Mapping of retinal projections in the living rat using high‐resolution 3D gradient‐echo MRI with Mn²⁺‐induced contrast

Abstract

This study describes the neuroaxonal tracing of the visual pathway in the living rat using high-resolution T 1 -weighted 3D gradient-echo MRI (195 ؋ 195 ؋ 125 In the visual system of mammals, which have eyes placed far laterally on the head, the great majority of the optic nerve fibers decussate at the chiasm (1). The fibers then enter the optic tract, which projects to three main subcortical targets (2,3): the lateral geniculate nucleus processes visual information that ultimately results in visual perception; the pretectal area of the midbrain uses retinal input to produce pupillary reflexes; and the superior colliculus generates eye movements (4). In addition, there is a direct retinohypothalamic projection to the suprachiasmatic nucleus (5,6) as the principal circadian pacemaker in mammals, which is responsible for the generation and regulation of rhythms in behavioral state, performance, hormonal secretion, and physiologic function (7-9).Conventional neuroanatomic techniques for tract tracing rely on sectioning of the brain and therefore preclude repeated measurements of the same animal. However, a method which is based on neuronal uptake and axonal transport of a suitable tracer compound can provide access to the neuroaxonal connectivity and, therefore, may develop into a functional tool that allows for multiple examinations of a specific tract in a living animal, e.g., at different stages after labeling or in response to various sensory or cognitive inputs. Considering this perspective, Pautler et al. (10) introduced manganese-enhanced MRI as an alternative method for neural tracing. The method utilizes free unchelated manganese ions (Mn 2ϩ ) which, analogous to calcium ions (Ca 2ϩ ), are taken up by neurons and transported along axons.Mn 2ϩ has long been used as an MRI contrast agent because the paramagnetic ion affects the longitudinal relaxation rate (1/T 1 ) of surrounding water protons (11). Provided that Mn 2ϩ remains compartmentalized after exogenous administration, it can be used for delineating targeted tissue elements. In fact, Sloot and Gramsbergen (12) provided evidence for the neuronal uptake and anterograde axonal transport of radioactive Mn 2ϩ after microinjection into the rat basal ganglia by revealing a regionspecific accumulation and retention for at least 72 h. Pautler et al. (10) demonstrated T 1 -weighted signal enhancement of the olfactory pathway after topical administration of MnCl 2 to the naris of mice as well as of the contralateral optic tract after intravitreal injection into a single eye. Extending neuroaxonal tract tracing in murine brain in situ, the purpose of the present work was to develop an in vivo protocol suitable for repeated studies of the visual pathway of behaving rodents using high-resolution 3D gradient-echo MRI with manganese-induced contrast.

Distribution and regulation of galanin receptor 1 messenger RNA in the forebrain of wild type and galanin-transgenic mice

“…In contrast, in the mouse we found GALR1 mRNA to be widely distributed throughout the midbrain, suggesting a more important role for galanin in these regions of this species compared with the rat. For example, the expression of GALR1 mRNA in the geniculate, pretectal and superior collicular areas implies that in the mouse, galanin has a role in visual processing, as these are all relay nuclei for input to visual cortex (Watanabe et al, 2001). Notably, a robust signal for GALR1 mRNA was observed in the peripeduncular nucleus, a region closely associated with maternal and sexual behaviors (Wedemeyer et al, 1999).…”

Manganese‐enhanced MRI of the optic visual pathway and optic nerve injury in adult rats

“…With this technique, serial tract tracing in vivo is feasible and it becomes possible to perform longitudinal studies. Since its introduction, Mn 2ϩ -enhanced MRI tract tracing of axons in the CNS has been demonstrated in both the visual and olfactory systems of rats and mice (16,19).…”

In Vivo Manganese MR Imaging of Calcium Influx in Spontaneous Rat Pituitary Adenoma

“…[1][2][3][4][5] In one study, Mn 2ϩ combined with serial MR imaging (Mn-MR imaging) and statistical brain mapping were used to investigate normal trans-synaptic axonal transport through the rat olfactory system. 6 Mn 2ϩ ions enter cells via voltage-gated calcium channels, [7][8][9] and this influx has been shown to be activity-dependent.…”