Three approaches to study the function of mammalian rod bipolar cells are described. Extracellular recordings from the intact cat eye under light- and dark-adapted conditions showed that in dark-adapted retina all light responses can be blocked by 2-amino-4-phosphonobutyrate (APB). Immunocytochemical staining with an antibody against protein kinase C (PKC) labeled rod bipolar cells in all mammalian retinae tested. When rat retinae were dissociated, PKC immunoreactivity was also found in isolated bipolar cells and could be used for their identification as rod bipolars. Patch-clamp recordings were performed from such dissociated rod bipolar cells and their responses to APB were measured. APB closed a nonselective cation channel in the cell membrane. The actions of GABA and glycine were also tested and both opened chloride channels in dissociated rod bipolar cells. These results suggest that rod bipolar cells are depolarized by a light stimulus and that GABA as well as glycine modulate their light responses.

A survey of the shapes of dopaminergic (DA) neurons in the retinas of representative vertebrates reveals that they are divisible into three groups. In teleosts and Cebus monkey, DA cells are interplexiform (IPC) neurons with an ascending process that ramifies to create an extensive arbor in the outer plexiform layer (OPL). All other vertebrates studied, including several primate species, have either DA amacrine cells or IPCs with an ascending process that either does not branch within the OPL or does so to a very limited degree. DA neurons of non-teleosts exhibit a dense plexus of fine caliber fibers which extends in the distal most sublamina of the inner plexiform layer (IPL). Teleosts lack this plexus. In all vertebrates, DA cells are distributed more or less evenly and at a low density (10–60 cells/mm2) over the retinal surface. Dendritic fields of adjacent DA neurons overlap. Most of the membrane area of the DA cell is contained within the plexus of fine fibers, which we postulate to be the major source of dopamine release. Thus, dopamine release can be modeled as occurring uniformly from a thin sheet located either in the OPL (teleosts) or in the distal IPL (most other vertebrates) or both (Cebus monkey). Assuming that net lateral spread of dopamine is zero, the fall of dopamine concentration with distance at right angles to the sheet (i.e. in the scleral-vitreal axis) will be exponential. The factors that influence the rate of fall – diffusion in extracellular space, uptake, and transport – are not yet quantified for dopamine, hence the dopamine concentration around its target cells cannot yet be assessed. This point is important in relation to the thresholds for activation of D1 and D2 dopamine receptors that are found on a variety of retinal cells.

Increasing evidence indicates that the retina takes part in the postnatal regulation of eye growth, functioning in this respect to minimize refractive error. The evidence derives both from clinical observations in man and from experiments in animals. The discovery that visual form deprivation leads to an axial overgrowth of the eye and to myopia has opened the way to many current research initiatives. Neurochemical and immunocytochemical experiments in chick and monkey suggest that definable retinal neurons participate in the regulatory pathway controlling eye growth. The most comprehensive data presently implicate dopaminergic amacrine cells. Other important issues to be addressed include the relevance of an intact connection to the central nervous system and the precise retinal mechanism by which eye growth is regulated.

Fish have large eyes, with short optic nerves that are continually flexed by compensatory eye movements during swimming. Here, I review the tissue construction of the fish optic nerve, to see how the glia and axons are adapted to withstand these mechanical stresses, which are not normally encountered by CNS tissue within the skull.

As in other lower vertebrates, the optic nerve astrocytes are highly unusual: their intermediate filaments are composed of cytokeratins (Giordano et al., 1989), not GFAP. Their processes are linked together by desmosomes, forming thin transverse lace-like partitions, placed at quasi-regular intervals longitudinally (Maggs & Scholes, 1990). This accordion-like arrangement is interpreted as providing a flexible tissue-skeleton for the optic nerve.

A new observation is that the optic axons run in coherent parallel waves. This pattern, which is complementary to that of the astroglia, reversibly accommodates limited axial stretches. The waves are equivalent to those underlying the optical banding of Fontana (1781) in peripheral nerves, but wavelength (30 μm) and amplitude (5 μm) are about an order of magnitude less, reflecting the much smaller average size of the optic axons. The pattern also occurs in mammals, and may be restricted to the visual pathway: if present elsewhere in the CNS, nerve-fiber waves are inconspicuous at best.

In fish, the astroglial partitions occur in register with the waves, suggesting that steric interactions between developing axons and glia may help to establish, or stabilize, the regular longitudinal spacing. This may have functional as well as mechanical implications, since the astrocytes form perinodal associations and their pattern is one which strongly clusters the nodes of Ranvier.

Mammalian retinae have a well-defined neuronal pathway that serves rod vision. In rabbit retina, the different populations of interneurons in the rod pathway can be selectively labeled, either separately or in combination. The rod bipolar cells show protein kinase C immunoreactivity; the rod (An) amacrine cells can be distinguished in nuclear-yellow labeled retina; the rod reciprocal (S1 & S2) amacrine cells accumulate serotonin; and the dopaminergic amacrine cells show tyrosine-hydroxylase immunoreactivity. Furthermore, intracellular dye injection of the microscopically identified interneurons enables whole-population and single-cell studies to be combined in the same tissue. Using this approach, we have been able to analyze systematically the neuronal architecture of the rod circuit across the rabbit retina and compare its organization with that of the rod circuit in central cat retina. In rabbit retina, the rod interneurons are not organized in a uniform neuronal module that is simply scaled up from central to peripheral retina. Moreover, peripheral fields in superior and inferior retina that have equivalent densities of each neuronal type show markedly different rod bipolar to An amacrine convergence ratios, with the result that many more rod photoreceptors converge on an An amacrine cell in superior retina. In rabbit retina, much of the convergence in the rod circuit occurs in the outer retina whereas, in central cat retina, it is more evenly distributed between the inner and outer retina.

A specific morphological class of ganglion cell, the alpha cell, was first defined in cat retina. Alpha cells have since been found in a wide range of mammalian retinae, including several orders of placental and marsupial mammals. Characteristically, they have the largest somata and a large dendritic field with a typical branching pattern. They occur as inner and outer stratifying subpopulations, presumably corresponding to ON-center and OFF-center receptive fields. In all species, alpha cells account for less than 10% of the ganglion cells, their somata are regularly spaced, and their dendritic fields evenly and economically cover the retina in a mosaic-like fashion. The morphology of alpha cells and many features, both of single cells and of the population, are conserved across species with different habitats and life-styles. This suggests that alpha cells are a consistent obligatory ganglion cell type in every mammalian retina and probably subserve some fundamental task(s) in visual performance.

Some general rules about the construction principles of ganglion cell classes are inferred from the alpha cells, stressing the importance of population parameters for the definition of a class. The principle, that a functionally and morphologically homogeneous population should have a regular arrangement and a complete and even coverage of the retina to perform its part in image processing at each retinal location, is especially evident across species and across ganglion cell types.