Elsevier

NeuroImage

Volume 59, Issue 3, 1 February 2012, Pages 2274-2283
NeuroImage

In vivo evaluation of retinal and callosal projections in early postnatal development and plasticity using manganese-enhanced MRI and diffusion tensor imaging

https://doi.org/10.1016/j.neuroimage.2011.09.055Get rights and content

Abstract

The rodents are an excellent model for understanding the development and plasticity of the visual system. In this study, we explored the feasibility of Mn-enhanced MRI (MEMRI) and diffusion tensor imaging (DTI) at 7 T for in vivo and longitudinal assessments of the retinal and callosal pathways in normal neonatal rodent brains and after early postnatal visual impairments. Along the retinal pathways, unilateral intravitreal Mn2+ injection resulted in Mn2+ uptake and transport in normal neonatal visual brains at postnatal days (P) 1, 5 and 10 with faster Mn2+ clearance than the adult brains at P60. The reorganization of retinocollicular projections was also detected by significant Mn2+ enhancement by 2%–10% in the ipsilateral superior colliculus (SC) of normal neonatal rats, normal adult mice and adult rats after neonatal monocular enucleation (ME) but not in normal adult rats or adult rats after monocular deprivation (MD). DTI showed a significantly higher fractional anisotropy (FA) by 21% in the optic nerve projected from the remaining eye of ME rats compared to normal rats at 6 weeks old, likely as a result of the retention of axons from the ipsilaterally uncrossed retinal ganglion cells, whereas the anterior and posterior retinal pathways projected from the enucleated or deprived eyes possessed lower FA after neonatal binocular enucleation (BE), ME and MD by 22%–56%, 18%–46% and 11%–15% respectively compared to normal rats, indicative of neurodegeneration or immaturity of white matter tracts. Along the visual callosal pathways, intracortical Mn2+ injection to the visual cortex of BE rats enhanced a larger projection volume by about 74% in the V1/V2 transition zone of the contralateral hemisphere compared to normal rats, without apparent DTI parametric changes in the splenium of corpus callosum. This suggested an adaptive change in interhemispheric connections and spatial specificity in the visual cortex upon early blindness. The results of this study may help determine the mechanisms of axonal uptake and transport, microstructural reorganization and functional activities in the living visual brains during development, diseases, plasticity and early interventions in a global and longitudinal setting.

Highlights

► MEMRI and DTI were sensitive to developmental and plastic changes in visual brains. ► MEMRI suggested differential transport mechanisms in developing retinal pathways. ► It also showed reorganization in retinal and callosal pathways upon early blindness. ► DTI indicated plasticity in left optic nerve after neonatal right eye enucleation. ► MEMRI and DTI may help determine mechanisms in developing and impaired living brains.

Introduction

The functions of the central nervous system depend upon precisely organized neuronal connections (Herrero et al., 2002, Scicolone et al., 2009, Silver and Kastner, 2009, Upadhyay et al., 2007). Among the complex neural networks across species, the rodents are an excellent model for understanding the developmental and neuroplastic mechanisms in the visual system. Along the visual pathways, the retinocollicular projection between retina and the superficial layers of superior colliculus (SC), and the retinogeniculate projection between retina and lateral geniculate nucleus (LGN) are commonly used for evaluating the cellular and molecular mechanisms of retinotopic map formation, neurodegeneration and plasticity in the subcortical brain in rodents (Chan et al., 2010b, Chandrasekaran et al., 2005, Hayakawa and Kawasaki, 2010, Jeffery and Thompson, 1986, Lund, 1972, O'Leary and McLaughlin, 2005, So, 1979). In addition, the V1/V2 border of the visual cortex is known to communicate interhemispherically via the splenium of corpus callosum (Cerri et al., 2010, Cusick and Lund, 1982, Olavarria and Safaeian, 2006, Olavarria and van Sluyters, 1984), which is sensitive to plastic changes during early postnatal development (Ankaoua and Malach, 1993, Olavarria and Safaeian, 2006, Olavarria et al., 1987, Rhoades et al., 1984, Toldi et al., 1996). Despite the increasing number of studies investigating retinotopic and callosal projections in rodent visual brain development and disorders, in vivo, high-resolution and longitudinal investigations of the developmental and plastic changes in the visual pathways have been limited. In particular, very little is known about the development of the structure–function relationships in the same visual brain in a systems level.

Mn2+ has been increasingly used as a T1-weighted MRI contrast agent for in vivo neuronal tract tracing (Chan et al., 2010a, Pautler et al., 1998, Thuen et al., 2005, Tucciarone et al., 2009, Watanabe et al., 2001) and functional brain mapping at lamina levels in the adult brains (Berkowitz et al., 2006, Bissig and Berkowitz, 2009, Yu et al., 2005). In the adult visual system, the paramagnetic Mn2+ act as a calcium analog and are hypothetically taken up by the retinal ganglion cells via L-type voltage-gated calcium channels upon neuronal activation (Merritt et al., 1989, Narita et al., 1990, Pautler, 2006). A fraction of the ions is then packed into organelles in the endoplasmic reticulum and transported along microtubules in the optic nerves via active anterograde axonal transport (Pautler, 2006, Thuen et al., 2005, Tjalve et al., 1996, Van der Linden et al., 2007). Mn-enhanced MRI has been used in combination with diffusion tensor imaging (DTI) for assessing the injury and reorganization in adult neuronal connections (Lin et al., 2003, Sun et al., 2011, Thuen et al., 2009, van der Zijden et al., 2008). In this study, we explore the capability of high-resolution MEMRI for in vivo, global and longitudinal assessments of the retinal and callosal projections in normal neonatal brains and after early postnatal visual impairments. In addition, DTI was acquired to examine the effect of early visual impairment and plasticity on the white matter microstructures in both anterior and posterior visual brains, and to complement the MEMRI findings. Results of this study are important for understanding the axonal uptake and transport, axoplasmic accumulation and clearance at nerve terminals, the microstructural reorganization as well as the functional activities in the living visual brains during development, diseases, plasticity, drug interventions and genetic modifications. The developed imaging approaches may also complement the conventional histological and electrophysiological techniques in examining the immature visual components in a global and longitudinal setting.

Section snippets

Animal preparation

Sprague–Dawley rats (n = 64; Charles River Lab, USA) were divided into 7 groups. In the normal brain development groups, 6 rats at postnatal days (P) 1, 5, 10 and 60 each were injected intravitreally with 100 mM MnCl2 solution (Sigma-Aldrich) into one eye using a 5 μL Hamilton microsyringe connected to a 30 G needle under isoflurane anesthesia. Considering the increasing vitreal volume and decreasing retinal ganglion cell and optic nerve counts in rats with age (Lam et al., 1982, Sha and Kwong, 2006

MEMRI of early postnatal visual development in retinal projections

In the T1W images in Fig. 1, Fig. 2, intravitreal Mn2+ injection into one eye resulted in T1W hyperintensity in the ipsilateral vitreous humor and optic nerve, and in the contralateral SC and LGN in all neonatal (P1, P5 and P10) and adult (P60) brains at Hour 8 and Day 1 (ANOVA, p < 0.05). Interestingly, while the T1W SI of contralateral SC and LGN continued to increase in the adult rats from 137% ± 2% and 128% ± 2% respectively at Hours 8 to 154% ± 3% and 143% ± 2% respectively at Day 1 relative to CTRL

Discussion

The results of this study showed that in vivo MEMRI and DTI were highly sensitive to the developmental and plastic changes in the living visual brains in rodents. MEMRI could not only assess both contralaterally and ipsilaterally projecting axons of the retinal ganglion cells in early postnatal brains, but also detect the reorganization of retinal and visual callosal pathways upon early blindness. Longitudinally, MEMRI also suggested the differential transport mechanisms in the developing

Acknowledgments

This work was supported by the Hong Kong Research Grant Council (, ).

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