Aberrant retinal projections to midbrain targets mediate spared visual orienting function in hamsters with neonatal lesions of superior colliculus

Summary Rodents, cats, and most nonmammalian vertebrates with bilateral tectal deafferentation or ablation in adulthood are extremely deficient at orienting to visual stimuli; yet animals with neonatal lesions of superficial layers of the superior colliculus (SC) show partial sparing of this response, particularly for targets in the central visual field. In this study, we sought to determine whether these spared orienting abilities are mediated by aberrant retinal projections to the remaining intermediate layers of the SC, or whether visual cortex (VC) mechanisms or alternative behavioral strategies are responsible. Neonatal golden hamsters received either bilateral heat lesions of the SC (rlSC), or a heat lesion of the right SC and enucleation of the right eye (rSCrE). This latter procedure causes axons from the left eye to recross the tectal midline and terminate in the wrong (left) SC (Schneider 1973). As adults, both groups of hamsters were extremely deficient in visually guided approach to stationary targets, although rlSC-lesioned hamsters showed some sparing for central field targets and rSCrE-lesioned hamsters often made wrong-direction turns for targets in the left peripheral field. We then subjected both groups of neonatally lesioned hamsters to bilateral aspiration lesions of the VC. Retesting showed no change in visual orienting behavior as a result of the cortical lesions. Labeling of the optic tract with horseradish peroxidase (HRP) revealed abundant aberrant retinal projections to remaining intermediate layers of the SC and thalamic nucleus lateralis posterior (LP), as well as supernormal innervation of pretectal nuclei, the dorsal terminal nucleus of the accessory optic tract, and the ventral nucleus of the lateral geniculate body (LGv). We conclude that the spared visual orienting capabilities of hamsters with rlSC and rSCrE lesions are mediated by the aberrant midbrain projections, and that cortical mechanisms are not involved in spared visual orienting functions following these neonatal lesions.     

Electrophysiological evidence for axonal sprouting of cerebellothalamic neurons in kittens after neonatal hemicerebellectomy

Summary Changes in cerebello-cerebral responses after hemicerebellectomy were investigated in 19 kittens by laminar field potential analysis in the cerebral cortex. In all of 11 kittens operated on before 11 days of age and kept for more than 16 days after surgery, marked cerebello-cerebral responses were evoked not only contralaterally as in intact animals but also ipsilaterally. In none of 16 intact kittens ranging in age from 2 to 14 days was there a detectable response in the cerebral cortex to stimulation of the ipsilateral cerebellar nucleus.Pathways responsible for the ipsilateral cerebello-cerebral responses were investigated by destruction of the thalamic VL nucleus and by unitary recordings from cerebellar nuclear neurons with antidromic activation on stimulation of the thalamus. From the latter investigation, a remarkable increase in the number of neurons with bilateral projections upon the thalamus was seen in the surgically treated kittens. Stimulation of the VL thalamic nucleus contralateral to the remaining hemicerebellum induced a marked response in the frontal cortex not only ipsilaterally as in intact animals but also contralaterally. The latter response was considered to be mediated by an axon reflex of the bilateral projection neurons. Destruction of that VL nucleus abolished the contralateral cerebello-cerebral response whereas the ipsilateral cerebello-cerebral response remained unchanged.It is concluded, that in kittens, hemicerebellectomized in the early postnatal period, nuclear neurons in the remaining cerebellum sprout axon collaterals growing into the thalamus ipsilateral to the spared hemicerebellum and that these sprouting axon collaterals make synapses on the thalamic neurons projecting upon the cerebral cortex.     

Morphological evidence for axonal sprouting of cerebellothalamic neurons in kittens after neonatal hemicerebellectomy

Summary Changes in cerebellothalamic projections in kittens after neonatal hemicerebellectomy were studied by the retrograde and anterograde horseradish peroxidase (HRP)-tract-tracing methods. The number of cerebellar nuclear neurons labeled retrogradely with HRP injected into the ipsilateral VA-VL complex of the thalamus was much more numerous in neonatally hemicerebellectomized kittens than in intact kittens. Presumed terminals of ipsilateral cerebellothalamic fibers labeled anterogradely with HRP injected into the cerebellar nuclei were also distributed more densely and extensively in the thalamic areas, especially in the VA-VL complex, of hemicerebellectomized kittens than in the thalamic areas of the control kittens. These results are in good accordance with those obtained from the previous electrophysiological study (Kawaguchi et al., 1979) and offer corroborating evidence for axonal sprouting of cerebellothalamic neurons after neonatal hemicerebellectomy.     

Impairment and recovery of visual functions after bilateral lesions of superior colliculus

Adult, male hooded rats were tested on a six-choice jumping stand apparatus designed to study their ability to perform visually guided orientation movements with a brightness discrimination task. Upon reaching criterion, the rats suffered either one- or two-stage, bilateral electrolytic lesions of the superior colliculi and then, after a brief recovery period, were retested for their ability to retain the preoperatively learned task and, in addition, perform a more difficult task. Although both brain damaged groups evidenced an impairment in comparison to sham-operated controls, the rats with two-stage lesions were less disabled than their simultaneously operated counterparts.     

Expression of GAP-43 during development and after monocular enucleation in the rat superior colliculus

The retinotectal projection of rodents presents a precise retinotopic organization that develops, from diffuse connections, from the day of birth to post-natal day 10. Previous data had demonstrated that these projections undergo reorganization after retinal lesions, nerve crush and monocular enucleation. The axonal growth seems to be directly related to growth-associated protein-43 (GAP-43) expression, a protein predominantly located in growth cones, which is regulated throughout development. GAP-43 is presented both under non-phosphorylated and phosphorylated (pGAP-43) forms. The phosphorylated form, has been associated to axon growth via polymerization of F-actin, and synaptic enhancement through neurotransmitter release facilitation. Herein we investigated the spatio-temporal expression of GAP-43 in the rat superior colliculus during normal development and after monocular enucleation in different stages of development. Lister Hooded rats ranging from post-natal day 0 to 70 were used for ontogeny studies. Another group of animals were submitted to monocular enucleation at post-natal day 10 (PND10) or PND21. After different survival-times, the animals were sacrificed and the brains processed for either immunohistochemistry or western blotting analysis. Our data show that GAP-43 is expressed in retinotectal axons in early stages of development but remains present in adulthood. Moreover, monocular enucleation leads to an increase in pGAP-43 expression in the deafferented colliculus. Taken together these results suggest a role for pGAP-43 in retinotectal morphological plasticity observed both during normal development and after monocular enucleation.     

Orienting behavior in hamsters with lesions of superior colliculus,pretectum, and visual cortex

Summary We examined cortical and subcortical mediation of visual locomotor orienting function by comparing the behavior of hamsters with discrete bilateral lesions affecting the pretectum, superior colliculus (SC), or visual cortex (VC). Orienting and approach to stationary targets was evaluated by measuring the accuracy of hamsters' approaches to small black apertures, located at eye level along the wall of a circular white arena. Hamsters with bilateral ablation of the visual cortex were slightly impaired for approaches to central field targets, whereas those with ibotenic acid lesions of the pretectum (which spares fibers of passage and thus leaves tectal afferents intact) were totally unimpaired. Hamsters with transection of the brachium of SC (BSC) at the prectectal-SC (PT-SC) border were severely impaired in their ability to approach stationary targets in central and peripheral fields. Thus, we did not detect any of the central field sparing that has been reported by others for rodents with similar lesions. Several possible reasons for the disparity between our results and those of others are discussed. Overall, our results indicate that in hamsters the SC is essential for normal visually guided approach to dark, stationary targets throughout the visual field. Further, our results and qualitative observations indicate that the approach errors are most likely due to deficits of visuomotor integration rather than to a lack of visual scanning.     

Blood pressure increased dramatically in hypertensive rats after left hemisphere lesions with 6-hydroxydopamine

Plasma angiotensinase activity, nitric oxide and systolic blood pressure (SBP) were differently affected after unilateral intrastriatal injection of 6-hydroxydopamine (6-OHDA), depending on the brain hemisphere injured. Moreover, normotensive and hypertensive rats responded differently suggesting an asymmetry in the organization of the autonomic nervous system of the vessels. The aim of this study was to investigate the evolution of SBP and heart rate (HR) over time after nigrostriatal lesions in normotensive and hypertensive rat strains. Unilateral depletions of brain dopamine were performed by injecting 6-OHDA into the left or right striatum of normotensive and hypertensive rats. Vehicle without 6-OHDA was unilaterally injected in control (sham) groups. SBP and heart rate (HR) were measured in un-anesthetised animals 10 and 3 days before administration of 6-OHDA or vehicle and 3 and 25 days after treatment. In normotensive rats, at the end of study, SBP increased significantly from pre-lesioned values in left-lesioned animals but no differences were observed in right-lesioned or sham groups. Before sacrifice, there was a significant reduction from pre-lesion values in HR. In hypertensive animals, there was a highly significant increase of SBP in left-lesioned and sham left rats and a slight increase in right-lesioned but no differences were observed in sham right group. No differences in HR were observed throughout the study in the groups studied. The present results represent direct experimental evidence of an asymmetrical cardiovascular response to unilateral brain lesions, suggesting that left injury may have a worst prognosis.     

Anatomical plasticity of the tectospinal tract after unilateral lesion of the superior colliculus in the neonatal rat

Summary After unilateral ablation of the superior colliculus (SC) in neonatal or adult rats, the reorganization of the tectospinal tract (TST) was examined using the technique of anterograde transport of horseradish peroxidase to which wheat germ agglutinin had been conjugated (WGA-HRP). In neonatally lesioned rats, aberrant labeled terminals of TST axons were found on the ipsilateral side of the spinal cord. Postnatal development of the TST was then studied by retrograde transport of HRP to determine whether the aberrant tectospinal projections resulted from normally transient ipsilateral projections that persisted in operated rats or were due to collateral sprouting of projections to the contralateral projection field. The results failed to show an ipsilateral projection from the SC to spinal cord in normal neonatal rats. However, in neonatally lesioned rats, aberrant labeled fibers were observed recrossing the midline of the cervical spinal cord. Therefore, the increase in labeled terminals on the ipsilateral side following unilateral SC ablation appeared to originate from collateral sprouting at the spinal cord level of TST fibers from the intact pathway.     

Magnification factors,receptive field images and point-image size in the superior colliculus of flying foxes: comparison with the primary visual cortex

The magnification factor (MF) of the stratum griseum superficialle (SGS) of the superior colliculus (SC) was calculated based on visual receptive fields recorded from anaesthetised and paralysed flying foxes (Pteropus spp.). In areal terms, the MF at the representation of central vision was 4–6 times larger than that in the peripheral representation. This variation is less marked than that observed in the primary visual area (VI), but is roughly that expected if the retinotopic map in the SC was defined by the distribution of ganglion cells in the retina. Two measures of the functional spread of activity in the SC, the receptive field images and the point-image size, were calculated. Receptive field images are remarkably similar throughout the SC. As in VI, the point-image size in the SGS of flying foxes is 0.5–0.6 mm and varies little with eccentricity. Bilateral ablation of the visual cortex results in a reduction of the mean receptive field size of neurones in the SGS, and the point-image size is reduced by half. However, the shape of the point-image function is not affected. These results demonstrate that the spread of activity in the SC is nearly constant throughout the retinotopic map and that this is primarily a result of the direct retinal projection. Although the visual cortex has an expanded central representation in comparison with the SC, the corticotectal pathway does not exert a preferential influence on the central representation of the SC.     

Loss of relative-motion sensitivity in the monkey superior colliculus after lesions of cortical area MT

 Many cells in the superficial layers of the monkey superior colliculus are sensitive to relative motion. The response to a small stimulus moving through a cell’s receptive field is strongly modulated by the relative motion between the stimulus and a textured pattern moving through the surrounding visual field; modulation is independent of absolute direction and speed of the stimulus. To determine whether cortical visual area MT is essential for this type of relative-motion sensitivity, colliculus cells were studied in the anesthetized, immobilized preparation after ablation of area MT. Unilateral MT lesions were made by either aspiration, kainic acid injection, or a combination of both methods. Data from the lesioned animals were compared with those from intact animals. Ipsilateral to the lesions, colliculus cells showed an almost total loss of sensitivity to relative motion. This loss was related neither to inadvertent injury of cortical areas neighboring MT nor to incidental optic radiation damage. Two other forms of motion-dependent, center-surround interactions were still present in the colliculus after the cortical lesions. These were a rudimentary sensitivity to differential motion between stimulus and background, which occurs for only one direction of stimulus movement, and a nonselective center-surround suppression, which is induced by movement of a background stimulus in any direction. Visual responsiveness, ocular dominance, and flash-evoked responses were also unaffected by the cortical lesions. We conclude that input from area MT is crucial for relative-motion sensitivity, but not for other response properties, in the superficial layers of the monkey colliculus. Received: 27 September 1996 / Accepted: 25 April 1997     

Behavioural and neurochemical effects of superior cervical ganglionectomy in rats with septo-hippocampal lesions

This longitudinal study, extending over 12 months, assessed the behavioural and biochemical effects of hippocampal sympathetic ingrowth (HSI) into the partially denervated hippocampus. Male Long-Evans rats received fimbria-fornix lesions (FIFO) or sham operations at 90 days of age. At the same time half of the rats from each group sustained bilateral ablation of the superior cervical ganglia (SCGX). A battery of behavioural tests, measuring spontaneous alternation, activity in the open field and home cage, and radial-maze performance, were employed, starting after one very short (16 days) and one extended (216 days) postoperative delay. Neurochemical analyses measuring choline acetyltransferase (ChAT) activity, high-affinity choline (HACU) and noradrenaline uptake by hippocampal synaptosomes (HANU), hippocampal noradrenaline ([NA]), serotonin ([5-HT]) and 5-hydroxyindoleacetic acid ([5-HIAA]) concentrations were carried out in a dorsal, a middle and a ventral region of the hippocampus. Lesion of the FIFO induced a significant and enduring deficit in radial-maze performance, in addition to a persistent locomotor hyperactivity. ChAT and HACU were significantly depleted in all three regions of the hippocampus at 12 months, and these deficits were negatively correlated with maze performance. SCGX in the presence of the FIFO lesion significantly reduced [NA] in the middle region of the hippocampus, as compared to SCGX rats, and contributed to a restoration of lesion-induced depletions in [5-HT] and [5-HIAA] in the middle and ventral hippocampal regions, whilst failing to elicit any behavioural changes at either time point. It is concluded that if lesion-induced HSI indeed occurred, as is suggested by neurochemical evidence, it had no effect upon the observed behavioural deficits elicited by transection of the FIFO in the rat.     

Selective lesions of mesostriatal dopamine neurons ameliorate hypoglycemic damage in the caudate-putamen

Summary Unilateral 6-hydroxydopamine lesion of the mesostriatal dopaminergic system was found to ameliorate neuronal necrosis in the caudate-putamen following 30 min of insulin-induced hypoglycemic coma. We propose that increased release of dopamine in the striatum during hypoglycemia or in the recovery period potentiates a deleterious neuronal hyperexcitation, probably induced by excessive release of glutamate or related compounds, thereby aggravating neuronal necrosis.     

Sympathetic sprouting: no evidence for muscarinic modulation of noradrenaline release in hippocampal slices of rats with fimbria-fornix lesions

 Lesions of the septohippocampal pathways elicit sprouting of sympathetic fibers from the superior cervical ganglion, a phenomenon which, within a few months, raises the hippocampal noradrenaline (NA) content above normal. In peripheral sympathetic fibers, the release of NA is modulated via presynaptic muscarinic receptors. Such receptors have not been detected so far on terminals of noradrenergic neurons originating in the locus coeruleus. Whether the release of NA could become sensitive to muscarinic modulation in the hippocampus following sympathetic fiber ingrowth was the major question in this experiment. The contribution of presynaptic nicotinic receptors was also studied. Slices from the ventral hippocampus (only dentate gyrus+CA3 region) of sham-operated (SHAM) and fimbria-fornix lesioned (LES) Long-Evans rats (8–10 months after surgery) were preincubated with [³H]NA and stimulated either once (S₁) with 100 μM nicotine or (in parallel experiments) twice electrically (S₁, S₂), using conditions (six pulses 100 Hz, 2 ms, 28 mA, 4 V/chamber) that precluded autoinhibition. In experiments using electrical stimulation, the superfusion medium contained desipramine (1 μM). In LES rats, the tissue NA content had almost doubled (171% of SHAM levels), but the amount of [³H]NA taken up by the slices was unchanged, and the overflow evoked at S₁ by both nicotinic and electrical stimulation was significantly reduced in comparison with SHAM rats. In both groups, the addition of oxotremorine or oxotremorine+atropine (1 μM, each) before S₂ failed to affect the electrically evoked overflow of ³H. Nicotine-induced NA release was inhibited by hexamethonium (100 μM) in both groups, although significantly less potently in LES rats. Tissue activity of choline acetyltransferase was reduced in LES rats to 15% of SHAM levels and the 5-hydroxytryptamine content was also strongly diminished (38% of SHAM values). It is concluded that lesion-induced sprouting of sympathetic fibers into the hippocampus is not accompanied by the emergence of a muscarinic modulation of NA release in this tissue, and that the sensitivity of the presynaptic stimulatory effect of nicotine was modified by the lesion. Received: 22 April 1998 / Accepted: 23 July 1998     

The principle of “conservation of total axonal arborizations”: massive compensatory sprouting in the hamster subcortical visual system after early tectal lesions

Summary Unilateral lesions of the right superior colliculus (SC) were made in hamsters on the day after birth. In order to quantify the extent of abnormal innervation by left eye fibers in the diencephalon and midbrain, the left eye was removed on postnatal day 12 or 36, and after an appropriate survival time, the brains were stained for degenerating axons and axon terminals with the Fink-Heimer method. In additional cases, anterograde transport of 3H proline-leucine or horseradish peroxidase was used to assess left eye connectivity. In agreement with previous reports we found abnormal projections in the ventral nucleus of the lateral geniculate body (LGv), in the lateral posterior nucleus (LP) of the thalamus, and in the left SC (the recrossing pathway). We also noted areas of abnormally heavy terminal fields arranged in patches in coronal sections in the dorsal nucleus of the lateral geniculate body (LGd). These patches arise from columns of dense innervation that are oriented along a rostral-to-caudal axis. If the right SC lesion was made large enough to diminish the recrossing pathway, retinofugal axons establish a significantly smaller distal terminal field in the left SC. In these cases, a corresponding increase in the size of terminal fields in all major proximal structures (LGd, LGv, LP, DTN) was observed. The sum of abnormal proximal growth (compensatory sprouting) was found to truly compensate for the distal loss of terminals. The evaluation of hamsters in which left eye connectivity was assessed at the age of 12 days revealed that lesion-induced patches of abnormal growth have already reached their full size by that time. These findings provide evidence for the pruning -effect and demonstrate that retinofugal axons support a fixed number of terminal arborizations (the principle of conservation of total axonal arborizations).     

Postnatal development of the superficial layers in the rat superior colliculus: a study with Golgi-Cox and Klüver-Barrera techniques

Summary The postnatal development of the superficial (optic) layers of the rat superior colliculus has been studied using Klüver-Barrera staining and Golgi impregnation in rats aged 3–45 days. The Klüver-Barrera staining reveals that the SC of 3 day old rats is morphologically immature with no obvious lamination. It contains densely packed cells of uniform size. The packing density of the cells gradually decreases between 9 and 15 days as the thickness of the layers increases. The first myelinated fibres in the SC appear at 15 days but the stratum opticum is still not recognizable. By 30 days, the SC has a distinctly laminated appearance, but the thickness of the superficial layers continues to increase until day 45 postnatal. Golgi-Cox impregnation displays the range of neuronal types in the superficial layers of the SC previously described by Langer and Lund (1974). Using the morphological criteria of these authors for classification of the neurons, the developmental changes of the marginal cells, horizontal cells, ganglion cells types I, II, III and stellate cells have been followed. The SC of 3 day old rats contains immature neurons; only a few larger cells have branched dendrites. In 9 days old SC the neuronal types present in the adult are recognizable, although their appearances are still immature. By 15 days neurons have adult-looking dendritic trees but dendritic growth continues beyond 30 days. The visual part of the SC has a protracted period of postnatal development, the sequence of developmental changes being similar for the different types of collicular neurons. Features common to development are the increasing size of neuronal somata, the increasing length of dendrites and the acquisition of a complex pattern of dendritic arborization. Larger cells appear to commence development earlier than small cells, although the rate of developmental changes is different for each of the various types of collicular neurons.