The organization of retinal projections to the diencephalon and pretectum in the cichlid fish, Haplochromis burtoni

The organization of retinofugal projections was studied in a cichlid fish by labelling small groups of retinal ganglion cell axons with either horseradish peroxidase or cobaltous lysine. Two major findings resulted from these experiments. First, optic tract axons show a greater degree of pathway diversity than was previously appreciated, and this pathway diversity is related to the target nuclei of groups of axons. The most striking example is the formation of the medial optic tract. Fibers that will become the medial optic tract move abruptly away from their neighbors, at about the level of the optic chiasm, and coalesce at the dorsomedial edge of the marginal optic tract. The medial optic tract projects to the thalamus, the dorsal pretectum, and the deep layer of the optic tectum. The axial optic tract is a group of fibers which segregates from the most medial portion of the marginal optic tract, at about the level of the optic chiasm. The axial tract stays medial to the marginal optic tract for a few hundred microns and then curves laterally to rejoin the marginal optic tract. At least some axial trat axons terminate in the suprachiasmatic nucleus. Within the marginal optic tract, retinal ganglion cell axons from a given retinal quadrant are always segregated into at least two groups. The smaller group projects to the superficial pretectal nucleus. The larger group projects to the superficial layer of the optic tectum. Second, each nontectal retinal termination site receives a unique pattern of retinal input. Within the pretectum the parvocellular superficial pretectal nucleus receives a highly retinotopically organized input from all retinal regions; the basal optic nucleus receives a roughly retinotopically organized input from all retinal regions; the dorsal pretectum receives an input from all retinal regions; and the central pretectal nucleus receives input only from the ventral hemiretina. Within the diencephalon the thalamus receives an input from all retinal regions, but this input is not retinotopically organized; the suprachiasmatic nucleus receives input from the region of central retina that lies just dorsal to the optic nerve head, via the axial optic tract. The accessory optic nucleus receives input from the dorsal hemiretina.     

Physiological Characterization of Pretectal Neurons Projecting to the Láteral Geniculate Nucleus in the Cat

Single neurons in the pretectal nucleus of the optic tract and posterior pretectal nucleus were extracellularly recorded in anaesthetized cats and tested for antidromic activation after electrical stimulation of the ipsilateral dorsal lateral geniculate nucleus. Cells were further characterized by their response latencies to electrical stimulation of the optic nerve head and the optic chiasm, and by responses to various visual stimuli. 46 out of 188 neurons (24%) were antidromically activated from the lateral geniculate nucleus at response latencies of 0.6 - 2.6 ms. They had low spontaneous activities and preferred fast-moving visual stimuli. 29 of the antidromically activated neurons (63%) could be activated from the optic chiasm with response latencies of 4–10 ms. Together with the mean conduction time of 0.8 ms between the optic nerve head and the optic chiasm, this indicates that they receive an indirect retinal input via fast-conducting Y-fibres. Sometimes antidromically activated neurons spontaneously showed irregular burst activity. During unidirectional stimulation with a large moving visual stimulus, burst activity became more regular, and interburst intervals and the duration of single bursts decreased. After the stimulus was stopped, interburst intervals slowly increased until prestimulation activity was restored. The response properties of these neurons could reflect the transfer of saccade-related visual as well as oculomotor signals through the pretectum to the visual thalamus.     

The pretectal nucleus lentiformis mesencephali of Rana pipiens

The pretectal nucleus lentiformis mesencephali (nLM) of Rana pipiens was investigated with autoradiographic, horseradish peroxidase (HRP), and Golgi techniques. Retinal afferents to nLM originate primarily from the central retina. The primary projection is contralateral with a small ipsilateral component. Following optic nerve transection and HRP impregnation, contralateral retinal afferents show a restricted, dense core of HRP label in the superficial portion of the nucleus with sparser HRP label in the surround. Ipsilateral retinal afferents arborize throughout nLM, except in the dense-core region. Additional afferents to nLM originate from the ipsilateral tectum, the nucleus rotundus, the mesencephalic pretectal gray, the contralateral nLM, and the nucleus of the basal optic root. Afferents from the accessory optic system arborize only in the dense-core region, following HRP injections into the nucleus of the basal optic root, while afferents from the mesencephalic pretectal gray arborize in all parts of nLM except the dense core. Afferents from the tectum and anterior thalamus appear to arborize throughout the nucleus without discernible pattern. The lamination of afferent terminals in nLM was correlated with Nissl-stained cytoarchitectural material in which the majority of large neurons cluster around the dense core of nLM. Three types of neurons occur in nLM: large neurons (25-micron dia.), fusiform neurons (12.5-micron dia.), and stellate neurons (10-micron dia.). Additionally, two cell groups outside nLM which send dendrites into the nucleus were observed: cells of the posterior lateral nucleus and cells of the posterior thalamic pretectal gray. Both large and fusiform neurons project to the deep layers of the optic tectum as well as to the ventral rhombencephalon superficial to the abducens nucleus. While a small number of fusiform neurons project to the nucleus of the basal optic root, the stellate neurons appear to be intrinsic to nLM. The anuran nLM strongly resembles the nucleus of the optic tract in mammals in terms of the site of origin of its retinal afferents, lamination of afferent terminations, its central connections, and its demonstrated involvement in horizontal optokinetic nystagmus.     

Gradients of ephrin-A2 and ephrin-A5b mRNA during retinotopic regeneration of the optic projection in adult zebrafish

Regeneration of optic axons in the continuously growing optic system of adult zebrafish was analyzed by anterograde tracing and correlated with the mRNA expression patterns of the recognition molecules ephrin-A2 and ephrin-A5b in retinal targets. The optic tectum and diencephalic targets are all reinnervated after a lesion. However, the rate of erroneous pathway choices was increased at the chiasm and the bifurcation between the ventral and dorsal brachium of the optic tract compared to unlesioned animals. Tracer application to different retinal positions revealed retinotopic reinnervation of the tectum within 4 weeks after the lesion. In situ hybridization analysis indicated the presence of rostral-low to caudal-high gradients of ephrin-A2 and ephrin-A5b mRNAs in unlesioned control tecta and after a unilateral optic nerve lesion. By contrast, the parvocellular superficial pretectal nucleus showed retinotopic organization of optic fibers but no detectable expression of ephrin-A2 and ephrin-A5b mRNAs. However, a row of cells delineating the terminal field of optic fibers in the dorsal part of the periventricular pretectal nucleus was intensely labeled for ephrin-A5b mRNA and may thus provide a stop signal for ingrowing axons. Ephrin-A2 and ephrin-A5b mRNAs were not detectable in the adult retina, despite their prominent expression during development. Thus, given a complementary receptor system in retinal ganglion cells, expression of ephrin-A2 and ephrin-A5b in primary targets of optic fibers in adult zebrafish may contribute to guidance of optic axons that are continuously added to the adult projection and of regenerating axons after optic nerve lesion.     

Retinal Projections to the Pretectum, Accessory Optic System and Superior Colliculus in Pigmented and Albino Ferrets

Retinal projections to the pretectal nuclei, accessory optic system and superior colliculus in pigmented and albino ferrets were studied using anterograde tracing techniques. Both Nissl- and myelin-stained material was used to identify the pretectal nuclei, nuclei of the accessory optic system and the layers of the superior colliculus. Following monocular injection of either horseradish peroxidase or rhodamine-B-isothiocyanate, four pretectal nuclei, including the nucleus of the optic tract, posterior pretectal nucleus, anterior pretectal nucleus and the olivary pretectal nucleus, could be identified to receive direct retinal input in both pigmented and albino strains. In the accessory optic system, retinal terminals were observed in the dorsal, lateral and medial terminal nuclei as well as in the interstitial nucleus of the superior fasciculus, posterior fibres. The retinal projection to the superior colliculus was found to innervate the three superficial layers. The retinal projections to the pretectal nuclei and nuclei of the accessory optic system in the pigmented animals were bilateral, although the label was most dense contralateral to the injected eye. Ipsilateral retinal projections to the pretectal nuclei and nuclei of the accessory optic system appeared to be absent in albino ferrets, i.e. they were invisible with our methods. In both pigmented and albino ferrets retinal terminals in the contralateral superior colliculus densely innervated the three superficial layers. In both strains the ipsilateral projection appeared as clusters which were absent in rostral and caudal poles. In pigmented animals the ipsilateral projection was much denser and more extensive than in albinos. Following injection of retrograde tracers into the brainstem at the level of the dorsal cap of the inferior olive, retrogradely labelled neurons in the pretectum were found in the ipsilateral nucleus of the optic tract. Their somata overlapped mainly with scattered retinal terminals close to the pretectal surface and rarely or not all with the deeper prominent terminal clusters. In the accessory optic system, inferior olive projecting neurons were observed in all four ipsilateral nuclei and fully coincided with the retino-recipient zones. In the superior colliculus, retrogradely labelled neurons were found contralateral to the injection site in the deep layers.     

Central pupillary light reflex circuits in the cat: I. The olivary pretectal nucleus

The central pathways subserving the feline pupillary light reflex were examined by defining retinal input to the olivary pretectal nucleus (OPt), the midbrain projections of this nucleus, and the premotor neurons within it. Unilateral intravitreal wheat germ agglutinin–conjugated horseradish peroxidase (WGA–HRP) injections revealed differences in the pattern of retinal OPt termination on the two sides. Injections of WGA–HRP into OPt labeled terminals bilaterally in the anteromedian nucleus, and to a lesser extent in the supraoculomotor area, centrally projecting Edinger–Westphal nucleus, and nucleus of the posterior commissure. Labeled terminals, as well as retrogradely labeled multipolar cells, were present in the contralateral OPt, indicating a commissural pathway. Injections of WGA–HRP into the anteromedian nucleus labeled fusiform premotor neurons within the OPt, as well as multipolar cells in the nucleus of the posterior commissure. Connections between retinal terminals and the pretectal premotor neurons were characterized by combining vitreous chamber and anteromedian nucleus injections of WGA–HRP in the same animal. Fusiform‐shaped, retrogradely labeled cells fell within the anterogradely labeled retinal terminal field in the OPt. Ultrastructural analysis revealed labeled retinal terminals containing clear spherical vesicles. They contacted labeled pretectal premotor neurons via asymmetric synaptic densities. These results provide an anatomical substrate for the pupillary light reflex in the cat. Pretectal premotor neurons receive direct retinal input via synapses suggestive of an excitatory drive, and project directly to nuclei containing preganglionic motoneurons. These projections are concentrated in the anteromedian nucleus, indicating its involvement in the pupillary light reflex. J. Comp. Neurol. 522:3960–3977, 2014. © 2014 Wiley Periodicals, Inc.     

Fetal tectal transplants in the cortex of adult rats become innervated both by retinal ganglion cell axons regenerating through peripheral nerve grafts and by cortical neurons

The present work elucidates the connectivity of adult retinal ganglion cell axons regenerating through grafted peripheral nerve segments with co-grafted immature brain target cells. The optic nerve of rats was transected intraorbitally and its segment distal to the transection was replaced by a 3 cm length of peroneus communis graft, that is known to permit regeneration of a certain proportion of the severed axonal population. Five weeks after optic nerve transection and peripheral nerve transplantation the regenerating optic tract axons were guided into rat fetal mesencephalic co-grafts (E14-16) placed in superficial cavities prepared in the occipital cortex. The rationale of the experimental setup was based on the fact that regrowth of retinal axons started at the 6th day after transection, whereas the fastest-growing axons reached the distal end of the transplanted peripheral nerve 4 weeks later growing with a velocity of about 1.33 mm/day. Therefore, grafting the fetal superior colliculus at the time axons arrive distally resulted in ingrowth of several hundreds of retinal axons into this immature, retinoreceptive brain tissue. Retinal axons which penetrated the fetal grafts contacted tectal neurons and GFAP-immunoreactive glia and formed typical retinocollicular axonal arbors as detected by anterograde labeling with RITC from the retina. In addition, sprouting fibers from the adjacent adult cortical neurons penetrated frequently the fetal transplants. By 'bridging' lesions with peripheral nerve pieces and providing immature neurons as targets for growing neurites, this transplantation model is suitable for investigations on whether regenerating adult neurites are capable of reforming connections. The co-transplantation technique may serve as a tool for understanding whether interrupted circuitries in the central nervous system can be functionally restored over long distances by the use of peripheral nerve grafts and immature nervous system tissue.     

The dendritic architecture of the visual pretectal nuclei of the rat: a study with the Golgi-Cox method

The dendritic architecture of the neurons of the visual pretectal nuclei in the rat was studied with the Golgi-Cox method. The olivary pretectal nucleus (PO) is characterized by distinctive neurons with a gnarled, tufted, richly branched dendritic arbor forming a dense neuropil within the nucleus. The distinct dendritic morphology of the olivary pretectal neurons enables this nucleus to be identified at all levels of the pretectum in Golgi-impregnated preparations. Rostromedially, the PO is surrounded by peripheral neurons whose dendrites wrap around the surface of the PO. The nucleus of the optic tract (NTO) contains three types of cells: (1) superficial horizontal cells whose dendrites extend out transversely; (2) large multipolar neurons whose dendrites spread out predominantly in a transverse plane, and (3) small to medium multipolar neurons with varying dendritic architecture. The posterior pretectal nucleus (PP) is composed predominantly of (1) multipolar cells with horizontally and vertically oriented dendrites extending out transverse to the optic axons; (2) piriform cells with dendrites extending dorsally toward the brachium; and (3) small multipolar neurons. The presence of superficial horizontal and large multipolar neurons in the NTO distinguishes the NTO from the PP in Golgi preparations. The horizontally oriented dendrites of many of the multipolar neurons in the PP give this nucleus an appearance distinct from that of the NTO. The differences in dendritic morphology between the visual pretectal nuclei in the rat permit identification of these nuclei at all levels within the pretectum. The boundaries of these nuclei, as determined in the Golgi-Cox preparations, correlate quite well with the boundaries defined by studying retinal projections (Scalia and Arango, '79).     

Topography of the retinal projection to the superficial pretectal parvicellular nucleus of goldfish: a cobaltous-lysine study

The retinal projection to the superficial pretectal parvicellular nucleus (SPp) of goldfish was examined by filling select groups of optic axons with cobaltous-lysine. The tracer was applied intraocularly to peripheral retinal slits in some fish. In other fish, it was applied to optic axons from an intact hemiretina after one-half of the retina was ablated and the corresponding optic axons had degenerated. The results indicated that SPp is a folded structure, having a dorsal surface innervated by axons from temporal retinal ganglion cells and a ventral surface innervated by axons from nasal retinal ganglion cells. Peripheral retina innervates the anterodorsal and anteroventral edges of SPp, while central retina innervates the posterior genu. Dorsal retina innervates lateral SPp and ventral retina innervates medial SPp. Thus, although SPp is a folded nucleus, the topography of the retino-SPp projection is similar to the topography of the retinotectal projection. That is, the relative position of optic axons within SPp mirrors the retinal location of the ganglion cells that project to SPp. Retino-SPp axons occupy the center of the main optic tract before it divides into the two optic brachia. These axons are topographically arranged, with temporal retino-SPp axons being flanked on both sides by nasal retino-SPp axons. Retino-SPp axons arborize within SPp and then continue to enter the superficial tectal retino-recipient lamina. Thus, these axons innervate both SPp and the optic tectum. These findings are discussed with respect to chemospecific and morphogenetic views of visual system topography.     

Retinofugal and retinopetal projections in the green sunfish, Lepomis cyanellus

The retinofugal and retinopetal connections in the green sunfish were studied by autoradiographic and horseradish peroxidase methods. All retinofugal fibers decussate in the optic chiasm. Some fibers project to contralateral preoptic and hypothalamic nuclei while others recross to project to the comparable ipsilateral nuclei. Contralaterally, the medial optic tract projects to the periventricular thalamic and pretectal nuclei and, sparsely, to the rostral optic tectum. The dorsal optic tract projects to the parvocellular portion of the superficial pretectal nucleus, the central pretectal nucleus, nucleus corticalis, and the rostral portion of the optic tectum. The ventral optic tract primarily projects to the caudal portion of the optic tectum, giving off fibers in route to innervate various nuclei, including the parvocellular superficial pretectal nucleus and the dorsal and ventral accessory optic nuclei. The axial optic tract projects to the dorsal accessory optic nucleus, the central pretectal nucleus, and the caudal optic tectum. Retinal fibers reach the ipsilateral thalamus, pretectum and other sites via a redecussation through the posterior commissure. From outgroup analysis it is concluded that such redecussating fibers are an independently derived character within actinopterygians and are homoplasous to nondecussating ipsilateral retinal projections in other vertebrates. Neurons retrogradely labeled with horseradish peroxidase were found to form a rostrocaudal column from the olfactory bulb and nerve through the ventral telencephalon to caudal diencephalic levels along the medial aspect of the optic tract. It is possible that all these neurons consist of one population of migrated ganglion cells of the nervus terminalis.     

The mormyrid mesencephalon. III. Retinal projections in a weakly electric fish, Gnathonemus petersii

The optic nerve and the retinal projections were studied in a mormyrid fish, Gnathonemus petersii, by using Fink-Heimer, HRP, cobalt labeling, and autoradiographic tracing techniques. The retinal fibers terminate bilaterally in the following places: suprachiasmatic nucleus, dorsolateral optic nucleus, optic nucleus of the posterior commissure, cortical nucleus, ventral pretectal area, optic tectum, and the accessory optic terminal field. The number of uncrossed fibers is relatively high in the suprachiasmatic nucleus, but negligibly small in the other retinal terminal fields. In the lateral geniculate nucleus and pretectal nucleus only crossed retinal fibers could be detected. The visual system of Gnathonemus is compared to that of other fishes, amphibians, and reptiles and the possible homologies are proposed. The comparison points to the conclusion that the visual system is less developed in Gnathonemus. This nocturnal species lives in turbid waters and has a special electric sense which may permit compensation for the reduced visual capacity.     

Cells in the pretectal olivary nucleus are in the pathway for the direct light reflex of the pupil in the rat

Extracellular microelectrode recordings from 148 single cells in the pretectum of the hooded rat were classified according to their temporal response properties to light stimulation of their retinal receptive fields. Fifty-six cells were classified as tonic-on cells, 22 cells were classified as tonic-off cells, and 53 cells were classified as phasic cells. Seventeen cells could not be assigned to one of these 3 groups. The diameters of the receptive field centers of the tonic-on pretectal cell were clustered about a mean of 31° and the temporal response of these cells was sustained. Constriction of the contralateral pupil was produced by electrical stimulation through the recording electrode at sites containing tonic-on pretectal cells, but not at sites containing tonic-off pretectal cells or phasic pretectal cells. For this reason, we argue that tonic-on cells are likely to mediate constriction in the light reflex of the rat's pupil. Receptive field maps together with electrolytic marking lesions at recording and stimulation sites showed that tonic-on pretectal cells are retinotopically organized and are aggregated in a strip running from the dorso-medial tip of the pretectum to the ventro-lateral boundary. The anatomical distribution of these cells is coextensive with the region known as the pretectal olivary nucleus (PO) in the rat^26,27.Using fine microelectrodes, recordings were obtained from 27 axons presumed origin (fibers). Of these, 14 were tonic-on, 10 were phasic, 2 were tonic-off, and 2 were unclassified. Recordings from tonic-on fibers were obtained near tonic-on pretectal cells, typically in the most dorsal light-responsiveness region of the pretectum. These fibers were activated by single pulse electrical stimulation of the optic chiasm. The mean receptive field center diameter of 6 tonic-on fibers was 10.1°, or about a factor of 3 less than that of pretectal tonic-on cells. The mean conduction velocity of 14 tonic-on fibers was 3.1 m/s.We argue that the tonic-on cells of the PO serve to integrate signals from tonic-on center retinal ganglion cells with adjacent receptive fields to provide signals for constriction of the pupil to neurons in the oculomotor nucleus.     

Kainic acid differently affects retinal projections to different pretectal nuclei.

Kainic acid (KA) damages retinal cells, thus impairing axonal anterograde transport of labeled aminoacids when injected intravitreally. In this study, Long-Evans rats were injected with KA into one eye, and seven days later were binocularly injected with 14C-valine. The extent of residual retinal afferents to two pretectal nuclei was calculated as the percentage of the contralateral, intact side. Projections to the nucleus of the optic tract (first relay station of the optokinetic pathway) appear significantly more affected than those to the olivary pretectal nucleus (involved in the pupillary light response). These results suggest a correlation between the functional properties of retinal ganglion cells and distinctive biochemical characteristics, such as their susceptibility to KA.     

Retinal graft-mediated pupillary responses in rats: restoration of a reflex function in the mature mammalian brain

We have shown previously that fetal retinae transplanted to neonatal rat brains are capable of making the pretectal connections necessary for driving a pupillary reflex in response to light. At birth, the rat brain is still developing and presents a favorable environment for fiber outgrowth and synaptogenesis. A remaining question is whether such grafts will also establish functional connections within the less plastic mature brain. Fetal retinae taken from Sprague-Dawley rats at embryonic day 13 or 14 were implanted in the pretectal region of mature host rats ranging in age from 6 to 11 weeks. The contralateral host eye was removed to reduce afferent competition within the pretectum between the optic input of graft and host. The remaining host optic nerve was cut before testing to eliminate all remaining host visual input. Beginning 1 month after transplantation, the retinae were surgically exposed and illuminated. In 6 of 24 animals, illumination elicited an obvious pupilloconstriction response in the host eye. The magnitude of this graft-mediated response varied between animals. Two animals produced very brisk responses, comparable to the best results seen following transplantation into neonatal hosts. In these cases, the degree of constriction was clearly dependent on the level of graft illumination. The 4 other animals produced responses that were less brisk. All 6 animals with clear-cut graft-mediated pupillary responses had well-formed grafts containing numerous rosettes and ganglion cells. In addition to these 6 animals, 9 others showed extremely small or variable pupillary changes on graft illumination. The remaining 9 animals showed no stimulus-associated pupillary activity. Grafts in this group tended to be poorly formed or were located outside the pretectal area. These results show that transplanted retinae are capable of making specific functional connections with the mature brain, since an appropriate visual reflex can be elicited by illuminating the graft in the absence of host visual input.     

Anatomical and behavioral correlates of a xenograft-mediated pupillary reflex

Retinae from mouse embryos were transplanted to the midbrain of neonatal rats which were unilaterally enucleated at the time of transplantation. At maturity the host's remaining optic nerve was cut and the skull over the transplant was removed. Illumination of the transplant caused pupilloconstriction of the host eye, a response abolished by removal of the transplant or damage to the olivary pretectal nucleus which is the pupilloconstriction center of the brain stem. The degree of constriction correlated with the intensity of transplant illumination. Using mouse-specific monoclonal antibodies, we demonstrated that the grafts projected only to areas of the brain stem normally innervated by the eye. The density of label in the olivary pretectal nucleus did not, however, correlate with the briskness of the graft-mediated pupillary reflex. In summary, this study shows that ectopic neural xenografts are capable of making specific connections which can drive an appropriate response to a natural stimulus in the host animal. While important in showing the ability of transplants to make specific connections, this study also provides a simple assay system for examining conditions which may influence the efficacy of host innervation by the transplant.     

Retinofugal and retinopetal projections in the cichlid fish Astronotus ocellatus

The retinofugal and retinopetal projections of the cichlid fish Astronotus ocellatus were studied by applying cobaltous-lysine to the optic nerve. Retinal axons terminate bilaterally in a preoptic-suprachiasmatic region between the base of the third ventricle and the anterior genu of the horizontal commissure and among periventricular cells along the sides of the ventricle. Other retinal axons innervate the tuberal region of the hypothalamus anterior to the infundibulum. Targets innervated in the pretectum include nucleus lateralis geniculatus and dorsal, medial, and ventral pretectal nuclei. Three other targets (nucleus opticus dorsolateralis, nucleus opticus commissurae posterior, nucleus opticus ventrolateralis) are innervated by fibers that leave the medial edge of the dorsal optic tract. Two other targets (basal optic nucleus and accessory optic nucleus) are innervated by fibers from the ventral optic tract. These retinal projections are similar to those previously reported for goldfish in an experiment that used the cobaltous-lysine method (Springer and Gaffney, J. Comp. Neurol. 203:401-424, '81). Retinotectal optic axons were found in a superficial lamina just above the stratum opticum, in the stratum opticum, in three layers of the stratum fibrosum et griseum superficiale, in a lamina just beneath the stratum fibrosum et griseum superficiale, and in the stratum album centrale just above the stratum periventriculare. This result is similar to that previously reported for goldfish; however, the spatial relationships between the various retinorecipient laminae differ for goldfish and Astronotus ocellatus. Efferents to the retina originate in two nuclei and both project contralaterally. The first is the nucleus olfactoretinalis, which is located ventrally between the olfactory lobe and telencephalon. It consists of about 400 cells, of which, approximately 200 cells project to the retina. The second retinopetal nucleus, nucleus thalamoretinalis, is a diffuse group of about 200 cells that project to the retina.     

Electrophysiology of optic nerve input to suprachiasmatic nucleus neurons in rats and degus

Neurons in the mammalian suprachiasmatic nucleus (SCN), the principal pacemaker of the circadian system, receive direct retinal input. Some SCN neurons respond to retinal illumination or optic nerve stimulation with changes in firing rates. In nocturnal rodents, retinal illumination increases firing rates of a large majority and decreases firing rates of a minority of responsive neurons. In two species of diurnal rodent, these proportions are altered or even reversed. Since retinal input to the SCN has been reported to involve release of the excitatory neurotransmitter glutamate, the mechanism mediating suppressions is unknown. We studied responses of neurons in SCN slices from diurnal degus and nocturnal rats to optic nerve stimulation. To test whether suppressions are mediated indirectly by release of the inhibitory neurotransmitter GABA from SCN neurons that are first activated by glutamate release, we attempted to block suppressions by adding to the bath either APV, an antagonist for excitatory glutamate receptors, or bicuculline, a GABA_A receptor antagonist. If glutamate is the only neurotransmitter released by optic nerves in the SCN, APV should prevent both activations and suppressions in response to optic nerve stimulation. We found that APV had little effect on suppressions although it effectively blocked activations. Bicuculline blocked most suppressions. These findings are inconsistent with a model in which the retina provides only excitatory glutamate input to the SCN via NMDA receptors. Since some retinal fibers in adult mammals contain GABA, it is possible that the retinal innervation of the SCN includes both glutamate- and GABA-containing axons.     

Basic optokinetic-ocular reflex pathways in the frog

Frogs (Rana temporaria) have two midbrain nuclei that receive contralateral retinal afferents, and whose neurons respond to optokinetic stimulation. The basal optic nucleus is composed of direction-selective neurons with different response types. One type is activated exclusively by upward moving optokinetic targets; another type is activated only by downward moving targets. Two other types of basal optic neurons show this vertical preference, but each is also activated by patterns moved horizontally from the nasal to temporal visual field. No activation of these cells was found with patterns moved horizontally from the temporal to nasal visual fields. Rather, cells in a discrete pretectal region have this type of sensitivity: they increase their resting rate with temporal to nasal stimulation and decrease it with nasotemporal stimulation. Oculomotor neurons (antidromically identified) have similar optokinetic sensitivities. As with basal optic neurons, these cells have exclusively upward or downward sensitivity, and some also have nasotemporal sensitivity. An additional type of oculomotor neuron and abducens motoneurons are activated by temporonasal pattern movement. In general, the extraocular motoneurons have similar velocity and pattern size preferences, as have the sensory nuclei. Investigations of the connectivity between the sensory and motor nuclei were primarily restricted to the relation between the pretectum and the abducens. A monosynaptic connection between the pretectum and the abducens is suggested by four points: (1) excitatory postsynaptic potential onset latency in antidromically identified abducens motoneurons, following optic nerve stimulation, is consistent with the interpretation of a disynaptic pathway to the abducens from the retina; (2) pretectal cells, sensitive to optokinetic stimulation, can be activated antidromically from stimulation of the abducens nucleus; (3) horseradish peroxidase injections into the pretectum result in labeling of axons, which terminate in the abducens nucleus; (4) horseradish peroxidase injections into the abducens result in labeling of cells in the pretectal region, where optokinetically sensitive cells are found. In the frog, there seem to be three-neuronal retino-ocular reflexes mediating optokinetic slow phase behavior as there are three-neuronal vestibulo-ocular reflexes that also mediate compensatory spatial behavior. It is suggested that these direct connections act to initiate ocular movements and accelerate the eye, whereas more indirect pathways may act to maintain eye position.     

Immunohistochemical studies on neurofilamentous hypertrophy in degenerating retinal terminals of the olivary pretectal nucleus in the rat

Following section of the optic nerve, degenerating retinal terminals reveal an accumulation of neurofilaments (neurofilamentous hypertrophy) as demonstrated by silver impregnation techniques or electron microscopy. The present study examined degenerating retinal terminals by means of immunohistochemistry and antibodies specific for the triplet of neurofilament proteins of low (NF-L), medium (NF-M), and high (NF-H) molecular weight class. Following unilateral optic nerve section in the rat and survival 1,2,4,8, and 21 days, brains were perfused with aldehyde fixative, sliced on a vibratome and stained for neurofilaments by using the peroxidase-antiperoxidase technique. Other brains were frozen, cut in the native state, and slid-mounted sections were fixed by acetone. Side comparisons in visual pathways were made in frontal sections, taking advantage of the near complete crossing of retinal fibers in the rat. Anterograde degeneration of axons occurred in the optic tract and brachium colliculi. Changes of terminals were investigated in the olivary pretectal nucleus, which contains a dense aggregation of retinal terminals in the core region. The optic tract and brachium coliculi showed a reduction in imunostaining for neurofilament proteins following axotomy. Within the core region of the olivary pretectal nucleus, strong increases of immunoreactivity of NF-L and NF-M were detected begining at 2 days postlesion and persisting at 8 days. No changes in NF-H proteins were found in the terminal regions with three different antibody probes. The increase in immunostaining reflects the accumulation of neurofilament proteins in the degenerating retinal terminals, i.e., neurofilamentous hypertrophy. A combination of increased influx of neurofilaments into the terminals and decreased local degradation by calciumactivated neutral protease might explain the accumulations. The selective occurrence of NF-L and NF-M suggests molecular specificity of the degenerative process, which may be related to differences in axonal transport, integration into the stationary cytoskeleton, and phosphorylation state of different neurofilament proteins. © 1993 Wiley-Liss, Inc.