Retinopetal Fibers Research Articles

Functional Consequences of Retinopetal Fibers Originating in the Dorsal Raphe Nucleus

The existence of centrifugal fibers projecting into the mammalian retina is well known. However, their precise physiological role is poorly understood. Here we report that stimulation of the dorsal raphe nucleus (DRN) in freely moving rats produces profound effects on the electroretinogram (ERG). Most notably, activation of the dorsal raphe–retinal pathway causes a significant decrease in the latency of the b-wave and accompanying oscillatory potentials. In addition, dorsal raphe stimulation leads to a significant increase in the amplitude of oscillatory potentials. These results, therefore, provide the first demonstration of a functional role for the retinopetal fiber system originating in the and suggest that this structure can exert a powerful influence over the temporal sharpness and efficacy of retinal responsiveness.

Distribution of hypothalamic, hippocampal and other limbic peptidergic neuronal cell bodies giving rise to retinopetal fibers: Anterograde and retrograde tracing and neuropeptide immunohistochemical studies

In our present work utilizing the retrograde or anterograde transport of tracers (biotinylated dextran amine and Fluorogold, respectively) we have provided direct evidence for the cells of origin of the limboretinal pathway in rats and their termination in the retina using light microscopic approach. Administration of biotinylated dextran amine into the vitreous body resulted in nerve cell body labeling in several structures: the supraoptic and paraventricular nuclei, the hippocampus (CA1, CA3), the dentate gyrus, the indusium griseum, the olfactory tubercle, and the medial habenula, all of them belong to the limbic system. We estimated that the total number of retrogradely labeled cells is 1495±516. We have seen fiber labeling in the retinorecipient suprachiasmatic nucleus and in the primary visual center, the lateral geniculate body, but labeled nerve cell bodies in these structures were never seen. Iontophoretic application of Fluorogold into the hippocampal formation, where the major part of the biotinylated dextran amine-labeled cell bodies was observed, resulted in labeled fibers in the optic nerve and in the retina indicating that the retrogradely labeled cells in the hippocampus and the dentate gyrus among others are the cells of origin of the centrifugal visual fibers. Sections showing biotinylated dextran amine labeling were stained for vasoactive intestinal polypeptide, pituitary adenylate cyclase activating polypeptide or luteinizing hormone-releasing hormone immunoreactivity using immunohistochemistry. Some biotinylated dextran amine-labeled cells also showed vasoactive intestinal polypeptide, pituitary adenylate cyclase activating polypeptide or luteinizing hormone-releasing hormone immunoreactivity. We conclude that the limboretinal pathway exists and that the cells of origin are partially vasoactive intestinal polypeptide, pituitary adenylate cyclase activating polypeptide or luteinizing hormone-releasing hormone immunoreactive.

GnRH-immunoreactive centrifugal visual fibers in the Nile crocodile ( Crocodylus niloticus)

Thin varicose centrifugal visual fibers, between 30–45 in number and displaying cGnRH-I immunoreactivity, were identified in Crocodylus niloticus. Approximately 80% of these fibers were also FMRF-amide-like immunoreactive. The cGnRH-I fibers extended from the preoptic region to the retina where they appeared to terminate in the external portion of the inner plexiform layer. The location of their neurons of origin could not be determined precisely following the intraocular injection of the retrograde axonal tracer RITC. Nevertheless, the presence of cGnRH-I-immunoreactive neurons exclusively within the complex comprising the terminal nerve and the septo-preoptic region, and of several retinopetal fibers labelled retrogradely with the axonal tracer at the septo-preoptic junction, indicates that the cGnRH-immunoreactive centrifugal visual system originates from within this complex.

Dual innervation of the lamprey retina by GABAergic and glutamatergic retinopetal fibers: A quantitative EM immunogold study

A quantitative electron microscopic analysis of glutamate and GABA immunocytochemistry, using the postembedding immunogold technique, was undertaken in the lamprey retina to determine the proportion of glutamate-immunoreactive (GLU-ir) centrifugal visual terminals which were identified by anterograde axonal transport after an iontophoretic deposit of HRP in the sectioned optic nerve. Single immunogold labeling carried out with two different GABA and GLU antibodies showed that about 45% of the retinopetal axon terminals were GABAergic, and that two types of GLU-ir terminals (GLU-ir/1 and GLU-ir/2) were observed in the inner plexiform layer. The former type showed a high density of gold particles (Neosystem: 19.38±0.74; Sigma: 106.26±5.70) which statistically differed from the GLU-ir/2 (Neosystem: 3.23±0.31; Sigma: 31.73±5.61). Subcellular estimates showed that gold particles were concentrated over the vesicular pool in the GLU-ir/1 terminals and over mitochondria in the second terminal type. Consecutive sections alternately processed for GABA and GLU revealed that the GABA-immunonegative terminals corresponded to the GLU-ir/1, whereas the GABA-ir terminals only contained few GLU-ir particles, mostly concentrated in mitochondria. The occurrence of GABAergic and glutamatergic retinopetal terminals in the adult lamprey retina is discussed in functional terms of their differential inhibitory and excitatory effects on ganglion cell activity and the possible role of the centrifugal visual system in visually-guided behavior.

Paradoxical increase of tyrosine hydroxylase-immunoreactive retinopetal fibers in the weaver mouse

Weaver mice undergo apoptosis of the granule cell precursors of the cerebellum and nonapoptotic death of mesencephalic dopaminergic cells during post-natal development. In contrast, the number of retinal dopaminergic cells was transiently increased in weaver compared to control mice [C. Savy, E. Martin-Martinelli, A. Simon, C. Duyckaerts, C. Verney, C. Adelbrecht, R. Raisman-Vozari, J. Nguyen-Legros, Altered development of dopaminergic cells in the retina of weaver mice, J. Comp. Neurol. 1999;412:656–668]. While re-examining the retinas, we observed, in the nerve fiber layer, retinopetal tyrosine hydroxylase-immunoreactive fibers, which were dramatically increased in number throughout development and adulthood in the weaver compared to control mice.

Serotonergic projections to the retina of rat and goldfish

Serotonin amacrine cells have been described in the retina of vertebrates, except mouse and rat. Moreover, serotonin immunoreactive fibers have been reported in the optic nerve of rodents, frog and stingray. The purpose of this work was to study serotonin dorsal raphe nucleus projections to the retina, and to determine whether this pathway occurs in teleosts. The existence of specific connections was investigated in the rat and in the goldfish by the use of the neurotoxic substance 5,7-dihydroxytryptamine followed by monoamines determination in the retina by HPLC. The administration of 5,7-dihydroxytryptamine into the central or the lateral area of the rat dorsal raphe nucleus decreased serotonin levels in the raphe area and in the hippocampus, but only the bilateral injection into the dorsal raphe nucleus decreased it in the retina. In the goldfish, the injection of 5,7-dihydroxytryptamine into the optic tectum decreased serotonin concentration in situ and in the retina. The binding of [3H]paroxetine, a marker of serotonin transporter, was reduced in the retina of both species after the central treatment with the neurotoxic substance. In addition, the administration of the serotonin precursor 5-hydroxytryptophan into the optic tectum increased serotonin levels in the site of the injection and in the retina. The intraocular administration of 5,7-dihydroxytryptamine produced a big decrease in the content of retinal serotonin. This indoleamine and 5-hydroxyindoleacetic acid were detected in the optic nerves of rat and goldfish. The results indicate the existence of serotonergic retinopetal fibers in the rat and in the goldfish, a pathway that was not specifically demonstrated for the rat and was not previously proposed for the fish. The study of these serotonergic projections from the brain to the retina could be of interest in the understanding of the functional role of serotonin in the retina.

Target cells for the isthmo-optic fibers in the retina of the Japanese quail

The isthmo-optic nucleus (ION) is the major origin of the centrifugal fibers projecting to the avian retina. The retinopetal fibers from the ION were labeled with biocytin and examined light- and electron-microscopically in the Japanese quail. The terminals were seen on cell bodies in the inner part of the inner nuclear layer. These neurons innervated with the isthmo-optic fibers appear to constitute a separate population different from the ‘ordinary’ amacrine cells.

Development of two morphological types of retinopetal fibers in chick embryos, as shown by the diffusion along axons of a carbocyanine dye in the fixed retina

Centrifugal fibers to the retinas of chick embryos and hatched chicks have been examined and traced following staining by diffusion along their axonal membranes of the carbocyanine dye DiI in fixed tissue. In the older embryos and hatched chicks, the report of Dogiel (Arch. Mikrosk. Anat. 44:622-648, 1895) has been confirmed that there are two very different morphological types of centrifugal fiber. The restricted type ends as a relatively thick fiber, lacking varicosities, that runs for a short distance in the most sclerad level of the inner plexiform layer before terminating in a pericellular nest overlying the flask-shaped body of a single amacrine cell. Thin filaments occasionally leave the pericellular net, apparently to terminate on adjacent cells. The widespread type also runs in the most sclerad level of the inner plexiform layer, but it is thin, varicose, and highly branched, and its terminal arbor may span more than 1 mm, remaining at the same level. Both types of terminal arbor issue from parent axons in the optic fiber layer of the retina. A single parent axon gives either a single terminal fiber of the restricted type or several terminals of the widespread type, but never a mixture of the two. It is argued that the restricted and widespread types originate respectively from the neurons of the contralateral isthmo-optic nucleus and from the "ectopic" neurons scattered outside the isthmo-optic nucleus. In development, the centrifugal fibers reach the retina between E9 and E10 and initially run radially in the optic fiber layer, parallel to the retinofugal fibers but avoiding the dorsal retina. They dive into the inner plexiform layer at about E12. By E13, the terminal arbors are forming, and the widespread and restricted types can already be distinguished. The widespread type continues to increase its territory until about E18, and then appears to remain stable, whereas the restricted type attains its maximum ramification between E13 and E15 and then contracts. Prior to the retraction, the terminal territories of the restricted type fibers overlap, which may provide the anatomical basis for the interaxonal competition that apparently contributes to neuronal death in the isthmo-optic nucleus between E13 and E16. Axons of ganglion cells exhibit transient side branches between E11 and E13; these never reach as deep as the level where the centrifugal fibers run.

The Centrifugal Visual System of Vertebrates: A Century-Old Search Reviewed

Publisher Summary This chapter reviews a comparative perspective from both anatomical and functional points of view, group by group, from the most primitive vertebrates to the most evolved vertebrates. The centrifugal system of birds is considered because of the large volume and diversity of work done in this vertebrate class. Extrinsic axons to the retina are found in most of the large taxonomic groups of vertebrates, from the lamprey to the human. These fibers always terminate upon amacrine cells, more rarely upon ganglion cells, and upon interplexiform cells (IPC). However, upon entering the retina, they show a considerable degree of collateralization and thus may be considered to be divergent. These fibers are generally of small diameter and unmyelinated (except in the human). These axons are usually of large diameter and myelinated. It is also demonstrated that the retinopetal fibers are predominantly convergent in birds. In teleosts, several neuropeptides are colocalized within retinopetal fibers, including luteinizing hormone-releasing hormones (LHRH)-like, molluscan cardioexcitatory tetrapeptide (FMRF) amide-like, and substance P-like peptides.

Optic nerve blockade influences the retinal responses to flash in rabbits

The presence of retinopetal fibers in mammals has been debated many times in the past two decades. Do rabbits have a retinopetal system? This question is addressed with the present investigations. In anesthetized and paralysed rabbits the b-wave and the oscillatory potentials (OP) are recorded at the cornea. The optic nerve is isolated retrobulbarly and is gently hooked to a curved injecting capillary. Through the latter lidocaine hydrochloride is pressure injected. This drug interrupts the neuronal flow travelling along the nerve. A steel electrode is positioned in the optic chiasm allowing us to monitor the evoked field potentials from the tested and untested eyes. The optic nerve blockade produces the following observations: (1) the amplitude of the b-wave is not significantly altered; and (2) the amplitudes of the long latency OP are significantly increased. The retinal capacity to respond to a second flash after the application of an initial light pulse was evaluated by varying the interval between the two flashes. After optic nerve blockade the recovery of the retinal responsiveness is considerably slower. Fourier analysis indicated that the highest power increases occurred around 200 Hz. It is difficult to escape the suggestion that rabbits possess retinopetal fibers.

FMRFamide-immunoreactive retinopetal fibers in the frog, Rana pipiens: demonstration by lesion and immunocytochemical techniques

Retinopetal fibers, immunoreactive to a molluscan cardioexcitatory-like peptide (FMRFamide-ir), were examined in Rana pipiens with the use of immunocytochemical and lesion techniques. In intact frogs, FMRFamide-ir retinopetal fibers were found in the optic nerve, optic nerve head, and nerve fiber, ganglion cell and inner plexiform layers of the retina. Presumptive monostratified amacrine cells were also labeled. As observed in flat-mounted retinas, the retinopetal fibers radiated from the optic disc toward the peripheral retina, branched many times along their course and were more prevalent in the dorsal retina. Crushing the optic nerve eliminated retinopetal fibers from all regions except the cerebral stump of the optic nerve, indicating that this projection was of central origin. Bilateral prechiasmatic lesions completely eliminated retinopetal fibers from both retinas, indicating that the fibers arose from the rostral forebrain. Within the rostral brain, FMRFamide-ir perikarya were found in olfactory bulb, diagonal band, medial septum, anterior commissure area, and two regions of the posterior preoptic area. Olfactory bulbectomy and midforebrain lesions equally reduced the numners of these fibers in the retina, implicating the nervus terminalis as a possible source for some of the retinopetal projection. These data will serve as a foundation for future studies on the function of retinopetal fibers in the frog retina.

Retinopetal neurons and fibers in the lamprey

The structure of the retinopetal system was studied in lampreys (Lampetra fluviatilis) using the HRP method. Preliminary chemical destruction of the retina or the optic nerve transsection ceased the anterograde axonal transport in the retinofugal fibres, and permitted observing the centrifugal visual projections without marking the retinofugal fibres. The cells of retinopetal system were found in the periventricular tegmental zone and in the reticular zone of mesencephalon. Retinopetal fibres followed the axial optic tract.

Pathways of the early propagation of virulent and avirulent rabies strains from the eye to the brain.

Penetration of the central nervous system of the adult rat by the CVS strain of rabies virus and its two avirulent derivatives Av01 and Av02 has been studied by inoculation of the virus into the anterior chamber of the eye. The primary sites of penetration of CVS were (i) the intraocular parasympathetic oculomotor fibers, (ii) the retinopetal fibers of pretectal origin, and (iii) the intraocular fibers of the ophthalmic nerve. The mutant strains, however, lost the capacity to invade the two former groups of fibers, although their penetration into the trigeminal system was not impaired. Neither strain CVS nor the mutants infected primarily the intraocular adrenergic terminals and the optic nerve. Mutant strains, but not CVS, were able to infect the lens. These results indicate that the cholinergic receptor may not be the only receptor for rabies virus and that rabies virus is conveyed in the nervous system by retrograde axoplasmic flow. Strain CVS spread throughout the brain and propagated eventually back to the retina. The mutants penetrated the brain as well, but the infection was slow, involved different cerebral structures, and cleared up completely in 3 weeks, probably because of an efficient immune response.

A direct projection from the nucleus oculomotorius to the retina in rats

The centrifugal projection to the eye has been studied in rats with anterograde and retrograde tracing techniques. As a retrograde tracer Nuclear Yellow (NY) was used. Following NY injections into the vitreous body of the eye, labeled neurons were exclusively found bilaterally in nucleus oculomotorius. The course and termination site of the retinopetal fibers were studied with the anterograde tracer Phaseolus vulgaris-leucoagglutinin (PHA-L). Iontophoretic injections of PHA-L in nucleus oculomotorius resulted in labeling of retinopetal fibers which reach the eye via the optic tract and optic nerve. Preterminal arborizations were found in the inner nuclear layer of the retina. In addition, labeled fibers have been observed which seem to terminate within the optic tract and optic nerve. It is suggested that the projection from the nucleus oculomotorius to the retina constitutes a link in the multisynaptic efferent pathway from the visual cortex to the eye, by which the visual cortex can influence the functioning of the retina.

Selective attention effects on retinal and forebrain responses in humans: A replication and extension

Eason, Oakley, and Flowers (1983) reported that the amplitude of the b-wave and afterpotential of the electroretinogram is affected by the attentional state of the subject. Two follow-up studies were conducted primarily to replicate their findings. The composite results confirmed those previously reported, providing further evidence for early sensory filtering of irrelevant, unattended information. The results also provide additional evidence for the existence of retinopetal fibers in humans.