Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Maze Learning”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,099 records · Page 61Linked to original sources
PubMed2005

Enhanced hippocampal neurogenesis by intraventricular S100B infusion is associated with improved cognitive recovery after traumatic brain injury.

Evidence of injury-induced neurogenesis in the adult hippocampus suggests that an endogenous repair mechanism exists for cognitive dysfunction following traumatic brain injury (TBI). One factor that may be associated with this restoration is S100B, a neurotrophic/mitogenic protein produced by astrocytes, which has been shown to improve memory function. Therefore, we examined whether an intraventricular S100B infusion enhances neurogenesis within the hippocampus following experimental TBI and whether the biological response can be associated with a measurable cognitive improvement. Following lateral fluid percussion or sham injury in male rats (n = 60), we infused S100B (50 ng/h) or vehicle into the lateral ventricle for 7 days using an osmotic micro-pump. Cell proliferation was assessed by injecting the mitotic marker bromodeoxyuridine (BrdU) on day 2 postinjury. Quantification of BrdU-immunoreactive cells in the dentate gyrus revealed an S100B-enhanced proliferation as assessed on day 5 post-injury (p < 0.05), persisting up to 5 weeks (p < 0.05). Using cell-specific markers, we determined the relative numbers of these progenitor cells that became neurons or glia and found that S100B profoundly increased hippocampal neurogenesis 5 weeks after TBI (p < 0.05). Furthermore, spatial learning ability, as assessed by the Morris water maze on day 30-34 post-injury, revealed an improved cognitive performance after S100B infusion (p < 0.05). Collectively, our findings indicate that an intraventricular S100B infusion induces neurogenesis within the hippocampus, which can be associated with an enhanced cognitive function following experimental TBI. These observations provide compelling evidence for the therapeutic potential of S100B in improving functional recovery following TBI.

Animals↗
PubMed1999

Interleukin-1 receptor antagonist attenuates regional neuronal cell death and cognitive dysfunction after experimental brain injury.

The effect of systemic administration of human recombinant interleukin-1 receptor antagonist (rhIL-1ra) on behavioral outcome and histopathologic damage after lateral fluid-percussion brain injury of moderate severity was evaluated. In study 1, brain-injured Sprague Dawley rats received timed subcutaneous injections beginning 15 minutes after injury of either 100 mg/kg rhIL-1ra (high dose, total dose = 1900 mg/kg), 10 mg/kg rhIL-1ra (low dose, total dose = 190 mg/kg), or vehicle over 7 days. No effect of low-dose rhIL-1ra was observed in study 1. High-dose rhIL-1ra significantly attenuated posttraumatic neuronal loss in the injured hippocampal CA3 region (P < 0.05), dentate hilus (P < 0.05), and cortex (P < 0.05) but impaired recovery of motor function at 7 days after trauma (P < 0.05). In study 2, rats were pretrained to learn a visuospatial task in a Morris water maze, subjected to fluid-percussion brain injury or sham treatment, and randomly assigned to receive multiple subcutaneous injections at timed intervals of 100 mg/kg rhIL-1ra (total dose = 900 mg/kg) or vehicle over 42 hours, followed by continuous infusion of a lower concentration of rhIL-1ra (20 mg/kg/day, total dose = 100 mg/kg), or vehicle for 5 days using subcutaneously implanted osmotic minipumps. Postinjury administration of rhIL-1ra significantly attenuated cognitive deficits compared with vehicle-treated animals at 42 hours (P < 0.05) but did not affect motor function at 48 hours, 1 week, and 2 weeks. These results suggest that inhibitors of cytokine pathways may be therapeutically useful for the treatment of brain trauma.

Animals↗
PubMed2002

Inhibition of cyclin-dependent kinases improves CA1 neuronal survival and behavioral performance after global ischemia in the rat.

Increasing evidence suggests that cyclin-dependent kinases participate in neuronal death induced by multiple stresses in vitro. However, their role in cell death paradigms in vivo is not well characterized. Accordingly, the authors examined whether cyclin-dependent kinase inhibition resulted in functionally relevant and sustained neuroprotection in a model of global ischemia. Intracerebroventricular administration of the cyclin-dependent kinase inhibitor flavopiridol, immediately or at 4 hours postreperfusion after a global insult, reduced injury in the CA1 of the hippocampus when examined 7 days after reperfusion. No significant protection was observed when flavopiridol was administered 8 hours after reperfusion. The tumor-suppressor retinoblastoma protein, a substrate of cyclin-dependent kinase, was phosphorylated on a cyclin-dependent kinase consensus site after the global insult; this phosphorylation was inhibited by flavopiridol administration. Importantly, flavopiridol had no effect on core body temperature, suggesting that the mechanism of neuroprotection was through cyclin-dependent kinase inhibition but not through hypothermia. Furthermore, inhibition of cyclin-dependent kinases improved spatial learning behavior as assessed by the Morris water maze 7 to 9 days after reperfusion. However, the histologic protection observed at day 7 was absent 28 days after reperfusion. These results indicate that cyclin-dependent kinase inhibition provides an extended period of morphologic and functional neuroprotection that may allow time for other neuroprotective modalities to be introduced.

Animals↗
PubMedDate not supplied

Parallel working memory for spatial location and food-related object cues in foraging pigeons: binocular and lateralized monocular performance.

During foraging, animals can increase their success by both remembering feeding sites and remembering food-related object cues. Because earlier studies have tested either the site or object memory in isolation, the aim of the present study was to evaluate how efficiently birds can utilize both memories simultaneously. Furthermore, the idea was tested that lateralization might be the principle of brain organization that allows for efficient parallel processing. Pigeons learned to search for food in a complex maze with 16 baited sites. To obtain the maximum reward they had to perform two tasks in parallel, a spatial working memory task and an object-specific working memory task. Birds performed well on this dual task but, compared with spatial working memory alone, they were impaired during the first choices of a trial (Experiment 1). When the left and the right brain hemispheres were tested separately by means of monocular occlusion (Experiment 2), object discrimination was better when birds used their right eye/left hemisphere. This was most pronounced during the first choices of a trial. On the spatial component of the task, performance on binocular trials was better than on monocular trials, but monocularly both hemispheres performed at the same level. Results show that on this dual task, discrimination of food-related object cues predominantly involved the left brain hemisphere whereas both hemispheres contributed equally to spatial performance.

Animal Feed↗
PubMed2004

Delayed onset of prepulse inhibition deficits following kainic acid treatment on postnatal day 7 in rats.

Abnormal activity in corticolimbic circuits during development may be a predisposing factor for schizophrenia. Permanent or temporary lesions of limbic structures such as the ventral hippocampus and basolateral amygdala in rats on postnatal day (PND) 7 result in functional changes similar to some behavioural and cognitive signs of schizophrenia. The present experiments tested whether transient increases in the neural activity of corticolimbic circuits on PND 7 would result in similar behavioural changes. Long-Evans rats were treated with either kainic acid (KA, 1.5 mg/kg, i.p.) or saline on PND 7 and tested for prepulse inhibition (PPI) of the acoustic startle response and spontaneous locomotor activity both in a novel environment and following amphetamine treatment before puberty (PND 35) and in early adulthood (PND 56). In subgroups of animals PPI was also measured following apomorphine administration (0.2 mg/kg) and spatial learning and memory were tested in the water maze. Rats treated with KA were indistinguishable from saline-treated animals on PND 35. However, on PND 56, KA-treated animals showed a subtle consistent decrease in PPI relative to control animals, but did not show increased sensitivity to the disruptive effects of a low dose of apomorphine on PPI. Locomotor responses to novelty or amphetamine were not reliably altered in the KA-treated animals. KA- and saline-treated animals performed similarly in the water maze. These results support the hypothesis that neural hyperactivity on PND 7 in rats causes behavioural changes in early adulthood that resemble some symptoms of schizophrenia. These pharmacological data suggest that the changes are not mediated by postsynaptic alterations in mesolimbic dopamine transmission.

Acoustic Stimulation↗
PubMed2004

TC-1734: an orally active neuronal nicotinic acetylcholine receptor modulator with antidepressant, neuroprotective and long-lasting cognitive effects.

The development of selective ligands targeting neuronal nicotinic acetylcholine receptors to alleviate symptoms associated with neurodegenerative diseases presents the advantage of affecting multiple deficits that are the hallmarks of these pathologies. TC-1734 is an orally active novel neuronal nicotinic agonist with high selectivity for neuronal nicotinic receptors. Microdialysis studies indicate that TC-1734 enhances the release of acetylcholine from the cortex. TC-1734, by either acute or repeated administration, exhibits memory enhancing properties in rats and mice and is neuroprotective following excitotoxic insult in fetal rat brain in cultures and against alterations of synaptic transmission induced by deprivation of glucose and oxygen in hippocampal slices. At submaximal doses, TC-1734 produced additive cognitive effects when used in combination with tacrine or donepezil. Unlike (-)-nicotine, behavioral sensitization does not develop following repeated administration of TC-1734. Its pharmacokinetic (PK) profile (half-life of 2 h) contrasts with the long lasting improvement in working memory (18 h) demonstrating that cognitive improvement extends beyond the lifetime of the compound. The very low acute toxicity of TC-1734 and its receptor activity profile provides additional mechanistic basis for its suggested potential as a clinical candidate. TC-1734 was very well tolerated in acute and chronic oral toxicity studies in mice, rats and dogs. Phase I clinical trials demonstrated TC-1734's favorable pharmacokinetic and safety profile by acute oral administration at doses ranging from 2 to 320 mg. The bioavailability, pharmacological, pharmacokinetic, and safety profile of TC-1734 provides an example of a safe, potent and efficacious neuronal nicotinic modulator that holds promise for the management of the hallmark symptomatologies observed in dementia.

Administration, Oral↗
PubMed2002

Systemic effects of dietary n-3 PUFA supplementation accompany changes of CNS parameters in cerebral hypoperfusion.

Dietary supplementation with long-chain polyunsaturated fatty acids (PUFAs) has become an attractive possibility to alleviate or prevent cerebrovascular pathophysiology. To characterize the potentially beneficial cerebrovascular action of n-3 PUFAs that predominantly occur in fish oil, we set up an experimental paradigm where rats with chronic cerebral hypoperfusion were supplied with n-3 PUFA-enriched diets. Cerebral hypoperfusion was created by a permanent, bilateral occlusion of the common carotid arteries (2VO) of rats at the age of 4 months, with a survival of 3 months. Simultaneously, the rats were provided with experimental diets from the time of weaning until the termination of the experiments. The control diet was comparable to standard rat chow, while diet 1 contained additional n-3 PUFAs and diet 2 was further enriched with structural phospholipids and neurotransmitter precursors. In summary, the data show that diet 2 improved spatial learning of 2VO rats in the Morris water maze. Both diet 1 and diet 2 augmented blood-brain barrier parameters and increased the density of the M1-type muscarinic cholinergic receptors in the hippocampus independent of the rate of cerebral perfusion. In addition to an overview of these results, changes that were supportive or accompanying those described in the CNS are also presented. Briefly, plasma corticosterone concentration was elevated most explicitly by 2VO, while the relative weight of the liver and spleen increased due to the diets. The data draw attention to changes not only in the CNS, but also in the periphery as a consequence of chronic supplementation with n-3 PUFA-enriched diets.

Animals↗
PubMed2005

Inhibition of neprilysin by infusion of thiorphan into the hippocampus causes an accumulation of amyloid Beta and impairment of learning and memory.

An imbalance between anabolism and catabolism causes an accumulation of amyloid beta-peptide (Abeta), which is a proposed trigger of the onset of Alzheimer's disease. Neprilysin is a rate-limiting peptidase that participates in the catabolism of Abeta in the brain. We examined whether rats continuously infused with thiorphan, a specific neprilysin inhibitor, into the hippocampus develop cognitive impairments through accumulation of Abeta. Thiorphan infusion elevated hippocampal Abeta40 and Abeta42 levels in the insoluble but not the soluble fraction. Thiorphan-infused rats displayed cognitive impairments in the ability to discriminate in the object recognition test, associative learning in the conditioned fear learning test, and spatial memory in the water maze test, tasks that depend on the hippocampus. These cognitive abilities in the battery of behavioral tasks inversely correlated with insoluble Abeta contents in the hippocampus. The nicotine-stimulated release of acetylcholine in the hippocampus of thiorphan-infused rats was significantly lower than that in vehicle-infused rats. These results indicate that continuous infusion of thiorphan into the hippocampus causes cognitive dysfunction and reduces cholinergic activity by raising the level of Abeta in the hippocampus and suggest that a reduction of neprilysin activity contributes to the deposition of Abeta and development of Alzheimer's disease.

Acetylcholine↗
PubMed1995

Preferential impairment of avoidance performances in amygdala-lesioned mice.

To clarify the role of the amygdala in the fulfillment of memory and/or learning, amygdala-lesioned mice were tested in passive and active avoidance performances and also in spatial learning tasks. Although the lesioned animals showed deteriorated performances in both passive and active avoidance tests, they executed the spatial learning tasks as well as the control mice. The learning deficit was prominent in the process of memory acquisition of passive and active avoidance tasks, suggesting that the amygdala might be involved in the acquisition processes of these avoidance tests. The locomotor activities of the lesioned animals were slightly increased, but there was no significant difference compared with the control mice. These findings indicate that the amygdala plays a crucial role preferentially in the avoidance learning rather than the spatial learning.

Amygdala↗
PubMed2004

Unique neural circuitry for neonatal olfactory learning.

Imprinting ensures that the infant forms the caregiver attachment necessary for altricial species survival. In our mammalian model of imprinting, neonatal rats rapidly learn the odor-based maternal attachment. This rapid learning requires reward-evoked locus ceruleus (LC) release of copious amounts of norepinephrine (NE) into the olfactory bulb. This imprinting ends at postnatal day 10 (P10) and is associated with a dramatic reduction in reward-evoked LC NE release. Here we assess whether the functional emergence of LC alpha2 inhibitory autoreceptors and the downregulation of LC alpha1 excitatory autoreceptors underlie the dramatic reduction in NE release associated with termination of the sensitive period. Postsensitive period pups (P12) were implanted with either LC or olfactory bulb cannulas, classically conditioned with intracranial drug infusions (P14), and tested for an odor preference (P15). During conditioning, a novel odor was paired with either olfactory bulb infusion of abeta-receptor agonist (isoproterenol) to assess the target effects of NE or direct LC cholinergic stimulation combined with alpha2 antagonists and alpha1 agonists in a mixture to reinstate neonatal levels of LC autoreceptor activity to assess the source of NE. Pups learned an odor preference when the odor was paired with either olfactory bulb isoproterenol infusion or reinstatement of neonatal LC receptor activity. These results suggest that LC autoreceptor functional changes rather than olfactory bulb changes underlie sensitive period termination.

Acetylcholine↗
PubMed2000

Neurobehavioral protection by the neuronal calcium channel blocker ziconotide in a model of traumatic diffuse brain injury in rats.

OBJECT: Abnormal accumulation of intracellular calcium following traumatic brain injury (TBI) is thought to contribute to a cascade of cellular events that lead to neuropathological conditions. Therefore, the possibility that specific calcium channel antagonists might exert neuroprotective effects in TBI has been of interest. The focus of this study was to examine whether Ziconotide produces such neuroprotective effects. METHODS: The authors report that the acceleration-deceleration model of TBI developed by Marmarou, et al., induces a long-lasting deficit of neuromotor and behavioral function. The voltage-sensitive calcium channel blocker Ziconotide (also known as SNX-111 and CI-1009) exerts neuroprotective effects in this model of diffuse brain injury (DBI) in rats. The dose and time of injection of Ziconotide chosen for the present study was based on the authors' previous biochemical studies of mitochondria. Rats were trained in a series of motor and memory tasks, following which they were subjected to DBI using the Marmarou, et al., model. At 3, 5, and 24 hours, all rats were injected with 2 mg/kg Ziconotide for a total cumulative dose of 6 mg/kg Ziconotide. Control brain-injured animals were injected with an equal volume of saline vehicle at each of these time points. The rats were tested for motor and cognitive performance at 1, 3, 7,14, 21, 28, 35, and 42 days postinjury. Saline-treated rats displayed severe motor and cognitive deficits after DBI. Compared with saline-treated control animals, rats treated with Ziconotide displayed better motor performance during inclined plane, beam balance, and beam walk tests; improved memory while in the radial arm maze; and improved learning while in the Morris water maze. CONCLUSIONS: These results demonstrated that the acceleration-deceleration model, which had been developed by Marmarou, et al., induces severe motor and cognitive deficits. We also demonstrated that Ziconotide exhibits substantial neuroprotective activity in this model of TBI. Improvement was observed in both motor and cognitive tasks, even though treatment was not initiated until 3 hours after injury. These findings support the development of neuronal N-type calcium channel antagonists as useful therapeutic agents in the treatment of TBI.

Animals↗
PubMed1999

Sex dimorphisms in the rate of age-related decline in spatial memory: relevance to alterations in the estrous cycle.

The present experiments demonstrate the existence of sex differences in the rate of development and the magnitude of age-dependent impairments in cognitive and sensorimotor abilities. Although no sex differences were found in spatial reference memory at a young age, the mnemonic ability of female rats deteriorated more rapidly than that of male rats. A major drop in reference memory of the females occurred at the age of 12 months, whereas in the males the onset of impairments occurred later, at the age of 18 months. In spatial working memory, on the other hand, the magnitude of decline was greater in females than in males, although the onset of these impairments occurred at the age of 24 months in both sexes. A sexual dimorphism-aging interaction also was observed in sensorimotor performance. Up to the age of 18 months the females outperformed the males. Subsequently, by the age of 24 months, the performance of the females declined to a level similar to that of the males. The deficits observed in reference and working memory seem to be cognitive in origin and not attributable to alterations in sensory and motor abilities. In addition, the earlier onset of reference memory impairments in females generally coincides with the onset of alterations in the estrous cycle, suggesting that a decline in the estrogenic milieu of the females could be a factor in accelerating the rate of age-related cognitive impairments in the female rat.

Aging↗
PubMed1999

Antioxidant stobadine and neurobehavioural development of the rat offspring.

Stobadine (STO) is a potential neuro- and cardioprotective drug with high antioxidative properties. The presented study investigated the effects of oral STO administration (5, 15 and 50 mg/kg/d) during pregnancy and lactation to dams on neurobehavioural development of their offspring (body growth and maturation, sensory functions, neuromotor and reflex development, levels of activity and emotional reactivity, memory and learning processes). The results of our experiments showed that long-term administration of STO had no adverse effects on the course of pregnancy and lactation in dams and on the neurobehavioural development of offspring.

Acoustic Stimulation↗
PubMed2001

Configural learning without configural training.

Rats learned discriminations in which 2 familiar compound visual stimuli AB and CD were nonreinforced, whereas less-familiar compounds (EF, GH, IJ...) were reinforced (constant-negative paradigm). Such discriminations can in principle be acquired through elemental (nonconfigural) learning. Three different types of compound--object/object, object/position, and shape/fill-pattern--were used, and the number of familiar compounds extended to 3 or 4. In all cases, when rats were tested for the first time with previously unseen recombinations of the familiar elements--for example, AC, BD--they preferred these to the familiar compounds, implying that they had encoded configural information during the original training. Moreover, preference remained constant despite extended exposure to configural training in the test phase. The findings extend the evidence that configural representations are formed independently of explicit configural training.

Animals↗
PubMedDate not supplied

[A special case of learning disruption as a model of a disintegration phenomenon].

Combination of two factors in rats such as the isolation (during 2-4 months, beginning from the 21st day of age) and procedure of space cyclic learning results in a rare kind of behavioral strategy (in 30% animals), when the cyclic behavior is realized without food reinforcement. Such a dissociation between the vital motivation and searching behavior may be considered as an analogue of the disintegration phenomenon in neuropsychotic patients. The deep depression of learning owing to lowering of search represents the dominant type of behavioral disorders in isolants. The cyclic habit training, including a 2-months pause between two sessions, significantly increases behavioral search activity. The behaviors are accompanied by morphological shifts in the sensomotor cortex: significant decrease of the fifth layer (giant pyramids) thickness, selective lowering in the satellite glia density and elimination of normal behavior-glia correlations.

Animals↗
PubMed2005

[Effects of prenatal methylmercury exposure on learning and memory ability of mice and ultrastructure of hippocampus neurons in mice].

OBJECTIVE: To study the effects of prenatal methylmercury exposure on learning and memory ability of mice and ultrastructure of hippocampus neurons in mice. METHODS: Methylmercury in doses of 0 and 4mg/(kg x d) were fed to pregnant mice at 7th-9th day after conception. Learning and memory ability of the mice offspring was detected. The ultrastructure of hippocampus neurons was observed by electron microscope after the completion of the experiment. RESULTS: The learning and memory ability of the mice offspring of 4 mg/(kg x d) dose group was lower than those of 0 mg/(kg x d) dose group (P < 0.05). Changes in the ultrastructure of hippocampus neurons were obvious in 4 mg/(kg x d) dose group as compared with the 0 mg/(kg x d) dose group. CONCLUSION: Methylmercury could affect the growth and development of central nerve system. The learning and memory ability of mice offspring was greatly damaged and the ultrastructure of hippocampus neurons was changed by methylmercury.

Animals↗
PubMed1995

Delayed postischemic hypothermia: a six month survival study using behavioral and histological assessments of neuroprotection.

In the gerbil, brief global forebrain ischemia induces profound habituation and working memory impairments that stem from delayed hippocampal CA1 death. Short duration postischemic hypothermia has been shown to reduce CA1 loss, but such reports are controversial, as it is thought that protection may be transient. The purpose of this study was to investigate whether prolonged postischemic hypothermia provided long-term CA1 and functional neuroprotection. Previously, 90% of anterior CA1 neurons were rescued (30 d survival) when 24 hr of hypothermia (32 degrees C) was induced 1 hr following a 5 min occlusion that otherwise produced more than 95% loss (Colbourne and Corbett, 1994). We now find about 70% CA1 savings with this same hypothermic treatment in gerbils that survived for 6 months postischemia. While this is a significant reduction from 30 day survival (medial CA1 only), it nonetheless shows, for the first time, persistent, if not permanent neuroprotection, especially in middle and lateral CA1. In addition, in non-treated animals, ischemia impaired learning in an open field and T-maze for up to 6 months. Postischemic hypothermia significantly reduced these deficits. Hypothermia (32 degrees), when initiated 4 hr after ischemia, rescued approximately 12% of CA1 neurons at 6 months with a slight behavioral benefit. Milder hypothermia (34 degrees C, 1-25 hr postischemia, 30 d survival) also reduced habituation impairments and saved approximately 60% of CA1 neurons. Similar trends were found at more caudal CA1 levels. These results clearly show that postischemic hypothermia provides effective and long-lasting neuroprotection, which depends upon the delay to initiation, duration, and degree of cooling and survival time. The protracted functional and histological benefit observed justifies further basic and clinical investigation.

Animals↗