Spatial Navigation Deficits Research Articles

Neonatal frontal cortex grafts fail to attenuate behavioural deficits or abnormal cortical morphogenesis

Following bilateral removal of the medial frontal cortex, which included the medial prefrontal and adjacent midline motor cortex, 4-day-old rats were given transplants of embryonic day 17 frontal cortical tissue. Other rats were given only frontal lesions or sham operations. In adulthood, the animals were trained on a spatial navigation task and a forelimb reaching task. The transplanted tissue grew well and interacted morphologically with the host but the grafts failed to reduce the spatial navigation and motor deficits resulting from the frontal removals. The grafts also failed to reduce the anatomical sequelae of the early lesions, which included cortical thinning and thalamic shrinkage. It appears unlikely that cortical transplantation will be a viable treatment for recovery from perinatal frontal cortical injury.

Anticholinergic sensitivity in the aging rat septohippocampal system as assessed in a spatial memory task

The effects of central cholinergic blockade on spatial memory were tested in aged and basal forebrain-lesioned rats using the Morris Water Maze. In Experiment 1, aged rats (18–21 months old) were characterized as behaviorally impaired or nonimpaired based on water maze performance prior to an atropine sulfate challenge. In the atropine test (50 mg/kg, IP), both the impaired and the nonimpaired rats showed a severe disruption of their search behavior compared to young subjects. This effect was due to blockade of central receptors since peripheral cholinergic blockade using atropine methylbromide did not produce any impairments. Experiment 2 investigated effects of atropine on rats with septal lesions (SL), nucleus basalis lesions (NBL), and rats with both lesions combined (SL + NBL). Before drug treatment, the groups with septal lesions (SL and SL + NBL groups) displayed a moderate impairment in locating the platform site. However, similar to the aged rats, the septal-lesioned rats exhibited severe impairments in the water maze during the atropine treatment. This effect was not seen in the normal controls or in the NBL rats. Aged rats, either impaired or nonimpaired in a spatial memory task, showed a pronounced sensitivity to pharmacological blockade of central cholinergic neurotransmission which resulted in severe deficits in spatial navigation in the water maze. Since the same behavioral deficit was produced by cholinergic blockade in young rats with septal lesions, we concluded that the impaired water maze performance seen in the aged rats during cholinergic blockade resulted from impaired function in the septohippocampal system.

Effects of fetal hippocampal field grafts on ischaemic-induced deficits in spatial navigation in the water maze

Transitory global cerebral ischaemia induced in rats by four vessel occlusion for 15 min produced substantial loss of CA1 cells in dorsal hippocampus, and minimal damage in other intra- and extrahippocampal forebrain regions examined. Ischaemic rats showed long-lasting deficits in spatial navigation in the water-maze, consisting of impaired learning to locate a hidden platform in a novel pool, a substantial increase in time spent searching close to the platform without finding it, and moderate deficits in matching to position in a working memory task. Groups of ischaemic rats were implanted with fetal tissue dissected from hippocampal CA1 field, containing glutamatergic CA1 pyramidal cells, from dentate gyrus, containing glutamatergic dentate granule cells, and from basal forebrain, containing cholinergic cells, with grafts sited in the alveus above the damaged CA1 region, for comparison with non-grafted ischaemic and non-ischaemic control groups, over a series of tests from four to 20 weeks after grafting. All ischaemic groups showed comparable acquisition deficits prior to transplantation, and similar loss of CA1 cells on post mortem examination. When tested in a familiar pool in retention and reversal learning of the original platform position, and a working memory task, all ischaemic rats performed better than in initial acquisition. However, rats receiving CA1 grafts showed the most consistent improvement relative to ischaemic controls. When tested in a second (i.e. novel) pool, ischaemic rats again showed marked impairment, whereas rats with CA1 grafts were significantly superior, and learned as rapidly as non-ischaemic controls. The performance of groups with dentate granule and basal forebrain grafts was similar to that of the non-grafted ischaemic control group throughout testing. These results suggest that ischaemic rats are impaired in the adaptive use of spatial information, as shown by acquisition and working memory deficits, but not in long- or short-term memory storage processes, and are also impaired in precise spatial localization. The effects of CA1 grafts in restoring spatial abilities, shown most clearly when rats were tested in a novel environment, suggest that these grafts may have assisted with repair to the damaged host circuit, rather than acted through the release of an appropriate neurotransmitter, since the glutamatergic dentate granule grafts were ineffective. However, CA1 grafts showed better survival and growth than the other types of transplant, so that functional recovery may have been related to graft viability rather than to the specific type of graft.

Effects of an inhibitor of GABA-aminotransferase (gamma-vinyl-GABA) on the spatial navigation deficit induced by nicotinic blockade

1. 1. The present study investigated whether stimulation of the GABA-ergic system affects spatial navigation (water-maze, WM) deficit induced by nicotinic blockade (mecamylamine). 2. 2. The effects of various doses of gamma-vinyl-GABA (GVG: 50, 150 and 300 mg/kg) and mecamylamine (2.5 and 10 mg/kg) were examined alone and in combination. 3. 3. GVG at the dose 150 mg/kg alone did not impair the performance of rats in the WM task. 4. 4. Mecamylamine at the dose 2.5 and 10 mg/kg clearly impaired the performance of rats in WM task. 5. 5. When the two drugs were co-administered, no interaction between mecamylamine and GVG was observed. 6. 6. Combined nicotinic and muscarinic blockade did not interact as well with GVG administration. 7. 7. Our results do not provide support for any interaction between cholinergic and GABA-ergic mechanisms.

Attenuation by the benzodiazepine receptor antagonist, ZK 93 426, of the deficit in spatial navigation induced by nucleus basalis lesions

The effects of the benzodiazepine receptor antagonist, beta-carboline ZK 93,426 treatment were studied both in NB-lesioned (ibotenic acid) and in unoperated Kuo-Wistar rats in a water maze task. The ZK 93,426 administered in the doses of 1 and 5 mg/kg, 30 min prior to the testing in a water maze apparatus, attenuated the NB lesion-induced spatial navigation deficit, although it had no effect on the performance of unoperated rats. The results suggest functional interactions between GABAergic system and ibotenic acid-induced lesion of the basal forebrain in rats.

Effects of an inhibitor of GABA-aminotransferase (γ-vinyl-GABA) on the spatial navigation deficit induced by muscarinic blockade

The present study investigated whether stimulation of the GABAergic system affects spatial navigation [water-maze (WM)] deficit induced by muscarinic blockade (scopolamine). The effects of various doses of γ-vinyl-GABA (GVG) (50, 150, and 300 mg/kg) and scopolamine (0.4 and 0.1 mg/kg) were examined alone and in combination. GVG at 50 and 150 mg/kg alone did not impair the performance of rats in the WM yask. At 300 mg/kg, GVG caused slight impairment, increasing latency and total distance swum during training trials. Scopolamine at 0.4 mg/kg clearly impaired the performance of rats in the WM task. When the two drugs were coadministered, no interaction between scopolamine and GVG was observed. Our results do not provide support for any interaction between cholinergic muscarinic and GABAergic mechanisms.

Dissociation of spatial navigation and visual guidance performance in Purkinje cell degeneration ( pcd) mutant mice

Spatial learning in rodents requires normal functioning of hippocampal and cortical structures. Recent data suggest that the cerebellum may also be essential. Neurological mutant mice with dysgenesis of the cerebellum provide useful models to examine the effects of abnormal cerebellar function. Mice with one such mutation, Purkinje cell degeneration (pcd), in which Purkinje cells degenerate between the third and fourth postnatal weeks, were evaluated for performance of spatial navigation learning and visual guidance learning in the Morris maze swim-escape task. Unaffected littermates and C57BL/6J mice served as controls. Separate groups of pcd and control mice were tested at 30, 50 and 110 days of age. At all ages, pcd mice had severe deficits in distal-cue (spatial) navigation, failing to decrease path lengths over training and failing to express appropriate spatial biases on probe trials. On the proximal-cue (visual guidance) task, whenever performance differences between groups did occur, they were limited to the initial trials. The ability of the pcd mice to perform the proximal-cue but not the distal-cue task indicates that the massive spatial navigation deficit was not due simply to motor dysfunction. Histological evaluations confirmed that the pcd mutation resulted in Purkinje cell loss without significant depletion of cells in the hippocampal formation. These data provide further evidence that the cerebellum is vital for the expression of behavior directed by spatial cognitive processes.

The effect of γ-vinyl-GABA on the performance of nucleus basalis-lesioned rats in spatial navigation task

The present study investigates whether the stimulation of γ-aminobutyric acid (GABA)ergic system affects spatial navigation deficits induced by the lesioning of the nucleus basalis (NB). Thus, the effect of γ-vinyl-GABA treatment which elevates the GABA levels in brain was studied on water maze task both in unoperated and NB-lesioned (ibotenic acid) rats. The subchronic administration of γ-vinyl-GABA aggravated dose-dependently NB lesion-induced deficits, although it did not impair the performance of unoperated rats in this task. The imbalance between GABAergic system and cholinergic or non-cholinergic systems of the NB may contribute to spatial navigation deficits in rats.

Interaction between raphe dorsalis and nucleus basalis magnocellularis in spatial learning

We compared the effects on spatial learning of an ibotenic acid lesion of the nucleus basalis magnocellularis (NBM), a 5,7-dihydroxytryptamine lesion of the raphe dorsalis (RD) and a combined NBM and RD lesion. The RD lesion reduced serotonin levels, and the NBM lesion reduced cholineacetyltransferase (ChAT) activity in the cortex. Although RD lesions alone did not affect spatial learning in the water-maze, the lesion aggravated the spatial navigation deficit produced by NMB lesioning. The current results a functional interaction between the RD and NBM in spatial navigation.

The role of stress and age in spatial navigation deficits following prenatal exposure to ethanol

The effects of prior experience with swimming on performance in a Morris water task were examined in 21- and 24-day-old rats whose dams consumed liquid diets containing either 35% or 0% ethanol-derived calories (EDO on Days 6-20 of pregnancy, or ad-lib lab chow and water (LC) throughout pregnancy. At 21 days of age, prenatal alcohol-exposed (35%EDC) rats displayed impaired performance relative to pair-fed (0%EDC) and chow-fed (LC) control groups, regardless of prior swimming experience. At 24 days of age, the performance of 35%EDC rats not given swimming experience prior to training did not differ from controls, which suggests that some recovery from fetal alcohol effects had occurred. Among groups given prior swimming experience, however, the 35%EDC rats took longer than the 0%EDC or the LC control groups to find the platform in the Morris maze at 24 days of age. The results suggest that in utero ethanol exposure produces a transient deficit in spatial navigation abilities at around 21 days of age, but that animals appear to recover by around 24 days of age. This deficit appeared to be revealed in 24-day-old rats by giving the animals swim experience prior to training. The results suggest that the present and similar deficits and in spatial navigation in prenatal alcohol-exposed rats may be due to increased and/or prolonged stress responses to the task in alcohol-exposed offspring, and not to a hippocampus-mediated deficit in spatial navigation per se.

Neurobehavioral deficit due to ischemic brain damage limited to half of the CA1 sector of the hippocampus

It is well known that ischemia causes neuronal necrosis in selectively vulnerable sectors of the hippocampus. Since the hippocampus is involved in spatial navigation, learning, and memory, selective deficits in these areas may arise from ischemic brain damage. The objective of this study was to test whether a minimal ischemic insult, producing selective neuronal necrosis restricted to only a portion of the CA1 pyramidal cells of the hippocampus, could produce a detectable spatial navigation deficit. Male Wistar rats received 9 min of forebrain ischemia induced by carotid clamping and hypotension or sham operation with exposure of the carotid arteries. The rats were allowed to recover and were tested on a simple place task, a place learning-set task, and a pattern discrimination task in swimming pools paradigms. Subsequently, the rats were perfusion-fixed and their entire brains subjected to quantitative histopathologic analysis. Although both ischemic and sham-operated groups learned the simple place task, the learning-set task revealed defects in spatial navigation, reflected as increased errors and latency in the performance of the ischemic rats. In the subsequent pattern discrimination task, the ischemic group was superior to the control group, which perseverated by attempting to use a place strategy to solve the discrimination. Quantitative neuropathology revealed neuronal necrosis in the ischemia group limited to 50% of the CA1 zone of the hippocampus. Extrahippocampal damage consisted of rare cortical neuronal necrosis in 2 of 6 animals.(ABSTRACT TRUNCATED AT 250 WORDS)