Pathfinding and target selection by developing geniculocortical axons

Abstract

During development of the mammalian cerebral cortex, thalamic axons must grow into the telencephalon and select appropriate cortical targets. In order to begin to understand the cellular interactions that are important in cortical target selection by thalamic axons, we have examined the morphology of axons from the lateral geniculate nucleus (LGN) as they navigate their way to the primary visual cortex. The morphology of geniculocortical axons was revealed by placing the lipophilic tracer Dil into the LGN of paraformaldehyde-fixed brains from fetal and neonatal cats between embryonic day 26 (E26; gestation is 65 d) and postnatal day 7 (P7). This morphological approach has led to three major observations. (1) As LGN axons grow within the intermediate zone of the telencephalon toward future visual cortex (E30-40), many give off distinct interstitial axon collaterals that penetrate the subplate of nonvisual cortical areas. These collaterals are transient and are not seen postnatally. (2) There is a prolonged period during which LGN axons are restricted to the visual subplate prior to their ingrowth into the cortical plate; the first LGN axons arrive within visual subplate by E36 but are not detected in layer 6 of visual cortex until about E50. (3) Within the visual subplate, LGN axons extend widespread terminal branches. This represents a marked change in their morphology from the simple growth cones present earlier as LGN axons navigate en route to visual cortex. The presence of interstitial collaterals suggests that there may be ongoing interactions between LGN axons and subplate neurons along the entire intracortical route traversed by the axons. From the extensive branching of LGN axons within the visual subplate during the waiting period, it appears that they are not simply "waiting." Rather, LGN axons may participate in dynamic cellular interactions within the subplate long before they contact their ultimate target neurons in layer 4. These observations confirm the existence of a prolonged waiting period in the development of thalamocortical connections and provide important morphological evidence in support of the previous suggestion that interactions between thalamic axons and subplate neurons are necessary for cortical target selection.

Activity-Dependent Regulation of NMDAR1 Immunoreactivity in the Developing Visual Cortex

“…We examined the period of development beginning at a time in fetal life before LGN axons have grown into the visual cortical plate (E30 ferret, E42 cat) (Ghosh and Shatz, 1992) through the period of ocular dominance column formation [cat P21-42 (LeVay et al, 1978) and ferret P36 -49 (Ruthazer et al, 1995; E. Finney and C.J. Shatz, unpublished observations)], through the critical period when abnormal experience can alter geniculocortical connectivity within layer 4, to adulthood.…”

Cellular Strategies of Axonal Pathfinding

“…These early-born neurons are thought to guide both crossed and uncrossed retinal axons past the midline (Sretavan et al 1994). The subplate cells in the developing cortex, a transient cell layer above the subventricular zone and below the emerging cortical layers, serve as a temporary way-station where axons pause before entering the emerging permanent cortical layers (Luskin and Shatz 1985;Ghosh and Shatz 1992). The subplate is crucial for proper guidance and afferent invasion of the cortex (Catalano and Shatz 1998;Kanold et al 2003).…”

Connecting thalamus and cortex: The role of ephrins

“…At E14, afferents invade the subplate (Auladell et al, 2000). As first described in monkeys and cats (Rakic, 1977;Ghosh and Shatz, 1992), before thalamocortical fibers enter their appropriate cortical targets, they accumulate and wait in the subplate zone. The exact duration of the waiting period in rodents is still somewhat controversial (Catalano et al, 1991(Catalano et al, , 1996Molnar et al, 1998a,b;Deng and Elberger, 2003), because it is much shorter than in larger mammals.…”