Feed-back loops in the retina
[General characteristics]
[Feedback in the outer retina]
[Interplexiform cells]
[Dopaminergic cells in mammals]
[Centrifugal fibers in mammalian retinas]
[References]
1. General characteristics.
At every level of the retina there are reciprocal or feed-back loops in the
circuitry so that certain neurons can interact laterally within the same layer,
vertically from one layer to the other and indeed from the brain to the retina.
The intra layer feed-back loops are typically provided by neurons that use
inhibitory neurotransmitters such as GABA, and have a function in sharpening
the image by adding lateral inhibition or antagonism to receptive fields of the
neurons, while the feed-back loops between the layers or from the brain are
less clear in function. The latter loops tend to use neuromodulators as their
transmitters and thereby have a more generalized effect on groups of neurons,
or on the state of excitability of the neuron chains (adaptation for
example). 2. Feedback in the outer retina.
 Fig. 1. Electron micrograph of a cone pedicle (59 K jpeg image) |
 Fig. 2. Electron micrograph of a rod spherule (98 K jpeg image) |
As mentioned in previous chapters, it has been well demonstrated in turtle and fish retinas that cones receive an antagonistic reciprocal feed-back message from horizontal cells (Baylor et al., 1971), which serves to provide a restricted concentric receptive field for the individual cones. Evidence for feed-back synapses have been difficult to demonstrate either electrophysiologically or morphologically in the cones of the mammalian retinas. However, the rod axon terminals of HI horizontal cells ending in the rod spherules are seen to make small punctate chemical synapses, consisting a small cluster of vesicles at a single dense projection in the membrane, upon both the rod spherule (above) and upon the rod bipolar cell dendrite (not illustrated) in human retina (Linberg and Fisher, 1988). A similar appearing small cluster of vesicles is occasionally seen in horizontal cell dendrites in the cone pedicle triads in human retina too.
Fig. 3. Diagram of the organization of a cone pedicle and a rod spherule (59 K jpeg image)
In the inner plexiform layer, many amacrine cell types probably
provide feed-back information to bipolar axon terminals. One we known something
about is the reciprocal synapses from the wide-field rod amacrine A17 upon the
rod bipolar axon terminal. It is intriguing that this IPL input/output
synaptology between the rod bipolar and A17 amacrine parallels the input/output
of the photoreceptor and horizontal cell at the OPL and suggests some necessity
of the rod system, in the mammalian retina at least, to be in repetitive
feed-back loops all through the retina.
Where A17 is a rod system bipolar cell feed-back amacrine cell, A4, A13 and wide-field amacrines like A19 are cone system feed-back amacrine cells. Like A17 cells of the rod system these amacrine cells are probably also GABAergic. The amacrine cell feed-back loop seen below occurs commonly at the midget bipolar axon terminal in the human retina in close proximity to the ribbon synapse to the related midget ganglion cell.
Fig. 5. Electron micrograph of a reciprocal GABAergic synapse (78 K jpeg image)
It is possible that feed-back (reciprocal) synapses, in these cases, are involved with phasic or transient components of these cell response characteristics. They may sharpen and speed up otherwise slow potential responses of the bipolar cell by feed-back to the bipolar before output to the ganglion cell.
CLICK HERE to see an animation of the feed-back synapses
(254 K quicktime movie)
3. Interplexiform cells.
A neuron in the retina of just about every species studied, including man,
links the two plexiform layers by receiving synaptic input in the IPL and
having synaptic output upon neurons of the OPL. It is known as the
interplexiform cell, an IPC. The interplexiform cell, first described by
Gallego (1971) in the cat retina has been extensively studied in the goldfish
retina by Dowling and coauthors (Dowling and Ehinger, 1975) and now also in the
cat and the human retinas (Kolb and West, 1977; Linberg and Fisher, 1986; Kolb
et al., 1992). In cat and human retinas such interplexiform, cells are medium
field and tri-stratified in branching pattern in the inner plexiform layer.
Either from the cell body or from one of the dendrites in stratum 1 of the IPL,
processes ascend through the inner nuclear layer to the outer plexiform layer.
There they run for a short distance (see below).
 Fig. 6. Wholemount view of an Interplexiform cell in human retina (59 K jpeg image) |
 Fig. 7. Vertical view of a golgi stained Interplexiform cell in human retina (39 K jpeg image) |
Electron microscopy has been performed on examples of this type of IPC in cat and human retinas. They prove to get input from amacrine cells of unknown type and to make some synapses upon rod and cone bipolar axons (Kolb and West 1977; Nakamura et al., 1980) with their inner plexiform layer branches. Through the inner nuclear layer and into the outer plexiform layer, processes of IPCs cell make numerous conventional synapses upon rod and cone bipolar cell bodies and dendrites (see below).
Fig. 8. Electron micrograph of output synapses of an interplexiform cell (59 K jpeg image)
In both cat and human, the interplexiform cell has processes that touch cone pedicles but make rather unspecialized junctions at this site, so we have been reluctant to call these synapses. The interplexiform cell, just described in the human and cat is known to be GABAergic. This differs considerably from the interplexiform cell of the fish retina where it is known to be dopaminergic (Ehinger et al., 1969). In the fish retina the dopaminergic interplexiform cell is known to have synapses in the OPL primarily upon horizontal cells. Thus, it seems that the fish interplexiform cell has a rather different role to play in the retina compared with the GABAergic interplexiform cell of the human.
4. Dopaminergic cells in mammals.
In both human and cat retinas there exists a dopaminergic amacrine cell,
called A18 which we think is involved in the rod system pathways of the IPL and
particularly with the rod amacrine AII cells (see previous chapters). However,
sometimes these A18 cells can be seen to have processes ascending from their
cell bodies or from their plexus of dendrites in stratum 1 of the inner
plexiform layer, to pass up to the outer plexiform layer. In these layers
dopaminergic processes may be presynaptic to horizontal cells in the human
retina (Frederick et al., 1982). In the cat retina, however, we have seen these
ascending dopaminergic processes (marked by their content of Toh
immunoreactivity) to be presynaptic to the conventional IPC of the cat i.e. the
cell described above (Kolb et al., 1990, 1991).
 Fig. 10. Light micrograph of a dopaminergic cell (39 K jpeg image) |
 Fig. 11. Electron micrograph of a dopaminergic cell (78 K jpeg image) |
5. Centrifugal fibers in mammalian retinas.
Centrifugal fibres arising in brain nuclei and passing back to the retina have
been noted sporadically in mammals but with few details and no ideas about
which brain centers they might derive from. Centrifugal fibers are
particularly well developed in the avian retina (Cajal, 1892; Maturana and
Frenck, 1965; Ogden, 1968). A few centrifugal fibres were described in the
monkey retina by Polyak (1941) and later by Honrubia and Elliot (1970).
According to Polyak (1941) the centrifugal fibres in monkey have varicose,
bulbous terminals that end in the inner plexiform layer close to amacrine cell
bodies. In the human retina they have been followed across the nerve fiber
layer into the inner nuclear layer before disappearing (Honrubia and Elliot,
1968) (see below).
Recently, it has been discovered that centrifugal axons arising in the hypothalamus project to various parts of the brain including the retina in the macaque monkey. Interestingly these axons contain histamine (Gastinger et al., 1999). The histamine-immunoreactive axons run from the optic nerve head in a broad circular band around the far side of the fovea in temporal retina and appear to return to the optic disc (see Figure 13). Many of these axons branch extensively and emerge out of the nerve fiber layer into the inner plexiform layer. Sometimes the histaminergic axons are associated with retinal blood vessels. It will be extremely interesting to discover whether these histamine containing centrifugal fibers have interactions with amacrine or other cells of the retina like is proposed for centrifugal fibers in other species.
In the fish retina we know that centrifugal fibres use the hormones FMRFamide and luteinizing hormone-releasing hormone as neurotransmitters (Stell, 1985). They synapse in the fish directly upon cell bodies of the dopamine interplexiform cell (Zucker and Dowling, 1987). In turtle retina only 3 -6 efferent fibers that are immunoreactive to the peptide met-enkephalin are known to enter the retina and pass up to the amacrine cell area. These fibers originate in the caudal mesencephalon but their function and action in the retina are still unknown (Weiler, 1985).
6. References.
Baylor, D. A., Fuortes, M. G. F. and O'Bryan, P. M. (1971) Receptive fields of
the cones in the retina of the turtle. J. Physiol., Lond., 214,
265-294.
Cajal, S. R. (1892) The Structure of the Retina, translated by S.A. Thorpe and
M. Glickstein, Springfield, IL., Thomas, 1972.
Dowling, J.E. and Ehinger, B. (1975) Synaptic organization of the
amine-containing interplexiform cells of the goldfish and Cebus monkey retinas.
Science 188, 270-273.
Ehinger, B., Falck, B. and Laties, A. M. (1969) Adrenergic neurons in teleost
retina. Z. Zellforsch. mikrosk. Anat., 97, 285-297.
Frederick, J. M., Rayborn, M. E., Laties, A. M., Lam, D. M-K. and Hollyfield,
J. G. (1982) Dopaminergic neurons in the human retina. J. Comp. Neurol.,
210, 65-79.
Gallego, A. (1971) Celules interplexiformes en la retine del gato. Arch.
Soc. Esp. Oftal., 31, 299-304.
Gastinger, M.J., O'Brian, J.J., Larsen, J.N.J. and Marshak, D.W. (1999) Histamine immunoreactive axons in the macaque retina. Invest. Ophthal. Vis. Sci. 40, 487-495.
Honrubia, F. M. and Elliott, J. H. (1968) Efferent innervation of the retina
I. Morphologic study of the human retina. Arch. Ophthal., 80, 98-103
Honrubia, F. M. and Elliott, J. H. (1970) Efferent innervation of the retina
II. Morphologic study of the monkey retina. Invest. Ophthal. 9,
971-976.
Kolb, H. and West, R. W. (1977) Synaptic connections of the interplexiform
cell in the retina of the cat. J. Neurocytol., 6, 155-170.
Kolb, H., Cuenca, N. and DeKorver, L. (1991) Postembedding immunocytochemistry
for GABA and glycine reveals the synaptic relationships of the dopaminergic
amacrine cell of the cat retina. J. Comp. Neurol. 310, 267-284.
Kolb, H., Linberg, K. A. and Fisher, S. K. (1992) The neurons of the human
retina: a Golgi study. J. Comp. Neurol. 318, 147-187.
Kolb, H. , Cuenca, N., Wang, H-H. and DeKorver, L. (1990) The synaptic
organization of the dopaminergic amacrine cell in the cat retina. J.
Neurocytol. 19, 343-366.
Linberg, K. A. and Fisher, S. K. (1988) Ultrastructural evidence that
horizontal cell axon terminals are presynaptic in the human retina. J. Comp.
Neurol., 268, 281-297.
Maturana, H. R. and Frenk, S. (1965) Synaptic connections of the centrifugal
fibres in the pigeon retina. Science 150, 359-361.
Nakamura, Y., McGuire B. A. and Sterling P. (1980) Interplexiform cell in cat
retina: identification by uptake of [gamma]-[3H] aminobutyric
acid and serial reconstruction. Proc. Natl. Acad. Sci. USA, 77,
658-661.
Ogden, T. E. (1968) On the function of efferent retinal fibres. In
"Structure and Function of inhibitory neuronal mechanisms ". pp. 89-109.
Pergamon Press, Oxford and New York.
Polyak, S.L. (1941) The Retina. University of Chicago Press, Chicago.
Stell, W. K. (1985) Putative peptide transmitters, amacrine cell diversity
and function in the inner plexiform layer. In " Neurocircuitry of the Retina:
a Cajal Memorial". (A. Gallego and G. Gouras, editors), pp. 171-187, Elsevier,
New York.
Weiler, R. (1985) Afferent and efferent peptidergic pathways in the turtle
retina. In "Neurocircuitry of the retina: A Cajal Memorial" (Eds. Gallego, A.
and Gouras, P.) Elsevier, New York, pp. 245-256.
Zucker, C. L. and Dowling, J. E. (1987) Centrifugal fibres synapse on
dopaminergic interplexiform cells in the teleost retina. Nature 330,
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[General characteristics]
[Feedback in the outer retina]
[Interplexiform cells]
[Dopaminergic cells in mammals]
[Centrifugal fibers in mammalian retinas]
[References]
