PRINCIPLES OF NEUROBIOLOGY
CHAPTER 4: VISION
JOURNAL CLUB
© 2016 GARLAND SCIENCE
Paper: Hubel DH and Wiesel TN (1962) Receptive fields, binocular interaction and functional
architecture in the cat’s visual cortex. J Physiol 160:106–154.
Principles of Neurobiology Reading: Chapter 4. Some of the findings of this paper are discussed in
Sections 4.23–4.25.
Background
David Hubel (1926–2013) and Torsten Wiesel (1924–) worked together from the late 1950s
through the mid-1970s to produce some of the twentieth century’s most influential discoveries in
neuroscience. Their earliest work focused on understanding the response properties of cells in the visual
system, particularly those in primary visual cortex, and how cells with different receptive fields are
physically organized in cortex. They also completed fundamental investigations into how the exquisite
organization of the visual system develops. Hubel and Wiesel were awarded the Nobel Prize in 1981 for
these contributions.
Hubel and Wiesel’s early work was performed in the laboratory of Stephen Kuffler at The Johns
Hopkins University and subsequently in their own lab at Harvard University. Regarded by many as ‘the
father of modern neuroscience,’ Kuffler made seminal contributions to understanding diverse aspects of
brain function, including the basic mechanisms of synaptic transmission, the role of GABA as a
neurotransmitter, properties of glial cells, and—of greatest relevance to the work of Hubel and Wiesel—
the response properties of retinal ganglion cells (RGCs). In 1952 and 1953, Kuffler reported the results of
experiments in which he recorded extracellularly from RGCs in anesthetized cats while stimulating the
retina with different patterns of light. Using this approach, he discovered the antagonistic center-surround
receptive field organization of RGCs: the receptive fields of RGCs are composed of two parts, a circular
center within which light will either activate or inhibit the cell, and an annulus surrounding the center, in
which light will have the opposite effect that it has in the center (see Section 4.14). When Hubel and
Wiesel began their work in Kuffler’s lab in 1958, they hoped to use the same approach to characterize the
receptive fields of neurons downstream of the retina in the lateral geniculate nucleus (LGN) and primary
visual cortex (V1).
Based on preliminary work by Hubel prior to his arrival in Kuffler’s lab, it was suspected that
LGN neurons have receptive fields similar to those of RGCs, a suspicion Hubel and Wiesel later
confirmed (see Section 4.22). Although at the time most scientists accepted that V1 was retinotopically
organized, nothing was known about the types of stimuli that activated V1 neurons. Hubel and Wiesel
thus initially focused on determining the receptive fields of neurons in V1 by recording action potentials
from V1 cells in anesthetized cats during delivery of different visual stimuli. The visual stimuli were
delivered using an apparatus consisting of a modified opthalmoscope in which slides containing different
stimulus patterns could be inserted. Hubel and Wiesel initially attempted to stimulate cells using small
spots of light on a dark background and small dark spots on a light background, similar to the stimuli that
optimally activate LGN neurons and RGCs. However, these stimuli did not strongly activate V1 neurons.
In the words of Hubel:
Our first real discovery came about as a surprise. We had been doing experiments for about a
month … and were not getting very far: the cells simply would not respond to our spots and
annuli. One day we made an especially stable recording … The cell in question lasted 9 hours, and
by the end we had a very different feeling about what the cortex might be doing. For 3 or 4 hours
we got absolutely nowhere. Then gradually we began to elicit some vague and inconsistent
responses by stimulating somewhere in the midperiphery of the retina. We were inserting the glass
Page 1 of 6
slide with its black spot into the slot of the ophthalmoscope when suddenly over the audiomonitor
the cell went off like a machine gun. After some fussing and fiddling we found out what was
happening. The response had nothing to do with the black dot. As the glass slide was inserted its
edge was casting onto the retina a faint but sharp shadow, a straight dark line on a light
background. That was what the cell wanted, and it wanted it, moreover, in just one narrow range
of orientations.1
Hubel and Wiesel’s initial characterization of V1 receptive fields was reported in an influential
1959 paper. The present paper, published in 1962, describes additional characterization of V1 receptive
fields and includes a description of two types of V1 cells—‘simple’ cells and ‘complex’ cells (see Section
4.23). In this paper, they also begin to elucidate the organization of V1, deducing how cells with different
response properties are organized in V1. Hubel and Wiesel were strongly influenced by the work of
Vernon Mountcastle, who reported in 1957 that in primary somatosensory cortex, cells aligned in
columns perpendicular to the cortical surface have similar receptive fields and are activated by similar
types of peripheral somatosensory stimulation. Remarkably, Hubel and Wiesel reported in this 1962 paper
that cells in V1 that have similar receptive fields and orientation preferences are also organized in cortical
columns, providing support for a now-well-accepted hypothesis that columnar structure is a fundamental
principle of cortical organization. They also started to examine the binocularity of V1 receptive fields,
paving the way for their subsequent work on the experience-dependent development of ocular dominance
columns (see Section 5.7).
Reading Guide
p. 106, ¶3, the technique of recording evoked slow waves: This refers to a method of recording field
potentials in which the electrical activity of a large population of neurons near the electrode is recorded
(see Section 13.20). Since the signal analyzed with this method includes the activities of hundreds or
thousands of cells, it can only reveal aspects of neuronal responses that are consistent among the cells
recorded by the electrode. Thus, field potential recordings were sufficient to reveal the tonotopic
organization of visual cortex, identify cortical areas that were activated by visual experience, and provide
insight into the binocularity of visual responses, but they did not have sufficient resolution to detect the
orientation-selective receptive fields of V1 neurons: for this purpose, recordings of individual cells
(‘units’) is necessary.
p. 106, ¶3, long micro-electrode penetrations through nervous tissue: Hubel and Wiesel’s method was
to insert an extracellular electrode into the surface of cortex and then to slowly drive the electrode deeper
into cortex, recording cells along the way. Several penetrations could be made in each animal. By passing
current into the electrode after recording at a particular location, they could generate small lesions. These
lesions, as well as the electrode penetration track, were visible in histological sections prepared after
completion of the experiment. Based on this histological information as well as information about the
depth of the electrode during each recording, Hubel and Wiesel were able to identify the approximate
locations of the cells from which they recorded.
p. 107, ¶1, receptive fields were mapped out separately for the two eyes: Normally in binocular
species, the focal points of the two eyes converge onto a single point in space. However, paralysis of the
extraocular muscles during Hubel and Wiesel’s experiments caused the eyes to diverge.
p. 107, ¶2, Points on the screen corresponding to the area centralis and the optic disk of the two
eyes were determined by a projection method: The ‘area centralis’ is the fovea—the place on the retina
where cone photoreceptors are most concentrated and where visual acuity is highest (see Section 4.8)—
while the optic disk is the location where the RGC axons leave the retina and that is thus devoid of
photoreceptors. To determine where these landmarks were located in the animal’s visual field, Hubel and
1
David H. Hubel Nobel Lecture: Evolution of ideas on the primary visual cortex, 1955–1978: A biased historical
account". Nobelprize.org. Nobel Media AB 2014. Web. 23 Nov 2014.
<http://www.nobelprize.org/nobel_prizes/medicine/laureates/1981/hubel-lecture.html>
Page 2 of 6
Wiesel used an ophthalmoscope to focus on each landmark; they then used a light pointing from the rear
of the ophthalmoscope to project this point onto the visual field.
p. 107, ¶3, most penetrations were well within the region generally accepted as ‘striate’: ‘Striate
cortex’ is another name for primary visual cortex (V1). In primates, layer 4 of V1, which receives input
from thalamus, is visible even in unstained brain sections, creating a stripe through cortex that earned this
region the name ‘striate cortex.’ Other areas of visual cortex are frequently referred to as ‘extrastriate
cortex.’
p. 108, ¶1, The unresolved background activity … served as a guide for determining the optimum
stimulus: While advancing the electrode, Hubel and Wiesel attempted to find individual cells that had
action potentials that could be isolated from those produced by nearby cells. A challenge with this
approach is that a cell must produce action potentials in order to be identified. Although this is not a
problem for cells that are ‘spontaneously active’ (that is, fire action potentials even in the absence of its
ideal stimulus), it is difficult to use this approach to identify cells that have low spontaneous activity: such
cells do not fire in the absence of their preferred stimulus, but their preferred stimulus can’t be identified
until the cell is isolated and its receptive field characterized. However, since cells with similar receptive
fields are clustered together, stimuli that induced high ‘background activity’ (that is, action potentials
from cells near the electrode that could not readily be discriminated from each other) were likely also to
be good stimuli for eliciting action potentials from other cells in the region. By adjusting the stimulus
such that it elicited high background activity, Hubel and Wiesel were able to induce the firing of cells
with low spontaneous activity that would not otherwise have been identified.
p. 109, ¶1, with the exception of afferent fibres of the lateral geniculate body: With Hubel and
Wiesel’s extracellular recording method, it is possible to record from axons innervating cortex from LGN
in addition to recording from cell bodies located in cortex. Since LGN neurons have concentric centersurround receptive fields, their axons in cortex also have such receptive fields. Action potentials produced
by cell bodies and axons can typically be distinguished based on a variety of properties, such as action
potential size and shape.
p. 110, ¶2, receptive field mapped with small spots: In their 1959 paper, Hubel and Wiesel used two
strategies for characterizing the receptive fields of simple cells. Their first strategy was to use as stimuli
spots of light much smaller than either ON or OFF receptive field regions. If the cell’s activity increased
when the light was shone on a region in visual space, then that region must be part of the cell’s ON field.
If the cell’s spontaneous activity decreased when the light was shone on a region in visual space or if the
cell fired when a light in a region of visual space was turned off, then that region must be part of the cell’s
OFF field. This strategy allowed Hubel and Wiesel to map ON and OFF receptive field regions in an
unbiased way: it did not require them to formulate a hypothesis about the shape of the receptive field and
to design stimuli based on the hypothesized receptive field shape. The second strategy was to use stimuli
tailored to simple cells’ receptive fields: bars of light of different orientations.
p. 111, ¶0, The most effective stationary stimulus: The ‘most effective stationary stimulus’ is the one
that Hubel and Wiesel identified as inducing the greatest response—either excitation during the stimulus
for cells with ON center receptive fields, or else inhibition during the stimulus or excitation at stimulus
offset for cells with OFF center receptive fields.
p. 121, ¶2, Over-all field dimensions: The width of one’s pinky held at arm’s length covers
approximately 1° of visual space, 4–6-fold larger than the smallest receptive fields mapped by Hubel and
Wiesel. The span between the tips of one’s thumb and pinky when they’re stretched as far apart as
possible and held at arm’s length covers approximately 25° of visual space.
p. 123, ¶2, Silver-degeneration studies: One classic method for analyzing neuronal connectivity relies
on the observation that degenerating axons can be selectively impregnated with silver when brain sections
are incubated with certain silver-containing solutions. In classic studies of the LGN, the optic nerve from
one eye was severed, leading to the degeneration of terminals from that eye in the LGN. By applying
Page 3 of 6
silver stains to degenerating axon terminals, it was found that the axons from one eye terminate in
restricted bands in the LGN (see Section 4.21).
p. 125, Text-fig. 10: The recordings from this figure show action potentials from three cells that are
discriminated based on action potential shape, which is influenced by the physiological properties of the
cell as well as its position relative to the electrode. Cell 1 evokes large action potentials that have positive
and negative deflections of approximately equal amplitude, cell 2 evokes small action potentials, and cell
3 evokes large action potentials that have large positive and small negative deflections. This process of
distinguishing between spikes produced by different cells is called ‘spike sorting.’ In theory, it’s possible
that two cells can produce action potentials of such similar shape that they cannot be distinguished.
Electrophysiologists typically use the term ‘unit’ to refer to the cell or cells that produce a set of action
potentials; in most cases, each unit probably is equivalent to a single cell, but in some cases each unit may
reflect the activity of two cells that produce action potentials of similar size and shape.
p. 129, ¶1, audible over the monitor as a crackling noise: Most electrophysiologists listen to cells
recorded extracellularly by converting recorded electrical signals into sound. It is often easier to discern
action potentials by ear than by eye.
p. 133, ¶1, angle between electrode and direction of fibre bundles (or apical dendrites): The apical
dendrites of cortical pyramidal cells point superficially upward in a direction perpendicular to the cortical
surface.
p. 134, ¶0, deeply pigmented non-tapetal part of the inferior retinas: The tapetum lucidum is a layer
of reflective cells present in some species, including cats; it is located caudal to the retina and serves to
increase photosensitivity by reflecting unabsorbed light back toward the photoreceptor layer. (The
presence of the tapetum lucidum accounts for the glowing appearance of cats’ eyes in dim light
conditions.) The retinal pigmented epithelium (RPE) is an additional layer of cells that serves a number of
functions, including absorption of scattered light and support of photoreceptors. In cats, the superior part
of the retina contains tapetum lucidum, and in this region the RPE is nonpigmented; the inferior part of
the retina contains pigmented RPE and is non-tapetal (that is, has no tapetum lucidum).
p. 138, ¶1, In Nissl-stained sections: Nissl stains label neuronal cell bodies and can often be used to
distinguish cortical layers based on the different cell body morphologies and cell densities in different
layers. Cresyl violet is the Nissl stain used by Hubel and Wiesel, and examples of Cresyl violet-stained
sections are shown in plates 1 and 2 in the paper (see Section 13.15).
p. 141, ¶1, In lateral geniculate, where one can, in effect, record simultaneously from a cell and one
of its afferents: As noted above, Hubel and Wiesel’s extracellular recording method can detect action
potentials from axons as well as cell bodies near the electrode tip. In work published prior to this paper,
Hubel and Wiesel were in some cases able to obtain simultaneous recordings of action potentials
produced by both an axon and a cell body in the LGN. In some instances of such recordings, a cell-body
action potential consistently followed an axon action potential, suggesting that the axon provided a direct
input to the cell body. Thus, Hubel and Wiesel were able to determine the receptive fields for both a
retinal input (the axon) and its putative postsynaptic partner (the cell body). Because of the greater
organizational complexity and cell type diversity of V1 compared to the LGN, a similar experiment has
not been possible in V1.
p. 147, ¶1, The normal eye is not stationary, but is subject to several types of fine movements: Even
during visual fixation (that is, looking at a single spot in space), the eye undergoes frequent movement.
These include, for instance, involuntary small-amplitude movements called microsaccades. One of the
many purposes potentially served by these movements is ensuring that the retina does not adapt to a
visual scene by constantly shifting the visual scene on the retina, thus preventing photoreceptor adaptation
(see Section 4.7).
Page 4 of 6
p. 149, ¶1, by binocular parallax alone … one can tell which of two objects is the closer: Parallax is
the apparent difference in the location of an object (relative to some reference point, such as other objects
in the scene) due to viewing the object from two different lines of sight. Because the two eyes of
binocular species are displaced horizontally, each eye will view the world from a slightly different angle,
producing binocular parallax. Hubel and Wiesel note that binocular parallax is sufficient for depth
perception and argue that in order to calculate the depth of an object based on the different locations of
that object’s image on the two retinas, there must be cells in the brain that are activated unequally by the
two eyes.
Questions
Question 1: Hubel and Wiesel write on p. 143, ¶1: “The properties of complex fields are not easily
accounted for by supposing that these cells receive afferents directly from the lateral geniculate body.” Do
you agree with this statement? What findings of Hubel and Wiesel’s might be used to directly or
indirectly support this claim?
Question 2: On pp. 127–128 (the last paragraph before the start of Part III), Hubel and Wiesel discuss
one explanation for their finding that V1 responses in the cat are influenced more by input from the
contralateral eye than from the ipsilateral eye. What is this explanation? Do Hubel and Wiesel accept or
reject this explanation, and what argument do they provide to support their conclusion?
Question 3: In the description of our current understanding of V1 functional architecture in Section 4.25,
evidence is presented to suggest that cells are organized into columns based on both orientation selectivity
and ocular dominance. Although in this 1962 paper Hubel and Wiesel are confident about the
arrangement of cells into columns based on orientation selectivity, they are more circumspect about the
arrangement of cell into ocular dominance columns. What factors might have contributed to Hubel and
Wiesel’s lack of confidence about the existence of ocular dominance columns?
Question 4: Hubel and Wiesel describe two types of cells in V1—simple cells and complex cells. What
properties characterize the receptive fields for each of these cell types? How are the receptive fields of
these two types of cells similar, and how are they different?
Question 5: One criterion that has been proposed for the classification of simple
versus complex cells is the response of a cell to a drifting sinusoidal grating. One
frame from such a stimulus is shown to the right, with the arrow indicating the
direction of stimulus motion in subsequent frames. The orientation, spatial and
temporal frequency, and direction of motion of the stimulus can be varied to match
a cortical cell’s receptive field. How would you expect the responses of simple and
complex cells to such a stimulus to differ?
Question 6: Hubel and Wiesel report that for binocular cells, the receptive fields in the two eyes are
similarly organized (for instance, binocular simple cells have similar ON and OFF subregions) and are
located in similar positions on the retina. They also report that for binocular simple cells the properties of
summation within ON or OFF subregions and antagonism between ON and OFF subregions hold across
receptive fields from the two eyes. However, subsequent work showed that in fact the receptive fields of
simple cells can occupy slightly different positions on the two retinas. What function might be served by
such binocular disparity in receptive field position?
Question 7: V1 simple cells are selectively activated by different stimuli depending on a number of
different stimulus features. The feature most strongly emphasized by Hubel and Wiesel is orientation:
cells respond only if the orientation of a stimulus falls within a narrow range determined by the
orientation of the cell’s receptive field. However, Hubel and Wiesel discuss some stimulus features for
which simple cells are also selective, and selectivity for other features has been proposed by other
scientists since the work of Hubel and Wiesel. These features include (1) spatial frequency that is, for a
grating such as the one shown in question 5, the spatial frequency would be the inverse of the distance
Page 5 of 6
between intensity peaks), (2) direction of stimulus movement, and (3) the speed of stimulus movement.
For each of these stimulus features, explain how the arrangement of ON and OFF subregions could
endow a simple cell with selectivity for that stimulus feature.
Suggestions for Further Reading
Hubel DH (1981) Evolution of ideas on the primary visual cortex, 1955–1978: a biased historical account.
Nobelprize.org. < http://www.nobelprize.org/nobel_prizes/medicine/laureates/1981/hubellecture.pdf>
Wiesel TN (1981) The postnatal development of the visual cortex and the influence of environment.
Nobelprize.org. < http://www.nobelprize.org/nobel_prizes/medicine/laureates/1981/wiesellecture.pdf>
The above two publications are written versions of Hubel’s and Wiesel’s Nobel Prize Lectures.
They describe the history of their work and the key experiments they conducted to understand the
function and development of primary visual cortex. Hubel’s lecture is more relevant to the
present paper: Wiesel’s lecture focused principally on their developmental work.
Hubel DH & Wiesel TN (1959) Receptive fields of single neurons in the cat’s striate cortex. J Physiol
148:574–591.
This paper reports Hubel and Wiesel’s initial findings on the response properties of primary
visual cortex neurons. The 1962 paper built off of these initial results.
Page 6 of 6