A crossed projection from the optic tectum to craniocervical premotor areas in the brainstem reticular formation. An anterograde and retrograde tracing study in the mallard (Anas platyrhynchos L.)

The optic tectum in birds receives visual information from the contralateral retina. This information is passed through to other brain areas via the deep layers of the optic tectum. In the present study the crossed tectobulbar pathway is described in detail. This pathway forms the connection between the optic tectum and the premotor area of craniocervical muscles in the contralateral paramedian reticular formation. It originates predominantly from neurons in the ventromedial part of stratum griseum centrale and to a lesser extent from stratum album centrale. The fibers leave the tectum as a horizontal fiber bundle, and cross the midline through the caudal radix oculomotorius and rostral nucleus oculomotorius. On the contralateral side fibers turn to ventral and descend caudally in the contralateral paramedian reticular formation to the level of the obex. Labeled terminals are found in the ipsilateral medial mesencephalic reticular formation lateral to the radix and motor nucleus of the oculomotor nerve, and in the contralateral paramedian reticular formation, along the descending tract. Neurons in the medial mesencephalic reticular formation in turn project to the paramedian reticular formation. Through the crossed tectobulbar pathway visual information can influence the activity of craniocervical muscles via reticular premotor neurons.     

Visual Stimuli Evoked Action Potentials Trigger Rapidly Propagating Dendritic Calcium Transients in the Frog Optic Tectum Layer 6 Neurons

The superior colliculus in mammals or the optic tectum in amphibians is a major visual information processing center responsible for generation of orientating responses such as saccades in monkeys or prey catching avoidance behavior in frogs. The conserved structure function of the superior colliculus the optic tectum across distant species such as frogs, birds monkeys permits to draw rather general conclusions after studying a single species. We chose the frog optic tectum because we are able to perform whole-cell voltage-clamp recordings fluorescence imaging of tectal neurons while they respond to a visual stimulus. In the optic tectum of amphibians most visual information is processed by pear-shaped neurons possessing long dendritic branches, which receive the majority of synapses originating from the retinal ganglion cells. Since the first step of the retinal input integration is performed on these dendrites, it is important to know whether this integration is enhanced by active dendritic properties. We demonstrate that rapid calcium transients coinciding with the visual stimulus evoked action potentials in the somatic recordings can be readily detected up to the fine branches of these dendrites. These transients were blocked by calcium channel blockers nifedipine CdCl₂ indicating that calcium entered dendrites via voltage-activated L-type calcium channels. The high speed of calcium transient propagation, >300 μm in <10 ms, is consistent with the notion that action potentials, actively propagating along dendrites, open voltage-gated L-type calcium channels causing rapid calcium concentration transients in the dendrites. We conclude that such activation by somatic action potentials of the dendritic voltage gated calcium channels in the close vicinity to the synapses formed by axons of the retinal ganglion cells may facilitate visual information processing in the principal neurons of the frog optic tectum.     

Competitive and positional cues in the patterning of nerve connections

The visual system of lower vertebrates has served as an important testing ground for the mechanisms that generate topographic neuronal connections. During both the outgrowth and the regeneration of the optic nerve, a smoothly ordered map of the retina is formed on its major target, the optic tectum (the retinotectal projection). Experiments performed on this projection have offered support for a variety of mechanisms, including the matching of positional cues in the retina and tectum, the guidance of nerve fibers by interactions between fibers, competition for synaptic space, and the refinement of connections based on neuronal activity. Unfortunately, individual experiments that support any one of these mechanisms have been taken at times as evidence against the involvement of any other mechanism; for example, experiments demonstrating the importance of positional cues have been thought mistakenly to indicate that activity-based interactions are unimportant. Computer simulations, in which multiple, somewhat opposed, mechanisms are allowed to operate in concert demonstrate that such a hybrid model is able to generate a full range of experimental results. More importantly, the elimination of any one of the mechanisms renders the model unable to fit entire classes of findings. Thus, the patterning of the retinotectal projection is best viewed as a process in which the optic nerve terminals attempt to satisfy multiple constraints in selecting their target sites.     

Larval size constraints determine directional ontogenetic shifts in the visual system of teleosts1

We summarize characteristic sequences of morphological change in the teleost visual system from larvae to large adults at the level of the retina, the optic tract and the optic tectum. These shifts include sizes and ratios of cone and rod receptor cells, sizes and types of retinal ganglion cells and optic tract fibers as well as features of the optic tectum. Teleost larvae are the smallest vertebrates known. We suggest that the utilization of color contrasts as an adaptive benefit dictates the starting point of morophological development, which is a pure cone retina in most fish larvae. The direction of morphological and functional shifts in the teleost visual system during growth is determined by continuous retinal stretch, which allows for improving visual abilities. The larval visual system probably provides just adequate photopic (cone-)acuity for plankton feeding, but limited space in the retina hampers optimization of both, photopic resolving power and sensitivity Limited space also Irevents the simultaneous development of the scotopic (rod-)system. Over a wide range of body sizes, morphological parameters change, photopic and scotopic resolving power, acuity and sensitivity improve. Size constraints in the teleost visual system and lifefong shifts in sensory capacities are discussed with respect to ecology and the niche concept.     

Neurotrophins, but not depolarization, regulate substance P expression in the developing optic tectum.

Neurotransmitter expression can be regulated by both activity and neurotrophins in a number of in vitro systems. We examined whether either of these factors was likely to play a role in the in vivo optic nerve-dependent regulation of a substance P-like immunoreactive (SP-ir) population of cells in the developing optic tectum of the frog. In contrast to our previous results with the adult system, blocking tectal cell responses to glutamate release by retinal ganglion cells with 6-cyano-7-nitroquinoxaline-2,3 dione (CNQX) did not affect the percent of SP-ir cells in the developing tectum. Treatment with d-(-)-2-amino-5-phosphonovaleric acid (d-AP-5) was also ineffective in this regard, although both it and CNQX treatment disrupted visual map topography. Chronic treatment with brain-derived neurotrophic factor (BDNF) and neurotrophin-4/5 (NT-4/5) produced increases in SP-ir cells in the treated lobes of normal animals, which were significant in the case of NT-4/5. Both substances also prevented the decrease of SP cells that would otherwise occur in the deafferented lobe of unilaterally optic nerve-transected tadpoles. These changes in the percent of SP-ir cells occurred without any detectable changes in the overall number of tectal cells. NGF had no effect on SP expression. Nor did it affect topographic map formation, which was disrupted by treatment with either BDNF or NT-4/5. Our results demonstrate that different mechanisms regulate SP expression in the developing and adult tectum. They indicate that neurotrophin levels in the developing optic tectum may selectively regulate a specific neuropeptide-expressing population of cells.     

Contributions of theoretical modeling to the understanding of neural map development

Theoretical/computational models have played an important role in developing our understanding of the fundamental mechanisms involved in neural map formation. I review models based on both chemospecific and activity-dependent matching of inputs to targets, with a particular focus on map development in the optic tectum and primary visual cortex.     

Two homeobox genes define the domain of EphA3 expression in the developing chick retina

Graded expression of the Eph receptor EphA3 in the retina and its two ligands, ephrin A2 and ephrin A5 in the optic tectum, the primary target of retinal axons, have been implicated in the formation of the retinotectal projection map. Two homeobox containing genes, SOHo1 and GH6, are expressed in a nasal-high, temporal-low pattern during early retinal development, and thus in opposing gradients to EphA3. Retroviral misexpression of SOHo1 or GH6 completely and specifically repressed EphA3 expression in the neural retina, but not in other parts of the central nervous system, such as the optic tectum. Under these conditions, some temporal ganglion cell axons overshot their expected termination zones in the rostral optic tectum, terminating aberrantly at more posterior locations. However, the majority of ganglion cell axons mapped to the appropriate rostrocaudal locations, although they formed somewhat more diffuse termination zones. These findings indicate that other mechanisms, in addition to differential EphA3 expression in the neural retina, are required for retinal ganglion axons to map to the appropriate rostrocaudal locations in the optic tectum. They further suggest that the control of topographic specificity along the retinal nasal-temporal axis is split into several independent pathways already at a very early time in development.     

Taurine trophic modulation of goldfish retinal outgrowth and its interaction with the optic tectum

Summary. Goldfish retinal explant outgrowth in the presence of fetal calf serum is stimulated by taurine. In the absence of it, but with glucose in the medium, length of neurites is still elevated by the amino acid. Using the medium in the presence of glucose, but in the absence of fetal calf serum, we explored the effect of optic tectum medium from cultures of them coming from goldfish without crush of the optic nerve or 3, 5, 10, 14 and 20 days after crush. Retinal explants, intact or from goldfish with crush of the optic nerve 10 days prior to starting the culture, were employed in order to measure the possible effect of optic tectum media and the inter action with taurine. In other type of experiments the optic nerve was crushed 1, 2, 4, 7 and 10 days before dissection of the optic tectum, and then co-cultured with intact or 10 days post-crush retinal explants. Optic tectum media produced a time-dependent effect on outgrowth in lesioned retinas with a maximum effect around 5 days after the lesion for the corresponding optic tectum. Taurine, 4 mM, did not further affect the outgrowth in the presence of optic tectum media, but did significantly increase length of neurites either in intact or in post-lesion retinas. Co-culture of optic tectum at different days post-lesion and retinas at 10 days post-lesion increased the outgrowth around 4 days post-lesion, in a preparation resulting in mutual effects of both types of tissues. The addition of taurine in these conditions did not further increase outgrowth, rather inhibited it according to the time after lesion of optic nerve corresponding to the co-cultured optic tectum. The effect of taurine was concentration-dependent, since 0.2 mM was more effective than 2 or 4 mM in the presence of optic tectum with lesion of 2 days. These results demonstrate the time-course of the regeneration processes in the visual system of goldfish, indicating the crucial periods after crush in which the tectum could produce stimulation and later decrease or no effect on outgrowth from the retina. In addition, they are evidences of the interaction between taurine and optic tectum production of time-produced specific agents. The mechanisms underlying these effects are closely related to calcium, as it was demonstrated by the addition of extracellular or intracellular chelators to the medium, which inhibited the effects of the optic tectum and the trophic properties of taurine in this system. The inhibitor of taurine transport, guanidoethylsulfonate, also decreased the stimulatory effects of the optic tectum and of taurine, indicating an interaction of substances produced by the tectum with taurine, and an effect of taurine mediated through its entrance to the cells. Overall, retinal explants outgrowth in the absence of fetal calf serum, the interaction of agents of the optic tectum and taurine modulates outgrowth from the retina, and these effects are mediated by calcium levels and by the levels of intracellular taurine.     

A simple model can unify a broad range of phenomena in retinotectal map development

A paradigm model system for studying the development of patterned connections in the nervous system is the topographic map formed by retinal axons in the optic tectum/superior colliculus. Starting in the 1970s, a series of computational models have been proposed to explain map development in both normal conditions, and perturbed conditions where the retina and/or tectum/superior colliculus are altered. This stands in contrast to more recent models that have often been simpler than older ones, and tend to address more limited data sets, but include more recent genetic manipulations. The original exploration of many of the early models was one-dimensional and limited by the computational resources of the time. This leaves open the ability of these early models to explain both map development in two dimensions, and the genetic manipulation data that have only appeared more recently. In this article, we show that a two-dimensional and updated version of the XBAM model (eXtended Branch Arrow Model), first proposed in 1982, reproduces a range of surgical map manipulations not yet demonstrated by more modern models. A systematic exploration of the parameter space of this model in two dimensions also reveals richer behavior than that apparent from the original one-dimensional versions. Furthermore, we show that including a specific type of axon?Caxon interaction can account for the map collapse recently observed when particular receptor levels are genetically manipulated in a subset of retinal ganglion cells. Together these results demonstrate that balancing multiple influences on map development seems to be necessary to explain many biological phenomena in retinotectal map formation, and suggest important constraints on the underlying biological variables.     

Evolutionary evaluation of reciprocity of connections in the turtle tectofugal visual system

In two turtle species—Emys orbicularis and Testudo horsfieldi—by the method of anterograde and retrograde traicing at the light and electron microscopy level, the existence is proven of direct descending projections from the thalamic nucleus of the tectofugal visual system n. rotunds (Rot) to the optic tectum. After injection of tracers into Rot alone and into Rot with involvement of the tectothalamic tract (Trtth), occasional labeled fibers with varicosities and terminals are revealed predominantly in the deep sublayers of SGFS of the rostral optic tectum, while in the lower amount—in other tectal layers. After the tracer injections into the optic tectum, a few retrogradely labeled neurons were found mainly in the Rot ventral parts and within Trtth. Their localization coincides with that of GABA-immunoreactive cells. Electron microscopy showed the existence of many retrogradely labeled dendrites throughout the whole Rot; a few labeled cell bodies were also present there, some of them being also GABA-immunoreactive. These results allow us to conclude about the existence of reciprocal connections between the optic tectum and Rot in turtles, these connections being able to affect processing of visual information in tectum. We suggest that reciprocity of tectothalamic connections might be the ancestral feature of the vertebrate brain; in the course of amniote evolution the functional significance of this feature can be decreased and even lost in parallel with a rise of the role of direct corticotectal projections.     

The role of visual experience in the formation of binocular projections in frogs

Many parts of the visual system contain topographic maps of the visual field. In such structures, the binocular portion of the visual field is generally represented by overlapping, matching projections relayed from the two eyes. One of the developmental factors which helps to bring the maps from the two eyes into register is visual input. The role of visual input is especially dramatic in the frog, Xenopus laevis. In tadpoles of this species, the eyes initially face laterally and have essentially no binocular overlap. At metamorphosis, the eyes begin to move rostrodorsally; eventually, their visual fields have a 170 degree region of binocular overlap. Despite this major change in binocular overlap, the maps from the ipsilateral and contralateral eyes to the optic tectum normally remain in register throughout development. This coordination of the two projections is disrupted by visual deprivation. In dark-reared Xenopus, the contralateral projection is nearly normal but the ipsilateral map is highly disorganized. The impact of visual input on the ipsilateral map also is shown by the effect of early rotation of one eye. Examination of the tectal lobe contralateral to the rotated eye reveals that both the contralateral and the ipsilateral maps to that tectum are rotated, even though the ipsilateral map originates from the normal eye. Thus, the ipsilateral map has changed orientation to remain in register with the contralateral map. Similarly, the two maps on the other tectal lobe are in register; in this case, both projections are normally oriented even though the ipsilateral map is from the rotated eye. The discovery that the ipsilateral eye's map reaches the tectum indirectly, via a relay in the nucleus isthmi, has made it possible to study the anatomical changes underlying visually dependent plasticity. Retrograde and anterograde tracing with horseradish peroxidase have shown that eye rotation causes isthmotectal axons to follow abnormal trajectories. An axon's route first goes toward the tectal site where it normally would arborize but then changes direction to reach a new tectal site. Such rearrangements bring the isthmotectal axons into proximity with retinotectal axons which have the same receptive fields. Anterograde horseradish peroxidase filling has also been used to study the trajectories and arborizations of developing isthmotectal axons. The results show that the axons enter the tectum before the onset of eye migration but do not begin to branch profusely until eye movement begins to create a zone of binocular space.(ABSTRACT TRUNCATED AT 400 WORDS)     

The instructive role of binocular vision in the Xenopus tectum

This review presents the fascinating neurobiology underlying the development of the frog optic tectum, the brain structure where the two separate inputs from the two eye are combined into a single, integrated map. In the species Xenopus laevis, binocular visual information has a dramatic impact on axon growth and connectivity, and the formation of binocular connections in this system provides a rich basis for both theoretical and experimental investigations.     

DC electrical stimulation of the pretectal thalamus and its effects on the feeding behavior of the toad (Bufo bufo)

The feeding motivation of the common European common toad (Bufo bufo) can be quantified by the feeding sequence of arousal-orientation-approach-fixate-snap. Previous work has found that the optic tectum is an important structure responsible for the mediation of feeding behaviors, and combined electrical and visual stimulation of the optic tectum was found to increase the animals feeding behaviors. However, the pretectal thalamus has an inhibitory influence upon the optic tectum and its lesion results in disinhibited feeding behaviors. This suggests that feeding behavior of anurans is also subject to influence from the pretectal thalamus. Previous studies involving the application of DC stimulation to brain tissue has generated slow potential shifts and these shifts have been implicated in the modulation of the neural mechanisms associated with behavior. The current study investigated the application of DC stimulation to the diencephalon surface dorsal to the lateral posterodorsal pretectal thalamic nucleus in Bufo bufo, in order to assess effects on feeding motivation. The application of DC stimulation increased the incidence of avoidance behaviors to a visual prey stimulus while reducing the prey catching behavior component of approach, suggesting that the DC current applied to the pretectum increased the inhibition upon the feeding elements of the optic tectum. This can be explained by the generation of slow potential shifts.     

Neurotrophins,but not depolarization,regulate substance P expression in the developing optic tectum

Neurotransmitter expression can be regulated by both activity and neurotrophins in a number of in vitro systems. We examined whether either of these factors was likely to play a role in the in vivo optic nerve‐dependent regulation of a substance P‐like immunoreactive (SP‐ir) population of cells in the developing optic tectum of the frog. In contrast to our previous results with the adult system, blocking tectal cell responses to glutamate release by retinal ganglion cells with 6‐cyano‐7‐nitroquinoxaline‐2,3 dione (CNQX) did not affect the percent of SP‐ir cells in the developing tectum. Treatment with d‐(‐)‐2‐amino‐5‐phosphonovaleric acid (d‐AP‐5) was also ineffective in this regard, although both it and CNQX treatment disrupted visual map topography. Chronic treatment with brain‐derived neurotrophic factor (BDNF) and neurotrophin‐4/5 (NT‐4/5) produced increases in SP‐ir cells in the treated lobes of normal animals, which were significant in the case of NT‐4/5. Both substances also prevented the decrease of SP cells that would otherwise occur in the deafferented lobe of unilaterally optic nerve‐transected tadpoles. These changes in the percent of SP‐ir cells occurred without any detectable changes in the overall number of tectal cells. NGF had no effect on SP expression. Nor did it affect topographic map formation, which was disrupted by treatment with either BDNF or NT‐4/5. Our results demonstrate that different mechanisms regulate SP expression in the developing and adult tectum. They indicate that neurotrophin levels in the developing optic tectum may selectively regulate a specific neuropeptide‐expressing population of cells. © 2001 John Wiley & Sons, Inc. J Neurobiol 48: 131–149, 2001     

Specific cell surface labels in the visual centers of Xenopus laevis tadpole identified using monoclonal antibodies

Monoclonal antibodies (MAbs) against the optic tectum of Xenopus tadpoles were generated and screened by the immunofluorescent staining of frozen sections of tadpole brains. MAb-A5 stains the 8th and 9th plexiform layers of the optic tectum, whereas MAb-B2 stains all but the eighth and ninth plexiform layers of the optic tectum. MAb-A5 antigen is also detectable in the nucleus of Belonci, the corpus geniculatum thalamicum, the pretectal area, and the basal optic nucleus, all targets of the optic nerve, but is not detectable in the optic nerve or the optic tract. On the other hand, MAb-B2 does not stain any of these visual centers, though many fibers surrounding them are stained. Eye-enucleation experiments showed that MAb-A5 antigen is expressed in the optic tectum even when it is not innervated by optic nerves. Staining of viable brains with these MAbs indicates that these antigens are cell surface molecules. Immunoadsorption followed by SDS-PAGE suggests that proteins are constituents of these antigens. The MAb-A5 antigen in the diencephalon and the mesencephalon is not detectable at stage 35/36, but is detectable at stage 39 when the optic nerves begin to innervate the optic tectum. The spatial as well as the temporal patterns of the expression of the MAb-A5 antigen suggest that this molecule may be involved in the target recognition of optic nerve fibers.     

Alterations in the Xenopus retinotectal projection by antibodies to Xenopus N-CAM

The patterned neural projection from the eye to the optic tectum of lower vertebrates (the retinotectal projection) has been proposed to be ordered by interactions between the optic nerve fibers and their surrounding tissues. To investigate the role of one such defined cell interaction, agarose implants containing antibodies to the neural cell adhesion molecule, N-CAM, were inserted into the tectum of the African clawed frog, Xenopus laevis. Both monoclonal and polyclonal antibodies against N-CAM reversibly and specifically distorted the pattern of the retinotectal projection, decreasing the precision of the projection as determined by electrophysiological techniques as well as decreasing the density of retinal innervation of the tectum and the branching of single axons as determined by horseradish peroxidase tracing. The anatomical effects became maximal at 4 to 6 days after implantation and returned to undetectable levels by 2 weeks, whereas the physiological effects became maximal by 8 to 10 days and a normal physiological map was reestablished within 4 weeks. The results are consistent with the hypothesis that anti-N-CAM antibodies perturb the ongoing growth and retraction of the terminal arbors of the optic nerve fibers, such that a region of the tectum becomes largely denuded of fibers. The physiological defects may then be a consequence both of the initial retraction of optic nerve terminals and of the rapid ingrowth of the perturbed and neighboring optic nerve fibers into the denuded region after the antibodies were cleared from the tectum. These results support the concept of a major role for N-CAM-mediated adhesion during map regeneration and maintenance.     

Functional imaging reveals rapid development of visual response properties in the zebrafish tectum

The visual pathway from the retina to the optic tectum in fish and frogs has long been studied as a model for neural circuit formation. Although morphological aspects, such as axonal and dendritic arborization, have been well characterized, less is known about how this translates into functional properties of tectal neurons during development. We developed a system to provide controlled visual stimuli to larval zebrafish, while performing two-photon imaging of tectal neurons loaded with a fluorescent calcium indicator, allowing us to determine visual response properties in intact fish. In relatively mature larvae, we describe receptive field sizes, visual topography, and direction and size selectivity. We also characterize the onset and development of visual responses, beginning when retinal axons first arborize in the tectum. Surprisingly, most of these properties are established soon after dendrite growth and synaptogenesis begin and do not require patterned visual experience or a protracted period of refinement.     

Retinotectal Connexions of a Heterotopic Eye

THE mechanisms which cause the formation of specific synaptic connections in the nervous system are rather obscure. The development of specific connexions between eye and brain indicates a stage-dependent functional specification of the retina¹ which allows the retina to form predictable, specific connexions with the optic tectum, but the manner in which optic nerve fibres terminate in the tectum and the mechanisms which restore the visual projection after optic nerve regeneration are as yet not fully determined².     

Eye-specific segregation of optic afferents in mammals,fish, and frogs: The role of activity

Eye-specific patches or stripes normally develop in the visual cortex and superior colliculus of many (but not all) mammals and are also formed, after surgically produced binocular innervation, in the optic tectum of fish and frogs. The segregation of ocular dominance patches or columns has been studied using a variety of anatomical pathway-tracing techniques, by electrophysiological recording of postsynaptic units or field potentials, and by the 2-deoxyglucose method following visual stimulation of only one eye. In the tectum of both fish and frogs and in the cortex and colliculus of mammals, eye-specific patches develop from initially diffuse, overlapping projections. Of the various mechanisms that might cause such segregation, the evidence favors an activity-dependent process that stabilizes synapses from the same eye because of their correlated activity. First, several environmental manipulations affect the segregation of afferents in visual cortex: strabismus and alternate monocular exposure apparently enhance segregation, whereas dark rearing slows the segregation process, and monocular deprivation causes the experienced eye to form larger patches at the expense of those of the deprived eye. Second, blocking activity in both eyes is effective in preventing the segregation both in the tectum of fish and frog and in the visual cortex of cat. With the eyes blocked, alternate stimulation of the optic nerves permits the segregation of ocular dominance, at least onto single cells in the cat visual cortex. These findings are discussed in terms of an activity-dependent stabilization of those synapses having correlated activity (those from neighboring ganglion cells within one eye) but not of those lacking correlated activity (those from left and right eyes). We suggest that the eye-specific patches represent a compromise between total segregation of the projections from the two eyes and the formation of a single continuous retinotopic map across the surface of the cortex or tectum.     

Neural mechanisms of sound localization in owls

Barn owls localize sound by using the interaural time difference of the horizontal plane and the interaural intensity difference for the vertical plane. The owl's auditory system possesses the two binaural cues in separate pathways in the brainstem. Owls use a process similar to cross-correlation to derive interaural time differences. Convergence of different frequency bands in the inferior colliculus solves the problems of phase-ambiguity which is inherent in cross-correlating periodic signals. The two pathways converge in the external nucleus of the inferior colliculus to give rise to neurons that are selective for combinations of the two cues. These neurons form a map of auditory space. The map projects to the optic tectum to form a bimodal map which, in turn, projects to a motor map for head turning. The visual system calibrates the auditory space map during ontogeny in which acoustic variables change. In addition to this tectal pathway, the forebrain can also control the sound-localizing behaviour.