To record from a cell in the nervous sys-
tem is one thing: it is another to record
from a cell and know exactly what kind of
cell it is. This microscopic picture shows a
single bipolar cell in the retina of a gold-
fish, recorded in 1971 by Akimichi
Kaneko, then at Harvard Medical School.
The fact that it is a bipolar cell and not an
amacrine or horizontal cell was proven by
injecting a fluorescent dye, procyon yel-
low, through the microelectrode. The dye
spread throughout the cell, revealing its
shape. In this cross section, receptors are
on top.

                        BIPOLAR CELLS AND
                             HORIZONTAL CELLS
Horizontal cells and bipolar cells occur, along with amacrine cells,
in the middle layer of the retina. The bipolar cells occupy a strategic position in
the retina, since all the signals originating in the receptors and arriving at the
ganglion cells must pass through them. This means that they are a part of both
the direct and indirect paths. In contrast, horizontal cells are a part of the
indirect path only. As you can see from the diagram on page 38, horizontal
cells are much less numerous than bipolar cells, which tend to dominate the
middle layer.
Before anyone had recorded from bipolar cells, the big unknown was
whether they would prove to have center-surround receptive fields, as gan-
glion cells do, and come in two types, on center and off center. If the answer
was yes, it would almost certainly mean that the organization discovered by
Kuffler for ganglion cells was a passive reflection of bipolar-cell organization.
The knowledge that the receptive fields of bipolar cells were indeed center-
surround and were of two types came from intracellular recordings first made
by John Dowling and Frank Werblin at Harvard Biological Laboratories and
by Akimichi Kaneko at Harvard Medical School. The next question is how
these receptive fields are built up. To answer it we have to begin by examining
the connections of receptors, bipolar cells, and horizontal cells.
The bipolar cell sends a single dendrite in the direction of the receptors. This
either synapses with one receptor (always a cone) or it splits into branches that
synapse with more than one receptor. When more than one receptor feeds into
a single bipolar cell, they collectively occupy a relatively small area of retina. In
either case, these receptors must account for the receptive-field center, because
the area they occupy matches the field center in size. The next question is
whether the synapses between receptors and bipolar cells are excitatory or
inhibitory, or both.
Bipolar cells, like receptors and horizontal cells, do not fire impulses, but we
still speak of an on response, meaning a depolarization to light and therefore
increased transmitter release from the cell's terminals, and an off response, to
imply hyperpolarization and decreased release. For the off-center bipolars
the synapses from the receptors must be excitatory, because the receptors
themselves are turned off (hyperpolarized) by light; for the on-center bipolars
the synapses must be inhibitory. To see why (if you, like me, find this confus-
ing), you need only think about the effects of a small spot of light. Receptors
are active in the dark: light hyperpolarizes them, turning them off. If the
synapse is excitatory, the bipolar will have been activated in the dark, and will
likewise be turned off by the stimulus. If the synapse is inhibitory, the bipolar
will have been suppressed in the dark, and the light, by turning off the recep-
tor, will relieve the suppression of the bipolar cell—that is, the bipolar cell will
be activated. (No one said this would be easy.)
Whether the receptor-to-bipolar synapse is excitatory or inhibitory could
depend on either the transmitter the receptor releases or the nature of the
channels in the bipolar cell's postsynaptic membrane. At present no one thinks
that one receptor releases two transmitters, and much evidence favors the idea
that the two biolar types have different receptor molecules.
Before we discuss where the receptive-field surrounds of the bipolar cells
come from, we have to consider the horizontal cells.
Horizontal cells are important because they are probably at least in part
responsible for the receptive-field surrounds of retinal ganglion cells; they rep-
resent the part of the indirect pathway about which we know the most. They
are large cells, and among the strangest in the nervous system. Their proc-
esses make close contact with the terminals of many photoreceptors distrib-
uted over an area that is wide compared with the area directly feeding a single
bipolar cell. Every receptor contacts both types of second-order cell, bipolar
and horizontal.
Horizontal cells come in several subtypes and can differ greatly from species
to species; their most unusual feature, which they share with amacrine cells, is
their lack of anything that looks like an ordinary axon. From the slightly
simplified account of nerve cells given in the last chapter you may rightly
wonder how a nerve without an axon could transmit information to other
neurons. When the electron microscope began to be used in neuroanatomy,
we soon realized that dendrites can, in some cases, be presynaptic, making
synapses onto other neurons, usually onto their dendrites. (For that matter,
axon terminals can sometimes be postsynaptic, with other axons ending on
them.) The processes that come off the cell bodies of horizontal cells and
amacrine cells apparently serve the functions of both axons and dendrites.

 

 

 

 

 

 

 

 

 

The synapses that horizontal cells make with receptors are likewise unusual,
lacking the electron-microscopic features that would normally tell us which
way the information is conveyed. It is clear that receptors feed information to
horizontal cells through excitatory synapses because horizontal cells, like re-
ceptors, are in most cases hyperpolarized, or turned off, by light. It is less clear
where the horizontal cell sends its output: in some species such as turtles we
know that they feed information back to receptors; in other species they make
synapses with the dendrites of bipolar cells and doubtless feed into them; in
primates we do not have either type of information. In summary, horizontal
cells get their input from receptors; their output is still uncertain, but is either
back to receptors, or to bipolar cells, or to both.
The relatively wide retinal area over which receptors supply horizontal cells
suggests that the receptive fields of horizontal cells should be large, and they
are. They are about the size of the entire receptive fields of bipolar cells or
ganglion cells, center plus surround. They are uniform, giving hyperpolariza-
tion wherever you stimulate, and more hyperpolarization the larger the spot.
Much evidence points to the horizontal cells as being responsible for the recep-
tive-field surrounds of the bipolar cells—indeed they are the only plausible
candidates, being the only cells that connect to receptors over so wide an
expanse. When horizontal cells connect directly to bipolars, the synapses to
on-bipolars would have to be excitatory (for the effect of light in the surround
to be inhibitory) and those to off-bipolars, inhibitory. If the influence is by
way of the receptors, the synapses would have to be inhibitory.
To sum this up: Bipolar cells have center-surround receptive fields. The
center is supplied by direct input from a small group of receptors; the surround
arises from an indirect path stemming from a wider expanse of receptors that
feed into horizontal cells, which probably feed into the bipolars. The indirect
path could also be the result of the horizontal cells feeding back and inhibiting
the receptors.