Developmental Neuroscience · Unit 9: Experience refines the wiring

Ocular Dominance and the Critical Period

Closing one eye of a young kitten for a few days changes which eye can drive the cells of its visual cortex, while the same closure in an adult cat does little. This lesson shows how that change is measured, why closing both eyes does far less harm than closing one, and what a critical period is. Afterwards you can read an ocular-dominance histogram, argue for competition over disuse, and explain why patching the good eye treats amblyopia.

Watch first The More Active Eye Wins · 3:12

Sew one eyelid of a kitten shut for about a week when it is a month old, and most cells in its visual cortex stop answering to that eye. Close an adult cat’s eye for months, and the cortex looks normal.

The eye itself is not harmed. When it is reopened, its retina still responds to light. What changed is in the brain, and it changed only because of what the animal saw, at an age when the wiring could still be rewritten. The lectures for this course put it in one line: “Sensory Environment influences synaptic connections.” The questions are how you measure that influence, what the closed eye lost, and why the window shuts.

The idea: experience decides which eye drives a cortical cell

Each eye sends its axons to the lateral geniculate nucleus (LGN), a relay station in the thalamus. There the two eyes’ axons end in separate layers, so an LGN cell answers to one eye only. LGN axons then carry the signal to the primary visual cortex, at the back of the brain, where they end mainly in layer 4. Above and below layer 4, many cortical cells receive input traced back to both eyes. The cortex is the first place where single cells combine the two eyes.

David Hubel and Torsten Wiesel measured that combination one cell at a time. In extracellular single-unit recording, a fine metal electrode sits next to one neuron and records its spikes from outside. With the animal anaesthetized, they showed a bar of light to one eye while the other was covered, then switched.

Each cell was placed on a scale of seven ocular dominance groups. Group 1 cells answer only to the contralateral eye (the eye on the opposite side from the hemisphere being recorded). Group 7 cells answer only to the ipsilateral eye (same side). Group 4 cells answer about equally to both, and groups 2, 3, 5 and 6 favor one eye to a lesser or greater degree. Some teaching versions, including the one in this course’s lectures, collapse this into fewer bins; this lesson uses the original seven.

Count the cells in each group and you get an ocular-dominance histogram. In a normal adult cat it is a hump: most cells sit in the middle groups, and the hump leans toward the contralateral side.

The anatomy has a matching pattern. Inject a radioactive amino acid such as tritiated proline into one eye. It is built into proteins, carried to the LGN, partly passed across to the LGN cells, and carried on to their endings in layer 4. Expose film to slices of cortex and the injected eye’s endings appear as stripes, alternating with unlabeled stripes that belong to the other eye. In macaque monkeys these ocular dominance columns are sharp in layer 4C; in cats the pattern is less regular.

Closing one eye: a large shift, but only in the young

In 1963 Wiesel and Hubel reported what happens when a kitten grows up with one eye closed. They sutured the lids of one eye at or near birth and recorded after about three months of closure. Very few cortical cells could be driven by the closed eye, though its retina and its LGN cells still responded. The LGN cells serving the closed eye did look smaller. An adult cat with one eye closed for months showed no such change.

In 1970 they asked when. They closed one eye in kittens of different ages for different lengths of time. In this kitten series, susceptibility began around the start of the fourth week, stayed high until somewhere between six and eight weeks, and declined through the third month. In kittens whose right eye was closed for only six days during the fourth or fifth week, the number of cells the closed eye could drive fell to a fraction of normal. Six days of unequal vision had moved most of the histogram toward the open eye.

The anatomy follows the physiology. Hubel, Wiesel and Simon LeVay closed one eye in infant macaque monkeys and later traced the stripes in layer 4C. The open eye’s stripes had widened and the closed eye’s had narrowed. Their 1980 study showed why that is possible: in newborn monkeys the two eyes’ territories in layer 4C still overlap more than in adults, and they separate over the first postnatal weeks. A closure during that time tilts the separation toward the open eye. In kittens, single thalamic axons serving a deprived eye were later seen to lose branches within about a week of closure.

Competition: the amount and timing of activity set the strength of a projection

There are two ways to read the closed eye’s loss. It could be disuse: connections that carry no patterned signal wither. Or it could be competition: the two eyes share the cortex, and the one that is more active takes territory from the other.

Design problem

You have kittens of the age at which one-eye closure causes a near-complete shift. You close both eyes for the same weeks. What should the cortex look like under the disuse hypothesis, what under the competition hypothesis, and how would you tell them apart?

One way to do it

Under disuse, each eye’s connections wither in proportion to how little they were used. With both eyes closed, each is as unused as the single closed eye was, so you would expect a large loss of responses to both eyes, perhaps a cortex with few responsive cells.

Under competition, what hurts a closed eye is the advantage of the open one. With both eyes closed, neither has an advantage, so you would expect little imbalance and many cells still responding to each eye.

Record from many cells, score each on the seven-group scale, and also count the cells that respond abnormally or not at all. Wiesel and Hubel did this in 1965. Many cells still responded to each eye, though a share were abnormal or unresponsive. The large loss that disuse predicts was absent. Closing both eyes caused far less harm to each eye’s share of cells than closing one, so the shift after one-eye closure comes mainly from competition between the eyes.

The lecture’s phrase for this result is the “Competition Hypothesis: differences in the amount of activity determine the strength of the projection.” Later experiments made “activity” literal. Stryker’s laboratory silenced one eye of kittens with tetrodotoxin, a toxin that blocks sodium channels and stops retinal cells from firing. Cortical responses shifted toward the eye that kept firing. Silencing both eyes during development kept the two eyes’ axons from separating into stripes.

Amount is not the whole story. Timing matters too. In strabismus, the eyes are misaligned, so each points at a different part of the scene. Hubel and Wiesel produced it in young kittens by cutting one eye muscle. Each eye still received a normal amount of patterned light. But the two eyes now sent unrelated signals to any cell they shared. The histogram changed shape: most cells answered to one eye or the other, and few answered to both. With equal amounts of activity, the eyes kept their territories but lost their shared cells.

A rule that fits both results is the one Donald Hebb proposed: an input that repeatedly takes part in firing a cell is strengthened. Inputs that fire together onto one cell support each other; inputs that fire out of step compete for it. One molecular candidate for detecting “together” is the NMDA receptor, which opens only when glutamate arrives while the cell is already depolarized (see that lesson). Activity also raises the cortex’s production of BDNF, a neurotrophin that acts through the receptor kinase TrkB (that lesson), and it has been proposed as one of the signals that rewards the winning input. Before the eyes open, structured activity of a different kind comes from the retina itself (that lesson).

Critical period versus sensitive period

A critical period is a time when a developing system is especially susceptible to, and requires, specific experience to develop normally. The lectures call such windows “windows of opportunity and vulnerability,” and draw a distinction: critical periods begin and end abruptly; sensitive periods rise and fall gradually. Real windows often fall between the two, and how sharp one looks depends on the species, the manipulation and the measure. A closure that does nothing detectable to an adult cat’s ocular dominance histogram does not mean the adult cortex cannot change in any way.

Name the species with every number. In the 1970 kitten series, sensitivity began near the start of week four and stayed high until some time between weeks six and eight. In macaques the effect of early closure is strongest in the first weeks after birth. In mice, Joshua Gordon and Michael Stryker found in 1996 that a few days of closure shifted responses most strongly near postnatal day 28, with little effect from the same closure in adults. Mice have no ocular dominance columns. Their binocular cortex is a small zone dominated by the contralateral eye, so plasticity is read from single cells, summarized as a contralateral bias index, or from evoked potentials and imaging. The mouse’s value is its genetics, which later work used to ask what opens and closes the window (that lesson).

The clinical version of this story is amblyopia: reduced vision in one eye that glasses alone do not fix, with no structural disease of the eye to explain it. It arises when the two eyes give the young brain unequal input. Common causes are strabismus, a large difference in focus between the eyes, and anything that blocks one eye’s image, such as a congenital cataract or a drooping lid. Strabismus affects a few percent of children.

The standard treatment follows from competition. After correcting the optics, the doctor covers the good eye with a patch for part of the day, or blurs it with atropine drops, so the weak eye is the more active one. Treatment generally works best in young children, consistent with a sensitive period, although trials have found that some older children still improve. A cataract that blocks one eye from birth is usually removed early in infancy for the same reason.

How we measure it

Extracellular single-unit recording

A fine metal electrode is placed next to one neuron in an anaesthetized animal and records its spikes from outside the cell. Stimuli are shown to each eye in turn, with the other eye covered, so the strength of each eye's drive on that one cell can be compared.

Monocular deprivation by lid suture

The eyelids of one eye are sewn shut for a chosen period at a chosen age, so that eye gets only diffuse light while the other sees normally. Reopening the eye and recording from the cortex shows how the balance between the eyes has changed.

Transneuronal autoradiography

A radioactive amino acid such as tritiated proline is injected into one eye. It is built into proteins, carried to the thalamus, partly passed to the thalamic neurons, and carried on to their endings in layer 4 of the cortex, where film exposed to brain sections shows that eye's stripes.

Ocular dominance in the mouse

Mouse visual cortex has a small binocular zone and no ocular dominance columns. Plasticity is read from single units scored for eye preference and summarized as a contralateral bias index, or from visually evoked potentials and imaging, before and after closing one eye.

Finish line

Test yourself

8 questions

Practice and MCAT-style, with explained answers.

Next · Lesson 40

Opening and Closing a Critical Period

A mouse that lacks one enzyme for making GABA keeps its critical period waiting for months. One drug starts it.

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← Lesson 38 · Activity Before Experience: Spontaneous Retinal Waves

NMDA receptor (GluN1 with GluN2B) — the coincidence detector at the synapse
NMDA receptor (GluN1 with GluN2B) — the coincidence detector at the synapse ● LIVE · RCSB PDB 4PE5
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Loading live structure 4PE5 from RCSB PDB…

Four subunits stand on the membrane like a tall hourglass, with glutamate- and glycine-binding clamshells above the channel. The pore opens only when glutamate is bound and the membrane is depolarized enough to clear magnesium from it, which lets the receptor report two events at once.

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Tetrodotoxin — the toxin used to silence one eye
Tetrodotoxin — the toxin used to silence one eye ● LIVE · PubChem CID 11174599
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A small, rigid cage of rings carrying a positively charged guanidinium group. It plugs the outer mouth of voltage-gated sodium channels, so retinal cells injected with it cannot fire action potentials.

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TrkB domain 5 bound to neurotrophin-4/5 — a neurotrophin meeting its receptor
TrkB domain 5 bound to neurotrophin-4/5 — a neurotrophin meeting its receptor ● LIVE · RCSB PDB 1HCF
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A neurotrophin dimer sits between two receptor domains, one on each side. BDNF binds TrkB in the same way, and BDNF made by cortical neurons rises with activity.

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Torsten Wiesel

Torsten Wiesel

With David Hubel, showed that closing one eye of a young kitten leaves few cortical cells that the closed eye can drive, and that closing both eyes does much less harm, which pointed to competition between the eyes.

Wiesel trained in medicine at the Karolinska Institute in Stockholm and came to Stephen Kuffler's laboratory at Johns Hopkins, where he began recording from the cat visual cortex with David Hubel. The group later moved to Harvard Medical School. Once the two had worked out what normal cortical cells respond to, they asked what happens when a kitten grows up with one eye closed. In 1963 they reported that after a long closure from birth, very few cortical cells could be driven by the deprived eye, although the retina of that eye still responded, while months of closure in an adult cat left the cortex looking normal. In 1965 they compared closing one eye with closing both and found the second far less damaging to the share of cells each eye could drive. That comparison turned a story about disuse into one about competition. His Nobel lecture in 1981 was titled for the postnatal development of the visual cortex and the influence of environment. He later led Rockefeller University.

✓ verbatim Wiesel & Hubel, J. Neurophysiol. 26:1003 (1963); Wiesel & Hubel, J. Neurophysiol. 28:1029 (1965); Wiesel, Nobel Lecture, 8 December 1981.
David Hubel

David Hubel

With Torsten Wiesel, defined the seven ocular-dominance groups used to describe how strongly each eye drives a cortical cell, and mapped the age window in which closing one eye shifts that balance in kittens.

Hubel trained in medicine at McGill University and joined Wiesel in Kuffler's group, where the pair recorded one cortical cell at a time in anaesthetized cats while showing patterns of light to each eye separately. In a 1962 paper in the Journal of Physiology they described cells that respond best to edges and bars at a given orientation, and they sorted each cell into one of seven groups according to which eye could drive it and how strongly. That scale is still the way the result of an eye closure is read. In 1970 they closed one eye in kittens of different ages for different lengths of time and found that susceptibility began around the start of the fourth week, stayed high for several weeks, and declined through the third month. The Nobel Prize in Physiology or Medicine for 1981 went half to Roger Sperry and half jointly to Hubel and Wiesel. Their age series gave later workers a window with coordinates: a species, a stage, a manipulation and a readout.

✓ verbatim Hubel & Wiesel, J. Physiol. 160:106 (1962); Hubel & Wiesel, J. Physiol. 206:419 (1970); Hubel, Nobel Lecture, 8 December 1981.
Simon LeVay

Simon LeVay

With Hubel and Wiesel, showed in monkeys that the layer 4 stripes of the open eye widen and those of the closed eye shrink after early monocular closure, so the anatomy follows the physiology.

Recording one cell at a time shows which eye drives a neuron but not where the axons from each eye end. LeVay worked on the anatomy with Hubel and Wiesel at Harvard. In macaque monkeys, a radioactive amino acid injected into one eye is carried to the thalamus, part of it crosses into the thalamic relay cells, and it is carried on to their endings in layer 4C of the visual cortex. Autoradiography of the cortex then shows alternating stripes belonging to the injected eye. In a 1977 paper with Hubel and Wiesel, monkeys that had one eye closed early in life showed wide stripes for the open eye and narrow ones for the closed eye. In 1980 the same three authors described how the stripes develop: in newborn monkeys the two eyes' territories in layer 4C overlap more than in adults and separate over the first weeks after birth. The work made it possible to say that a closure in this window changes the territory each eye's axons hold in the cortex, not only how cells respond.

✓ verbatim Hubel, Wiesel & LeVay, Phil. Trans. R. Soc. Lond. B 278:377 (1977); LeVay, Wiesel & Hubel, J. Comp. Neurol. 191:1 (1980).
Michael Stryker

Michael Stryker

Showed in kittens that an imbalance of retinal activity between the eyes drives the shift, and with Joshua Gordon established the mouse as a model for the critical period of ocular dominance plasticity.

Stryker's laboratory at the University of California, San Francisco, asked what in the closed eye's input matters. In 1986, with William Harris, Stryker reported that silencing both eyes of kittens with the sodium channel toxin tetrodotoxin prevents the axons serving the two eyes from separating into stripes in the cortex. In the same year, with Barbara Chapman and colleagues, the laboratory reported in Nature that silencing one eye's retina with tetrodotoxin shifts cortical responses toward the active eye, so an imbalance of electrical activity is enough. In 1993, with Antonella Antonini, it showed that the thalamic axons serving a deprived eye lose branches within about a week. In 1996, with Joshua Gordon, it showed that brief closure of one eye shifts responses in mouse visual cortex most strongly near four weeks after birth and much less in adults. That result let later work use mouse genetics to ask how the window opens and closes.

✓ verbatim Chapman, Jacobson, Reiter & Stryker, Nature 324:154 (1986); Gordon & Stryker, J. Neurosci. 16:3274 (1996).
Test yourself
Question 1 of 8 Score 0 / 0

On Hubel and Wiesel's seven-group scale, what is true of a cell placed in group 1?
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Every structure, slide, simulation, and clip on this page is listed below with the source it came from. None of the 3D structures is drawn by hand or by AI: each one loads by accession ID from RCSB PDB or PubChem. This panel is generated from the lesson's own data file, so what it lists is what the page loads.

Molecular structures live data

  • NMDA receptor (GluN1 with GluN2B) — the coincidence detector at the synapse — RCSB PDB 4PE5 · coordinates CC0 · Rat GluN1a/GluN2B NMDA receptor, X-ray crystal structure (Karakas & Furukawa, Science, 2014)
  • TrkB domain 5 bound to neurotrophin-4/5 — a neurotrophin meeting its receptor — RCSB PDB 1HCF · coordinates CC0 · Human TrkB ligand-binding domain 5 with NT-4/5, X-ray crystal structure (Banfield et al., Structure, 2001)
  • Tetrodotoxin — the toxin used to silence one eye — PubChem CID 11174599 · PubChem compound record for tetrodotoxin

Scientist profiles & quotes

  • Torsten Wiesel — Wiesel & Hubel, J. Neurophysiol. 26:1003 (1963); Wiesel & Hubel, J. Neurophysiol. 28:1029 (1965); Wiesel, Nobel Lecture, 8 December 1981.
  • David Hubel — Hubel & Wiesel, J. Physiol. 160:106 (1962); Hubel & Wiesel, J. Physiol. 206:419 (1970); Hubel, Nobel Lecture, 8 December 1981.
  • Simon LeVay — Hubel, Wiesel & LeVay, Phil. Trans. R. Soc. Lond. B 278:377 (1977); LeVay, Wiesel & Hubel, J. Comp. Neurol. 191:1 (1980).
  • Michael Stryker — Chapman, Jacobson, Reiter & Stryker, Nature 324:154 (1986); Gordon & Stryker, J. Neurosci. 16:3274 (1996).

Quotes are verbatim from the cited source. Profile text is original to this site and was checked against the sources cited.

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The More Active Eye Wins · narration: an AI narrator voice (Gemini, Charon) reading narration written from this lesson's text · animation: AI-generated in code (Manim) by Claude, a schematic with no drawn molecular structures, plots computed from their equations · captions from the narration script.

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Like I'm five

Your two eyes take turns talking to the same cells in your brain. When you are very little, those cells listen most to whichever eye talks more. If one eye is covered for a while, the other eye does all the talking, and the cells stop listening to the covered one. Grown-up brains do not switch like that, which is why eye doctors fix eye problems in small children early.
High school

Signals from both eyes meet in the visual cortex, at the back of the brain, and many cells there respond to either eye. In young kittens, closing one eye for a few days makes most of those cells respond only to the open eye. The same closure in an adult cat does little. Closing both eyes does much less harm than closing one, so the eyes seem to compete for the cortical cells, and the more active eye wins. This only works during an early window called a critical period. In children, a turned eye or a blurry eye can lose out the same way, a condition called amblyopia, and covering the strong eye gives the weak one a chance to compete.
College

Ocular dominance describes which eye drives a cortical neuron and how strongly, scored by Hubel and Wiesel on seven groups from contralateral only (group 1) to ipsilateral only (group 7). In normal cats most cells in primary visual cortex are binocular. Monocular lid suture during a kitten's critical period, which begins around the fourth postnatal week and declines through the third month, shifts the histogram toward the open eye, while adult closure has little effect in this assay. In monkeys, the open eye's thalamic axons in layer 4C take more territory and the closed eye's take less. Binocular closure causes much less imbalance, and strabismus, which keeps the amount of activity normal but decorrelates the eyes, removes binocular cells. The data fit a competition in which the amount and timing of presynaptic activity set the strength of each eye's projection.
Graduate

The ocular-dominance shift is a readout of activity-dependent competition between two populations of thalamocortical and intracortical inputs onto shared targets. Silencing one retina with tetrodotoxin shifts responses toward the active eye in kittens, while silencing both preserves the balance, so the signal is the interocular difference in activity. Blocking NMDA receptors in kitten cortex has been reported to reduce the shift, consistent with a Hebbian rule in which correlated pre- and postsynaptic activity strengthens an input. In mice, which lack columns, four days of closure near P28 lowers the contralateral bias index, and the change is later described in two phases: depression of the deprived eye's responses, then potentiation of the open eye's.

An open question is how much of the window's closure reflects the loss of a plasticity mechanism and how much reflects brakes added on top of a mechanism that persists, since adult mice show slower ocular dominance changes under some conditions and some adult amblyopes improve with treatment.
The edge of a glass slide

In their retrospective accounts, Hubel and Wiesel described how their first attempts to drive cat cortical cells with small spots of light, the stimulus that worked well in the retina, gave them little. A cell finally fired vigorously as they slid a glass slide carrying a black spot into the slot of the stimulator that projected spots onto the retina, and the response came from the faint shadow of the slide's edge, not from the spot on it. That episode led them to cells tuned to lines at a given orientation. It also set the method on which the deprivation work rests: hold one cell and ask it precise questions about each eye.

— Hubel, Nobel Lecture, 8 December 1981; Hubel & Wiesel, Neuron 20:401 (1998).
Two closed eyes, less damage

If a closed eye loses the cortex because it is unused, closing both eyes should be at least as bad for each eye as closing one. Wiesel and Hubel sutured both eyes of kittens for the same weeks that caused a dramatic shift after one-eye closure. Many cortical cells still responded to each eye, though a share were abnormal or unresponsive. The result recast the effect of monocular closure: what cost the closed eye its cells was mainly the open eye's advantage.

— Wiesel & Hubel, J. Neurophysiol. 28:1029 (1965); Wiesel, Nobel Lecture, 8 December 1981.
Silencing an eye without closing it

Lid suture blurs an eye's image but leaves its retina firing. To ask whether electrical activity itself was the currency, Stryker's laboratory injected one eye of kittens with tetrodotoxin, which blocks sodium channels and stops retinal cells from producing action potentials. Cortical responses shifted toward the eye that kept firing. The paper's title stated the conclusion: the shift was caused by an imbalance in retinal electrical activity.

— Chapman, Jacobson, Reiter & Stryker, Nature 324:154 (1986).

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