Cross‐hierarchical plasticity of corticofugal projections to dLGN after neonatal monocular enucleation

Abstract

Perception is the result of interactions between the sensory periphery, thalamus, and cerebral cortex. Inputs from the retina project to the first‐order dorsal lateral geniculate nucleus (dLGN), which projects to the primary visual cortex (V1). In return, the cortex innervates the thalamus. While layer 6 projections innervate all thalamic nuclei, cortical layer 5 neurons selectively project to the higher order lateral posterior nucleus (LP) and not to dLGN. It has been demonstrated that a subpopulation of layer 5 (Rbp4‐Cre+) projections rewires to dLGN after monocular or binocular enucleation in young postnatal mice. However, the exact cortical regional origin of these projections was not fully determined, and it remained unclear whether these changes persisted into adulthood. In this study, we report gene expression changes observed in the dLGN after monocular enucleation at birth using microarray, qPCR at P6, and in situ hybridization at P8. We report that genes that are normally enriched in dLGN, but not LP during development are preferentially downregulated in dLGN following monocular enucleation. Comparisons with developmental gene expression patters in dLGN suggest more immature and delayed gene expression in enucleated dLGN. Combined tracing and immuno‐histochemical analysis revealed that the induced layer 5 fibers that innervate enucleated dLGN originate from putative primary visual cortex and they retain increased VGluT1+ synapse formation into adulthood. Our results indicate a new form of plasticity when layer 5 driver input takes over the innervation of an originally first‐order thalamic nucleus after early sensory deficit.

The parabigeminal nucleus is a source of “retinogeniculate replacement terminals” in mice that lack retinofugal input

“…Scale in c = 50 µm and also applies to d with and without retinofugal input. While previous reports have suggested that layer V cortical neurons provide an anomalous source of input following monocular or binocular enucleation (Frangeul et al, 2016;Giasafaki et al, 2022;Grant et al, 2016), we found no differences in the ultrastructure of corticogeniculate terminals in wild-type versus math5 -/mice. We also found no changes in the overall pattern of tectogeniculate or PPT projections in wild-type versus math5 -/mice.…”

“…These results seem at odds with previous studies using RpB4-cre mice crossed with reporter lines to demonstrate changes in cortical innervation patterns following monocular enucleation (Giasafaki et al, 2022;Grant et al, 2016). Although a subset of tectogeniculate cells contain cre-recombinase in the Rpb4-cre line, we found no apparent expansion of tectogeniculate projections in math5 -/mice.…”

“…These results indicate that the SC is one source of terminals labeled in the dLGN of Rbp4-cre mice crossed with reporter mice (Giasafaki et al, 2022;Grant et al, 2016). Tectogeniculate terminals are large "driver-like" terminals (Bickford et al, 2015) and therefore could account for some of the previously noted "retinogeniculate replacement terminals."…”

“…There is no significant difference in the size of ipsilateral and contralateral retinogeniculate terminals in WT mice and no significant difference in the sizes of corticogeniculate terminals in WT and math5 -/mice (ns) projects to the shell region of the dLGN (Bickford et al, 2015). The presence of cre-recombinase in SC neurons in Rpb4-cre mice could explain why terminals are detected in the shell of the dLGN in Rpb4-cre mice crossed with reporter mice (Giasafaki et al, 2022;Grant et al, 2016).…”

“…Corticogeniculate terminals in WT, math5 -/-, RPB4-cre, and RPB4-cre/math5 -/mice Following perinatal monocular enucleation, cortical inputs to the dLGN arise exclusively from V1 (Giasafaki et al, 2022;Grant et al, 2016). Thus, we labeled corticogeniculate terminals via V1 BDA injections in wild-type and math5 -/mice.…”