Retinal Input Regulates the Timing of Corticogeniculate Innervation

Abstract

Neurons in layer VI of visual cortex represent one of the largest sources of nonretinal input to the dorsal lateral geniculate nucleus (dLGN) and play a major role in modulating the gain of thalamic signal transmission. However, little is known about how and when these descending projections arrive and make functional connections with dLGN cells. Here we used a transgenic mouse to visualize corticogeniculate projections to examine the timing of cortical innervation in dLGN. Corticogeniculate innervation occurred at postnatal ages and was delayed compared with the arrival of retinal afferents. Cortical fibers began to enter dLGN at postnatal day 3 (P3) to P4, a time when retinogeniculate innervation is complete. However, cortical projections did not fully innervate dLGN until eye opening (P12), well after the time when retinal inputs from the two eyes segregate to form nonoverlapping eye-specific domains. In vitro thalamic slice recordings revealed that newly arriving cortical axons form functional connections with dLGN cells. However, adult-like responses that exhibited paired pulse facilitation did not fully emerge until 2 weeks of age. Finally, surgical or genetic elimination of retinal input greatly accelerated the rate of corticogeniculate innervation, with axons invading between P2 and P3 and fully innervating dLGN by P8 to P10. However, recordings in genetically deafferented mice showed that corticogeniculate synapses continued to mature at the same rate as controls. These studies suggest that retinal and cortical innervation of dLGN is highly coordinated and that input from retina plays an important role in regulating the rate of corticogeniculate innervation.

Cortical Feedback Regulates Feedforward Retinogeniculate Refinement

“…Enucleation of the eye or genetic reduction of RGCs alters the timing of corticothalamic innervation (Brooks et al, 2013; Seabrook et al, 2013), while RGC axons fail to project to the dLGN in mice that develop without a cortex (Shanks et al, 2016). In the superior colliculus, the retinal input instructs alignment of the feedback projection, as genetic duplication of the retinocollicular map leads to bifurcation of the corticocollicular projection (Triplett et al, 2009).…”

Birthdate and Outgrowth Timing Predict Cellular Mechanisms of Axon Target Matching in the Developing Visual Pathway

“…Indeed, Chen and coworkers described a critical role for early-arriving ‘pioneer’ axons in targeting of subsequent-arriving axons to the zebrafish tectum (Pittman et al, 2008). Notably, the arrival of RGC axons in the dLGN regulates ingrowth timing of cortico-geniculate afferents by influencing repellent expression (Brooks et al, 2013; Seabrook et al, 2013). Thus, whether or not an axon chooses to bypass, transiently innervate, or stably connect to a given target may instruct that immediate target and downstream targets that together comprise parallel pathways.…”

Development, evolution and pathology of neocortical subplate neurons

“…Over the next 4 days, this nucleus becomes filled with eGFP-expressing fibres, and they coalesce into a barreloid pattern. Despite close spatial proximity, the dorsal lateral geniculate nucleus does not become filled by eGFP-expressing fibres until P10-P14 in normally developing mice [76][77][78] . This temporal pattern of axon extension is dependent on spontaneous retinal activity 78 because the eyes are closed at this time.…”