Development of Retinal Ganglion Cell Structure and Function
Introduction
Retinal ganglion cells (RGCs) process and convey information from the retina to visual centers in the brain. These output neurons comprise subpopulations with distinct structure and function. The morphology of RGCs is highly disparate; their somata and dendritic field vary in size, and they exhibit strikingly varied dendritic architecture (Cajal, 1893; Wässle and Boycott, 1991; Rodieck, 1998) and axonal projection patterns (Friedlander and Tootle, 1990; Garraghty and Sur, 1993; Yamagata and Sanes (1995a), Yamagata and Sanes (1995b)). Functionally, RGCs differ in their response to light in a variety of ways (reviewed by Wässle and Boycott, 1991; Rodieck, 1998; Dacey, 1999). Their response to light may be transient or sustained, brisk or sluggish, tonic or phasic. Some RGCs are good motion detectors and may prefer a specific direction of stimulus movement, whereas others are sensitive to the orientation of the stimulus but not its direction. In addition, RGCs show different contrast sensitivity, visual acuity, and color-coding. Despite the enormous diversity in structure and function, combined anatomical and electrophysiological studies have revealed a close correlation between the morphology and function of RGCs in vertebrates (Saito, 1983; Stanford and Sherman, 1984; Amthor et al (1984), Amthor et al (1989a), Amthor et al (1989b); Dacey, 1999).
Within a species, structure–function studies have enabled classification of RGCs into broad subclasses (see Cook, 1998). For example, in the well-studied cat retina, small-field beta RGCs are the anatomical correlate of physiologically identified brisk-sustained or X-RGCs, and large-field alpha RGCs are correlated with brisk-sustained or Y-RGCs (reviewed by Wässle and Boycott, 1991). Major subclasses of RGCs, such as the alpha and beta cells in cat, can be further divided into subtypes, notably those which are depolarized (ON RGCs), or hyperpolarized (OFF RGCs), by light. In general, within a species, each subtype of RGC shares key features: (i) their dendritic branching patterns and arbor size are similar at any fixed retinal location; (ii) their dendritic fields overlap forming mosaics that cover the retinal surface effectively (Wässle et al., 1983; Cook and Chalupa, 2000); (iii) they receive the same complement of presynaptic inputs; (iv) they project to common regions within targets in the brain. But not all RGC subclasses defined within one species are present in all species. However, in all species studied thus far, the inner plexiform layer (IPL), the plexus within which RGCs form intraretinal connections, is organized into structurally and functionally distinct sublaminae (Fig. 1). Irrespective of RGC subclass, ON RGCs have dendritic arbors that stratify in the inner region (sublamina b) of the IPL, whereas OFF RGCs stratify in the outer sublamina (sublamina a) of the IPL (Famiglietti and Kolb, 1976; Nelson et al., 1978). Cells with arbors in both sublaminae have ON and OFF responses (e.g. Amthor et al., 1984).
The diverse morphological and physiological properties of RGCs have presented an enormous challenge to investigators seeking to understand how the visual image is encoded and relayed to the brain. For developmental neurobiologists, the rich diversity of RGC structure and function make these neurons ideal for studies of cell-fate determination (reviewed by Cepko et al., 1996; Harris, 1997; Rapaport and Dorsky, 1998) and axonal and dendritic development (Goodman and Shatz, 1993; Wong, 1999a; Wong and Wong, 2000). Here, we have chosen to focus primarily on the structural and functional development of RGCs in a variety of species (see Table 1 for a summary of the developmental periods of some of these events). In recent years, there has been an increasing interest in obtaining a more unified view of the coordinated development of structure and function in RGCs. Although a complete understanding is still far off, many studies in the last decade have provided important insights into the complex yet highly organized manner by which RGCs differentiate, establish their synaptic connections and begin the task of sensory coding.
Section snippets
Structural development
RGCs are invariably amongst the first retinal cells to differentiate. Labeling of dividing cells with tritiated thymidine demonstrates that no other retinal cells are generated before RGCs and few RGCs are produced late in development (Polley et al., 1989; Snow and Robson, 1994; Rapaport et al., 1996; Belecky-Adams et al., 1996; Cepko et al., 1996). Although overlapping to some degree, the sequence of cell generation is similar across species: typically, after RGCs, and then cones, the next
Physiological development
RGCs also undergo functional development and refinement concurrent with the growth and remodeling of their structure. Functional maturation of RGCs include the development of intrinsic membrane properties (the complement of ion channels and receptors), the formation and refinement of their circuitry, both within the retina and with their central targets, and the production of appropriate output signals. Although there is much interest in how RGCs develop their visual responses (receptive field
Summary
In the last decade, the development of structure and function of retinal ganglion cells has continued to be intensely studied. On the structural side, we know that RGC dendrites do not grow in a simple fashion, but instead undergo rapid remodeling. We also know some of the intracellular signaling pathways involved in such restructuring. Here we have highlighted several external influences likely to be involved, in addition to intrinsic influences, in controlling dendritic development. On the
Acknowledgements
Supported by NIH, MRC, NATO, BBSRC, Newcastle Univ. Hospitals Special Trustees and Newcastle Univ. Research Committee (Sernagor), Wellcome Trust (Eglen) and NIH, NSF (Wong). We thank Daniel Osorio, Christian Lohmann, and Rebecca Stacy for helpful comments on the manuscript.
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