Retinopetal System Research Articles

Current state of knowledge on the centrifugal visual system (including the pinealo-to-retinal connection) in mammals and its hypothesized role in circadian rhythms

The ubiquity of circadian rhythms in living organisms has generally been accepted by researchers over the last century. Indeed, morphology and molecular biology of the circadian clock were described during the last fifty years. This main biological clock is located in the suprachiasmatic nucleus of the hypothalamus. This nucleus is connected with the retina by the retinohypothalamic tract. This way, light regulates the functioning of the biological clock and biological rhythms such as the sleep-wake cycle and other cyclic functions by releasing melatonin from the pineal body (PB) into the general circulation. Melatonin reaches the retina via the bloodstream as humoral feedback. More than a hundred years ago a reverse neuronal connection between the central nervous system and the retina was hypothesized. This so-called centrifugal visual or retinopetal system has been explored in detail in birds, but less information is available in mammals. In this work, the morphology and physiology of mammalian centrifugal visual pathways are reviewed. It is generally accepted that the centrifugal (retinopetal) fibers terminate mainly on the amacrine cells of the retina. Histaminergic fibers terminate on dopaminergic amacrine cells. Serotoninergic synapses were identified on ganglion cells. In addition, serotoninergic fibers were also associated with photoreceptor terminals. Luteinizing hormone releasing hormone fibers have been observed in birds, but not in mammalian retinas. In summary, based on the data available in the literature, it seems that the retinopetal system has a mandatory role in lower vertebrates, but a modulatory role in mammals. There is currently no adequate way to eliminate the centrifugal visual system that would better explain its true function.

Bipolar cells containing protein kinase Cα mediate attentional facilitation of the avian retinal ganglion cells by the retinopetal signal.

Birds have a well-developed retinopetal system projecting from the midbrain to the contralateral retina. The signal sent to the retina through the retinopetal system facilitates visual responses of the retinal ganglion cells (RGCs), and the retinopetal signals function as attentional signals during visual search. Thus, the retinopetal signal somehow reaches and facilitates visual responses of the RGCs. However, the tertiary neuron of the retinopetal system, the isthmo-optic target cell (IOTC), is unlikely to contact most RGCs directly, because the IOTCs form axon terminals localized in the outermost sublayer (lamina 1) of the inner plexiform layer (IPL) where few RGC dendrites terminate. Therefore, some other intrinsic retinal neurons must be involved in the centrifugal attentional enhancement of visual responses of the RGCs. We investigated connections of the target cells of the IOTCs in chicken and quail, using light and electron microscopic immunohistochemistry. We show that axon terminals of the IOTC make synaptic contacts with protein kinase Cα (PKCα)-immunoreactive (ir) bipolar cells (PKCα-BCs) in lamina 1 of the IPL. Furthermore, with prolonged electrical stimulation of the isthmo-optic nucleus (ION) on one side, whose neurons send their axons to the contralateral retina and make synaptic contacts there with IOTCs, phosphorylation of cAMP response element-binding protein was observed in the PKCα-BCs in the contralateral retina, but not in the ipsilateral retina. This suggests that electrical stimulation of ION activated PKCα-BCs through synapses from IOTCs to PKCα-BCs, thus stimulating transcription in PKCα-BCs. Thus, centrifugal attentional signals may facilitate visual responses of RGCs via the PKCα-BCs.

Attentional signals projecting centrifugally to the avian retina: A dual contribution to visual search

Among vertebrates, birds have a particularly well-developed retinopetal system, i.e., the centrifugal system projecting from the brain to the retina. Primary, secondary and tertiary neurons of the retinopetal system connect serially in a one-to-one-to-one fashion, thereby assembling several thousand retinopetal modules projecting in parallel to the retina. The signal conveyed by the retinopetal system enhances the visual responses of retinal ganglion cells (RGCs), and each retinopetal module may facilitate the RGCs in a topographically restricted area. We investigated how the retinopetal signal contributes to visual search by first training Japanese quail to search and peck a target stimulus presented on one of three touch-sensor monitors around the bird and then examining the effect of retinopetal signal blockage on the task. Our results indicate that the retinopetal signal improves both stimulus detectability and target discriminability. Thus, this study confirms that the avian retinopetal system functions specifically in attentional facilitation of the retina; this new finding suggests that this system benefits early detection and late selection phases of visual search. The fast and precise target detection facilitated by the retinopetal signal may be transformed into quick and correct orienting to the target through visuomotor transformation mechanisms implemented in the optic tectum.

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.

Early development and organization of the retinopetal system in the larval sea lamprey, Petromyzon marinus L.

Development of the retinopetal system of the larval sea lamprey, Petromyzon marinus, was investigated following labelling of this system by injection of horseradish peroxidase into the orbit. This study extends our previous report on larval stages and provides a detailed description of the development of this system. We present quantitative and qualitative evidence suggesting that the retinopetal nuclei of Schober's M2-M5 nucleus, the mesencephalic reticular area and the tectum arise sequentially in that order, that the three retinopetal nuclei originate from a common anlage in the ventricular zone of the mesencephalic tegmentum and that the retinopetal cell population increases throughout the larval period. No neuronal death was observed. We also describe and discuss the significance of a transitory phase of retinopetal cell differentiation characterized by the presence of ventricular dendrites. Finally, we compare the development of retinopetal and retinofungal systems.

Birds that feed-on-the-wing have few isthmo-optic neurons

The isthmo-optic system is less developed in birds feeding-on-the-wing, than in pecking avians. This was suggested previously. By intraocular horseradish peroxidase applications, we studied the central origin of this retino-petal system in thrush, haw finch, swift and swallow. Our data support the assumption on a correlation between feeding habits and the development of the isthmo-optic nucleus in adult avians as this brainstem region is more highly developed in thrush and finch than in swift and swallow. This is particularly relevant since the latter species is taxonomically related to the two pecking birds whereas it is unrelated to the swift that also feeds-on-the-wing.

Presumptive GABAergic centrifugal input to the lamprey retina: a double-labeling study with axonal tracing and GABA immunocytochemistry

The distribution of GABA-like immunoreactivity (GABA-LI) was performed in the lamprey retinopetal system which was previously identified by either anterograde or retrograde axonal tracing methods. This study was carried out at the ultrastructural level for the retina and under both the light and electron microscope for the mesencephalic retinopetal centers (M5 and RMA). The GABA-LI was distributed in about 40% of anterogradely HRP-labeled axon terminals in the inner retina. These made synaptic contacts upon either HRP-labeled ganglion cell dendrites or mostly on GABA-LI or on immunonegative amacrine cell dendrites and somata. The other immunonegative HRP-labeled axon terminals also established synaptic contacts on amacrine cell dendrites and somata. The mesencephalic retinopetal neurons, retrogradely labeled with HRP or [ 3H]proline, were GABA-LI in 65% of M5 somata and only in 15% of RMA neurons. M5 and RMA retinopetal neurons and dendrites, either GABA-LI or immunonegative, were contacted: (1) asymmetrically by HRP-labeled or unlabeled axon terminals containing rounded synaptic vesicles, always immunonegative and (2) symmetrically by HRP-unlabeled axon terminals containing pleiomorphic synaptic vesicles, which were either GABA-LI or immunonegative. The role of GABA as a putative neurotransmitter in the centrifugal visual system is discussed.

Retinopetal neuronal system in the brain of an air-breathing teleost fish, Channa punctata

Retinopetal neurons were visualised in the telencephalon and diencephalon of an air-breathing teleost fish, Channa punctata, following administration of cobaltous lysine to the optic nerve. The labelled perikarya (n=45–50) were always located on the side contralateral to the optic nerve that had received the neuronal tracer. The rostral-most back-filled cell bodies were located in the nucleus olfactoretinalis at the junction between the olfactory bulb and the telencephalon. In the area ventralis telencephali, two groups of telencephaloretinopetal neurons were identified near the ventral margin of the telencephalon. The rostral hypothalamus exhibited retrogradely labelled cells in three discrete areas of the lateral preoptic area, which was bordered medially by the nucleus praeopticus periventricularis and nucleus praeopticus, and laterally by the lateral forebrain bundle. In addition to a dorsal and a ventral group, a third population of neurons was located ventral to the lateral forebrain bundle adjacent to the optic tract. The dorsal group of neurons exhibited extensive collaterals; a few extended laterally towards the lateral forebrain bundle, whereas others ran into the dorsocentral area of the area dorsalis telencephali. A few processes extended via the anterior commissure into the telencephalon ipsilateral to the optic nerve that had been exposed to cobaltous lysine. However, the ventral cell group did not possess collaterals. In the diencephalon, retinopetal cells were visualised in the nucleus opticus dorsolateralis located in the pretectal area; these were the largest retinopetal perikarya of the brain. The caudal-most nucleus that possessed labelled somata was the retinothalamic nucleus; it contained the largest number of retinopetal cells. The limited number of widely distributed neurons in the forebrain, some with extensive collaterals, might participate in functional integration of different brain areas involved in feeding, which in this species is influenced largely by taste, not solely by vision.

Organization of the visual system in larval lampreys: An HRP study

The organization of the visual system of larval lampreys was studied by anterograde and retrograde transport of HRP injected into the eye. The retinofugal system has two different patterns of organization during the larval period. In small larvae (less than 60-70 mm in length) only a single contralateral tract, the axial optic tract, is differentiated. This tract projects to regions in the diencephalon, pretectum, and mesencephalic tegmentum. In larvae longer than 70-80 mm, there is an additional contralateral tract, the lateral optic tract, which extends to the whole tectal surface. In addition, ipsilateral retinal fibers are found in both small and large larvae. Initially, the ipsilateral projection is restricted to the thalamus-pretectum, but it reaches the optic tectum in late larvae. Changes in the organization of the optic tracts coincide with the formation of the late-developing retina and consequently, the origin of the optic tracts can be related to specific retinal regions. The retinopetal system is well developed in all larvae. Most retinopetal neurons are labeled contralaterally and are located in the M2-M5 nucleus of the mesencephalic tegmentum, in the caudolateral mesencephalic reticular area and adjacent ventrolateral portions of the optic tectum. Dendrites of these cells are apparent, especially those directed dorsally, which in large larvae extend to the optic tectum overlapping with the retino-tectal projection. These results indicate that in lampreys, visual projections organize mainly during the blind larval period before the metamorphosis, their development being largely independent of visual function.

Centrifugal pathways to the retina: Influence of the optic tectum

Two types of centrifugal pathways to the retina have been found in the vertebrates, according to the location of the cell bodies and presence or absence of connections with the optic tectum. One type is represented by the isthmo-optic nucleus (ION) of birds and, therefore, termed "ION-type" retinopetal system. The other type is termed "non-ION-type" retinopetal system. The ION-type retinopetal systems have been found in the cyclostomes, teleosts, reptiles, and birds. This review describes the anatomy and physiology of the ION-type retinopetal systems, mainly of birds and teleosts. On the basis of anatomical and physiological evidence cited in this review, the ION-type retinopetal systems can be regarded as the tectofugal pathways to the retina. The function of the ION-type retinopetal systems is discussed in detail, with special emphasis on their relation to the role of the tectum in mediating visuomotor behavior.

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.

The retinopetal system in the rat

After horseradish peroxidase had been applied to the ends of the optic nerves of Sprague-Dawley rats that had been sectioned at their entry into the eyeball, retrogradely labelled neurons were found in the pretectal region (mostly in the contralateral medial pretectal area) and in the ventrolateral area of the contralateral central grey matter at the level of the mesencephalic-metencephalic junction. In some cases a few weakly labelled neurons were also observed in the oculomotor or trochlear nuclei. These findings confirm the existence of a retinopetal system in this mammal.

Mesencephalic innervation of the turtle retina by a single serotonin-containing neuron

Co-localization of retrograde transported Nuclear yellow and serotonin immunoreactivity revealed the existence of a central serotonergic projection to the retina in the turtle Pseudemys scripta elegans. This serotonergic retinopetal system consists of only one fiber originating in the contralateral caudal mesencephalon. In the retina, the fiber arborizes exclusively in the temporal hemisphere, covering about one third of the total retinal surface. Interestingly this projecting area lies in the part of the retina, to which binocular perception can be attributed.

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.

Is there a retinopetal system in the rat?

The centrifugal innervation of the retina was reinvestigated in albino and pigmented rats with intraocular injections of horseradish peroxidase (HRP), radioactive wheat germ agglutinin (WGA) and proline. No labeled cells were found in the brains injected with HRP and proline, except some eye muscle motoneurons in one case apparently involving orbital contamination from the injection. In the cases injected with WGA and having a survival time of at least two days cells were labeled in the lateral mesencephalic tegmentum, ventral to the parabigeminal nucleus and in the periaqueductal gray. Both these findings are most likely due to transneuronal anterograde-retrograde transport of the tracer through the superior colliculus. The results yielded no compelling evidence for the existence of a direct retinopetal pathway in the rat, which is in contrast to a recently claimed retinal projection originating from the pretectum. Special attention was paid to the labeling in the lateral mesencephalic tegmentum, an area giving rise to retinal projections in various submammalian species. This finding is discussed with regard to the possibility that also in the rat the lateral tegmentum exerts an early influence on visual input, but at the "higher" collicular level and not at the "original" retinal one.

An anatomical and electrophysiological study of the centrifugal visual system in the lamprey ( Lampetra fluviatilis)

The centrifugal visual system of the lamprey Lampetra fluviatilis was investigated using various neurohistophysiological methods: intraocular injections of [ 3H]adenosine, fluorescent tracer (Evans Blue) and the iontophoretic deposit of HRP on the optic nerve. Retrogradely labeled neurons were identified bilaterally within the nucleus M5 of Schober and contralaterally in the reticular mesencephalic area (RMA). Comparison of the various orthograde and retrograde labeling results indicated that the neurons of M5 and RMA were labeled via retrograde axonal transport of the different tracers in the retinopetal system and not by orthograde transneuronal processes or from extraretinal pathways. Part of the anatomical data regarding RMA as a site of origin of the centrifugal visual system was confirmed using electrophysiological techniques involving evoked potential and unit cell recordings in RMA following electrical stimulation of the optic nerve. The experiments were performed in the curarized animal under conditions of either normal blood circulation perfusions of adapted physiological saline, or with a solution known to block chemical synaptic transmission. Various electrophysiological criteria, including the results obtained during the conditions of reversible chemical synaptic blockade, indicated that the responses in RMA reflect an antidromic process. The anatomical organization of the centrifugal visual system in the lamprey is compared to that found in different gnathostome vertebrate species. Several hypotheses concerning the marked interspecies differences related either to the number and the topographical location of the centrifugal neurons as well as the evolution of this system are advanced.

Radioautographic evidence for both orthograde and retrograde axonal transport of labeled compounds after intraocular injection of [ 3H]proline in the lamprey ( Lampetra fluviatilis)

[ 3H] Proline injected intraocularly in lampreys has been shown to be bidirectionally transported: 24–96 h after the injection, retinofugal fibers and terminals as well as nerve cell bodies at the origin of the retinopetal system were intensely labeled. These results are at variance with the generally held belief that [ 3H]proline is taken up only by cell bodies and transported by the anterograde flow. The significance of the retrograde axonal transport of [ 3H]proline in the lamprey retinopetal system is discussed.

Distribution of neurons projecting to the retina of Caiman crocodilus.

Horseradish peroxidase (HRP) was injected into the vitreous of the eye, the orbital cavity, or the optic tectum of Caiman crocodilus. Following intravitreal injections, retrograde transport of the enzyme was observed bilaterally, but predominantly contralaterally, in a large oblong field of cells at the isthmic level of the midbrain, bounded medially by the trochlear nucleus and laterally by the nucleus isthmi. Control injections of HRP into the orbital cavity and eye muscles labelled motoneurons of the extraocular muscles but not cells of this isthmic field. The field is therefore the source of a projection efferent to the retina in Caiman. Injections of HRP into the dorsal optic tectum produced a fine pattern of anterograde labelling in fibers projecting to the region in which retinopetal cells were identified, but no retrograde labelling of cells in this area. In contrast, the nucleus isthmi showed dense anterograde labelling of fibers and terminals as well as retrograde labelling of cells following tectal injections. These results extend recent evidence for a close evolutionary relationship between the order Crocodilia and modern birds, since birds also possess a well-developed retinopetal system derived from a cell group in the isthmic midbrain.