An autoradiographic study of the retinal projections in the Formosan monkey

This study investigated the retinal projections of the adult Formosan rock monkey by monocular injection of radioactive proline and fucose. We found that the retinofugal fibers terminated bilaterally in the suprachiasmatic, pregeniculate, lateral geniculate, pretectal complex, pulvinar nucleus, superior colliculus, dorsal and lateral terminal nuclei of the accessory optic system. More crossed retinal terminations were observed, with the exception that the suprachiasmatic nucleus received almost equally of both retinal projections. The existence of the retinal projection to the medial terminal nucleus of the accessory nucleus was in doubt. In the geniculate nucleus, the retinal fibers terminated contralaterally in layers 1, 4 and 6; and ipsilaterally in 2, 3 and 5. In the superior colliculus, most retinal fibers were aggregated superficially in a band located in the contralateral striatum griseum superficialis of the superior colliculus, and had few gaps on the ipsilateral one. The present investigation shows that the Formosan rock monkey has a similar pattern of optic fiber distribution to that of other macaques.     

Retinofugal projections in the eel,Anguilla anguilla L. (Teleostei), visualized by the cobalt-filling technique

The retinofugal projections in the eel were studied by use of the cobalt-filling technique. The optic tract projects contralaterally to the hypothalamic optic nucleus, the anterior periventricular nucleus, the lateral geniculate nucleus, the dorsomedial optic nucleus, four pretectal recipient areas, the optic tectum, and the tegmentum. Small ipsilateral projections were demonstrated in the hypothalamic optic nucleus, the dorsomedial optic nucleus, and the optic tectum.     

Topography of retinal axons in the diencephalon of goldfish

Summary The projections of horseradish peroxidase-filled axons from each quadrant of the retina were studied to determine whether retinal projections of goldfish are topographically organized in diencephalic target nuclei. A distinct topography of the dorsal, nasal, ventral and temporal retina exists in the lateral geniculate nucleus and in the dorsolateral optic nucleus of the thalamus. The projections of retinal quadrants show minimal spatial overlap in each of these nuclei. The suprachiasmatic nucleus of the hypothalamus is extensively innervated by ventral retinal fibers, whereas the nucleus is sparsely innervated by fibers from the other three retinal quadrants. A rudimentary topography also exists in the pretectum where the dorsal pretectal area receives projections primarily from the ventral retina and the ventral pretectal area receives projections mostly from the dorsal retina. These data show that retinal projections to some diencephalic nuclei are topographically organized.This work was supported by Research Grant EY-01426 to S.C.S.     

Retinofugal and retinopetal connections in the upside-down catfish (Synodontis nigriventris)

Summary The retinofugal and retinopetal connections in the upside-down catfish Synodontis nigriventris were studied by use of the horseradish-peroxidase (HRP) techniques, autoradiography, and degeneration-silver methods. An unusual retinal projection to the torus semicircularis as well as projections to the retina from three different sources in the brain are described. After intra-ocular injections of HRP, labeled cells were found in the optic tectum, the dorsomedial optic nucleus and one of the pretectal nuclei. These new findings support the basic hypothesis (i) that neuronal connections are more extensive in primitive brains, and (ii) that the evolutionary development of more complex brains involves the loss of some selected connections.     

Retinal projections in European Salamandridae

Summary The retinal projections to the brain were studied in three species of European Salamandridae using anterograde transport of horseradish peroxidase and autoradiography. The results obtained were basically identical for all species and confirmed earlier findings on the fiber supply to the preoptic nucleus and the basal optic neuropil. In the anterior thalamus projections to three distinct terminal fields are clearly visible: (i) the diffusely stained corpus geniculatum thalamicum, (ii) the neuropil of Bellonci, pars lateralis, and (iii) a dorsomedial terminal field, the neuropil of Bellonci, pars medialis. Caudal to these terminal fields is an almost terminal-free region, the lateral neuropil. In the posterior thalamus a medial terminal field, the uncinate field, and a laterally located terminal field, the posterior thalamic neuropil, are distinguishable. The tectum opticum displays as many as four dense layers of retinofugal fibers and terminals in the rostral part and, in addition, a more densely stained strip of neuropil running from rostral to caudal over the tectum. The extent of ipsilateral fibers is greater than previously reported in other urodele species. They supply the medial and the lateral parts of the neuropil of Bellonci, the uncinate field, and reach the tectum opticum via the medial optic tract. Further, they form terminals in the innermost optic fiber layer throughout the rostral half of the ipsilateral tectum. A small proportion of ipsilateral fibers contributes very sparsely to all other thalamic terminal fields, leaving only the caudal part of the tectum and several layers of the rostral tectum completely free of a direct retinofugal fiber supply.     

Terminal distribution of retinal fibers in the tegu lizard (Tupinambis nigropunctatus)

Summary The retinal projections in the tegu lizard were traced using degeneration-silver methods. Bilateral projections were found to the dorsolateral geniculate and the posterodorsal nuclei. Unilateral, crossed projections were traced to the suprachiasmatic nucleus, the ventrolateral geniculate nucleus, the mesencephalic lentiform nucleus, nucleus geniculatus praetectalis, the ectomammillary nucleus, and the optic tectum. Some of these connections are distinctly different from those reported in other reptiles and suggest that important interspecific variations occur among reptiles.     

The development of the retinogeniculate pathways in normal and albino ferrets

The retinogeniculate pathways of normal and albino ferrets have been studied with horseradish peroxidase and tritiated proline used as axonal markers. The uncrossed retinogeniculate projection of adult albino ferrets is abnormally small and occupies only a fraction of the geniculate area normally occupied by uncrossed afferents. The crossed pathway is correspondingly expanded, occupying almost the entire nucleus. The geniculate laminae in the albino ferret are abnormal, showing abnormal fusions between layers receiving crossed input and abnormal discontinuities next to the small cell islands receiving uncrossed afferents. In early development, retinofugal fibres can be labelled within the optic tracts on the 28th intrauterine day and a few crossed fibres can be traced into the lateral geniculate nucleus. At this stage, the uncrossed component is extremely small in normal and albino animals and cannot be traced beyond the tract. By day 32 retinal fibres are invading the lateral geniculate nucleus bilaterally, the invasion by the crossed component being significantly more advanced than that by the uncrossed component. The uncrossed pathway of the albinos is already abnormal in terms of its size, in terms of the position it occupies in the optic tract, and in terms of its limited invasion of the lateral geniculate nucleus. The abnormally reduced size of the uncrossed component appears earlier than the abnormal segregation of the retinogeniculate terminals, suggesting that the primary action of the albino gene upon central visual pathways is prechiasmatic. At postnatal stages (41 days after conception and older) the normal, gradual withdrawal of the uncrossed fibres from the monocular segment, and the separation of crossed from uncrossed retinogeniculate terminal arbors is significantly delayed in the albinos. The uncrossed retinogeniculate terminals are abnormally sparse initially and become distributed in an abnormal, interrupted pattern as development proceeds. The abnormal pattern of geniculate lamination appears to be secondary to the abnormal distribution of retinogeniculate afferents.     

Target areas innervated by PACAP-immunoreactive retinal ganglion cells

The retinohypothalamic tract (RHT) originates from a subset of retinal ganglion cells (RGCs). The cells of the RHT co-store the neurotransmitters PACAP and glutamate, which in a complex interplay mediate light information to the circadian clock located in the suprachiasmatic nuclei (SCN). These ganglion cells are intrinsically photosensitive probably due to expression of melanopsin, a putative photoreceptor involved in light entrainment. In the present study we examined PACAP-containing retinal projections to the brain using intravitreal injection of the anterograde tracer cholera toxin subunit B (ChB) and double immunostaining for PACAP and ChB. Our results show that the PACAP-containing nerve fibres not only constituted the major projections to the SCN and the intergeniculate leaflet of the thalamus but also had a large terminal field in the olivary pretectal nucleus. The contralateral projection dominated except for the SCN, which showed bilateral innervation. PACAP-containing retinal fibres were also found in the ventrolateral preoptic nucleus, the anterior and lateral hypothalamic area, the subparaventricular zone, the ventral part of the lateral geniculate nucleus and the nucleus of the optic tract. Retinal projections not previously described in the rat also contained PACAP. These new projections were found in the lateral posterior nucleus, the posterior limitans nucleus, the dorsal part of the anterior pretectal nucleus and the posterior and medial pretectal nuclei. Only a few PACAP-containing retinal fibres were found in the superior colliculus. Areas innervated by PACAP-immunoreactive fibres also expressed the PACAP-specific PAC1 receptor as shown by in situ hybridization histochemistry. The findings suggest that PACAP plays a role as neurotransmitter in non-imaging photoperception to target areas in the brain regulating circadian timing, masking, regulation of sleep-wake cycle and pupillary reflex.Abbreviations 3v Third ventricle - ac Anterior commissure - AD Anterodorsal thalamic nucleus - AH Anterior hypothalamic area - APTD Anterior pretectal nucleus, dorsal part - ChB Cholera toxin subunit B - CPu Caudate putamen - CPT Commissural pretectal nucleus - DGL Dorsal geniculate nucleus - IGL Intergeniculate leaflet - LH Lateral hypothalamic area - LP Lateral posterior thalamic nucleus - LS Lateral septum - MB Mammillary body - MPO Medial preoptic nucleus - MPT Medial pretectal nucleus - oc Optic chiasma - OPT Olivary pretectal nucleus - OT Nucleus of the optic tract - PACAP Pituitary adenylate cyclase-activating polypeptide - PAC1 PACAP receptor type 1 - PAG Periaqueductal gray - Pe Periventricular hypothalamic nucleus - PLi Posterior limitans thalamic nucleus - PPT Posterior pretectal nucleus - PVT Paraventricular thalamic nucleus - PVN Paraventricular hypothalamic nucleus - RGCs Retinal ganglion cells - RHT Retinohypothalamic tract - SCN Suprachiasmatic nucleus - SC Superior colliculus - SNR Substantia nigra, reticular part - SON Supraoptic nucleus - SPVZ Subparaventricular zone - VGL Ventral geniculate nucleus - VIP Vasoactive intestinal peptide - VPAC1 VIP/PACAP receptor type 1 - VPAC2 VIP/PACAP receptor type 2 - VLPO Ventrolateral preoptic nucleus - VTA Ventral tegmental areaThis study was supported by The Danish Biotechnology Center for Cellular Communication and The Danish Neuroscience Programme. J.H. is postdoc funded by the Danish Medical Research Council (Jr. No. 0001716)     

Primary optic projections in the rabbit. Study using the horseradish peroxidase anterograde labeling technic

The primary visual pathways, in particular those to the lateral geniculate body, of 11 albino and 7 pigmented rabbits, were studied using the method of anterograde labelling with horseradish peroxidase following injection of the tracer into the vitreous body of one eye. A heavy projection to the contralateral dorsal lateral geniculate nucleus was seen in all animals. In both albino and pigmented animals a region devoid of label was present in the medial part of the alpha sector of the nucleus. This region corresponded to a compact, oval or wedge-shaped field of terminal label in the ipsilateral nucleus, which was much heavier in pigmented than in albino rabbits. In the ventral lateral geniculate nucleus, contralateral retinal input was almost entirely confined to the caudal half of the lateral sector of the nucleus, where two laminae of dense terminal label, separated by a less densely labelled area, were oriented parallel to one another and to the optic tract. This bilaminar distribution of retinal afferents to the ventral lateral geniculate nucleus has not been described in previous studies. The ipsilateral projection was to the dorsal part of the lateral sector and was most prominent in pigmented animals. The "intergeniculate leaflet" received a prominent contralateral input in all animals, and a clear ipsilateral input in pigmented animals, which overlapped with the contralateral input. Projections to other primary visual centres (pretectal nuclei, superior colliculus, nuclei of the accessory optic tract) are also described.     

Retinal projections in the electric catfish (Malapterurus electricus)

Summary The poorly developed visual system of the electric catfish was studied with silver-degeneration methods. Retinal projections were entirely contralateral to the hypothalamic optic nucleus, the lateral geniculate nucleus, the dorsomedial optic nucleus, the pretectal nuclei including the cortical nucleus, and the optic tectum. The small size and lack of differentiation of the visual system in the electric catfish suggest a relatively small role for this sensory system in this species.     

Retinal projections in sockeye salmon smolts (Oncorhynchus nerka)

Summary The retinal projections in 2-year-old salmon smolt (Oncorhynchus nerka) are significantly different from those observed in other teleosts examined to date in that the projections are more extensive. Very noticeable are extensive projections to most of the dorsal thalamus, to all layers of the optic tectum, and into the periaqueductal gray of the torus semicircularis. The salmon smolt has bilateral retinal projections to the diencephalon and pretectum. A small retinal projection to the lateral habenular nucleus has not been described previously. Although these findings suggest striking differences in retinal projections among teleosts, this variation may relate to age differences since the previously studied teleosts were adults.     

Retinal projections in the catfish,Mystus vittatus (Bloch) as revealed by tracer studies with horseradish peroxidase

Summary The retinal efferents of the catfish, Mystus vittatus, were investigated with the use of the horseradish peroxidase (HRP) technique. Most retinal fibres extended contralateral to the eye that had received HRP label, while a few fascicles projected to the ipsilateral side without decussation in the optic chiasma. The contralateral fibres projected to the suprachiasmatic nucleus, the nucleus opticus dorsolateralis, the nucleus of the posterior commissure, the nucleus geniculatus lateralis, pretectal nuclear complex, and to two layers of the optic tectum, i.e., stratum fibrosum et griseum superficiale and stratum griseum centrale. The accessory optic tract arose from the inner area of the optic tract and extended ventromedially to the accessory optic nucleus. The ipsilateral fascicles projected to almost all the above mentioned nuclei, but these projections were comparatively sparse. The ipsilateral retinal projection was restricted to the rostral tectum.     

Bilateral retinal projections in the black piranah (Serrasalmus niger)

Summary The retinal projections were studied in the black piranah (Serrasalmus niger) with degeneration and autoradiographic methods. The projections are bilateral to the hypothalamic optic nucleus, the dorsomedial optic nucleus, corpus geniculatum ipsum of Meader (1934) and the optic tectum. Unilateral, crossed projections were traced to the pretectal nucleus and the cortical nucleus. The visual system of the black piranah is exceptionally well developed but has retained many primitive features including the extensive bilateral projections.     

Retinal projections of the pigmented guinea pig

Using 3H-proline autoradiography we found in the pigmented guinea pig that retinal fibres terminated bilaterally in the suprachiasmatic, lateral geniculate, some pretectal nuclei and in the superior colliculi. The medial, lateral and dorsal terminal nuclei of the accessory optic system appeared to receive only contralateral retinal fibres. The retinal projections of the guinea pig follow the general plan recognized in the visual system of rodents demonstrated by modern tract-tracing techniques.     

Demonstration of retinal afferents in the RCS rat,with reference to the retinohypothalamic projection and suprachiasmatic nucleus

In the Royal College of Surgeons (RCS) rat, characterized by inherited retinal dystrophy, retinal projections to the brain were studied using anterograde neuronal transport of cholera toxin B subunit upon injection into one eye. The respective immunoreactivity was found predominantly contralateral to the injection site in the lateral geniculate nucleus, superior colliculus, nucleus of the optic tract, medial terminal nucleus of the accessory optic tract, and bilateral hypothalamic suprachiasmatic nuclei. Although terminal density was somewhat reduced in dystrophic rats, the projection patterns in these animals appeared similar to those seen in their congenic controls and were comparable to the visual pathways described for the rat previously. In dystrophic rats, the number of cell bodies exhibiting immunoreactivity to vasoactive intestinal polypeptide, viz. a population of suprachiasmatic neurons receiving major retinohypothalamic input, was reduced by one-third, and some differences were observed in the termination pattern of the geniculohypothalamic tract, as revealed by immunoreactivity to neuropeptide Y in the suprachiasmatic nucleus.This study was supported by grants from the DFG (Re 644/2-1) and the NMFZ, Mainz (to S.R.).     

Retinofugal projections of the big brown bat, Eptesicus fuscus and the neotropical fruit bat, Artibeus jamaicensis

Retinal connections were studied in Eptesicus fuscus and Artibeus jamaicensis using anterograde axonal degeneration and autoradiographic techniques following unilateral enucleations and uniocular injections of radioactive amino acids. Although each retina projected bilaterally to the brainstem, the number of silver grains in the emulsion of autoradiographs indicated that nearly all fibers in the optic nerve entered the contralateral optic tract. Ipsilaterally, a major portion of the projection ended in the suprachiasmatic nucleus; caudal to the suprachiasmatic nucleus, the amount of label was so small that individual silver grains were counted to determine the location and quantity of label in other ipsilateral nuclei. In both species the retinal projection terminated bilaterally in the suprachiasmatic, dorsal lateral geniculate, ventral lateral geniculate, and pretectal olivary nuclei and contralaterally in the posterior pretectal nucleus, superficial gray layers of the superior colliculus, and nuclei of the accessory optic system. In Eptesicus the projection to the nucleus of the optic tract ended contralaterally, and in Artibeus it ended in this nucleus bilaterally. The results of this study revealed a basic theme in the optic projection of the two ecologically different microchiropterans. The results differed, however, in that the projection was larger and visually related nuclei were better developed in Artibeus. Such variations are presumed to relate to eye size and the relative use of vision by the two chiropterans.     

Termination of retinofugal fibers and lamination pattern in the lateral geniculate nucleus of the gibbon

The lateral geniculate nucleus (LGN) of the gibbon (Hylobates sp.) consists of four principal layers, i.e., layers 1 and 2 containing large somata and layers 3 and 4 comprising medium-sized neurons. In addition, there are intercalated layers S, imm and imp, each consisting of small cells. Tracing of retinofugal fibers with the autoradiographic method revealed that the retina projects to the ipsilateral layers 2, 3 and imp and to the contralateral layers 1, 4, S and imm. No 'hidden' layers have been found. This type of lamination pattern sets the LGN of the gibbon apart from that of all Old World monkeys, chimpanzee and man. Retinal projections to other subcortical regions are also described.     

Lagged cells

The timing of the retinal input to the lateral geniculate nucleus is highly modified in lagged cells. Evidence is reviewed for how the responses of these cells are generated, how their structure and function differs from their nonlagged neighbors, and what their projections to cortex might do.     

Retinofugal Projections from Melanopsin-Expressing Retinal Ganglion Cells Revealed by Intraocular Injections of Cre-Dependent Virus

To understand visual functions mediated by intrinsically photosensitive melanopsin-expressing retinal ganglion cells (mRGCs), it is important to elucidate axonal projections from these cells into the brain. Initial studies reported that melanopsin is expressed only in retinal ganglion cells within the eye. However, recent studies in Opn4-Cre mice revealed Cre-mediated marker expression in multiple brain areas. These discoveries complicate the use of melanopsin-driven genetic labeling techniques to identify retinofugal projections specifically from mRGCs. To restrict labeling to mRGCs, we developed a recombinant adeno-associated virus (AAV) carrying a Cre-dependent reporter (human placental alkaline phosphatase) that was injected into the vitreous of Opn4-Cre mouse eyes. The labeling observed in the brain of these mice was necessarily restricted specifically to retinofugal projections from mRGCs in the injected eye. We found that mRGCs innervate multiple nuclei in the basal forebrain, hypothalamus, amygdala, thalamus and midbrain. Midline structures tended to be bilaterally innervated, whereas the lateral structures received mostly contralateral innervation. As validation of our approach, we found projection patterns largely corresponded with previously published results; however, we have also identified a few novel targets. Our discovery of projections to the central amygdala suggests a possible direct neural pathway for aversive responses to light in neonates. In addition, projections to the accessory optic system suggest that mRGCs play a direct role in visual tracking, responses that were previously attributed to other classes of retinal ganglion cells. Moreover, projections to the zona incerta raise the possibility that mRGCs could regulate visceral and sensory functions. However, additional studies are needed to investigate the actual photosensitivity of mRGCs that project to the different brain areas. Also, there is a concern of "overlabeling" with very sensitive reporters that uncover low levels of expression. Light-evoked signaling from these cells must be shown to be of sufficient sensitivity to elicit physiologically relevant responses.     

Afferent connections of the optic tectum in channel catfish Ictalurus punctatus

Summary Horseradish peroxidase was injected unilaterally into the optic tectum of the channel catfish, Ictalurus punctatus. The sources of tectal afferents were thereby revealed by retrogradely labeled neurons in various brain centers. Retrogradely labeled cells were seen in both the ipsilateral and contralateral telencephalon. The superficial pretectal area was labeled on both sides of the brain. Ipsilateral projections were also observed coming from the entopeduncular nucleus. Both the anterior thalamic nucleus and the ventro-medial thalamic nucleus projected to the ipsilateral optic tectum. Cells in the ipsilateral nucleus of the posterior commissure were seen to project to the tectum. Labeled fibers were visualized in the lateral geniculate nucleus ipsilateral to the injected tectum, however, no labeled cell bodies were observed. Therefore, tectal cells project to the lateral geniculate nucleus, but this projection is not reciprocal. No labeled cells were found in the cerebellum. Labeled cells occurred in both the ipsilateral and contralateral medial reticular formation; they were also observed in the ipsilateral nucleus isthmi. A projection was seen coming from the dorsal funicular nucleus. Furthermore, labeled cells were shown in the inferior raphe nucleus.Abbreviations AP Area pretectalis - C Cerebellum - DPTN Dorsal posterior tegmental nucleus - H Habenula - IRF Inferior reticular formation - LI Inferior lobe - LGN Lateral geniculate nucleus - LR Lateral recess - MB Mammillary body - MRF Medial reticular formation - MZ Medial zone of the telencephalon - NC Nucleus corticalis - NDL-M Nucleus opticus dorsolateralis/pars medialis - NI Nucleus isthmi - NPC Nucleus of the posterior commissure - OPT Optic tectum - OT Optic tract - PC Posterior commissure - PN Pineal organ - PrOP Preoptic nucleus - PT Pretectum - TBt Tectobulbar tract - TEL Telencephalon - TL Torus longitudinalis - TS Torus semicircularis - VC Valvula cerebelli - VLTN Ventrolateral thalamic nucleus - VMTN Ventromedial thalamic nucleus