Download Making the retina approachable

J Neurophysiol 93: 3034 –3035, 2005;
doi:10.1152/classicessays.00029.2005.
Editorial Focus
ESSAYS ON APS CLASSIC PAPERS
Making the retina approachable
Gary Matthews
Department of Neurobiology and Behavior, State University of New York at Stony Brook, Stony Brook, New York
OVER 50 YEARS AGO, the Journal of Neurophysiology published a paper that ranks as one of the milestones in sensory
physiology: Stephen Kuffler’s (5) discovery of the centersurround receptive field of retinal ganglion cells, with antagonism between the effects of light falling on the central and
surrounding portions of the field. It was immediately obvious,
as Kuffler explicitly pointed out, that this receptive field
organization would form the basis for spatial contrast enhancement. It was not obvious, however, how this spatial processing
might arise within the retina. Sixteen years later, the Journal of
Neurophysiology also published an influential pair of papers by
Frank Werblin (Fig. 1) and John Dowling (Fig. 2) on the
synaptic organization of the retina (3, 8), and the broad strokes
of the basis for Kuffler’s (Fig. 3) findings began to take shape.
(Photographs courtesy of E. Kravitz.)
The period from the mid-1960s to the mid-1970s witnessed
an explosion of information about the electrophysiology of all
the major cell types involved in retinal signal processing, from
photoreceptors through horizontal, bipolar, and amacrine cells
to the ganglion cells. A number of laboratories contributed to
this explosive growth, of course, but the papers by Werblin and
Dowling figured prominently. In a single classic figure (Fig. 3,
Ref. 8), they provided a concise yet complete overview of the
response to light stimuli at each level of retinal processing. The
foundation established in these papers is still being built on:
both papers received multiple citations in research publications
in 2003–2004, indicating their continuing influence today.
When the Werblin and Dowling papers appeared, it had
already been clear for decades that retinal ganglion cells—the
output cells of the retina whose axons form the optic nerve—
represent visual information in distinct ON and OFF pathways,
which fire at light onset and offset, respectively. Kuffler’s (5)
remarkable paper immediately focused attention on the importance of spatial factors, as well. How might the ON and OFF
Address for correspondence: G. Matthews, Dept. of Neurobiology and
Behavior, SUNY at Stony Brook, Stony Brook, NY 11794.
3034
pathways arise within the retina? What synaptic interactions
give rise to the concentric receptive fields of the ganglion cells?
Answering these questions required detailed neurophysiological analysis of the retinal neurons interposed between the
receptor cells and the ganglion cells, a task that occupied
retinal neurophysiologists for the next 20 years after Kuffler’s
paper.
Cajal (1) had laid the anatomic groundwork for understanding the synaptic organization of the retina in the 19th century,
with his extensive characterization of the cell types and the
beautifully layered structure of the vertebrate retina. Given this
background of detailed anatomic information, why was it so
hard to move from ganglion cells to photoreceptors in the
neurophysiological analysis of retinal function? In two words:
action potentials. Or rather their lack. Kuffler could monitor
ganglion cell activity with extracellular recordings of action
potentials, but most of the other retinal neurons do not fire
action potentials and rely instead on graded changes in membrane potential, as shown clearly by Werblin and Dowling (8).
FIG.
1.
Frank Werblin.
0022-3077/05 $8.00 Copyright © 2005 The American Physiological Society
http://www.the-aps.org/publications/classics
Downloaded from http://jn.physiology.org/ by 10.220.33.3 on November 19, 2016
This essay looks at the historical significance of three APS classic papers that are
freely available online:
Kuffler SW. Discharge patterns and functional organization of mammalian
retina. J Neurophysiol 16: 37– 68, 1953 (http://jn.physiology.org/cgi/reprint/16/1/37).
Dowling JE and Werblin FS. Organization of retina of the mudpuppy, Necturus maculosus. I. Synaptic structure. J Neurophysiol 32: 315–338, 1969 (http://jn.
physiology.org/cgi/reprint/32/3/315).
Werblin FS and Dowling JE. Organization of the retina of the mudpuppy,
Necturus maculosus. II. Intracellular recording. J Neurophysiol 32: 339 –355, 1969
(http://jn.physiology.org/cgi/reprint/32/3/339).
Editorial Focus
ESSAYS ON APS CLASSIC PAPERS
FIG.
3.
Stephen Kuffler.
receptive field, but ON bipolar cells depolarize. The molecular
basis for this separation is still under study 35 years later. It
also became clear from Werblin and Dowling’s and Kaneko’s
work that bipolar cells, like ganglion cells, have center-surround receptive fields, with opposing responses to illumination
in the center and in the surrounding regions. Again, the
underlying mechanisms are still being studied.
When John Dowling (2) published a book about the retina in
1987, he chose the title, The Retina: An Approachable Part of
the Brain, to emphasize that the retina is fertile ground for
working out the mechanisms of information processing in the
central nervous system. Kuffler’s seminal publication and the
Werblin and Dowling papers in the Journal of Neurophysiology unquestionably played a significant role in making the
retina so approachable.
REFERENCES
FIG.
2.
1. Cajal SR. La rétine des vertébrés. La Cellule 9: 17–257, 1893.
2. Dowling JE. The Retina: An Approachable Part of the Brain. Cambridge,
MA: Belknap Press, 1987.
3. Dowling JE and Werblin FS. Organization of retina of the mudpuppy,
Necturus maculosus. I. Synaptic structure. J Neurophysiol 32: 315–338,
1969.
4. Kaneko A. Physiological and morphological identification of horizontal,
bipolar and amacrine cells in goldfish retina. J Physiol 207: 623– 633, 1970.
5. Kuffler SW. Discharge patterns and functional organization of mammalian
retina. J Neurophysiol 16: 37– 68, 1953.
6. Svaetichin G. The cone action potential. Acta Physiol Scand 29 (Suppl
106): 565– 600, 1953.
7. Tomita T. Electrophysiological study of the mechanisms subserving color
coding in the fish retina. Cold Spring Harb Symp Quant Biol 30: 559 –566,
1965.
8. Werblin FS and Dowling JE. Organization of the retina of the mudpuppy,
Necturus maculosus. II. Intracellular recording. J Neurophysiol 32: 339 –
355, 1969.
John Dowling.
J Neurophysiol • VOL
93 • JUNE 2005 •
www.jn.org
Downloaded from http://jn.physiology.org/ by 10.220.33.3 on November 19, 2016
Monitoring these signals requires intracellular recording,
which is quite challenging in the small cells of the vertebrate
retina. Graded hyperpolarizations in response to illumination—
the so-called S-potentials— had been described much earlier in
intracellular recordings from the retina by Svaetichin (6).
However, a great deal of confusion reigned about the origin of
these responses (which turned out to arise from horizontal
cells) and whether they arose from neurons or glia. Indeed,
because the resting potentials of retinal neurons are commonly
not very negative and their light responses are small and
graded, there was serious concern that the S-potentials might
actually be extracellular field potentials and not intracellular
recordings at all. Given this uncertainty, it is perhaps not
surprising that the discovery of hyperpolarizing light responses
of vertebrate photoreceptors (7) came only a few years before
the Werblin and Dowling papers.
As is commonly true in neurophysiology, the selection of the
experimental preparation was an important part of Werblin and
Dowling’s success. Like many of their compatriots in the early
days of retinal neurophysiology (and today), Werblin and
Dowling turned to a cold-blooded vertebrate, the mudpuppy
(Necturus maculosus), in their case, because the large neurons
in these animals facilitate intracellular recording. To establish
which cell class gives rise to which response type, they intracellularly stained cells with Niagara Sky Blue to mark the
recording site. In similar work done contemporaneously in
goldfish retina, Aki Kaneko (4) stained cells with the then new
dye Procion Yellow, which had the advantage of diffusing
throughout the stained cell to better reveal the complete morphology. From these papers, it was finally clear that the ON
and OFF visual pathways arise in bipolar cells: OFF bipolar
cells hyperpolarize to light applied in the center of their
3035