Inaugural Article: Parallel information processing
channels created in retina
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Schiller, Peter H. “Parallel information processing channels
created in the retina.” Proceedings of the National Academy of
Sciences 107.40 (2010): 17087 -17094. © 2010 by the National
Academy of Sciences
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http://dx.doi.org/10.1073/pnas.1011782107
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INAUGURAL ARTICLE
Parallel information processing channels created in
the retina
Peter H. Schiller1
Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139
This contribution is part of the special series of Inaugural Articles by members of the National Academy of Sciences elected in 2007.
In the retina, several parallel channels originate that extract different
attributes from the visual scene. This review describes how these
channels arise and what their functions are. Following the introduction four sections deal with these channels. The first discusses the
“ON” and “OFF” channels that have arisen for the purpose of rapidly
processing images in the visual scene that become visible by virtue of
either light increment or light decrement; the ON channel processes
images that become visible by virtue of light increment and the
OFF channel processes images that become visible by virtue of light
decrement. The second section examines the midget and parasol
channels. The midget channel processes fine detail, wavelength information, and stereoscopic depth cues; the parasol channel plays
a central role in processing motion and flicker as well as motion
parallax cues for depth perception. Both these channels have ON
and OFF subdivisions. The third section describes the accessory optic
system that receives input from the retinal ganglion cells of Dogiel;
these cells play a central role, in concert with the vestibular system, in
stabilizing images on the retina to prevent the blurring of images
that would otherwise occur when an organism is in motion. The
last section provides a brief overview of several additional
channels that originate in the retina.
midget channels
| ON/OFF channels | parasol channels
I
n the past 120 years, great strides have been made in uncovering
how the brain processes visual information. Several of the discoveries were quite surprising and unexpected. It was found that, in
the retina, the photoreceptors faced away from the incoming light
and were closest to the pigment epithelium. All the other cell types
in the retina were positioned between the photoreceptors and the
vitreous humor. This meant that, except for the central foveal region, the incoming photons had to pass through all these cells and
their processes before impinging on the photoreceptors. It was also
discovered that there are two distinct photoreceptor types, the rods
and the cones. When Schultze established this in the 1860s with
anatomical methods he had developed (1), his findings were met
with considerable skepticism. Undaunted, he went on to ask what
the reason might be for having two different kinds of photoreceptors. He noted that the rods are absent in the fovea and that
night vision is poor when incoming light is confined to this region.
So he proposed that the rods are for night vision, a fact now fully
accepted. Further studies have identified several distinct classes of
cells in the retina that included the horizontal cells, the bipolar
cells, the amacrine cells, and the ganglion cells that send their axons
to the central nervous system exiting the eye at the optic disk.
Studies have yielded yet another unexpected discovery, showing
that there are several distinct classes of retinal ganglion cells. The
use of the Golgi stain by its inventor, Camillo Golgi, and by Santiago Ramon y Cajal, was central in establishing these facts (2). For
the numerous remarkable findings they made about the organization of the brain, Golgi and Cajal received the Nobel Prize in 1906.
The subsequent emergence of physiological methods has made
it possible to examine the functions of the neurons in the retina.
The first to do so was Haldan Keffer Hartline, who developed
procedures that enabled him to record the electrical activity of
www.pnas.org/cgi/doi/10.1073/pnas.1011782107
individual retinal ganglion cells (3). Doing so, he discovered three
classes of retinal ganglion cells: “ON” cells that discharged vigorously when the retina was illuminated, “OFF” cells that discharged
when the light was turned off, and ON/OFF cells that responded
transiently to both the onset and the termination of light. He also
established that each cell is sensitive to only a small area of illumination on the retinal surface, a region called the receptive field
of the cell. Hartline received the Nobel Prize for these discoveries
in 1967. Subsequently, Steven Kuffler discovered in the cat, as did
Horace Barlow in the frog, that the receptive field of each ganglion
cell is actually composed of two regions that are concentrically
arranged: an excitatory center area and an antagonistic surround
region (4, 5). Stimulating the center with a small spot elicited
a vigorous response, whereas a larger spot that impinged also on
the surround produced an attenuated response. Stimulation of the
surround alone with an annulus produced a weak response of the
opposite polarity. The ON/OFF cells gave vigorous transient
responses to both the onset and the termination of light when
confined to the center of their receptive fields; in these cells, the
responses were also attenuated when the size of the stimulus was
increased. Similar results were obtained subsequently in many
species suggesting that the ON, OFF, and ON/OFF cells of the
retina and their antagonistic center-surround organization form
a basic ground plan for the visual systems of all vertebrates (6–9).
ON and OFF Channels
Origins of the ON and OFF Channels in the Retina. In the 1960s, it
became possible to place finely drawn micropipettes inside the
various cell types of the retina (10, 11). Such intracellular recordings provided accurate measurements of the graded potentials
produced by the neurons and made possible their subsequent anatomic identification by minute dye injections. Studies using these
procedures, beginning with the pioneering work in John Dowling’s
laboratory, revealed that the basic organization of the retina in
vertebrate species is quite similar (12–16). The photoreceptors in
all cases hyperpolarize to light and use the neurotransmitter glutamate, which acts differently on the two major classes of bipolar
cells: OFF bipolars, which have sign-conserving ionotropic receptors (iGluRs), and ON bipolars, which have sign-inverting metabotropic receptors (mGluR6). Thus, the OFF cells polarize in the
same manner as do the photoreceptors whereas the ON bipolars
polarize in the direction opposite to the photoreceptors. Fig. 1A
shows this arrangement schematically. The majority of cones in
central retina connect with at least two bipolar cells, one of which
is ON and the other OFF. The ON and OFF bipolars in turn
connect with ON and OFF retinal ganglion cells, respectively.
Further complexities in this arrangement will be described later.
Author contributions: P.H.S. designed research, performed research, and wrote the paper.
The author declares no conflict of interest.
Freely available online through the PNAS open access option.
1
E-mail: phschill@mit.edu.
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.
1073/pnas.1011782107/-/DCSupplemental.
PNAS | October 5, 2010 | vol. 107 | no. 40 | 17087–17094
NEUROSCIENCE
Contributed by Peter H. Schiller, August 13, 2010 (sent for review July 10, 2010)
A
B
C
Fig. 1. (A) The basic connections a cone makes with ON and OFF ganglion cells
via ON and OFF bipolar cells. The ON bipolar cells have sign inverting synapses
as described in the text. (B) The basic connections rods, cones, bipolar cells,
horizontal cells, and amacrine cells make in the retina. [Reprinted from Progress in Retinal and Eye Research, Vol 15, Schiller PH, The ON and OFF channels
of the mammalian visual system, 173–195, Copyright (1995), with permission
from Elsevier]. (C) The responses of an ON and OFF monkey LGN cell before,
17088 | www.pnas.org/cgi/doi/10.1073/pnas.1011782107
The intracellular recording studies have also revealed that
photoreceptors, horizontal cells, and bipolar cells produce only
graded potentials. Center-surround organization appears at the
level of the bipolar cell (11). Action potentials are first seen in
some amacrine cells and are produced by all ganglion cells. The
axons of the ganglion cells project to a number of different nuclei
in the brain, the largest of which, in primates, is the lateral geniculate nucleus (LGN) of the thalamus. This is a structure with
several lamina in which the left and right eye inputs are segregated.
In addition, there is a propensity for the various retinal ganglion
cell types to terminate in different layers (6, 8, 9, 17). In a few
species, there is a clear or partial segregation of the ON and OFF
cells in the LGN (8, 9, 18, 19). Neurons from the LGN project to
the visual cortex. Although the receptive field characteristics of
LGN neurons are similar to those of retinal ganglion cells, in the
cortex several new properties are found (6, 20); the majority of
cells in primary visual cortex show selectivity for the orientation of
edges, and many cells respond selectively to the direction of motion of these edges.
Anatomical studies have revealed that the ON and OFF bipolar
cells are distinct structurally and make connections in the inner
retina in different subregions of the inner plexiform layer (IPL), as
depicted in Fig. 1B; the OFF bipolars make contact with OFF
retinal ganglion cell arbors in sublamina a of the IPL and ON
bipolars make contact with ON ganglion cells in sublamina b of the
IPL (7, 16, 21). The layout of the ON and OFF retinal ganglion
cells has been effectively examined in retinal whole mounts, in
which the retina is viewed as a flattened preparation. The dendritic
arbors of the ON and OFF ganglion cells, once properly labeled,
can readily be identified because they come into focus at different
depths within the specimen. Using such methods, Heinz Wässle
and collaborators discovered that the spacing of the arbors within
each of the ON and OFF cell classes, but not between them, is
highly orderly (22). This systematic arrangement suggests that the
ON and OFF systems provide separate, and probably independent, coverage of the visual field. The synapses bipolar cells make
in the inner retina are glutamatergic. Horizontal and amacrine
cells come in many different subtypes and use a variety of neurotransmitters that include gamma-aminobutyric acid (GABA), glycine, and acetylcholine. The diversity of horizontal and amacrine
cell types appears to decrease in higher mammals in which more
complex visual analysis is increasingly relegated to neocortex.
That nature has gone to such complexities to create the ON and
OFF systems suggests that great benefits must be reaped for the
analysis of visual information. The initial ideas were that the ON
system signals the onset of light and the OFF system the termination of light. As first suggested by Jung (23), another idea that
has gained some degree of acceptance was that the ON system
gives rise to the perception of brightness and the OFF system to
the perception of darkness. A third consideration was advanced by
more physiologically minded investigators, who suggested that the
ON and OFF systems have evolved to provide for the antagonistic
center-surround organization of receptive fields in retinal ganglion
cells and in the cortex (24). Two major schemes have been proposed as to how the preganglionic neural elements of the retina
connect to the ganglion cells to yield their antagonistic center/
surround organization. According to the first, the surround
mechanism is supplied by the lateral connections of the horizontal
and amacrine cells of the retina. According to the second, the
center-surround arrangement of the retinal ganglion cells is produced by convergent connections from ON and OFF bipolars (8, 9,
25). The data gathered during the past few years in primates favor
the idea that those cells of the retina that can be unequivocally
identified as being ON-center or OFF-center types form separate
pathways and do not interact extensively. The surround mecha-
during, and after the infusion of APB into the eye. APB blocks the ON cell response and has no significant effect on the OFF cell (25). (Reprinted by permission from Macmillan Publishers Ltd: Nature, 297:580–583, copyright 1982.)
Schiller
Physiological Studies Using 2-Amino-4-Phosphonobutyrate. The use
of a glutamate neurotransmitter agonist has provided an important
line of support for the claim that the ON- and OFF-center ganglion
cells form independent pathways to the central nervous system. This
substance, 2-amino-4-phosphonobutyrate (APB), was discovered
by Slaughter and Miller (32) to act differently on the ON and OFF
bipolar cells of the mudpuppy (Necturus maculosus) retina. By decreasing membrane conductance, APB produces prolonged hyperpolarization in the ON bipolar cells, as a result of which they
become unresponsive to subsequent light stimulation (32, 33).
Current evidence shows that ON bipolar cells have a specific
metabotropic glutamate receptor termed mGluR6 that is coupled
to a G protein. The activation of this receptor leads to the closing
of cGMP-gated cation channels by increasing the rate of cGMP
hydrolysis by a G protein-mediated process (34). The mGluR6
receptor responds selectively to L-2-amino-4-phosphonobutyrate
(35). In a remarkable recent study, Masu et al. (36) have succeeded
in generating KO mice that lacked mGluR6 expression and hence
lacked the ON system. This work further attests to the unique and
distinct nature of the ON bipolar cells and the ON system in the
mammalian retina.
Schiller
PNAS | October 5, 2010 | vol. 107 | no. 40 | 17089
INAUGURAL ARTICLE
Except for a transient initial excitatory response, the OFF
bipolars are largely unaffected by APB. As there is no ready uptake
mechanism for this artificial substance, it is effective in small
quantities and is broken down slowly. It seems to have little or no
direct effect on the synaptic networks of the inner plexiform layer.
Effect of APB on the responses of single cells in the mammal. To determine the effect of APB on the mammalian visual system, several
investigators have applied this substance to the retina while recording from various visual structures. It became immediately
evident that the effects of APB noted in the mudpuppy are similar
in the mammalian retina. When APB is administered in appropriate concentrations to the monkey eye, the ON response in
retinal ganglion cells is abolished whereas the OFF response is
largely unaffected (9, 24, 25, 37). Fig. 1C shows recordings made
from an ON and OFF cell in the LGN before, during, and after the
infusion of APB into the retina. The ON cell stops responding to
the visual stimulus presented in the receptive field of the cell
whereas the OFF cell continues to respond.
Having established that APB blocks the ON system in the
monkey as it does in the mudpuppy, investigators moved on to
determine to what extent the ON and OFF bipolar cells make interactive connections with the retinal ganglion cells to produce their
antagonistic center-surround organization. To do so, the center and
the surround of receptive fields can be selectively stimulated before
and after APB administration. Fig. 2 shows a typical result obtained
by recording in the parvocellular LGN of a monkey. The cells
shown had color-opponent characteristics and were consequently
stimulated with colored spots that preferentially activated the
center and the surround mechanism. The center mechanism was
activated with a small spot of the appropriate wavelength composition; the surround mechanism was activated briefly both when the
center was stimulated and during the off cycle using a large spot of
a different wavelength composition appropriate for the surround.
The inhibitory effect of the surround stimulation is evident for both
the ON and the OFF cell under normal conditions. Following administration of APB, the responses of the ON cell are eliminated
whereas the responses of the OFF cell, including the center-surround antagonism produced by the stimulus that activated the
surround mechanism, are mostly unaffected. These findings support the idea that the center-surround organization of retinal
ganglion cells and LGN cells is not a product of ON and OFF cell
interactions, but rather a product of the lateral networks of the
retina that involve the horizontal and perhaps the amacrine cells.
Thus the model of retinal organization these findings support is that
the ON- and OFF-center ganglion cells, most of which send their
axons to the LGN, form separate pathways (25, 37, 38). Also favoring this model is an elegant study by Mangel and Miller (39) in
which hyperpolarizing current, injected intracellularly into rabbit
horizontal cells, produced a decrease in the firing rate of ON
ganglion cells and an increase in OFF ganglion cells.
Effects of APB on ON/OFF cells. The ON/OFF cells that respond
transiently to both light increment and light decrement comprise
the third category of retinal ganglion cells that had been identified
by Hartline (3); these cells are thought to arise as a result of convergent input from the ON and OFF bipolar cells onto individual
retinal ganglion cells where the dendritic arbors of the ON/OFF
ganglion cell are bistratified. In the primate retina, the ON/OFF
retinal ganglion cells project extensively to the superior colliculus
(40). In many species, such cells also project into the geniculostriate
system (6, 41). Retinal administration of APB eliminates the response to light increment but not to light decrement in collicular
cells (42).
Effects of APB on single cells in area V1. The retinal input through the
LGN to primary visual cortex, commonly referred to as V1, is
transformed in a number of ways, as already noted, yielding neurons that are orientation and direction-specific (6, 20). Many of
the neurons receive convergent input from the left and right eyes.
V1 neurons are most effectively activated by edges with specific
orientations. The characteristics of V1 neurons were first revealed
by Hubel and Wiesel (20), who received the Nobel Prize in 1981.
NEUROSCIENCE
nism of these cells is a product of the lateral connections in the
retina rather than a product of an interactive connection between
the ON and OFF bipolar cells. In the following sections, three lines
of evidence will be considered in support of this view, which come
from anatomical, physiological, and behavioral studies.
When Ramon y Cajal et al. (2) examined the organization of the
retina after the duality of the rod and cone photoreceptors had been
established by Schultze (1), the evidence he gathered suggested to
him that these two systems form separate pathways to the central
nervous system. Subsequent studies have established, however,
that, for the most part, where the rods and cones coexist in any
region of the retina, their signals converge upon the retinal ganglion
cells (26, 27). Furthermore, current studies have shown that, unlike
for the cones, the rod system in some mammals—including the cat,
monkey, and human—has only ON-type rod bipolars. This has
raised some interesting questions about the manner in which the
rods might make their connections with the retinal ganglion cells.
The nature of this connectivity has been worked out in some detail
recently. The rod photoreceptor cells form sign-inverting synapses
with the rod ON bipolars (28). Examination of the connections of
the rods has also established that each rod ON bipolar cell contacts
many rod photoreceptors; thus the rods have been said to pool their
signals and, by doing so, form relatively large receptive field centers
(29). In the inner retina of the cat and probably the monkey, the rod
bipolars terminate in the inner portions of the inner plexiform layer,
but do not contact ganglion cells directly. Instead, they terminate on
amacrine cells, most commonly on the AII type. Each of these
amacrine cells in turn makes two major kinds of contacts: one is
a gap synaptic junction with ON cone bipolar cells and the other is
a glycinergic synaptic junction with OFF ganglion cells, as depicted
in Fig. 1B (28–30). This arrangement appears to accomplish for the
rods in the inner retina what is accomplished for the cones in the
outer retina: it turns the single-ended photoreceptor system into
a double-ended one. As a result of these connections, under darkadapted conditions when the cones are unresponsive, the ON
ganglion cells are excited by light increment and the OFF ganglion
cells by light decrement.
The organization of the receptive fields under light- and darkadapted conditions is quite different, as was first shown by Barlow
et al. (31). This difference, which was subject to considerable incredulity at the time, is now readily understandable. The receptivefield center under dark-adapted conditions is driven by the rods
through the bipolar and amacrine cells. The surround mechanism
is the product of those portions of bitufted horizontal cells that
make lateral connections only with the rods (16). As a result of this
arrangement, several superimposed receptive fields can be created
for any given patch of retina.
10 0
On-Center LGN Cell -- Normal
80
60
40
20
time
5 00
1000
1500
2000ms
On-Center LGN Cell -- APB
100
80
60
40
Number of spikes
20
ti me
100
500
1 0 00
15 00
2000ms
Off-Center LGN Cell -- Normal
80
60
40
20
time
100
500
1000
1 50 0
2000ms
Off-Center LGN Cell -- APB
80
60
40
20
ti me
5 00
10 00
1500
2000ms
R F c e n te r s tim u la tio n
R F s u r r o u n d s t im u l a tio n
Fig. 2. The responses of an ON and an OFF cell in the monkey LGN before
and after APB infusion into the eye when the center and the surround of the
receptive fields are stimulated with red and green spots of different sizes.
The surround activated by the large green spot is turned on briefly during
both the on and off cycles of the small red spot. APB application (Lower)
silences the ON ganglion cell for both center and surround stimulation. The
response of the OFF ganglion cell is unaffected; the cell retains its centersurround antagonism (25). (Reprinted by permission from Macmillan Publishers Ltd: Nature, 297:580–583, copyright 1982.)
Two major classes of cells they have identified in area V1 are the
simple and complex cells. Simple cells have receptive fields in
which there are spatially distinct ON and OFF regions, whereas
in complex cells the ON and OFF regions overlap spatially (6, 20,
43). When a properly oriented bar is swept across the receptive
field of V1 complex cells, a response is elicited by both the light
and dark edges of the bar as it sweeps across the receptive field.
This is shown in Fig. S1A. When the ON channel is inactivated by
APB infusion into the eye, the light edge response is eliminated but
the dark edge response remains. This indicates that the light edge
response is caused by the input from the ON system and the dark
edge response to a result of the input from the OFF system.
It has been proposed that the direction and orientation specificity of V1 neurons is a product of the interaction between the ON
and OFF systems. An alternative hypothesis proposed was that
inhibitory intracortical circuitry achieves these attributes in V1
cells (6, 20, 43). Inactivation of the ON channel with APB shows
that direction specificity and orientation selectivity remain unaffected. Fig. S1B shows the responses of a complex cell in monkey
V1 that under normal conditions responds preferentially to
17090 | www.pnas.org/cgi/doi/10.1073/pnas.1011782107
downward motion. After APB infusion, the leading light edge
response is blocked but the directional selectivity of the cell persists. In Fig. S1C, orientation tuning curves are shown before and
after APB infusion. The orientation tuning function is unaffected
by the APB block. These findings indicate that orientation and
direction specificities are a product of intracortical circuitry rather
than interactions between the ON and OFF channels. That retinal
APB infusion does not significantly affect orientation and direction selectivities in area V1 has also been established in the cat
by Sherk and Horton (44).
Behavioral Studies of ON and OFF Channels Using APB. Further
insights into the role of the ON and OFF channels in vision come
from behavioral studies in which the visual capacities of animals
were assessed before and after the ON channel was blocked with
APB. In monkeys, the most notable deficit observed under lightadapted conditions was for the detection of stimulus spots made
visible by virtue of increases in light energy; that is, spots that are
perceived as brighter than the background (9, 24, 45, 46). There
was little or no deficit in the detection of spots that were darker
than the background. Examples of this are shown in Fig. 3, in which
both percent correct and reaction-time data are presented. Following APB administration the percent correct responses for the
detection of light increments decreases dramatically, which is accompanied by large increases in the response latencies; performance with stimuli seen by virtue of light decrement is unaffected.
These observations fit with the idea that the ON channel is sensitive
to light incremental stimuli and signals lightness, whereas the OFF
channel is sensitive to light decrement and signals darkness—an
idea, as already noted, that had been advanced earlier by Jung (23).
Behavioral studies in monkeys have also shown that, under
dark-adapted conditions, when only the rods are functional, APB
blocks the detection of stimuli seen by virtue of either light increment or light decrement; in other words, the rod system is
blocked in its entirety and, consequently, the animal becomes
night-blind (9, 47). These findings provide additional support for
the claim that the rod bipolars in the primate are all ON types.
Midget and Parasol Channels
Anatomy and Physiology of Midget and Parasol Systems. In 1966,
Enroth-Cugell and Robson (48) published an influential article
showing that, in the cat, they distinguished three distinct classes of
retinal ganglion cells, which they called the X, Y, and W. Subsequently, it has been found that similar subclasses of retinal
ganglion cells exist in most mammalian species (49, 50). In the
primate, two of these classes were named the midget and parasol
systems. The ganglion cells of the midget system, as the name
implies, are quite small. The parasol cells, by contrast, are much
larger, with their dendritic arbors and receptive field diameters
being approximately three times greater than the midget cells. The
axons of the parasol ganglion cells are larger and have faster
conduction velocities than do the axons of the midget cells. Fig. 4A
provides a cross-sectional view of the midget and parasol cells as
created by Polyak (51). Fig. 4B shows the dendritic arbor arrangement of these cells as seen in a whole-mount preparation by
Watanabe and Rodiek (52).
The midget and parasol cells come in both ON and OFF
subvarieties. The input to the receptive field center of the midget
cells of the monkey is composed of a single cone in the central
retina. Thus, a single cone will give rise to both an ON and OFF
bipolar cell, as shown in Fig. 1 A and B. By contrast, the receptive
field center of the parasol cells is comprised of several cones that
are not segregated according to type (16, 50). The receptive field
sizes of these two classes of cells are quite different as are their
inputs. The excitatory center of the midget cells in central retina
is comprised of a single cone, thereby rendering them color-selective. The excitatory center of the parasol ganglion cell receptive fields is comprised of several cones, as is the surround,
indicating that these cells cannot convey information about
color. The parasol cells, however, are not insensitive to stimuSchiller
Midget cells
Parasol cells
INAUGURAL ARTICLE
A
Light
Increment
100
Before APB
injection
60
60
40
40
30
20
20
Mean = 253ms
10
After APB
injection
60
100
80
60
50
30
20
20
Mean = 406ms
10
100 200 300 400 500 600 700
Light
Decrement
Percent Correct Detection
80
Saccadic latency distribution
Before APB
injection
60
50
60
40
40
30
20
20
Mean = 249ms
10
After APB
injection
60
100
80
parasol cell
dendritic arbor
Fig. 4. (A) Cross-section of Golgi-stained midget and parasol cells (51).
[Reprintedwith permission from Polyak SL (1957) The vertebrate visual system: Its origin, structure, and function and its manifestations in disease with
an analysis of its role in the life of animals and in the origin of man, preceded by a historical review of investigations of the eye, and of the visual
pathways and centers of the brain (University of Chicago Press, Chicago).] (B)
The dendritic arbors of a midget and parasol cell at comparable eccentricities
(52). [Reprinted from Watanabe M, Rodieck RW (1989) Parasol and midget
ganglion cells of the primate retina. J Comp Neurol 289:434–454 (Copyright
1989 with permission from Wiley).]
Reaction Time in milliseconds
100
midget cell
dendritic arbor
40
40
50
60
40
40
30
20
20
Mean = 251ms
10
100 200 300 400 500 600 700
Reaction Time in milliseconds
Fig. 3. Percent correct performance and eye-movement reaction times
made to light and dark stimuli presented in various locations of the visual
field to which a trained rhesus monkey had to make saccadic eye movements
to be rewarded. Following APB administration, percent correct performance
declines and reaction times increase to a bright spot. Percent correct responses
and reaction times to a dark spot are unaffected.
lation by different wavelengths; they are capable of responding
to chrominance changes as long as the stimuli contain reasonable
color contrast. The signals so generated can lead to the perception of stimuli without leading to specific color sensations.
One might imagine that, to the parasol system, the world looks
a bit like a black-and-white movie.
It is generally believed that the midget and parasol systems
have their own set of ON and OFF bipolars. This arrangement in
the midget and parasol cells makes it evident that there is a much
higher number of bipolar cells in the primate retina than there
are cone photoreceptors, yielding a ratio greater than three to
one (16, 53). The receptive fields of the parasol ganglion cells at
any given retinal eccentricity are approximately three times
Schiller
B
50
larger in diameter, as are their dendritic arbors, and they respond to visual stimuli in a transient fashion; midget cells, by
contrast, produce a rather sustained response.
The ability to experience different colors lies within the domain
of the midget system (54–58). Until recently it was believed that the
midget system is organized in a pure color-opponent fashion. Thus
it was assumed that any given midget cell whose receptive field
center is made up of a long-wavelength cone, has a surround that is
driven by middle-wavelength cones. Serious questions have been
raised during the past few years about the validity of this inference.
It has been shown that the horizontal cells of the retina, even for
the midget system, are “promiscuous”: they make contact with all
cones within the area they sample (16). If color opponency is the
product of interaction between the center and the surround
mechanism created by the horizontal cells, it appears that the
opponency is not pure; it does not arise by pitting red cones against
green ones (red/green opponency) and blue cones against red plus
green ones (blue/yellow opponency), but by pitting individual
short-, middle-, and long-wavelength cones forming the center
mechanism against all cones that feed into the surround mechanism. That this is a computationally viable alternative has been
established by Lennie et al. (59). It must be recognized, however,
that possible interconnections in the inner retina could provide
a clear color-opponent system. The midget and parasol cells of the
retina project predominantly to the LGN in the trichromatic primate, where the midget cells make connections within the parvocellular layers and the parasol cells within the magnocellular layers.
In turn, the cells in these two sets of layers project to the striate
cortex, where they terminate predominantly in layers 4cα and 4cβ,
respectively. Within the striate cortex, some cells, after a cascade of
connections, receive a convergent input from these two systems
(60). Some of the cortical cells, however, are driven exclusively by
one or the other system, although there is commonly a convergence
of the ON and OFF subtypes, as has already been noted. Recent
studies of the connections from the striate cortex to extrastriate
PNAS | October 5, 2010 | vol. 107 | no. 40 | 17091
NEUROSCIENCE
Percent Correct Detection
80
Saccadic latency distribution
regions have shown that the input to area MT is dominated by the
parasol system, whereas the input to area V4 is mixed (61, 62).
The ratio of the midget and parasol cells changes notably as
a function of eccentricity. In the center of the fovea (sometimes
called the foveola), there are virtually no parasol cells. Near the
fovea, the midget cells outnumber the parasol cells by approximately eight to one. This ratio changes gradually until, in the far
peripheral representation, they become equally represented (63).
This arrangement is clearly reflected in the LGN. In central representation, out to approximately 18°, the LGN most commonly
has six layers. The dorsal four layers are called parvocellular and
contain medium-sized cells. These layers receive input from the
retinal midget cells (64, 65). The ventral two layers are called
magnocellular and contain large cells that receive input from the
retinal parasol cells. Beyond 18° of the visual field representation
in the LGN, the layers are reduced to four: two parvocellular and
two magnocellular ones. Thus, in central representation, the
midget cells are far more numerous than the parasol cells, whereas
in peripheral representation, they are equal in number (60).
Behavioral Studies Examining Functions of Midget and Parasol
Systems. A variety of behavioral experiments have been carried
out that examined the functions of the midget and parasol systems.
Some of these experiments have used visual stimulus conditions
that selectively activated the midget or parasol systems (50, 66–68).
Another set of experiments blocked the midget or parasol systems
by making selective lesions in the parvocellular and magnocellular
portions of the LGN (49, 50, 67).
To assess the role of these two systems in vision, monkeys had
been trained to perform a variety of visual tasks using detection
and discrimination tasks. Each trial began with a fixation spot
appearing in the center of a monitor the monkey faced. Upon
fixation, as determined by monitoring the monkeys’ eye movements, either a single stimulus appeared (the detection paradigm)
or an array of stimuli was presented, one of which, the target, was
different from the others, called distractors (i.e., oddity task). The
monkey was rewarded for making a saccadic eye movement directly to the target. The contrast, size, color, and/or shape of the
target or the distractors was systematically varied. The target was
presented in intact regions of the visual field or in regions where
the midget or the parasol system was blocked (50, 67). Fig. S2
shows data obtained from a monkey that assessed color, texture,
and pattern processing. Fig. S2A shows data obtained in a color
discrimination task using the oddity task. The target in this case
had a different color from that of the isoluminant distractors of
a different color. The data show that, after a midget system block,
the monkey was no longer able to make color discriminations.
Conversely, the parasol system block did not have much of an effect on color discrimination. These findings establish the fact that
color processing is accomplished by the midget system. Fig. S2B
shows the texture detection task. A single target appeared on
a textured background with the target consisting of a small square
area within which the diagonal lines were reversed relative to the
background. Blocking the midget system brought performance to
chance, whereas blocking the parasol system had no effect on
texture detection. Fig. S2C shows a pattern discrimination task; the
target is different from the distractors by having checkerboards of
a lower spatial frequency. The data show that a midget system
block eliminates the ability of the monkey to discriminate fine
differences in the perception of patterns whereas a parasol system
block has no significant effect on pattern perception. In contrast
with these dramatic effects, when monkeys were tested for
brightness discrimination, it was found that this capacity was unaffected by a midget or parasol block, indicating that both these
systems can process this capacity.
Fig. S3 shows data obtained on stereoscopic depth perception,
motion detection, and flicker detection. Stereoscopic depth perception has been studied extensively using random-dot stereograms as initially developed by Julesz (68, 69). To study this in
monkeys, the monkeys were trained to look through a stereoscope.
17092 | www.pnas.org/cgi/doi/10.1073/pnas.1011782107
A small region in the stereogram was arranged to appear in depth
by virtue of the disparity introduced. A saccadic eye movement
made to this region was rewarded. The top section of Fig. S3 shows
data obtained using this procedure. Following a midget system
block, the monkeys’ ability to perform on this task was devastated.
The deficit was complete at the lowest disparity. There was no
deficit when the parasol system was blocked. These findings suggest that the midget system plays a central role in stereopsis, especially at high spatial frequencies and low disparities. The parasol
system, however, seems to be able to contribute to this mechanism
at low spatial frequencies and high disparities.
To study motion, the display consisted of an array of randomly
placed small dots. On each trial in a small region of the visual field,
the dots were set in motion. A saccadic eye movement made to that
location was rewarded. The contrast of the dots was systematically
varied. The data in the center section of Fig. S3 show that a midget
system block had no effect on motion discrimination whereas the
block of the parasol system created a major deficit. In another
study, depth analysis based on motion parallax was examined,
which showed that the parasol system plays a central role in processing this information (68).
The bottom section of Fig. S3 shows data obtained when the
task was to discriminate flicker from nonflicker. To do so, an array
of light-emitting diodes (LEDs) was used, the flicker rate of which
could be varied over an extensive range. The data show that, when
the parasol system is blocked, a major deficit arises in flicker perception. These data establish that the parasol system plays a central
role in temporal processing that includes motion and flicker.
Based on these data, we can conclude that the midget system
plays a central role in color, pattern, texture, and stereoscopic
depth perception whereas the parasol system plays a central role in
motion perception, flicker perception, and depth processing based
on motion parallax. Both systems contribute to brightness perception. As a result of this work, we believe the midget and parasol
systems have evolved to extend the range over which visual information can be effectively processed. The midget system extends
it in the high spatial frequency and wavelength domains whereas
the parasol system extends it in the temporal domain.
Accessory Optic System
The accessory optic system (AOS) originates in the retina. Its
ganglion cells project to three target nuclei in the anterior portion
of the midbrain: the dorsal, medial, and lateral terminal nuclei
(70–72). The morphology of retinal ganglion cells projecting to the
terminal nuclei was first studied in the pigeon by Karten and collaborators in the 1970s (72–74). They showed that these were the
displaced ganglion cells of Dogiel whose distribution on the retinal
surface was remarkably orderly. In the rabbit, which has approximately 350,000 ganglion cells, there are approximately 6,000 to
7,000 directionally selective cells of Dogiel that project to the
nuclei of the AOS (75).
The responses of direction-specific retinal ganglion cells in the
rabbit retina were first studied by Barlow and Levick (76). Based
on their work and that of others, it was established that those
direction-selective cells of the rabbit retina that respond best to
very slow velocities of image motion (0.1–1°/s) are all ON types
(75). They have a trilobed spatial distribution of preferred excitatory directions (77). Striking about these observations was the
discovery that the three axes of direction selectivity correspond
to the planes of three principal axes of the semicircular canals.
The neurons in the terminal nuclei of the rabbit to which the
displaced ON-type direction selective cells of Dogiel project
have similar properties but have much larger receptive fields.
The preferred direction of cells in the dorsal terminal nucleus
was found to be from posterior to anterior in the horizontal
plane. Cells in the medial and lateral terminal nuclei had upward
or downward excitatory directions, both with a posterior component. Inhibition plays a prominent role in the AOS as approximately 50% of the cells have positive glutamic acid decarboxylase
reactions (78, 79). The terminal nuclei project to the dorsal cap of
Schiller
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Schiller
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INAUGURAL ARTICLE
Other Parallel Channels Originating in the Retina
In addition to the systems discussed so far, several others have
been found to originate in the retina. These include the so-called
W system, directionally selective cells other than those that project
to the terminal nuclei, the pupillary system, a small complement of
cells that project to the hypothalamus, and the so-called koniocellular (K) system.
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also to the pretectal nuclei. Prominent among the pretectal nuclei is the nucleus of the optic tract that receives input from those
direction-selective retinal ganglion cells that respond to higher
velocities and come in both ON and OFF subtypes. Another
visually driven structure in the pretectum is the olivary nucleus,
which is involved in the generation of the pupillary reflex. As
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olivary pretectal nucleus. However, when the pupillary reflex was
examined in rabbit and monkey following APB blockage of the
ON system in the retina, the reflex was only mildly impaired. This
suggests that other pathways and the OFF system can make
a contribution to light activation of the ciliary muscles (42).
Yet another class of retinal ganglion cells that has been
identified are the K cells that express αCAM kinase/calbindin.
This system has been extensively studied; several reviews describe it in detail (91–98). Many of the K ganglion cells have
bistratified dendritic arbors, as a result of which they receive both
ON and OFF inputs from bipolar cells. Some of them are driven
by blue cones. A subgroup of these cells project to the intralaminar layers of the LGN, from which the projections are predominantly to the upper layers of area V1 (91–93, 95).
On the basis of the foregoing it is evident that, from the single
layer of photoreceptors, a series of parallel pathways are created
by the stunningly complex and elaborate circuitry of the retina.
There are many different retinal ganglion cells that project selectively to a variety of central nuclei and are involved in different aspects of visual information processing. Furthermore, in
some of these systems, the same set of retinal ganglion cells can
carry several kinds of different messages. For example, the
midget cells, when excited in the daytime by the cones, can carry
information about both color and luminance; at night, when they
are driven by the rods, the receptive fields of these same cells
take on a different configuration and convey messages about only
luminance. This arrangement renders these cells multifunctional.
NEUROSCIENCE
Kooy of the inferior olive (80, 81), which gives rise to climbing
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The dorsal cap of the inferior olive also receives a projection from
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and others (82, 83). This structure, like the terminal nuclei,
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a different class that gives both ON and OFF responses and
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generation of tracking eye movements for large stimulus constellations. This curious arrangement of having only ON-type cells
that project into the AOS in the rabbit is not found in all species.
Although in the turtle and zebrafish, similar results have been
obtained (85, 86), this was not the case in the cat or monkey. In
these species, only mild effects of APB were found on OKN, which
was restricted to high spatiotemporal frequencies (84). This suggests that in these species both the ON and OFF channels contribute to the OKN. In the goldfish, APB also failed to abolish the
OKN (87); it was subsequently discovered, however, that in teleosts there are two mechanisms of ON-bipolar generation, one of
which is not sensitive to APB (88).
On the basis of these observations, a specific function for the
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retinal surface. The detection of this slip by the direction- and
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