Prenatal development of retinal ganglion cell axons: segregation into eye-specific layers within the cat's lateral geniculate nucleus

Abstract

The morphological changes in individual retinal ganglion cell axons associated with the formation of the eye-specific layers in the dorsal lateral geniculate nucleus (LGN) were studied during the prenatal development of the cat's visual system. Previous work has shown that the pattern of segregated eye inputs found in the adult arises from an immature state in which inputs from the two eyes are intermixed within the nucleus (Shatz, 1983). Here, this developmental process is examined at its fundamental unit of connectivity--the individual retinal ganglion cell axon. To do so, an in vitro method was used to label fetal cat optic tract axons with HRP at various times during development between embryonic day 38 (E38) and postnatal day 2 (P2) (gestation = 65 d). The results presented here are based on reconstructions of 172 axons. During the initial period of intermixing (E38-43), axons are relatively simple in morphology. Many axons studied at the earliest ages (E38) end in growth cones and have very few branches along the main axon trunk as they traverse the nucleus. By E43, the number of side branches given off along the main axon trunk has increased and most axons also have a simple terminal arbor. Over the next 2 weeks (E43-55), the majority of axons are studded with side branches and the terminal arbor is well defined. Then, between E55 and birth, axons lose their side branches and the eye-specific layers appear. By birth, nearly all axons have a smooth trunk and an elaborate terminal arbor restricted to the LGN layer appropriate to the eye of axon origin. When the number of side branches per axon was quantified, the time course of appearance and subsequent loss of side branches was found to parallel the time course of the initial intermixing of inputs and subsequent reduction in territory shared by the two eyes as determined from previous intraocular injection experiments. Our results also showed that the side branches along each axon were located primarily within LGN territory destined to be occupied by the other eye. Thus, the side branches are likely to represent a morphological substrate for the intermixing of inputs from the two eyes. These observations suggest that the segregation of eye input to the LGN involves two fundamental and simultaneous events. One event is the remodeling of the branching pattern along the length of the main axon trunk so that the side branches present early on are eliminated and the main axon trunk becomes smooth.(ABSTRACT TRUNCATED AT 400 WORDS)

Ion Channel Development, Spontaneous Activity, and Activity-Dependent Development in Nerve and Muscle Cells

“…513, 615 for reviews). These layers form by pruning of an initial innervation pattern in which axon terminals originating from different eyes are intermixed (560). Blockade of spontaneous activity originating in the retina at the stages during which this layering occurs (see above) prevents eye-specific layers from forming and leaves the earlier, wider branching patterns of axons in the LGN in place (535,561).…”

The role of nAChR‐mediated spontaneous retinal activity in visual system development

“…This eye-specific segregation emerges from an initial distribution where the inputs from the two eyes are extensively intermingled (Sretavan and Shatz, 1986). This process of segregation is known to be activity dependent because intracranial infusion of TTX, a blocker of voltage-activated sodium channels, prevents the formation of layers (Shatz and Stryker, 1988).…”

ERK signaling is required for eye-specific retino-geniculate segregation

“…In the visual system, during early development, RGC axons from the two eyes are intermixed within the dLGN; then the adult pattern of segregated zones gradually emerges, as axons remodel their branches and become restricted into eye-specific territories (Hahm et al, 1999;Linden et al, 1981;Sretavan and Shatz, 1986).…”