lead to almost total blindness in the
deprived eye
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Clinical case of monocular deprivation in humans
Unilateral congenital cataracts longer duration
worse effect
20/20
Children will be legally blind (VAlt20/200) if
congenital unilateral cataract is not removed
before 15 weeks.
VA
20/200
20/2000
0.5
5
50
Age (weeks)
2. Patching therapy sensitivity to monocular
deprivation still exists at 2 years.
See examples from literature in which clinicians
have used patching or unilateral blurring with
atropine of a good eye in an attempt to treat an
amblyopic eye.
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Binocularity in human strabismics

• Poor or absent stereopsis
• Reduced or absent Inter-ocular transfer of
  After-Effects
• Deep suppression of the deviated eye

Most 4-6 month old normal infants exhibit
stereopsis
of infants demonstrating coarse stereopsis
Stereopsis fails to appear in esotropic infants
2
4
6
8
10
Post-term age in months