Kuffler at a laboratory picnic,
taken around 1965.
tween the receptors and bipolars, and amacrine cells between bipolars
and retinal ganglion cells. (See the drawing of these direct and indirect
connections on this page). These connections were already worked out in much detail
by Ramon y Cajal around 1900. The direct path is highly specific or compact,
in the sense that one receptor or only relatively few feed into a bipolar
cell, and only one or relatively few bipolars feed into a ganglion cell. The indirect
path is more diffuse, or extended, through wider lateral connections. The
total area occupied by the receptors in the back layer that feed one ganglion cell
in the front layer, directly and indirectly, is only about one millimeter.
That area, as you may remember from Chapter i, is the receptive field of the ganglion
the region of retina over which we can influence the ganglion cell's
firing by light stimulation.
This general plan holds for the entire retina, but the details of connections vary markedly between the fovea, which corresponds to exactly where
we are looking—our center of gaze, where our ability to make out fine
detail is highest—and the far outer reaches, or periphery, where vision
becomes relatively crude. Between fovea and periphery, the direct part of the path
from receptor to ganglion cell changes dramatically. In and near the fovea,
the rule for the direct path is that a single cone feeds a single bipolar cell,
and a single bipolar in turn feeds into one ganglion cell. As we go progressively
farther out, however, more receptors converge on bipolars and more bipolars
converge on ganglion cells. This high degree of convergence, which we find
over much of the retina, together with the very compact pathway in and near
the very center, helps to explain how there can be a 125:1 ratio of receptors
to optic nerve fibers without our having hopelessly crude vision.
The general scheme of the retinal path, with its direct and indirect
components, was known for many years and its correlation with visual acuity
long recognized before anyone understood the significance of the indirect
path. An understanding suddenly became possible when the physiology of ganglion cells began to be studied.
RECEPTIVE FIELDS OF RETINAL
OUTPUT OF THE EYE
In studying the retina we are confronted with two main problems:
First, how do the rods and cones translate the light they receive
and then chemical, signals? Second, how do the subsequent cells in
the next two layers—the bipolar, horizontal, amacrine, and ganglion cells—interpret this information? Before discussing the physiology of the receptors
and intermediate cells, I want to jump ahead to describe the output of the
represented by the activity of the ganglion cells. The map of the
receptive field of a cell is a powerful and convenient shorthand description of the
cell's behavior, and thus of its output. Understanding it can help us to understand
why the cells in the intermediate stages are wired up as they are, and will
help explain the purpose of the direct and indirect paths. If we know what ganglion
cells are telling the brain, we will have gone far toward understanding the
Around 1950, Stephen Kuffler became the first to record the responses
of retinal ganglion cells to spots of light in a mammal, the cat. He
was then working at the Wilmer Institute of Ophthalmology at the Johns Hopkins
Hospital. In retrospect, his choice of animals was lucky because the
cat's retina seems to have neither the complexity of movement responses we find
in the frog or rabbit retina nor the color complications we find in the retinas
birds, or monkeys. Kuffler used an optical stimulator designed by
Samuel Talbot. This optical device, a modified eye doctor's ophthalmoscope,
made it possible to flood the retina with steady, weak, uniform background
light and also to project small, more intense stimulus spots, while directly
observing both the stimulus and the electrode tip. The background light made
it possible to stimulate either rods or cones or both, because only the cones
work when the prevailing illumination is very bright, and only the rods work
in very dim light. Kuffler recorded extracellularly from electrodes inserted through
the sclera (white of the eye) directly into the retina from the front.
He had little difficulty finding retinal ganglion cells, which are just under the
surface and are fairly large.
With a steady, diffuse background light, or even in utter darkness,
most retinal ganglion cells kept up a steady, somewhat irregular firing
at rates of from 1to 2 up to about 20 impulses per second. Because
one might have expected the cells to be silent in complete darkness, this firing
itself came as a surprise.
By searching with a small spot of light, Kuffler was able to find
a region in the retina through which he could influence—increase or suppress—the
retinal ganglion cell's firing. This region was the ganglion cell's receptive
field. As you might expect, the receptive field was generally centered at or
very near the tip of the electrode. It soon became clear that ganglion cells were
of two types,
and for reasons that I will soon explain, he called them on-center
cells and offcenter cells. An on-center cell discharged at a markedly increased
rate when a small spot was turned on anywhere within a well-defined area in or
near the center of the receptive field. If you listen to the discharges of
such a cell over a loudspeaker, you will first hear spontaneous firing, perhaps an occasional click, and then, when the light goes on, you will hear a barrage of
impulses that sounds like a machine gun firing. We call this form of response
an on response. When Kuffler moved the spot of light a small distance away
from the center of the receptive field, he discovered that the light suppressed
the spontaneous firing of the cell, and that when he turned off the light the
cell gave a brisk burst of impulses, lasting about i second. We call this entire
suppression during light and discharge following light—an off
response. Exploration of the receptive field soon showed that it was cleanly subdivided
into a circular on region surrounded by a much larger ring-shaped off region.
The more of a given region, on or off, the stimulus filled, the greater
was the response, so that maximal on responses were obtained to just the
right size circular spot, and maximal off responses to a ring of just the right
dimensions (inner and outer diameters). Typical recordings of responses to such
stimuli are shown on this page. The center and surround regions interacted in
an antagonistic way: the effect of a spot in the center was diminished by shining
a second spot in the surround—as if you were telling the cell to fire
faster and slower at the same time. The most impressive demonstration of this interaction
between center and surround occurred when a large spot covered the entire
receptive field of the ganglion cell. This evoked a response that was much weaker
than the response to a spot just filling the center; indeed, for some cells
the effects of stimulating the two regions cancelled each other completely.
An off-center cell had just the opposite behavior. Its receptive field
consisted of a small center from which off responses were obtained, and a surround
that gave on responses. The two kinds of cells were intermixed and seemed
to be equally common. An off-center cell discharges at its highest rate
in response to a black spot on a white background, because we are now illuminating
only the surround of its receptive field. In nature, dark objects are probably
just as common as light ones, which may help explain why information from
the retina is in the form of both on-center cells and off-center cells.
If you make a spot progressively larger, the response improves until
the receptive-field center is filled, then it starts to decline as more
and more of the surround is included, as you can see from the graph on the next page.
With a spot covering the entire field, the center either just barely wins
out over the surround, or the result is a draw. This effect explains why neurophysiologists before Kuffler had such lack of success: they had recorded from these
cells but had generally used diffuse light—clearly far from the ideal
You can imagine what a surprise it must have been
to observe that shining a flashlight directly into the eye of an animal evoked such feeble responses
or no response at all. Illuminating all the receptors, as a flashlight surely
does, might have been expected to be the most effective stimulus, not the least.
The mistake is to forget how important inhibitory synapses are in the nervous
With nothing more than a wiring diagram such as the one on page
7, we cannot begin to predict the effects of a given stimulus on any given
cell if we do not know which synapses are excitatory and which are inhibitory.
In the early 1950s, when Kuffler was recording from ganglion cells, the importance of inhibition in the nervous system was just beginning to be realized.