Impaired associative learning in schizophrenia: behavioral and computational studies

PubMed Central

Diwadkar, Vaibhav A.; Flaugher, Brad; Jones, Trevor; Zalányi, László; Ujfalussy, Balázs; Keshavan, Matcheri S.

2008-01-01

Associative learning is a central building block of human cognition and in large part depends on mechanisms of synaptic plasticity, memory capacity and fronto–hippocampal interactions. A disorder like schizophrenia is thought to be characterized by altered plasticity, and impaired frontal and hippocampal function. Understanding the expression of this dysfunction through appropriate experimental studies, and understanding the processes that may give rise to impaired behavior through biologically plausible computational models will help clarify the nature of these deficits. We present a preliminary computational model designed to capture learning dynamics in healthy control and schizophrenia subjects. Experimental data was collected on a spatial-object paired-associate learning task. The task evinces classic patterns of negatively accelerated learning in both healthy control subjects and patients, with patients demonstrating lower rates of learning than controls. Our rudimentary computational model of the task was based on biologically plausible assumptions, including the separation of dorsal/spatial and ventral/object visual streams, implementation of rules of learning, the explicit parameterization of learning rates (a plausible surrogate for synaptic plasticity), and learning capacity (a plausible surrogate for memory capacity). Reductions in learning dynamics in schizophrenia were well-modeled by reductions in learning rate and learning capacity. The synergy between experimental research and a detailed computational model of performance provides a framework within which to infer plausible biological bases of impaired learning dynamics in schizophrenia. PMID:19003486

Gender Dimorphism in Aspartame-Induced Impairment of Spatial Cognition and Insulin Sensitivity

PubMed Central

Collison, Kate S.; Makhoul, Nadine J.; Zaidi, Marya Z.; Saleh, Soad M.; Andres, Bernard; Inglis, Angela; Al-Rabiah, Rana; Al-Mohanna, Futwan A.

2012-01-01

Previous studies have linked aspartame consumption to impaired retention of learned behavior in rodents. Prenatal exposure to aspartame has also been shown to impair odor-associative learning in guinea pigs; and recently, aspartame-fed hyperlipidemic zebrafish exhibited weight gain, hyperglycemia and acute swimming defects. We therefore investigated the effects of chronic lifetime exposure to aspartame, commencing in utero, on changes in blood glucose parameters, spatial learning and memory in C57BL/6J mice. Morris Water Maze (MWM) testing was used to assess learning and memory, and a random-fed insulin tolerance test was performed to assess glucose homeostasis. Pearson correlation analysis was used to investigate the associations between body characteristics and MWM performance outcome variables. At 17 weeks of age, male aspartame-fed mice exhibited weight gain, elevated fasting glucose levels and decreased insulin sensitivity compared to controls (P<0.05). Females were less affected, but had significantly raised fasting glucose levels. During spatial learning trials in the MWM (acquisition training), the escape latencies of male aspartame-fed mice were consistently higher than controls, indicative of learning impairment. Thigmotactic behavior and time spent floating directionless was increased in aspartame mice, who also spent less time searching in the target quadrant of the maze (P<0.05). Spatial learning of female aspartame-fed mice was not significantly different from controls. Reference memory during a probe test was affected in both genders, with the aspartame-fed mice spending significantly less time searching for the former location of the platform. Interestingly, the extent of visceral fat deposition correlated positively with non-spatial search strategies such as floating and thigmotaxis, and negatively with time spent in the target quadrant and swimming across the location of the escape platform. These data suggest that lifetime exposure to aspartame

Gender dimorphism in aspartame-induced impairment of spatial cognition and insulin sensitivity.

PubMed

Collison, Kate S; Makhoul, Nadine J; Zaidi, Marya Z; Saleh, Soad M; Andres, Bernard; Inglis, Angela; Al-Rabiah, Rana; Al-Mohanna, Futwan A

2012-01-01

Previous studies have linked aspartame consumption to impaired retention of learned behavior in rodents. Prenatal exposure to aspartame has also been shown to impair odor-associative learning in guinea pigs; and recently, aspartame-fed hyperlipidemic zebrafish exhibited weight gain, hyperglycemia and acute swimming defects. We therefore investigated the effects of chronic lifetime exposure to aspartame, commencing in utero, on changes in blood glucose parameters, spatial learning and memory in C57BL/6J mice. Morris Water Maze (MWM) testing was used to assess learning and memory, and a random-fed insulin tolerance test was performed to assess glucose homeostasis. Pearson correlation analysis was used to investigate the associations between body characteristics and MWM performance outcome variables. At 17 weeks of age, male aspartame-fed mice exhibited weight gain, elevated fasting glucose levels and decreased insulin sensitivity compared to controls (P<0.05). Females were less affected, but had significantly raised fasting glucose levels. During spatial learning trials in the MWM (acquisition training), the escape latencies of male aspartame-fed mice were consistently higher than controls, indicative of learning impairment. Thigmotactic behavior and time spent floating directionless was increased in aspartame mice, who also spent less time searching in the target quadrant of the maze (P<0.05). Spatial learning of female aspartame-fed mice was not significantly different from controls. Reference memory during a probe test was affected in both genders, with the aspartame-fed mice spending significantly less time searching for the former location of the platform. Interestingly, the extent of visceral fat deposition correlated positively with non-spatial search strategies such as floating and thigmotaxis, and negatively with time spent in the target quadrant and swimming across the location of the escape platform. These data suggest that lifetime exposure to aspartame

Hippocampal Volume Reduction in Humans Predicts Impaired Allocentric Spatial Memory in Virtual-Reality Navigation

PubMed Central

Dzieciol, Anna M.; Gadian, David G.; Jentschke, Sebastian; Doeller, Christian F.; Burgess, Neil; Mishkin, Mortimer

2015-01-01

The extent to which navigational spatial memory depends on hippocampal integrity in humans is not well documented. We investigated allocentric spatial recall using a virtual environment in a group of patients with severe hippocampal damage (SHD), a group of patients with “moderate” hippocampal damage (MHD), and a normal control group. Through four learning blocks with feedback, participants learned the target locations of four different objects in a circular arena. Distal cues were present throughout the experiment to provide orientation. A circular boundary as well as an intra-arena landmark provided spatial reference frames. During a subsequent test phase, recall of all four objects was tested with only the boundary or the landmark being present. Patients with SHD were impaired in both phases of this task. Across groups, performance on both types of spatial recall was highly correlated with memory quotient (MQ), but not with intelligence quotient (IQ), age, or sex. However, both measures of spatial recall separated experimental groups beyond what would be expected based on MQ, a widely used measure of general memory function. Boundary-based and landmark-based spatial recall were both strongly related to bilateral hippocampal volumes, but not to volumes of the thalamus, putamen, pallidum, nucleus accumbens, or caudate nucleus. The results show that boundary-based and landmark-based allocentric spatial recall are similarly impaired in patients with SHD, that both types of recall are impaired beyond that predicted by MQ, and that recall deficits are best explained by a reduction in bilateral hippocampal volumes. SIGNIFICANCE STATEMENT In humans, bilateral hippocampal atrophy can lead to profound impairments in episodic memory. Across species, perhaps the most well-established contribution of the hippocampus to memory is not to episodic memory generally but to allocentric spatial memory. However, the extent to which navigational spatial memory depends on

Hippocampal Volume Reduction in Humans Predicts Impaired Allocentric Spatial Memory in Virtual-Reality Navigation.

PubMed

Guderian, Sebastian; Dzieciol, Anna M; Gadian, David G; Jentschke, Sebastian; Doeller, Christian F; Burgess, Neil; Mishkin, Mortimer; Vargha-Khadem, Faraneh

2015-10-21

The extent to which navigational spatial memory depends on hippocampal integrity in humans is not well documented. We investigated allocentric spatial recall using a virtual environment in a group of patients with severe hippocampal damage (SHD), a group of patients with "moderate" hippocampal damage (MHD), and a normal control group. Through four learning blocks with feedback, participants learned the target locations of four different objects in a circular arena. Distal cues were present throughout the experiment to provide orientation. A circular boundary as well as an intra-arena landmark provided spatial reference frames. During a subsequent test phase, recall of all four objects was tested with only the boundary or the landmark being present. Patients with SHD were impaired in both phases of this task. Across groups, performance on both types of spatial recall was highly correlated with memory quotient (MQ), but not with intelligence quotient (IQ), age, or sex. However, both measures of spatial recall separated experimental groups beyond what would be expected based on MQ, a widely used measure of general memory function. Boundary-based and landmark-based spatial recall were both strongly related to bilateral hippocampal volumes, but not to volumes of the thalamus, putamen, pallidum, nucleus accumbens, or caudate nucleus. The results show that boundary-based and landmark-based allocentric spatial recall are similarly impaired in patients with SHD, that both types of recall are impaired beyond that predicted by MQ, and that recall deficits are best explained by a reduction in bilateral hippocampal volumes. In humans, bilateral hippocampal atrophy can lead to profound impairments in episodic memory. Across species, perhaps the most well-established contribution of the hippocampus to memory is not to episodic memory generally but to allocentric spatial memory. However, the extent to which navigational spatial memory depends on hippocampal integrity in humans is

Mice with a fra-1 knock-in into the c-fos locus show impaired spatial but regular contextual learning and normal LTP.

PubMed

Gass, Peter; Fleischmann, Alexander; Hvalby, Oivind; Jensen, Vidar; Zacher, Christiane; Strekalova, Tatyana; Kvello, Ane; Wagner, Erwin F; Sprengel, Rolf

2004-11-04

The immediate early gene c-fos is part of the AP-1 transcription factor complex, which is involved in molecular mechanisms underlying learning and memory. Mice that lack c-Fos in the brain show impairments in spatial reference and contextual learning, and also exhibit a reduced long-term potentiation of synaptic transmission (LTP) at CA3-to-CA1 synapses. In the present study, we investigated mice in which c-fos was deleted and replaced by fra-1 (c-fos(fra-1) mice) to determine whether other members of the c-fos gene family can substitute for the functions of the c-fos gene. In c-fos(fra-1) mice, both CA3-to-CA1 LTP and contextual learning in a Pavlovian fear conditioning task were similar to wild-type littermates, indicating that Fra-1 expression restored the impairments caused by brain-specific c-Fos depletion. However, c-Fos-mediated learning deficits in a reference memory task of the Morris watermaze were also present in c-fos(fra-1) mice. These findings suggest that different c-Fos target genes are involved in LTP, contextual learning, and spatial reference memory formation.

Lanthanum chloride impairs spatial memory through ERK/MSK1 signaling pathway of hippocampus in rats.

PubMed

Liu, Huiying; Yang, Jinghua; Liu, Qiufang; Jin, Cuihong; Wu, Shengwen; Lu, Xiaobo; Zheng, Linlin; Xi, Qi; Cai, Yuan

2014-12-01

Rare earth elements (REEs) are used in many fields for their diverse physical and chemical properties. Surveys have shown that REEs can impair learning and memory in children and cause neurobehavioral defects in animals. However, the mechanism underlying these impairments has not yet been completely elucidated. Lanthanum (La) is often selected to study the effects of REEs. The aim of this study was to investigate the spatial memory impairments induced by lanthanum chloride (LaCl3) and the probable underlying mechanism. Wistar rats were exposed to LaCl3 in drinking water at 0 % (control, 0 mM), 0.25 % (18 mM), 0.50 % (36 mM), and 1.00 % (72 mM) from birth to 2 months after weaning. LaCl3 considerably impaired the spatial learning and memory of rats in the Morris water maze test, damaged the synaptic ultrastructure and downregulated the expression of p-MEK1/2, p-ERK1/2, p-MSK1, p-CREB, c-FOS and BDNF in the hippocampus. These results indicate that LaCl3 exposure impairs the spatial learning and memory of rats, which may be attributed to disruption of the synaptic ultrastructure and inhibition of the ERK/MSK1 signaling pathway in the hippocampus.

NMDA Receptor Antagonism Impairs Reversal Learning in Developing Rats

PubMed Central

Chadman, Kathryn K.; Watson, Deborah J.; Stanton, Mark E.

2014-01-01

Four experiments examined the effect of dizocilpine maleate (MK-801), a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, on reversal learning during development. On postnatal days (PND) 21, 26, or 30, rats were trained on spatial discrimination and reversal in a T-maze. When MK-801 was administered (intraperitoneally) before both acquisition and reversal, 0.18 mg/kg generally impaired performance, whereas doses of 0.06 mg/kg and 0.10 mg/kg, but not 0.03 mg/kg, selectively impaired reversal learning (Experiments 1 and 3). The selective effect on reversal was not a result of sensitization to the second dose of MK-801 (Experiment 2) and was observed when the drug was administered only during reversal in an experiment addressing state-dependent learning (Experiment 4). Spatial reversal learning is more sensitive to NMDA-receptor antagonism than is acquisition. No age differences in sensitivity to MK-801 were found between PND 21 and 30. PMID:17014258

Spatial learning impairment induced by chronic stress is related to individual differences in novelty reactivity: search for neurobiological correlates.

PubMed

Touyarot, K; Venero, C; Sandi, C

2004-02-01

Although chronic stress has been reported to induce deleterious effects on hippocampal structure and function, the possible existence of individual differences in the vulnerability to develop stress-induced cognitive alterations was hypothesized. This study was designed to evaluate (i) whether individual variability in behavioural reactivity to novelty could be related to a differential vulnerability to show spatial learning deficits after chronic stress in young adult rats, and (ii) to what extent, could individual differences in stress-induced cognitive alterations be related to alterations in specific neurobiological substrates. Four month-old Wistar male rats were classified according to their locomotor reactivity to a novel environment, as either low (LR) or highly (HR) reactive, and then either submitted to psychosocial stress for 21-days (consisting of the daily cohabitation of each young adult rat with a new middle-aged rat) or left undisturbed. The results showed that psychosocial stress induced a marked deficit in spatial learning in the water maze in HR, but not in LR, rats. Then, a second experiment investigated the possible differential expression of corticosteroid receptors (MR and GR) and cell adhesion molecules (NCAM and L1) in the hippocampus of HR and LR rats, both under basal conditions and after exposure to chronic social stress. Although chronic stress induced a reduction on the hippocampal expression of MRs and the NCAM-140 isoform, the levels of these molecules did not differ between stressed rats with and without spatial learning impairments; i.e., between HR- and LR-stressed rats, respectively. Nevertheless, it should be noted that the reduction of the hippocampal expression of NCAM-140 induced by psychosocial stress was particularly marked in HR stressed rats. However, the expression of GRs, NCAM-120 and NCAM-180 isoforms, and L1, was not affected by stress, regardless of the reactivity of the animals. Therefore, although we failed to find

Sex-dependent effects of developmental exposure to different pesticides on spatial learning. The role of induced neuroinflammation in the hippocampus.

PubMed

Gómez-Giménez, Belén; Llansola, Marta; Hernández-Rabaza, Vicente; Cabrera-Pastor, Andrea; Malaguarnera, Michele; Agusti, Ana; Felipo, Vicente

2017-01-01

The use of pesticides has been associated with impaired neurodevelopment in children. The aims of this work were to assess: 1) the effects on spatial learning of developmental exposure to pesticides 2) if the effects are sex-dependent and 3) if hippocampal neuroinflammation is associated with the impairment of spatial learning. We analyzed the effects of developmental exposure to four pesticides: chlorpyrifos, carbaryl, endosulfan and cypermethrin. Exposure was from gestational day 7 to post-natal day 21 and spatial learning and memory was assessed when the rats were young adults. The effects of pesticides on spatial learning were pesticide and gender-dependent. Carbaryl did not affect spatial learning in males or females. Endosulfan and chlorpyrifos impaired learning in males but not in females. Cypermethrin improved spatial learning in the Morris water maze both in males and females while impaired learning in the radial maze only in males. Spatial learning ability was lower in control female rats than in males. All pesticides induced neuroinflammation, increasing IL-1b content in the hippocampus and there is a negative correlation between IL-1b levels in the hippocampus and spatial learning. Neuroinflammation would contribute to the effects of pesticides on spatial learning. Copyright © 2016 Elsevier Ltd. All rights reserved.

Mice deficient in collapsin response mediator protein-1 exhibit impaired long-term potentiation and impaired spatial learning and memory.

PubMed

Su, Kang-Yi; Chien, Wei-Lin; Fu, Wen-Mei; Yu, I-Shing; Huang, Hsiang-Po; Huang, Pei-Hsing; Lin, Shu-Rung; Shih, Jin-Yuan; Lin, Yi-Ling; Hsueh, Yi-Ping; Yang, Pan-Chyr; Lin, Shu-Wha

2007-03-07

Collapsing response mediator protein-1 (CRMP-1) was initially identified in brain and has been implicated in plexin-dependent neuronal function. The high amino acid sequence identity among the five CRMPs has hindered determination of the functions of each individual CRMP. We generated viable and fertile CRMP-1 knock-out (CRMP-1(-/-)) mice with no evidence of gross abnormality in the major organs. CRMP-1(-/-) mice exhibited intense microtubule-associated protein 2 (MAP2) staining in the proximal portion of the dendrites, but reduced and disorganized MAP2 staining in the distal dendrites of hippocampal CA1 pyramidal cells. Immunoreactivity to GAP-43 (growth-associated protein-43) and PSD95 (postsynaptic density-95) (a postsynaptic membrane adherent cytoskeletal protein) was also decreased in the CA1 region of the knock-out mice. These changes were consistent with the mutant mice showing a reduction in long-term potentiation (LTP) in the CA1 region and impaired performance in hippocampal-dependent spatial learning and memory tests. CRMP-1(-/-) mice showed a normal synapsin I labeling pattern in CA1 and normal paired-pulse facilitation. These findings provide the first evidence suggesting that CRMP-1 may be involved in proper neurite outgrowth in the adult hippocampus and that loss of CRMP-1 may affect LTP maintenance and spatial learning and memory.

[Impairment of spatial learning and memory and changes of oxidative stress in hippocampus from Type 1 diabetic mice].

PubMed

Wang, Chun; Lü, Gaoyou; Li, Yan; Zhao, Shidi; Huang, Li

2018-05-28

To investigate the relevance between spatial learning and memory impairment and the changes of inducible nitric oxide synthase (iNOS) activity, superoxide dismutase (SOD) activity and malondiadehyde (MDA) content in hippocampus from Type 1 diabetic mice.
 Methods: Sixty male mice were randomly assigned into a control group (NC group, 20 mice) and a Type 1 diabetic group (DM group, 40 mice). Type 1 diabetic mouse models were established by a large dose intraperitoneal injection of streptozotocin (100 mg/kg). The spatial learning and memory abilities of mice were assessed by Morris water maze (MWM) test. After MWM test, we chose 20 mice (diabetic encephalopathy mice) with the worst spatial learning and memory abilities from diabetic model group, and detected the iNOS activity, SOD activity and MDA content in hippocampus in both groups.
 Results: Compared with the NC group, the escape latency was significantly extended and platform crossings were significantly declined in diabetic mice (P<0.01). Furthermore, the activity of iNOS and the content of MDA were markedly increased, and the activity of SOD was significantly decreased in hippocampus of diabetic encephalopathy mice (P<0.01).
 Conclusion: The established Type 1 diabetic mice show symptoms of cognitive dysfunction, which might be related to the increase of oxidative stress in hippocampus.

Zinc deficiency with reduced mastication impairs spatial memory in young adult mice.

PubMed

Kida, Kumiko; Tsuji, Tadataka; Tanaka, Susumu; Kogo, Mikihiko

2015-12-01

Sufficient oral microelements such as zinc and fully chewing of foods are required to maintain cognitive function despite aging. No knowledge exists about the combination of factors such as zinc deficiency and reduced mastication on learning and memory. Here we show that tooth extraction only in 8-week-old mice did not change the density of glial fibrillary acidic protein-labeled astrocytes in the hippocampus or spatial memory parameters. However, tooth extraction followed by zinc deprivation strongly impaired spatial memory and led to an increase in astrocytic density in the hippocampal CA1 region. The impaired spatial performance in the zinc-deficient only (ZD) mice also coincided well with the increase in the astrocytic density in the hippocampal CA1 region. After switching both zinc-deficient groups to a normal diet with sufficient zinc, spatial memory recovered, and more time was spent in the quadrant with the goal in the probe test in the mice with tooth extraction followed by zinc deprivation (EZD) compared to the ZD mice. Interestingly, we found no differences in astrocytic density in the CA1 region among all groups at 22 weeks of age. Furthermore, the escape latency in a visible probe test at all times was longer in zinc-deficient groups than the others and demonstrated a negative correlation with body weight. No significant differences in escape latency were observed in the visible probe test among the ZD, EZD, and normal-fed control at 4 weeks (CT4w) groups in which body weight was standardized to that of the EZD group, or in the daily reduction in latency between the normal-fed control and CT4w groups. Our data showed that zinc-deficient feeding during a young age impairs spatial memory performance and leads to an increase in astrocytic density in the hippocampal CA1 region and that zinc-sufficient feeding is followed by recovery of the impaired spatial memory along with changes in astrocytic density. The combination of the two factors, zinc deficiency

Val8-glucagon-like peptide-1 protects against Aβ1-40-induced impairment of hippocampal late-phase long-term potentiation and spatial learning in rats.

PubMed

Wang, X H; Li, L; Hölscher, C; Pan, Y F; Chen, X R; Qi, J S

2010-11-10

Amyloid β protein (Aβ) is considered to be partly responsible for the impairment of learning and memory in Alzheimer disease (AD). In addition, it has been found recently that type 2 diabetes mellitus (T2DM) is a risk factor for developing AD. One promising treatment for AD is using analogues for the insulin-release facilitating gut hormone glucagon-like peptide-1 (GLP-1) that has been developed as a T2DM therapy. GLP-1 has been shown to have neuroprotective properties. However, if GLP-1 can protect the late phase-long term potentiation (L-LTP) and related cognitive function against Aβ-induced impairment it is still an open question. To further characterize the neuroprotective function of GLP-1 in the brain, we investigated the effects of i.c.v. injected Val(8)-GLP-1(7-36) on the Aβ fragment-induced impairment of in vivo hippocampal L-LTP and spatial learning and memory in rats. The results showed that (1) Aβ1-40 (5 nmol) injection did not affect the baseline field excitatory postsynaptic potentials (fEPSPs), but significantly suppressed multiple high frequency stimulation (HFS)-induced L-LTP in hippocampal CA1 region; (2) Val(8)-GLP-1(7-36) (0.05 pmol) administration alone did not affect the baseline synaptic transmission and the maintenance of L-LTP; (3) pretreatment with Val(8)-GLP-1(7-36) (0.05 pmol) effectively prevented Aβ1-40-induced deficit of L-LTP; (4) i.c.v. injection of 5 nmol Aβ1-40 resulted in a significant decline learning a spatial Morris water maze (MWM) test; (5) Val(8)-GLP-1(7-36) (0.05 pmol) administration alone did not affect spatial learning in this task, while pretreatment with Val(8)-GLP-1(7-36) effectively reversed the impairment of spatial learning and memory induced by Aβ1-40. At the same time, the swim speeds and escape latencies of rats among all groups in the visible platform tests did not show any difference. These results suggest that increase of GLP-1 signalling in the brain may be a promising strategy to ameliorate the

Long-lasting spatial learning and memory impairments caused by chronic cerebral hypoperfusion associate with a dynamic change of HCN1/HCN2 expression in hippocampal CA1 region.

PubMed

Luo, Pan; Lu, Yun; Li, Changjun; Zhou, Mei; Chen, Cheng; Lu, Qing; Xu, Xulin; He, Zhi; Guo, Lianjun

2015-09-01

Chronic cerebral hypoperfusion (CCH) causes learning and memory impairments and increases the risk of Alzheimer disease (AD) and vascular dementia (VD) through several biologically plausible pathways, yet the mechanisms underlying the disease process remained unclear particularly in a temporal manner. We performed permanent bilateral occlusion of the common carotid arteries (two-vessel occlusion, 2VO) to induce CCH. To determine whether hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are altered at different stages of cognitive impairment caused by CCH, adult male SD rats were randomly distributed into sham-operated 4, 8 and 12weeks group, 2VO 4, 8 and 12weeks group. Learning and memory performance were evaluated with Morris water maze (MWM) and long-term potentiation (LTP) was used to address the underlying synaptic mechanisms. Expression of NeuN, HCN1 and HCN2 in hippocampal CA1, DG and CA3 areas was quantified by immunohistochemistry and western blotting. Our data showed that CCH induced a remarkable spatial learning and memory deficits in rats of 2VO 4, 8, and 12weeks group although neuronal loss only occurred after 4weeks of 2VO surgery in CA1. In addition, a significant reduction of HCN1 surface expression in CA1 was observed in the group that suffered 4weeks ischemia but neither 8 nor 12weeks. However, HCN2 surface expression in CA1 increased throughout the ischemia time-scales (4, 8 and 12w). Our findings indicate spatial learning and memory deficits in the CCH model are associated with disturbed HCN1 and HCN2 surface expression in hippocampal CA1. The altered patterns of both HCN1 and HCN2 surface expression may be implicated in the early stage (4w) of spatial learning and memory impairments; and the stable and long-lasting impairments of spatial learning and memory may partially attribute to the up-regulated HCN2 surface expression. Copyright © 2015 Elsevier Inc. All rights reserved.

The spatial learning and memory performance in methamphetamine–sensitized and withdrawn rats

PubMed Central

Bigdeli, Imanollah; Asia, Masomeh Nikfarjam- Haft; Miladi-Gorji, Hossein; Fadaei, Atefeh

2015-01-01

Objective(s): There is controversial evidence about the effect of methamphetamine (METH) on spatial memory. We tested the time- dependent effects of METH on spatial short-term (working) and long-term (reference) memory in METH –sensitized and withdrawn rats in the Morris water maze. Materials and Methods: Rats were sensitized to METH (2 mg/kg, daily/5 days, SC). Rats were trained in water maze (4 trials/day/for 5 days). Probe test was performed 24 hr after training. Two days after probe test, working memory training (2 trials/day/for 5 days) was conducted. Acquisition–retention interval was 75 min. The treatment was continued per day 30 and 120 min before the test. Two groups of METH –sensitized rats were trained in reference memory after a longer period of withdrawal (30 days). Results: Sensitized rats exhibited significantly longer escape latencies on the training, spent significantly less time in the target zone (all, P<0.05), and their working memory impaired 30 min after injection. While, METH has no effect on the spatial learning process 120 min after injection, and rats spent significantly less time in the target zone (P<0.05), as well it has no effect on working memory. Also, impairment of reference memory persisted after prolonged abstinence. Conclusion: Our findings indicated that METH impaired spatial learning and memory 30 min after injection, but spared spatial learning, either acquisition or retention of spatial working, but partially impaired retention of spatial reference memory following 120 min after injection in sensitized rats, which persisted even after prolonged abstinence. PMID:25945235

Neural correlates of reward-based spatial learning in persons with cocaine dependence.

PubMed

Tau, Gregory Z; Marsh, Rachel; Wang, Zhishun; Torres-Sanchez, Tania; Graniello, Barbara; Hao, Xuejun; Xu, Dongrong; Packard, Mark G; Duan, Yunsuo; Kangarlu, Alayar; Martinez, Diana; Peterson, Bradley S

2014-02-01

Dysfunctional learning systems are thought to be central to the pathogenesis of and impair recovery from addictions. The functioning of the brain circuits for episodic memory or learning that support goal-directed behavior has not been studied previously in persons with cocaine dependence (CD). Thirteen abstinent CD and 13 healthy participants underwent MRI scanning while performing a task that requires the use of spatial cues to navigate a virtual-reality environment and find monetary rewards, allowing the functional assessment of the brain systems for spatial learning, a form of episodic memory. Whereas both groups performed similarly on the reward-based spatial learning task, we identified disturbances in brain regions involved in learning and reward in CD participants. In particular, CD was associated with impaired functioning of medial temporal lobe (MTL), a brain region that is crucial for spatial learning (and episodic memory) with concomitant recruitment of striatum (which normally participates in stimulus-response, or habit, learning), and prefrontal cortex. CD was also associated with enhanced sensitivity of the ventral striatum to unexpected rewards but not to expected rewards earned during spatial learning. We provide evidence that spatial learning in CD is characterized by disturbances in functioning of an MTL-based system for episodic memory and a striatum-based system for stimulus-response learning and reward. We have found additional abnormalities in distributed cortical regions. Consistent with findings from animal studies, we provide the first evidence in humans describing the disruptive effects of cocaine on the coordinated functioning of multiple neural systems for learning and memory.

Predicting Efficiency of Travel in Young, Visually Impaired Children from Their Other Spatial Skills.

ERIC Educational Resources Information Center

Hill, Anita; And Others

1985-01-01

To test ways of predicting how efficiently visually impaired children learn travel skills, a criteria checklist of spatial skills was developed for close-body space, local space, and geographical/travel space. Comparison was made between predictors of efficient learning including subjective ratings of teachers, personal qualities and factors of…

Perinatal exposure to genistein, a soy phytoestrogen, improves spatial learning and memory but impairs passive avoidance learning and memory in offspring.

PubMed

Kohara, Yumi; Kuwahara, Rika; Kawaguchi, Shinichiro; Jojima, Takeshi; Yamashita, Kimihiro

2014-05-10

This study investigated the effects of perinatal genistein (GEN) exposure on the central nervous system of rat offspring. Pregnant dams orally received GEN (1 or 10 mg/kg/day) or vehicle (1 ml/kg/day) from gestation day 10 to postnatal day 14. In order to assess the effects of GEN on rat offspring, we used a battery of behavioral tests, including the open-field, elevated plus-maze, MAZE and step-through passive avoidance tests. MAZE test is an appetite-motivation test, and we used this mainly for assessing spatial learning and memory. In the MAZE test, GEN groups exhibited shorter latency from start to goal than the vehicle-treated group in both sexes. On the other hand, performances in the step-through passive avoidance test were non-monotonically inhibited by GEN in both sexes, and a significant difference was observed in low dose of the GEN-treated group compared to the vehicle-treated group in female rats. Furthermore, we found that perinatal exposure to GEN did not significantly alter locomotor activity or emotionality as assessed by the open-field and elevated-plus maze tests. These results suggest that perinatal exposure to GEN improved spatial learning and memory of rat offspring, but impaired their passive avoidance learning and memory. Copyright © 2014 Elsevier Inc. All rights reserved.

Age-related changes in rostral basal forebrain cholinergic and GABAergic projection neurons: Relationship with spatial impairment

PubMed Central

Bañuelos, C.; LaSarge, C. L.; McQuail, J. A.; Hartman, J. J.; Gilbert, R. J.; Ormerod, B. K.; Bizon, J. L.

2013-01-01

Both cholinergic and GABAergic projections from the rostral basal forebrain have been implicated in hippocampal function and mnemonic abilities. While dysfunction of cholinergic neurons has been heavily implicated in age-related memory decline, significantly less is known regarding how age-related changes in co-distributed GABAergic projection neurons contribute to a decline in hippocampal-dependent spatial learning. In the current study, confocal stereology was used to quantify cholinergic (choline acetyltransferase (ChAT) immunopositive) neurons, GABAergic projection (glutamic decarboxylase 67 (GAD67) immunopositive) neurons, and total (NeuN immunopositive) neurons in the rostral basal forebrain of young and aged rats that were first characterized on a spatial learning task. ChAT immunopositive neurons were significantly but modestly reduced in aged rats. Although ChAT immunopositive neuron number was strongly correlated with spatial learning abilities among young rats, the reduction of ChAT immunopositive neurons was not associated with impaired spatial learning in aged rats. In contrast, the number of GAD67 immunopositive neurons was robustly and selectively elevated in aged rats that exhibited impaired spatial learning. Interestingly, the total number of rostral basal forebrain neurons was comparable in young and aged rats, regardless of their cognitive status. These data demonstrate differential effects of age on phenotypically distinct rostral basal forebrain projection neurons, and implicate dysregulated cholinergic and GABAergic septohippocampal circuitry in age-related mnemonic decline. PMID:22817834

Sex-specific impairment and recovery of spatial learning following the end of chronic unpredictable restraint stress: potential relevance of limbic GAD.

PubMed

Ortiz, J Bryce; Taylor, Sara B; Hoffman, Ann N; Campbell, Alyssa N; Lucas, Louis R; Conrad, Cheryl D

2015-04-01

Chronic restraint stress alters hippocampal-dependent spatial learning and memory in a sex-dependent manner, impairing spatial performance in male rats and leaving intact or facilitating performance in female rats. Moreover, these stress-induced spatial memory deficits improve following post-stress recovery in males. The current study examined whether restraint administered in an unpredictable manner would eliminate these sex differences and impact a post-stress period on spatial ability and limbic glutamic acid decarboxylase (GAD65) expression. Male (n=30) and female (n=30) adult Sprague-Dawley rats were assigned to non-stressed control (Con), chronic stress (Str-Imm), or chronic stress given a post-stress recovery period (Str-Rec). Stressed rats were unpredictably restrained for 21 days using daily non-repeated combinations of physical context, duration, and time of day. Then, all rats were tested on the radial arm water maze (RAWM) for 2 days and given one retention trial on the third day, with brains removed 30min later to assess GAD65 mRNA. In Str-Imm males, deficits occurred on day 1 of RAWM acquisition, an impairment that was not evident in the Str-Rec group. In contrast, females did not show significant outcomes following chronic stress or post-stress recovery. In males, amygdalar GAD65 expression negatively correlated with RAWM performance on day 1. In females, hippocampal CA1 GAD65 positively correlated with RAWM performance on day 1. These results demonstrate that GABAergic function may contribute to the sex differences observed following chronic stress. Furthermore, unpredictable restraint and a recovery period failed to eliminate the sex differences on spatial learning and memory. Copyright © 2014 Elsevier B.V. All rights reserved.

Sex-specific impairment and recovery of spatial learning following the end of chronic unpredictable restraint stress: Potential relevance of limbic GAD

PubMed Central

Ortiz, J. Bryce; Taylor, Sara B.; Hoffman, Ann N.; Campbell, Alyssa N.; Lucas, Louis R.; Conrad, Cheryl D.

2015-01-01

Chronic restraint stress alters hippocampal-dependent spatial learning and memory in a sex-dependent manner, impairing spatial performance in male rats and leaving intact or facilitating performance in female rats. Moreover, these stress-induced spatial memory deficits improve following post-stress recovery in males. The current study examined whether restraint administered in an unpredictable manner would eliminate these sex differences and impact a post-stress period on spatial ability and limbic glutamic acid decarboxylase (GAD65) expression. Male (n=30) and female (n=30) adult Sprague-Dawley rats were assigned to non-stressed control (Con), chronic stress (Str-Imm), or chronic stress given a post-stress recovery period (Str-Rec). Stressed rats were unpredictably restrained for 21 days using daily non-repeated combinations of physical context, duration, and time of day. Then, all rats were tested on the radial arm water maze (RAWM) for two days and given one retention trial on the third day, with brains removed 30 minutes later to assess GAD65 mRNA. In Str-Imm males, deficits occurred on day 1 of RAWM acquisition, an impairment that was not evident in the Str-Rec group. In contrast, females did not show significant outcomes following chronic stress or post-stress recovery. In males, amygdalar GAD65 expression negatively correlated with RAWM performance on day 1. In females, hippocampal CA1 GAD65 positively correlated with RAWM performance on day 1. These results demonstrate that GABAergic function may contribute to the sex differences observed following chronic stress. Furthermore, unpredictable restraint and a recovery period failed to eliminate the sex differences on spatial learning and memory. PMID:25591480

Spatial and reversal learning in the Morris water maze are largely resistant to six hours of REM sleep deprivation following training

PubMed Central

Walsh, Christine M.; Booth, Victoria; Poe, Gina R.

2011-01-01

This first test of the role of REM (rapid eye movement) sleep in reversal spatial learning is also the first attempt to replicate a much cited pair of papers reporting that REM sleep deprivation impairs the consolidation of initial spatial learning in the Morris water maze. We hypothesized that REM sleep deprivation following training would impair both hippocampus-dependent spatial learning and learning a new target location within a familiar environment: reversal learning. A 6-d protocol was divided into the initial spatial learning phase (3.5 d) immediately followed by the reversal phase (2.5 d). During the 6 h following four or 12 training trials/day of initial or reversal learning phases, REM sleep was eliminated and non-REM sleep left intact using the multiple inverted flowerpot method. Contrary to our hypotheses, REM sleep deprivation during four or 12 trials/day of initial spatial or reversal learning did not affect training performance. However, some probe trial measures indicated REM sleep-deprivation–associated impairment in initial spatial learning with four trials/day and enhancement of subsequent reversal learning. In naive animals, REM sleep deprivation during normal initial spatial learning was followed by a lack of preference for the subsequent reversal platform location during the probe. Our findings contradict reports that REM sleep is essential for spatial learning in the Morris water maze and newly reveal that short periods of REM sleep deprivation do not impair concurrent reversal learning. Effects on subsequent reversal learning are consistent with the idea that REM sleep serves the consolidation of incompletely learned items. PMID:21677190

Exposure to activity-based anorexia impairs contextual learning in weight-restored rats without affecting spatial learning, taste, anxiety, or dietary-fat preference.

PubMed

Boersma, Gretha J; Treesukosol, Yada; Cordner, Zachary A; Kastelein, Anneke; Choi, Pique; Moran, Timothy H; Tamashiro, Kellie L

2016-02-01

Relapse rates are high amongst cases of anorexia nervosa (AN) suggesting that some alterations induced by AN may remain after weight restoration. To study the consequences of AN without confounds of environmental variability, a rodent model of activity-based anorexia (ABA) can be employed. We hypothesized that exposure to ABA during adolescence may have long-term consequences in taste function, cognition, and anxiety-like behavior after weight restoration. To test this hypothesis, we exposed adolescent female rats to ABA (1.5 h food access, combined with voluntary running wheel access) and compared their behavior to that of control rats after weight restoration was achieved. The rats were tested for learning/memory, anxiety, food preference, and taste in a set of behavioral tests performed during the light period. Our data show that ABA exposure leads to reduced performance during the novel object recognition task, a test for contextual learning, without altering performance in the novel place recognition task or the Barnes maze, both tasks that test spatial learning. Furthermore, we do not observe alterations in unconditioned lick responses to sucrose nor quinine (described by humans as "sweet" and "bitter," respectively). Nor Do we find alterations in anxiety-like behavior during an elevated plus maze or an open field test. Finally, preference for a diet high in fat is not altered. Overall, our data suggest that ABA exposure during adolescence impairs contextual learning in adulthood without altering spatial leaning, taste, anxiety, or fat preference. © 2015 Wiley Periodicals, Inc.

Whole Brain Radiation-Induced Impairments in Learning and Memory Are Time-Sensitive and Reversible by Systemic Hypoxia

PubMed Central

Warrington, Junie P.; Csiszar, Anna; Mitschelen, Matthew; Lee, Yong Woo; Sonntag, William E.

2012-01-01

Whole brain radiation therapy (WBRT) is commonly used for treatment of primary and metastatic brain tumors; however, cognitive impairment occurs in 40–50% of brain tumor survivors. The etiology of the cognitive impairment following WBRT remains elusive. We recently reported that radiation-induced cerebrovascular rarefaction within hippocampal subregions could be completely reversed by systemic hypoxia. However, the effects of this intervention on learning and memory have not been reported. In this study, we assessed the time-course for WBRT-induced impairments in contextual and spatial learning and the capacity of systemic hypoxia to reverse WBRT-induced deficits in spatial memory. A clinical fractionated series of 4.5Gy WBRT was administered to mice twice weekly for 4 weeks, and after various periods of recovery, behavioral analyses were performed. To study the effects of systemic hypoxia, mice were subjected to 11% (hypoxia) or 21% oxygen (normoxia) for 28 days, initiated 1 month after the completion of WBRT. Our results indicate that WBRT induces a transient deficit in contextual learning, disruption of working memory, and progressive impairment of spatial learning. Additionally, systemic hypoxia completely reversed WBRT-induced impairments in learning and these behavioral effects as well as increased vessel density persisted for at least 2 months following hypoxia treatment. Our results provide critical support for the hypothesis that cerebrovascular rarefaction is a key component of cognitive impairment post-WBRT and indicate that processes of learning and memory, once thought to be permanently impaired after WBRT, can be restored. PMID:22279591

Spatial cognition in autism spectrum disorders: superior, impaired, or just intact?

PubMed

Edgin, Jamie O; Pennington, Bruce F

2005-12-01

The profile of spatial ability is of interest across autism spectrum disorders (ASD) because of reported spatial strengths in ASD and due to the recent association of Asperger's syndrome with Nonverbal Learning Disability. Spatial functions were examined in relation to two cognitive theories in autism: the central coherence and executive function (EF) theories. Performance on spatial tasks, EFs, and global/local processing was compared in children with ASD and controls. While the ASD group had faster reaction times on the Embedded Figures task, spatial performance was intact, but not superior, on other tasks. There was no evidence for impairments in EF or in processing global/local information, therefore contradicting these two theories. The implications of these results for these two theories are discussed.

Spatial affect learning restricted in major depression relative to anxiety disorders and healthy controls.

PubMed

Gollan, Jackie K; Norris, Catherine J; Hoxha, Denada; Irick, John Stockton; Hawkley, Louise C; Cacioppo, John T

2014-01-01

Detecting and learning the location of unpleasant or pleasant scenarios, or spatial affect learning, is an essential skill that safeguards well-being (Crawford & Cacioppo, 2002). Potentially altered by psychiatric illness, this skill has yet to be measured in adults with and without major depressive disorder (MDD) and anxiety disorders (AD). This study enrolled 199 adults diagnosed with MDD and AD (n=53), MDD (n=47), AD (n=54), and no disorders (n=45). Measures included clinical interviews, self-reports, and a validated spatial affect task using affective pictures (IAPS; Lang, Bradley, & Cuthbert, 2005). Participants with MDD showed impaired spatial affect learning of negative stimuli and irrelevant learning of pleasant pictures compared with non-depressed adults. Adults with MDD may use a "GOOD is UP" heuristic reflected by their impaired learning of the opposite correlation (i.e., "BAD is UP") and performance in the pleasant version of the task.

Hippocampal 5-HT1A Receptor and Spatial Learning and Memory

PubMed Central

Glikmann-Johnston, Yifat; Saling, Michael M.; Reutens, David C.; Stout, Julie C.

2015-01-01

Spatial cognition is fundamental for survival in the topographically complex environments inhabited by humans and other animals. The hippocampus, which has a central role in spatial cognition, is characterized by high concentration of serotonin (5-hydroxytryptamine; 5-HT) receptor binding sites, particularly of the 1A receptor (5-HT1A) subtype. This review highlights converging evidence for the role of hippocampal 5-HT1A receptors in spatial learning and memory. We consider studies showing that activation or blockade of the 5-HT1A receptors using agonists or antagonists, respectively, lead to changes in spatial learning and memory. For example, pharmacological manipulation to induce 5-HT release, or to block 5-HT uptake, have indicated that increased extracellular 5-HT concentrations maintain or improve memory performance. In contrast, reduced levels of 5-HT have been shown to impair spatial memory. Furthermore, the lack of 5-HT1A receptor subtype in single gene knockout mice is specifically associated with spatial memory impairments. These findings, along with evidence from recent cognitive imaging studies using positron emission tomography (PET) with 5-HT1A receptor ligands, and studies of individual genetic variance in 5-HT1A receptor availability, strongly suggests that 5-HT, mediated by the 5-HT1A receptor subtype, plays a key role in spatial learning and memory. PMID:26696889

Nucleus incertus inactivation impairs spatial learning and memory in rats.

PubMed

Nategh, Mohsen; Nikseresht, Sara; Khodagholi, Fariba; Motamedi, Fereshteh

2015-02-01

Nucleus incertus (NI) is a pontine nucleus which releases mainly GABA and relaxin-3 in rats. Its suggested functions include response to stress, arousal, and modulation of hippocampal theta rhythm. Since the role of NI in learning and memory has not been well characterized, therefore the involvement of this nucleus in spatial learning and memory and the aftermath hippocampal levels of c-fos and pCREB were evaluated. NI was targeted by implanting cannula in male rats. For reference memory, NI was inactivated by lidocaine (0.4 μl, 4%) at three stages of acquisition, consolidation and retrieval in Morris water maze paradigm. For working memory, NI was inactivated in acquisition and retrieval phases. Injection of lidocaine prior to the first training session of reference memory significantly increased the distance moved, suggesting that inactivation of NI delays acquisition in this spatial task. Inactivation also interfered with the retrieval phase of spatial reference memory, as the time in target quadrant for lidocaine group was less, and the escape latency was higher compared to the control group. However, no difference was observed in the consolidation phase. In the working memory task, with inter-trial intervals of 75 min, the escape latency was higher when NI was inactivated in the retrieval phase. In addition, c-fos and pCREB/CREB levels decreased in NI-inhibited rats. This study suggests that nucleus incertus might participate in acquisition of spatial reference, and retrieval of both spatial reference and working memory. Further studies should investigate possible roles of NI in the hippocampal plasticity. Copyright © 2014 Elsevier Inc. All rights reserved.

Spatial versus verbal memory impairments in patients with fibromyalgia.

PubMed

Kim, Seong-Ho; Kim, Sang-Hyon; Kim, Seong-Kyu; Nam, Eun Jung; Han, Seung Woo; Lee, Seung Jae

2012-05-01

Mounting evidence suggests that individuals with fibromyalgia (FM) have impairments in general cognitive functions. However, few studies have explored the possibility of dissociation between verbal and visuospatial memory impairments in FM. Therefore, the purpose of this study was to investigate the asymmetrical impairment of cognitive functions between verbal and visuospatial memory and between short-term and long-term memory. Neuropsychological assessments were carried out on 23 female patients with FM and 24 healthy female controls. Verbal memory abilities were assessed using the Korean version of the Rey auditory verbal learning test (KAVLT) and digit span task, and visuospatial memory abilities were assessed using the Korean version of the Rey complex figure test (KCFT) and spatial span task. The analysis of covariance was used to assess group differences in performance on cognitive tests after controlling for depression. The two groups did not significantly differ in terms of age, years of education, or in their estimated verbal and performance IQ, but FM patients reported more severe depressive symptoms than did controls on the Beck depression inventory. Significant group differences were found in immediate and delayed recall on the KCFT (F (1,44) = 6.49, p = 0.014 and F (1,44) = 6.96, p = 0.011, respectively), whereas no difference was found in immediate and delayed recall on the KAVLT. In terms of short-term memory, neither the digit span task nor spatial span task showed any difference between groups, regardless of whether repetition was forward or backward. These findings suggest that spatial memory abilities may be more impaired than verbal memory abilities in patients with FM.

Exendin-4, a glucagon-like peptide 1 receptor agonist, protects against amyloid-β peptide-induced impairment of spatial learning and memory in rats.

PubMed

Jia, Xiao-Tao; Ye-Tian; Yuan-Li; Zhang, Ge-Juan; Liu, Zhi-Qin; Di, Zheng-Li; Ying, Xiao-Ping; Fang, Yan; Song, Er-Fei; Qi, Jin-Shun; Pan, Yan-Fang

2016-05-15

Type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD) share specific molecular mechanisms, and agents with proven efficacy in one may be useful against the other. The glucagon-like peptide-1 (GLP-1) receptor agonist exendin-4 has similar properties to GLP-1 and is currently in clinical use for T2DM treatment. Thus, this study was designed to characterize the effects of exendin-4 on the impairment of learning and memory induced by amyloid protein (Aβ) and its probable molecular underlying mechanisms. The results showed that (1) intracerebroventricular (i.c.v.) injection of Aβ1-42 resulted in a significant decline of spatial learning and memory of rats in water maze tests; (2) pretreatment with exendin-4 effectively and dose-dependently protected against the Aβ1-42-induced impairment of spatial learning and memory; (3) exendin-4 treatment significantly decreased the expression of Bax and cleaved caspase-3 and increased the expression of Bcl2 in Aβ1-42-induced Alzheimer's rats. The vision and swimming speed of the rats among all groups in the visible platform tests did not show any difference. These findings indicate that systemic pretreatment with exendin-4 can effectively prevent the behavioral impairment induced by neurotoxic Aβ1-42, and the underlying protective mechanism of exendin-4 may be involved in the Bcl2, Bax and caspase-3 pathways. Thus, the application of exendin-4 or the activation of its signaling pathways may be a promising strategy to ameliorate the degenerative processes observed in AD. Copyright © 2016 Elsevier Inc. All rights reserved.

Pilocarpine and physostigmine attenuate spatial memory impairments produced by lesions of the nucleus basalis magnocellularis.

PubMed

Murray, C L; Fibiger, H C

1986-02-01

The effects of bilateral ibotenic acid-induced lesions of the nucleus basalis magnocellularis (nBM) on the acquisition and retention of several spatial memory tasks were studied in the rat. Maintenance of spatial memory in a food search task was impaired following nBM lesions. Acquisition of spontaneous alternation and reinforced alternation in a T-maze was also significantly impaired in animals with these lesions. In contrast, the animals with nBM lesions were not impaired in the acquisition of a position habit in a T-maze. In several of the tasks there was evidence of some learning in the lesion animals after substantial training, although they were significantly deficient when compared with the controls. Administration of the cholinergic agonists physostigmine sulfate or pilocarpine nitrate prior to behavioral testing resulted in a rapid and significant improvement in the performance of the lesion animals. The ibotenate-induced lesions significantly reduced the activity of choline acetyltransferase (CAT) in the anterior and the posterior neocortex. Hippocampal CAT activity was not changed. The results indicate that the cholinergic projections originating in the nBM are involved in the learning and memory of spatial tasks.

Improving effect of mild foot electrical stimulation on pentylenetetrazole-induced impairment of learning and memory.

PubMed

Abasi-Moghadam, Monir; Ghasemi-Dehno, Arefe; Sadegh, Mehdi; Palizvan, Mohammad Reza

2018-05-10

Epilepsy is a common neurological disorder that affects learning and memory. Recently it has been shown that mild foot electrical stimulation (MFES) can increase learning and memory in normal rats. Pentylenetetrazole (PTZ) kindling is a model of human epilepsy. As with human epilepsy, PTZ kindling impairs learning and memory in rats. The purpose of this study was to investigate the effect MFES on kindling-induced learning and memory deficits in rats. Forty-nine male Wistar rats weighting 200 to 250 g were divided into the following seven groups: PTZ only, phenytoin only, MFES only, PTZ plus phenytoin, PTZ plus MFES, phenytoin plus MFES, and saline (control), with the treatments administered for 26 days. Forty-eight hours after the last injection, the animals performed the Morris water maze (MWM) task, and spatial learning and memory were measured. The results indicated that although chronic administration of phenytoin inhibited the development of PTZ kindling, it did not exert a protective effect against kindling-induced spatial learning and memory impairment in rats. On the other hand, pretreatment of PTZ-kindled animals with MFES significantly improved spatial working and reference memory. The results point to potential novel beneficial effects of MFES on learning and memory impairment induced by PTZ kindling in rats. Copyright © 2018 Elsevier Inc. All rights reserved.

Postnatal TLR2 activation impairs learning and memory in adulthood.

PubMed

Madar, Ravit; Rotter, Aviva; Waldman Ben-Asher, Hiba; Mughal, Mohamed R; Arumugam, Thiruma V; Wood, W H; Becker, K G; Mattson, Mark P; Okun, Eitan

2015-08-01

Neuroinflammation in the central nervous system is detrimental for learning and memory, as evident form epidemiological studies linking developmental defects and maternal exposure to harmful pathogens. Postnatal infections can also induce neuroinflammatory responses with long-term consequences. These inflammatory responses can lead to motor deficits and/or behavioral disabilities. Toll like receptors (TLRs) are a family of innate immune receptors best known as sensors of microbial-associated molecular patterns, and are the first responders to infection. TLR2 forms heterodimers with either TLR1 or TLR6, is activated in response to gram-positive bacterial infections, and is expressed in the brain during embryonic development. We hypothesized that early postnatal TLR2-mediated neuroinflammation would adversely affect cognitive behavior in the adult. Our data indicate that postnatal TLR2 activation affects learning and memory in adult mice in a heterodimer-dependent manner. TLR2/6 activation improved motor function and fear learning, while TLR2/1 activation impaired spatial learning and enhanced fear learning. Moreover, developmental TLR2 deficiency significantly impairs spatial learning and enhances fear learning, stressing the involvement of the TLR2 pathway in learning and memory. Analysis of the transcriptional effects of TLR2 activation reveals both common and unique transcriptional programs following heterodimer-specific TLR2 activation. These results imply that adult cognitive behavior could be influenced in part, by activation or alterations in the TLR2 pathway at birth. Copyright © 2015 Elsevier Inc. All rights reserved.

Caloric restriction and spatial learning in old mice.

PubMed

Bellush, L L; Wright, A M; Walker, J P; Kopchick, J; Colvin, R A

1996-08-01

Spatial learning in old mice (19 or 24 months old), some of which had been calorically restricted beginning at 14 weeks of age, was compared to that of young mice, in two separate experiments using a Morris water maze. In the first experiment, only old mice reaching criterion performance on a cued learning task were tested in a subsequent spatial task. Thus, all old mice tested for spatial learning had achieved escape latencies equivalent to those of young controls. Despite equivalent swimming speeds, only about half the old mice in each diet group achieved criterion performance in the spatial task. In the second experiment, old and young mice all received the same number of training trials in a cued task and then in a spatial task. Immediately following spatial training, they were given a 60-s probe trial, with no platform in the pool. Both groups of old mice spent significantly less time in the quadrant where the platform had been and made significantly fewer direct crosses over the previous platform location than did the young control group. As in Experiment 1, calorie restriction failed to provide protection against aging-related deficits. However, in both experiments, some individual old mice evidenced performance in spatial learning indistinguishable from that of young controls. Separate comparisons of "age-impaired" and "age-unimpaired" old mice with young controls may facilitate the identification of neurobiological mechanisms underlying age-related cognitive decline.

Acute genistein treatment mimics the effects of estradiol by enhancing place learning and impairing response learning in young adult female rats

PubMed Central

Pisani, Samantha L.; Neese, Steven L.; Doerge, Daniel R.; Helferich, William G.; Schantz, Susan L.; Korol, Donna L.

2012-01-01

Endogenous estrogens have bidirectional effects on learning and memory, enhancing or impairing cognition depending on many variables, including the task and the memory systems that are engaged. Moderate increases in estradiol enhance hippocampus-sensitive place learning, yet impair response learning that taps dorsal striatum function. This memory modulation likely occurs via activation of estrogen receptors, resulting in altered neural function. Supplements containing estrogenic compounds from plants are widely consumed despite limited information about their effects on brain function, including learning and memory. Phytoestrogens can enter the brain and signal through estrogen receptors to affect cognition. Enhancements in spatial memory and impairments in executive function have been found following treatment with soy phytoestrogens, but no tests of actions on striatum-sensitive tasks have been made to date. The present study compared the effects of acute exposure to the isoflavone genistein with the effects of estradiol on performance in place and response learning tasks. Long-Evans rats were ovariectomized, treated with 17β-estradiol benzoate, genistein-containing sucrose pellets, or vehicle (oil or plain sucrose pellets) for two days prior to behavioral training. Compared to vehicle controls, estradiol treatment enhanced place learning at a low (4.5 μg/kg) but not high dose (45 μg/kg), indicating an inverted pattern of spatial memory facilitation. Treatment with 4.4 mg of genistein over two days also significantly enhanced place learning over vehicle controls. For the response task, treatment with estradiol impaired learning at both the low and high doses; likewise, genistein treatment impaired response learning compared to rats receiving vehicle. Overall, genistein was found to mimic estradiol-induced shifts in place and response learning, facilitating hippocampus-sensitive learning and slowing striatum-sensitive learning. These results suggest signaling

Implicit learning of non-spatial sequences in schizophrenia

PubMed Central

MARVEL, CHERIE L.; SCHWARTZ, BARBARA L.; HOWARD, DARLENE V.; HOWARD, JAMES H.

2006-01-01

Recent studies have reported abnormal implicit learning of sequential patterns in patients with schizophrenia. Because these studies were based on visuospatial cues, the question remained whether patients were impaired simply due to the demands of spatial processing. This study examined implicit sequence learning in 24 patients with schizophrenia and 24 healthy controls using a non-spatial variation of the serial reaction time test (SRT) in which pattern stimuli alternated with random stimuli on every other trial. Both groups showed learning by responding faster and more accurately to pattern trials than to random trials. Patients, however, showed a smaller magnitude of sequence learning. Both groups were unable to demonstrate explicit knowledge of the nature of the pattern, confirming that learning occurred without awareness. Clinical variables were not correlated with the patients' learning deficits. Patients with schizophrenia have a decreased ability to develop sensitivity to regularly occurring sequences of events within their environment. This type of deficit may affect an array of cognitive and motor functions that rely on the perception of event regularity. PMID:16248901

Low Dose Prenatal Alcohol Exposure Does Not Impair Spatial Learning and Memory in Two Tests in Adult and Aged Rats

PubMed Central

Cullen, Carlie L.; Burne, Thomas H. J.; Lavidis, Nickolas A.; Moritz, Karen M.

2014-01-01

Consumption of alcohol during pregnancy can have detrimental impacts on the developing hippocampus, which can lead to deficits in learning and memory function. Although high levels of alcohol exposure can lead to severe deficits, there is a lack of research examining the effects of low levels of exposure. This study used a rat model to determine if prenatal exposure to chronic low dose ethanol would result in deficits in learning and memory performance and if this was associated with morphological changes within the hippocampus. Sprague Dawley rats were fed a liquid diet containing 6% (vol/vol) ethanol (EtOH) or an isocaloric control diet throughout gestation. Male and Female offspring underwent behavioural testing at 8 (Adult) or 15 months (Aged) of age. Brains from these animals were collected for stereological analysis of pyramidal neuron number and dendritic morphology within the CA1 and CA3 regions of the dorsal hippocampus. Prenatal ethanol exposed animals did not differ in spatial learning or memory performance in the Morris water maze or Y maze tasks compared to Control offspring. There was no effect of prenatal ethanol exposure on pyramidal cell number or density within the dorsal hippocampus. Overall, this study indicates that chronic low dose prenatal ethanol exposure in this model does not have long term detrimental effects on pyramidal cells within the dorsal hippocampus or impair spatial learning and memory performance. PMID:24978807

An intra-hippocampal injection of nandrolone induces learning and memory impairments in rat.

PubMed

Karamian, A; Pakdel, F G; Ilkhanipoor, M; Farokhi, F; Ahmadi, A

2015-01-01

This study was investigated to evaluate the effect of intra-hippocampal injection of the nandrolone on spatial learning task in rats. The drug or vehicle was manually injected into the hippocampus with a 10-µl Hamilton syringe attached via polyethylene tubing to 27-gauge stainless-steel injection cannula. After 6 days of recovery, learning behaviors were evaluated using an 8-arm radial maze. The results showed that intra-hippocampal injection of nandrolone can impair trained spatial learning at a dose of 5 µl. We also observed a dense cytoplasm and nucleus in CA1 neurons as well as signs of necrosis. Nandrolone can impair the time required to reach the baited arm as well as the frequency of successful arm entries. At the 10 µl dose of nandrolone, neural hypertrophy and increased dentate gyrus volume were also observed. © Georg Thieme Verlag KG Stuttgart · New York.

MDMA pretreatment leads to mild chronic unpredictable stress-induced impairments in spatial learning.

PubMed

Cunningham, Jacobi I; Raudensky, Jamie; Tonkiss, John; Yamamoto, Bryan K

2009-10-01

3,4-Methylenedioxymethamphetamine (MDMA) is a drug of abuse worldwide and a selective serotonin (5-HT) neurotoxin. An important factor in the risk of drug abuse and relapse is stress. Although multiple parallels exist between MDMA abuse and stress, including effects on 5-HTergic neurotransmission, few studies have investigated the consequences of combined exposure to MDMA and chronic stress. Therefore, rats were pretreated with MDMA and exposed 7 days later to 10 days of mild chronic unpredictable stress (CUS). MDMA pretreatment was hypothesized to enhance the effects of CUS leading to enhanced 5-HT transporter (SERT) depletion in the hippocampus and increased anxiety and cognitive impairment. Whereas MDMA alone increased anxiety-like behavior on the elevated plus maze, CUS alone or in combination with MDMA pretreatment did not increase anxiety-like behavior. In contrast, MDMA pretreatment led to CUS-induced learning impairment in the Morris water maze but not an enhanced depletion of hippocampal SERT protein. These results show that prior exposure to MDMA leads to stress-induced impairments in learning behavior that is not otherwise observed with stress alone and appear unrelated to an enhanced depletion of SERT.

SPATIAL MEMORY IMPAIRMENT AND HIPPOCAMPAL CELL LOSS INDUCED BY OKADAIC ACID (EXPERIMENTAL STUDY).

PubMed

Chighladze, M; Dashniani, M; Beselia, G; Kruashvili, L; Naneishvili, T

2016-01-01

In the present study, we evaluated and compared effect of intracerebroventricular (ICV) and intrahippocampal bilateral microinjection of okadaic acid (OA) on spatial memory function assessed in one day water maze paradigm and hippocampal structure in rats. Rats were divided in following groups: Control(icv) - rats injected with ICV and aCSF; Control(hipp) - rats injected intrahippocampally with aCSF; OAicv - rats injected with ICV and OA; OAhipp - rats injected intrahippocampally with OA. Nissl staining of hippocampal sections showed that the pyramidal cell loss in OAhipp group is significantly higher than that in the OAicv. The results of behavioral experiments showed that ICV or intrahippocampal bilateral microinjection of OA did not affect learning process and short-term spatial memory but induced impairment in spatial long-term memory assessed in probe test performance 24 h after training. OA-induced spatial memory impairment may be attributed to the hippocampal cell death. Based on these results OA induced memory deficit and hippocampal cell loss in rat may be considered as a potential animal model for preclinical evaluation of antidementic drug activity.

Rats Fed a Diet Rich in Fats and Sugars Are Impaired in the Use of Spatial Geometry.

PubMed

Tran, Dominic M D; Westbrook, R Frederick

2015-12-01

A diet rich in fats and sugars is associated with cognitive deficits in people, and rodent models have shown that such a diet produces deficits on tasks assessing spatial learning and memory. Spatial navigation is guided by two distinct types of information: geometrical, such as distance and direction, and featural, such as luminance and pattern. To clarify the nature of diet-induced spatial impairments, we provided rats with standard chow supplemented with sugar water and a range of energy-rich foods eaten by people, and then we assessed their place- and object-recognition memory. Rats exposed to this diet performed comparably with control rats fed only chow on object recognition but worse on place recognition. This impairment on the place-recognition task was present after only a few days on the diet and persisted across tests. Critically, this spatial impairment was specific to the processing of distance and direction. © The Author(s) 2015.

Reduced spatial learning in mice infected with the nematode, Heligmosomoides polygyrus.

PubMed

Kavaliers, M; Colwell, D D

1995-06-01

Parasite modification of host behaviour influences a number of critical responses, but little is known about the effects on host spatial abilities. This study examined the effects of infection with the intestinal trichostrongylid nematode, Heligmosomoides polygyrus, on spatial water maze learning by male laboratory mice, Mus musculus. In this task individual mice had to learn the spatial location of a submerged hidden platform using extramaze visual cues. Determinations of spatial performance were made on day 19 post-infection with mice that had been administered either 50 or 200 infective larvae of H. polygyrus. The infected mice displayed over 1 day of testing (6 blocks of 4 trials) significantly poorer acquisition and retention of the water maze task than either sham-infected or control mice, with mice that had received 200 infective larvae displaying significantly poorer spatial performance than individuals receiving 50 larvae. The decrease in spatial learning occurred in the absence of either any symptoms of illness and malaise, or any evident motor, visual and motivational impairments. It is suggested that in this single host system the parasitic infection-induced decrease in spatial learning arises as a side-effect of the host's immunological and neuromodulatory responses and represents a fitness cost of response to infection.

Selective white matter pathology induces a specific impairment in spatial working memory.

PubMed

Coltman, Robin; Spain, Aisling; Tsenkina, Yanina; Fowler, Jill H; Smith, Jessica; Scullion, Gillian; Allerhand, Mike; Scott, Fiona; Kalaria, Rajesh N; Ihara, Masafumi; Daumas, Stephanie; Deary, Ian J; Wood, Emma; McCulloch, James; Horsburgh, Karen

2011-12-01

The integrity of the white matter is critical in regulating efficient neuronal communication and maintaining cognitive function. Damage to brain white matter putatively contributes to age-related cognitive decline. There is a growing interest in animal models from which the mechanistic basis of white matter pathology in aging can be elucidated but to date there has been a lack of systematic behavior and pathology in the same mice. Anatomically widespread, diffuse white matter damage was induced, in 3 different cohorts of C57Bl/6J mice, by chronic hypoperfusion produced by bilateral carotid stenosis. A comprehensive assessment of spatial memory (spatial reference learning and memory; cohort 1) and serial spatial learning and memory (cohort 2) using the water maze, and spatial working memory (cohort 3) using the 8-arm radial arm maze, was conducted. In parallel, a systematic assessment of white matter components (myelin, axon, glia) was conducted using immunohistochemical markers (myelin-associated glycoprotein [MAG], degraded myelin basic protein [dMBP], anti-amyloid precursor protein [APP], anti-ionized calcium-binding adapter molecule [Iba-1]). Ischemic neuronal perikarya damage, assessed using histology (hematoxylin and eosin; H&E), was absent in all shams but was present in some hypoperfused mice (2/11 in cohort 1, 4/14 in cohort 2, and 17/24 in cohort 3). All animals with neuronal perikaryal damage were excluded from further study. Diffuse white matter damage occurred, throughout the brain, in all hypoperfused mice in each cohort and was essentially absent in sham-operated controls. There was a selective impairment in spatial working memory, with all other measures of spatial memory remaining intact, in hypoperfused mice with selective white matter damage. The results demonstrate that diffuse white matter pathology, in the absence of gray matter damage, induces a selective impairment of spatial working memory. This highlights the importance of assessing

The Effects of Restricted Peripheral Field-of-View on Spatial Learning while Navigating.

PubMed

Barhorst-Cates, Erica M; Rand, Kristina M; Creem-Regehr, Sarah H

2016-01-01

Recent work with simulated reductions in visual acuity and contrast sensitivity has found decrements in survey spatial learning as well as increased attentional demands when navigating, compared to performance with normal vision. Given these findings, and previous work showing that peripheral field loss has been associated with impaired mobility and spatial memory for room-sized spaces, we investigated the role of peripheral vision during navigation using a large-scale spatial learning paradigm. First, we aimed to establish the magnitude of spatial memory errors at different levels of field restriction. Second, we tested the hypothesis that navigation under these different levels of restriction would use additional attentional resources. Normally sighted participants walked on novel real-world paths wearing goggles that restricted the field-of-view (FOV) to severe (15°, 10°, 4°, or 0°) or mild angles (60°) and then pointed to remembered target locations using a verbal reporting measure. They completed a concurrent auditory reaction time task throughout each path to measure cognitive load. Only the most severe restrictions (4° and blindfolded) showed impairment in pointing error compared to the mild restriction (within-subjects). The 10° and 4° conditions also showed an increase in reaction time on the secondary attention task, suggesting that navigating with these extreme peripheral field restrictions demands the use of limited cognitive resources. This comparison of different levels of field restriction suggests that although peripheral field loss requires the actor to use more attentional resources while navigating starting at a less extreme level (10°), spatial memory is not negatively affected until the restriction is very severe (4°). These results have implications for understanding of the mechanisms underlying spatial learning during navigation and the approaches that may be taken to develop assistance for navigation with visual impairment.

Age-dependent effects of neonatal methamphetamine exposure on spatial learning

PubMed Central

Vorhees, Charles V.; Skelton, Matthew R.; Williams, Michael T.

2009-01-01

Neonatal rats exposed to (+)-methamphetamine (MA) display spatial learning and reference memory deficits in the Morris water maze. In separate experiments the emergence and permanence of these effects were determined. Twenty litters were used in each experiment, and two male/female pairs/litter received saline or MA (5 mg/kg four times a day) on postnatal days (P) 11–20. In experiment 1, one MA and one saline pair from each litter began testing on either P30 or P40, whereas in experiment 2, testing began on P180 or P360. Animals received trials in a straight swimming channel and then in the Morris maze (acquisition, reversal, and reduced platform phases). In both experiments, MA-treated groups showed impaired learning in the platform trials and impaired reference memory in the probe trials, which were largely independent of age. The P30 and P40 MA impairments were seen on acquisition and reduced platform trials but not on reversal. In the probe trials, MA effects were seen during all phases. The P180 and P360 MA-induced deficits were seen in all phases of the platform trials. In probe trials, deficits were only seen during the reversal and reduced platform phases. The results demonstrate that neonatal MA treatment induces spatial learning and reference memory deficits that emerge early and persist until at least 1 year of age, suggesting permanence. PMID:17762523

Adult-onset hyperthyroidism impairs spatial learning: possible involvement of mitogen-activated protein kinase signaling pathways.

PubMed

Bitiktaş, Soner; Kandemir, Başak; Tan, Burak; Kavraal, Şehrazat; Liman, Narin; Dursun, Nurcan; Dönmez-Altuntaş, Hamiyet; Aksan-Kurnaz, Işil; Suer, Cem

2016-08-03

Given evidence that mitogen-activated protein kinase (MAPK) activation is part of the nongenomic actions of thyroid hormones, we investigated the possible consequences of hyperthyroidism for the cognitive functioning of adult rats. Young adult rats were treated with L-thyroxine or saline. Twenty rats in each group were exposed to Morris water maze testing, measuring their performance in a hidden-platform spatial task. In a separate set of rats not exposed to Morris water maze testing (untrained rats), the expression and phosphorylated levels of p38-MAPK and of its two downstream effectors, Elk-1 and cAMP response element-binding protein, were evaluated using quantitative reverse transcriptase-PCR and western blotting. Rats with hyperthyroidism showed delayed acquisition of learning compared with their wild-type counterparts, as shown by increased escape latencies and distance moved on the last two trials of daily training in the water maze. The hyperthyroid rats, however, showed no difference during probe trials. Western blot analyses of the hippocampus showed that hyperthyroidism increased phosphorylated p38-MAPK levels in untrained rats. Although our study is correlative in nature and does not exclude the contribution of other molecular targets, our findings suggest that the observed impairments in acquisition during actual learning in rats with hyperthyroidism may result from the increased phosphorylation of p38-MAPK.

Search strategy selection in the Morris water maze indicates allocentric map formation during learning that underpins spatial memory formation.

PubMed

Rogers, Jake; Churilov, Leonid; Hannan, Anthony J; Renoir, Thibault

2017-03-01

Using a Matlab classification algorithm, we demonstrate that a highly salient distal cue array is required for significantly increased likelihoods of spatial search strategy selection during Morris water maze spatial learning. We hypothesized that increased spatial search strategy selection during spatial learning would be the key measure demonstrating the formation of an allocentric map to the escape location. Spatial memory, as indicated by quadrant preference for the area of the pool formally containing the hidden platform, was assessed as the main measure that this allocentric map had formed during spatial learning. Our C57BL/6J wild-type (WT) mice exhibit quadrant preference in the highly salient cue paradigm but not the low, corresponding with a 120% increase in the odds of a spatial search strategy selection during learning. In contrast, quadrant preference remains absent in serotonin 1A receptor (5-HT 1A R) knockout (KO) mice, who exhibit impaired search strategy selection during spatial learning. Additionally, we also aimed to assess the impact of the quality of the distal cue array on the spatial learning curves of both latency to platform and path length using mixed-effect regression models and found no significant associations or interactions. In contrast, we demonstrated that the spatial learning curve for search strategy selection was absent during training in the low saliency paradigm. Therefore, we propose that allocentric search strategy selection during spatial learning is the learning parameter in mice that robustly indicates the formation of a cognitive map for the escape goal location. These results also suggest that both latency to platform and path length spatial learning curves do not discriminate between allocentric and egocentric spatial learning and do not reliably predict spatial memory formation. We also show that spatial memory, as indicated by the absolute time in the quadrant formerly containing the hidden platform alone (without

Synaptophysin and the dopaminergic system in hippocampus are involved in the protective effect of rutin against trimethyltin-induced learning and memory impairment.

PubMed

Zhang, Lei; Zhao, Qi; Chen, Chun-Hai; Qin, Qi-Zhong; Zhou, Zhou; Yu, Zheng-Ping

2014-09-01

This study aimed to investigate the protective effect of rutin against trimethyltin-induced spatial learning and memory impairment in mice. This study focused on the role of synaptophysin, growth-associated protein 43 and the action of the dopaminergic system in mechanisms associated with rutin protection and trimethyltin-induced spatial learning and memory impairment. Cognitive learning and memory was measured by Morris Water Maze. The expression of synaptophysin and growth-associated protein 43 in hippocampus was analyzed by western blot. The concentrations of dopamine, homovanillic acid, and dihyroxyphenylacetic acid in hippocampus were detected using reversed phase high-performance liquid chromatography with electrochemical detection. Trimethyltin-induced spatial learning impairment showed a dose-dependent mode. Synaptophysin but not growth-associated protein 43 was decreased in the hippocampus after trimethyltin administration. The concentration of dopamine decreased, while homovanillic acid increased in the hippocampus after trimethyltin administration. Mice pretreated with 20 mg/kg of rutin for 7 consecutive days exhibited improved water maze performance. Moreover, rutin pretreatment reversed the decrease of synaptophysin expression and dopamine alteration. These results suggest that rutin may protect against spatial memory impairment induced by trimethyltin. Synaptophysin and the dopaminergic system may be involved in trimethyltin-induced neuronal damage in hippocampus.

Hippocampus-dependent spatial memory impairment due to molar tooth loss is ameliorated by an enriched environment.

PubMed

Kondo, Hiroko; Kurahashi, Minori; Mori, Daisuke; Iinuma, Mitsuo; Tamura, Yasuo; Mizutani, Kenmei; Shimpo, Kan; Sonoda, Shigeru; Azuma, Kagaku; Kubo, Kin-ya

2016-01-01

Teeth are crucial, not only for mastication, but for overall nutrition and general health, including cognitive function. Aged mice with chronic stress due to tooth loss exhibit impaired hippocampus-dependent learning and memory. Exposure to an enriched environment restores the reduced hippocampal function. Here, we explored the effects of an enriched environment on learning deficits and hippocampal morphologic changes in aged senescence-accelerated mouse strain P8 (SAMP8) mice with tooth loss. Eight-month-old male aged SAMP8 mice with molar intact or with molars removed were housed in either a standard environment or enriched environment for 3 weeks. The Morris water maze was performed for spatial memory test. The newborn cell proliferation, survival, and differentiation in the hippocampus were analyzed using 5-Bromodeoxyuridine (BrdU) immunohistochemical method. The hippocampal brain-derived neurotrophic factor (BDNF) levels were also measured. Mice with upper molars removed (molarless) exhibited a significant decline in the proliferation and survival of newborn cells in the dentate gyrus (DG) as well as in hippocampal BDNF levels. In addition, neuronal differentiation of newly generated cells was suppressed and hippocampus-dependent spatial memory was impaired. Exposure of molarless mice to an enriched environment attenuated the reductions in the hippocampal BDNF levels and neuronal differentiation, and partially improved the proliferation and survival of newborn cells, as well as the spatial memory ability. These findings indicated that an enriched environment could ameliorate the hippocampus-dependent spatial memory impairment induced by molar tooth loss. Copyright © 2015 Elsevier Ltd. All rights reserved.

Impairments of spatial learning and memory following intrahippocampal injection in rats of 3-mercaptopropionic acid-modified CdTe quantum dots and molecular mechanisms.

PubMed

Wu, Tianshu; He, Keyu; Ang, Shengjun; Ying, Jiali; Zhang, Shihan; Zhang, Ting; Xue, Yuying; Tang, Meng

2016-01-01

With the rapid development of nanotechnology, quantum dots (QDs) as advanced nanotechnology products have been widely used in neuroscience, including basic neurological studies and diagnosis or therapy for neurological disorders, due to their superior optical properties. In recent years, there has been intense concern regarding the toxicity of QDs, with a growing number of studies. However, knowledge of neurotoxic consequences of QDs applied in living organisms is lagging behind their development, even if several studies have attempted to evaluate the toxicity of QDs on neural cells. The aim of this study was to evaluate the adverse effects of intrahippocampal injection in rats of 3-mercaptopropionic acid (MPA)-modified CdTe QDs and underlying mechanisms. First of all, we observed impairments in learning efficiency and spatial memory in the MPA-modified CdTe QD-treated rats by using open-field and Y-maze tests, which could be attributed to pathological changes and disruption of ultrastructure of neurons and synapses in the hippocampus. In order to find the mechanisms causing these effects, transcriptome sequencing (RNA-seq), an advanced technology, was used to gain the potentially molecular targets of MPA-modified CdTe QDs. According to ample data from RNA-seq, we chose the signaling pathways of PI3K-Akt and MPAK-ERK to do a thorough investigation, because they play important roles in synaptic plasticity, long-term potentiation, and spatial memory. The data demonstrated that phosphorylated Akt (p-Akt), p-ERK1/2, and c-FOS signal transductions in the hippocampus of rats were involved in the mechanism underlying spatial learning and memory impairments caused by 3.5 nm MPA-modified CdTe QDs.

Effects of organic selenium on lead-induced impairments of spatial learning and memory as well as synaptic structural plasticity in rats.

PubMed

Han, Xiao-jie; Xiao, Yong-mei; Ai, Bao-min; Hu, Xiao-xia; Wei, Qing; Hu, Qian-sheng

2014-01-01

To study the effect of organic Se on spatial learning and memory deficits induced by Pb exposure at different developmental stages, and its relationship with alterations of synaptic structural plasticity, postnatal rat pups were randomly divided into five groups: Control; Pb (Weaned pups were exposed to Pb at postnatal day (PND) 21-42); Pb-Se (Weaned pups were exposed to Se at PND 43-63 after Pb exposure); maternal Pb (mPb) (Parents were exposed to Pb from 3 weeks before mating to the weaning of pups); mPb-Se (Parents were exposed to Pb and weaned pups were exposed to Se at PND 43-63). The spatial learning and memory of rat pups was measured by Morris water maze (MWM) on PND 63. We found that rat pups in Pb-Se group performed significantly better than those in Pb group (p<0.05). However, there was no significant difference in the ability of spatial learning and memory between the groups of mPb and mPb-Se (p>0.05). We also found that, before MWM, the numbers of neurons and synapses significantly decreased in mPb group, but not in Pb group. After MWM, the number of synapses, the thickness of postsynaptic density (PSD), the length of synaptic active zone and the synaptic curvature increased significantly in Pb-Se and mPb-Se group; while the width of synaptic cleft decreased significantly (p<0.05), compared to Pb group and mPb group, respectively. However, the number of synapses in mPb-Se group was still significantly lower than that in the control group (p<0.05). Our data demonstrated that organic Se had protective effects on the impairments of spatial learning and memory as well as synaptic structural plasticity induced by Pb exposure in rats after weaning, but not by the maternal Pb exposure which reduced the numbers of neurons and synapses in the early neural development.

LTP saturation and spatial learning disruption: effects of task variables and saturation levels.

PubMed

Barnes, C A; Jung, M W; McNaughton, B L; Korol, D L; Andreasson, K; Worley, P F

1994-10-01

The prediction that "saturation" of LTP/LTE at hippocampal synapses should impair spatial learning was reinvestigated in the light of a more specific consideration of the theory of Hebbian associative networks, which predicts a nonlinear relationship between LTP "saturation" and memory impairment. This nonlinearity may explain the variable results of studies that have addressed the effects of LTP "saturation" on behavior. The extent of LTP "saturation" in fascia dentata produced by the standard chronic LTP stimulation protocol was assessed both electrophysiologically and through the use of an anatomical marker (activation of the immediate-early gene zif268). Both methods point to the conclusion that the standard protocols used to induce LTP do not "saturate" the process at any dorsoventral level, and leave the ventral half of the hippocampus virtually unaffected. LTP-inducing, bilateral perforant path stimulation led to a significant deficit in the reversal of a well-learned spatial response on the Barnes circular platform task as reported previously, yet in the same animals produced no deficit in learning the Morris water task (for which previous results have been conflicting). The behavioral deficit was not a consequence of any after-discharge in the hippocampal EEG. In contrast, administration of maximal electroconvulsive shock led to robust zif268 activation throughout the hippocampus, enhancement of synaptic responses, occlusion of LTP produced by discrete high-frequency stimulation, and spatial learning deficits in the water task. These data provide further support for the involvement of LTP-like synaptic enhancement in spatial learning.

Effects of Housing on Methamphetamine-Induced Neurotoxicity and Spatial Learning and Memory.

PubMed

Gutierrez, Arnold; Jablonski, Sarah A; Amos-Kroohs, Robyn M; Barnes, Anna C; Williams, Michael T; Vorhees, Charles V

2017-07-19

Severe stress potentiates methamphetamine (MA) neurotoxicity. However, whether moderate stress increases or decreases the neurotoxic effects of MA is unknown. We assessed the effects of MA (4 × 10 mg/kg at 2 h intervals) in combination with prior barren-cage housing in adult male Sprague-Dawley rats on monoamines and glial fibrillary acid protein (GFAP) in one cohort and spatial learning and memory in the Morris water maze in another cohort. MA reduced dopamine (DA) and serotonin (5-HT) in the neostriatum and nucleus accumbens, 5-HT in the hippocampus, and increased GFAP in neostriatum and nucleus accumbens compared with saline controls. In neostriatum, barren-cage housing protected against MA-induced increases in GFAP, but it did not prevent DA and 5-HT reductions, although it did increase hippocampal norepinephrine. MA impaired spatial learning during acquisition, reversal, and shift phases and impaired reference memory on reversal and shift probe trials. Barren-cage housing enhanced performance during acquisition but not during reversal or shift or on probe trials. The data indicate that prior barren-cage housing moderates MA-induced neostriatal astrogliosis and initial spatial learning, but has no protective effect when the platform is smaller and relocated and therefore requires cognitive flexibility in relearning.

Dorsolateral striatal lesions impair navigation based on landmark-goal vectors but facilitate spatial learning based on a “cognitive map”

PubMed Central

Poulter, Steven L.; Austen, Joe M.

2015-01-01

In three experiments, the nature of the interaction between multiple memory systems in rats solving a variation of a spatial task in the water maze was investigated. Throughout training rats were able to find a submerged platform at a fixed distance and direction from an intramaze landmark by learning a landmark-goal vector. Extramaze cues were also available for standard place learning, or “cognitive mapping,” but these cues were valid only within each session, as the position of the platform moved around the pool between sessions together with the intramaze landmark. Animals could therefore learn the position of the platform by taking the consistent vector from the landmark across sessions or by rapidly encoding the new platform position on each session with reference to the extramaze cues. Excitotoxic lesions of the dorsolateral striatum impaired vector-based learning but facilitated cognitive map-based rapid place learning when the extramaze cues were relatively poor (Experiment 1) but not when they were more salient (Experiments 2 and 3). The way the lesion effects interacted with cue availability is consistent with the idea that the memory systems involved in the current navigation task are functionally cooperative yet associatively competitive in nature. PMID:25691518

Hilar GABAergic Interneuron Activity Controls Spatial Learning and Memory Retrieval

PubMed Central

Andrews-Zwilling, Yaisa; Gillespie, Anna K.; Kravitz, Alexxai V.; Nelson, Alexandra B.; Devidze, Nino; Lo, Iris; Yoon, Seo Yeon; Bien-Ly, Nga; Ring, Karen; Zwilling, Daniel; Potter, Gregory B.; Rubenstein, John L. R.; Kreitzer, Anatol C.; Huang, Yadong

2012-01-01

Background Although extensive research has demonstrated the importance of excitatory granule neurons in the dentate gyrus of the hippocampus in normal learning and memory and in the pathogenesis of amnesia in Alzheimer's disease (AD), the role of hilar GABAergic inhibitory interneurons, which control the granule neuron activity, remains unclear. Methodology and Principal Findings We explored the function of hilar GABAergic interneurons in spatial learning and memory by inhibiting their activity through Cre-dependent viral expression of enhanced halorhodopsin (eNpHR3.0)—a light-driven chloride pump. Hilar GABAergic interneuron-specific expression of eNpHR3.0 was achieved by bilaterally injecting adeno-associated virus containing a double-floxed inverted open-reading frame encoding eNpHR3.0 into the hilus of the dentate gyrus of mice expressing Cre recombinase under the control of an enhancer specific for GABAergic interneurons. In vitro and in vivo illumination with a yellow laser elicited inhibition of hilar GABAergic interneurons and consequent activation of dentate granule neurons, without affecting pyramidal neurons in the CA3 and CA1 regions of the hippocampus. We found that optogenetic inhibition of hilar GABAergic interneuron activity impaired spatial learning and memory retrieval, without affecting memory retention, as determined in the Morris water maze test. Importantly, optogenetic inhibition of hilar GABAergic interneuron activity did not alter short-term working memory, motor coordination, or exploratory activity. Conclusions and Significance Our findings establish a critical role for hilar GABAergic interneuron activity in controlling spatial learning and memory retrieval and provide evidence for the potential contribution of GABAergic interneuron impairment to the pathogenesis of amnesia in AD. PMID:22792368

Lesions of the fornix and anterior thalamic nuclei dissociate different aspects of hippocampal-dependent spatial learning: implications for the neural basis of scene learning.

PubMed

Aggleton, John P; Poirier, Guillaume L; Aggleton, Hugh S; Vann, Seralynne D; Pearce, John M

2009-06-01

The present study used 2 different discrimination tasks designed to isolate distinct components of visuospatial learning: structural learning and geometric learning. Structural learning refers to the ability to learn the precise combination of stimulus identity with stimulus location. Rats with anterior thalamic lesions and fornix lesions were unimpaired on a configural learning task in which the rats learned 3 concurrent mirror-image discriminations (structural learning). Indeed, both lesions led to facilitated learning. In contrast, anterior thalamic lesions impaired the geometric discrimination (e.g., swim to the corner with the short wall to the right of the long wall). Finally, both the fornix and anterior thalamic lesions severely impaired T-maze alternation, a task that taxes an array of spatial strategies including allocentric learning. This pattern of dissociations and double dissociations highlights how distinct classes of spatial learning rely on different systems, even though they may converge on the hippocampus. Consequently, the findings suggest that structural learning is heavily dependent on cortico-hippocampal interactions. In contrast, subcortical inputs (such as those from the anterior thalamus) contribute to geometric learning. Copyright (c) 2009 APA, all rights reserved.

Selective cognitive impairments associated with NMDA receptor blockade in humans.

PubMed

Rowland, Laura M; Astur, Robert S; Jung, Rex E; Bustillo, Juan R; Lauriello, John; Yeo, Ronald A

2005-03-01

Hypofunction of the N-methyl-D-aspartate receptor (NMDAR) may be involved in the pathophysiology of schizophrenia. NMDAR antagonists like ketamine induce schizophrenia-like features in humans. In rodent studies, NMDAR antagonism impairs learning by disrupting long-term potentiation (LTP) in the hippocampus. This study investigated the effects of ketamine on spatial learning (acquisition) vs retrieval in a virtual Morris water task in humans. Verbal fluency, working memory, and learning and memory of verbal information were also assessed. Healthy human subjects participated in this double-blinded, placebo-controlled study. On two separate occasions, ketamine/placebo was administered and cognitive tasks were assessed in association with behavioral ratings. Ketamine impaired learning of spatial and verbal information but retrieval of information learned prior to drug administration was preserved. Schizophrenia-like symptoms were significantly related to spatial and verbal learning performance. Ketamine did not significantly impair attention, verbal fluency, or verbal working memory task performance. Spatial working memory was slightly impaired. In conclusion, these results provide evidence for ketamine's differential impairment of verbal and spatial learning vs retrieval. By using the Morris water task, which is hippocampal-dependent, this study helps bridge the gap between nonhuman animal and human NMDAR antagonism research. Impaired cognition is a core feature of schizophrenia. A better understanding of NMDA antagonism, its physiological and cognitive consequences, may provide improved models of psychosis and cognitive therapeutics.

Short-term sleep deprivation impairs spatial working memory and modulates expression levels of ionotropic glutamate receptor subunits in hippocampus.

PubMed

Xie, Meilan; Yan, Jie; He, Chao; Yang, Li; Tan, Gang; Li, Chao; Hu, Zhian; Wang, Jiali

2015-06-01

Hippocampus-dependent learning memory is sensitive to sleep deprivation (SD). Although the ionotropic glutamate receptors play a vital role in synaptic plasticity and learning and memory, however, whether the expression of these receptor subunits is modulated by sleep loss remains unclear. In the present study, western blotting was performed by probing with specific antibodies against the ionotropic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunits GluA1, GluA2, GluA3, and against the N-methyl-d-aspartate (NMDA) glutamate receptor subunits GluN1, GluN2A, GluN2B. In hippocampus, down regulation of surface GluA1 and GluN2A surface expression were observed in both SD groups. However, surface expression level of GluA2, GluA3, GluN1 and GluN2B was significantly up-regulated in 8h-SD rats when compared to the 4h-SD rats. In parallel with the complex changes in AMPA and NMDA receptor subunit expressions, we found the 8h-SD impaired rat spatial working memory in 30-s-delay T-maze task, whereas no impairment of spatial learning was observed in 4h-SD rats. These results indicate that sleep loss alters the relative expression levels of the AMPA and NMDA receptors, thus affects the synaptic strength and capacity for plasticity and partially contributes to spatial memory impairment. Copyright © 2015. Published by Elsevier B.V.

Cholinesterase inhibitors, donepezil and rivastigmine, attenuate spatial memory and cognitive flexibility impairment induced by acute ethanol in the Barnes maze task in rats.

PubMed

Gawel, Kinga; Labuz, Krzysztof; Gibula-Bruzda, Ewa; Jenda, Malgorzata; Marszalek-Grabska, Marta; Filarowska, Joanna; Silberring, Jerzy; Kotlinska, Jolanta H

2016-10-01

Central cholinergic dysfunction contributes to acute spatial memory deficits produced by ethanol administration. Donepezil and rivastigmine elevate acetylcholine levels in the synaptic cleft through the inhibition of cholinesterases-enzymes involved in acetylcholine degradation. The aim of our study was to reveal whether donepezil (acetylcholinesterase inhibitor) and rivastigmine (also butyrylcholinesterase inhibitor) attenuate spatial memory impairment as induced by acute ethanol administration in the Barnes maze task (primary latency and number of errors in finding the escape box) in rats. Additionally, we compared the influence of these drugs on ethanol-disturbed memory. In the first experiment, the dose of ethanol (1.75 g/kg, i.p.) was selected that impaired spatial memory, but did not induce motor impairment. Next, we studied the influence of donepezil (1 and 3 mg/kg, i.p.), as well as rivastigmine (0.5 and 1 mg/kg, i.p.), given either before the probe trial or the reversal learning on ethanol-induced memory impairment. Our study demonstrated that these drugs, when given before the probe trial, were equally effective in attenuating ethanol-induced impairment in both test situations, whereas rivastigmine, at both doses (0.5 and 1 mg/kg, i.p.), and donepezil only at a higher dose (3 mg/kg, i.p.) given prior the reversal learning, attenuated the ethanol-induced impairment in cognitive flexibility. Thus, rivastigmine appears to exert more beneficial effect than donepezil in reversing ethanol-induced cognitive impairments-probably due to its wider spectrum of activity. In conclusion, the ethanol-induced spatial memory impairment may be attenuated by pharmacological manipulation of central cholinergic neurotransmission.

Spatial Navigation in Complex and Radial Mazes in APP23 Animals and Neurotrophin Signaling as a Biological Marker of Early Impairment

ERIC Educational Resources Information Center

Hellweg, Rainer; Huber, Roman; Kuhl, Alexander; Riepe, Matthias W.; Lohmann, Peter

2006-01-01

Impairment of hippocampal function precedes frontal and parietal cortex impairment in human Alzheimer's disease(AD). Neurotrophins are critical for behavioral performance and neuronal survival in AD. We used complex and radial mazes to assess spatial orientation and learning in wild-type and B6-Tg(ThylAPP)23Sdz (APP23) animals, a transgenic mouse…

Hippocampus-dependent place learning enables spatial flexibility in C57BL6/N mice

PubMed Central

Kleinknecht, Karl R.; Bedenk, Benedikt T.; Kaltwasser, Sebastian F.; Grünecker, Barbara; Yen, Yi-Chun; Czisch, Michael; Wotjak, Carsten T.

2012-01-01

Spatial navigation is a fundamental capability necessary in everyday life to locate food, social partners, and shelter. It results from two very different strategies: (1) place learning which enables for flexible way finding and (2) response learning that leads to a more rigid “route following.” Despite the importance of knockout techniques that are only available in mice, little is known about mice' flexibility in spatial navigation tasks. Here we demonstrate for C57BL6/N mice in a water-cross maze (WCM) that only place learning enables spatial flexibility and relearning of a platform position, whereas response learning does not. This capability depends on an intact hippocampal formation, since hippocampus lesions by ibotenic acid (IA) disrupted relearning. In vivo manganese-enhanced magnetic resonance imaging revealed a volume loss of ≥60% of the hippocampus as a critical threshold for relearning impairments. In particular the changes in the left ventral hippocampus were indicative of relearning deficits. In summary, our findings establish the importance of hippocampus-dependent place learning for spatial flexibility and provide a first systematic analysis on spatial flexibility in mice. PMID:23293591

Impaired spatial memory and enhanced long-term potentiation in mice with forebrain-specific ablation of the Stim genes

PubMed Central

Garcia-Alvarez, Gisela; Shetty, Mahesh S.; Lu, Bo; Yap, Kenrick An Fu; Oh-Hora, Masatsugu; Sajikumar, Sreedharan; Bichler, Zoë; Fivaz, Marc

2015-01-01

Recent findings point to a central role of the endoplasmic reticulum-resident STIM (Stromal Interaction Molecule) proteins in shaping the structure and function of excitatory synapses in the mammalian brain. The impact of the Stim genes on cognitive functions remains, however, poorly understood. To explore the function of the Stim genes in learning and memory, we generated three mouse strains with conditional deletion (cKO) of Stim1 and/or Stim2 in the forebrain. Stim1, Stim2, and double Stim1/Stim2 cKO mice show no obvious brain structural defects or locomotor impairment. Analysis of spatial reference memory in the Morris water maze revealed a mild learning delay in Stim1 cKO mice, while learning and memory in Stim2 cKO mice was indistinguishable from their control littermates. Deletion of both Stim genes in the forebrain resulted, however, in a pronounced impairment in spatial learning and memory reflecting a synergistic effect of the Stim genes on the underlying neural circuits. Notably, long-term potentiation (LTP) at CA3-CA1 hippocampal synapses was markedly enhanced in Stim1/Stim2 cKO mice and was associated with increased phosphorylation of the AMPA receptor subunit GluA1, the transcriptional regulator CREB and the L-type Voltage-dependent Ca2+ channel Cav1.2 on protein kinase A (PKA) sites. We conclude that STIM1 and STIM2 are key regulators of PKA signaling and synaptic plasticity in neural circuits encoding spatial memory. Our findings also reveal an inverse correlation between LTP and spatial learning/memory and suggest that abnormal enhancement of cAMP/PKA signaling and synaptic efficacy disrupts the formation of new memories. PMID:26236206

Long-term acarbose administration alleviating the impairment of spatial learning and memory in the SAMP8 mice was associated with alleviated reduction of insulin system and acetylated H4K8.

PubMed

Yan, Wen-Wen; Chen, Gui-Hai; Wang, Fang; Tong, Jing-Jing; Tao, Fei

2015-04-07

Age-associated memory impairment (AAMI) not only reduces the quality of life for the elderly but also increases the costs of healthcare for society. Methods that can regulate glucose metabolism, insulin/insulin-like growth factor 1 (IGF-1) system and acetylated histone H4 lysine 8 (H4K8ac), one of the most well-researched facets of histone acetylation modification associating with cognition, tend to ameliorate the AAMI. Here, we used SAMP8 mice, the excellent animal model of aging and AAMI, to study the effect of long-term treatment with acarbose, an inhibitor of a-glucosidase, on AAMI and explore whether blood glucose, insulin/IGF-1 system and H4K8ac are associated with potential effects. The treatment group received acarbose (20mg/kg/d, dissolved in drinking water) at the age of 3-month until 9-month old before the behavioral test, and the controls only received water. Compared to the young controls (3-month-old, n=11), the old group (9-month-old, n=8) had declined abilities of spatial learning and memory and levels of serum insulin, hippocampal insulin receptors (InsRs) and H4K8ac. Interestingly, the acarbose group (9-month-old, n=9) showed better abilities of spatial learning and memory and higher levels of insulin, InsRs and H4K8ac relative to the old controls. Good performance of spatial learning and memory was positively correlated with the elevated insulin, InsRs and H4K8ac. All these results suggested that long-term administration of acarbose could alleviate the age-related impairment of spatial learning and memory in the SAMP8 mice, and the alleviated reduction of an insulin system and H4K8ac might be associated with the alleviation. Copyright © 2015 Elsevier B.V. All rights reserved.

Place and direction learning in a spatial T-maze task by neonatal piglets

PubMed Central

Elmore, Monica R. P.; Dilger, Ryan N.; Johnson, Rodney W.

2013-01-01

Pigs are a valuable animal model for studying neurodevelopment in humans due to similarities in brain structure and growth. The development and validation of behavioral tests to assess learning and memory in neonatal piglets are needed. The present study evaluated the capability of 2-wk old piglets to acquire a novel place and direction learning spatial T-maze task. Validity of the task was assessed by the administration of scopolamine, an anti-cholinergic drug that acts on the hippocampus and other related structures, to impair spatial memory. During acquisition, piglets were trained to locate a milk reward in a constant place in space, as well as direction (east or west), in a plus-shaped maze using extra-maze visual cues. Following acquisition, reward location was reversed and piglets were re-tested to assess learning and working memory. The performance of control piglets in the maze improved over time (P < 0.0001), reaching performance criterion (80% correct) on day 5 of acquisition. Correct choices decreased in the reversal phase (P < 0.0001), but improved over time. In a separate study, piglets were injected daily with either phosphate buffered saline (PBS; control) or scopolamine prior to testing. Piglets administered scopolamine showed impaired performance in the maze compared to controls (P = 0.03), failing to reach performance criterion after 6 days of acquisition testing. Collectively, these data demonstrate that neonatal piglets can be tested in a spatial T-maze task to assess hippocampal-dependent learning and memory. PMID:22526690

Selective verbal and spatial memory impairment after 5-HT1A and 5-HT2A receptor blockade in healthy volunteers pre-treated with an SSRI.

PubMed

Wingen, M; Kuypers, K P C; Ramaekers, J G

2007-07-01

Serotonergic neurotransmission has been implicated in memory impairment. It is unclear however if memory performance is mediated through general 5-HT availability, through specific 5-HT receptors or both. The aim of the present study was to assess the contribution of 5-HT reuptake inhibition and specific blockade of 5-HT(1A) and 5-HT(2A) receptors to memory impairment. The study was conducted according to a randomized, double-blind, placebo-controlled, four-way cross-over design including 16 healthy volunteers. The treatment consisted of oral administration of escitalopram 20 mg + placebo, escitalopram 20 mg + ketanserin 50 mg, escitalopram 20 mg + pindolol 10 mg and placebo on 4 separate days with a washout period of minimum 7 days. Different memory tasks were performed including verbal memory, spatial working memory and reversal learning. Escitalopram showed an impairing effect on immediate verbal recall which nearly reached statistical significance. No effects of escitalopram were found on other types of memory. In combination with pindolol, immediate verbal recall was significantly impaired. Escitalopram in combination with ketanserin impaired spatial working memory significantly. No effects were found on reversal learning. Selective impairment of immediate verbal recall after a 5-HT(1A) partial agonist and selective impairment of spatial working memory performance after 5-HT(2A) receptor antagonist, both in combination with a selective serotonergic reuptake inhibitor (escitalopram), suggests that 5-HT(1A) and 5-HT(2A) receptors are distinctly involved in verbal and spatial memory.

Simulated systemic recurrent Mycoplasma infection in rats induces recurrent sickness responses without residual impairment in spatial learning and memory.

PubMed

Swanepoel, Tanya; Harvey, Brian H; Harden, Lois M; Laburn, Helen P; Mitchell, Duncan

2012-02-01

In spite of their prevalence and importance, recurrent acute infections seldom have been investigated in the laboratory. We set out to measure fever and sickness behaviour in simulated recurrent Mycoplasma infection; Mycoplasma is a common clinical cause of recurrent acute infection. Male Sprague-Dawley rats had radiotransponders implanted to measure abdominal temperature and cage activity. After recovery, rats received three intraperitoneal (I.P.) injections, 10 days apart, of either fibroblast-stimulating lipopeptide-1 (FLS-1), a pyrogenic moiety of Mycoplasma salivarium, at a dose of 500 μg.kg(-1) in 1 ml.kg(-1) phosphate-buffered saline (PBS), or vehicle (PBS, 1 ml.kg(-1)). Body mass and food intake were measured daily. For measurement of learning and memory, training in a Morris Water Maze commenced 10 days after the last of the three successive injections and continued daily for 4 days. Spatial memory was assessed on the following day. Hippocampal tissue of rats was collected on the day of the last exposure to the maze. Recurrent FSL-1 administration induced recurrent fevers (~1°C) for about 9h, recurrent lethargy (~40-60%) for 1 day, recurrent anorexia (~16-30%) for 1 day, and recurrent reductions in the rate of mass gain (~112%) for 1 day, but did not induce persistent stunting. Recurrent FSL-1 administration did not result in tolerance to fever, lethargy or anorexia. There was no residual histological damage to the hippocampus and no residual detrimental effect in learning or memory in rats. Though we cannot extrapolate our results directly to humans, clinical recurrent acute Mycoplasma infection may not impose a high risk of stunting or impaired spatial learning and memory. Copyright © 2011 Elsevier Inc. All rights reserved.

Spatial Discrimination Reversal Learning in Weanling Rats Is Impaired by Striatal Administration of an NMDA-Receptor Antagonist

ERIC Educational Resources Information Center

Watson, Deborah J.; Stanton, Mark E.

2009-01-01

The striatum plays a major role in both motor control and learning and memory, including executive function and "behavioral flexibility." Lesion, temporary inactivation, and infusion of an N-methyl-d-aspartate (NMDA)-receptor antagonist into the dorsomedial striatum (dmSTR) impair reversal learning in adult rats. Systemic administration of MK-801…

Fluoxetine Restores Spatial Learning but Not Accelerated Forgetting in Mesial Temporal Lobe Epilepsy

ERIC Educational Resources Information Center

Barkas, Lisa; Redhead, Edward; Taylor, Matthew; Shtaya, Anan; Hamilton, Derek A.; Gray, William P.

2012-01-01

Learning and memory dysfunction is the most common neuropsychological effect of mesial temporal lobe epilepsy, and because the underlying neurobiology is poorly understood, there are no pharmacological strategies to help restore memory function in these patients. We have demonstrated impairments in the acquisition of an allocentric spatial task,…

Effect of pregabalin on fear-based conditioned avoidance learning and spatial learning in a mouse model of scopolamine-induced amnesia.

PubMed

Sałat, Kinga; Podkowa, Adrian; Malikowska, Natalia; Trajer, Jędrzej

2017-03-01

Cognitive deficits are one of the frequent symptoms accompanying epilepsy or its treatment. In this study, the effect on cognition of intraperitoneally administered antiepileptic drug, pregabalin (10 mg/kg), was investigated in scopolamine-induced memory-impaired mice in the passive avoidance task and Morris water maze task. The effect of scopolamine and pregabalin on animals' locomotor activity was also studied. In the retention phase of the passive avoidance task, pregabalin reversed memory deficits induced by scopolamine (p < 0.05). During the acquisition phase of the Morris water maze pregabalin-treated memory-impaired mice performed the test with longer escape latencies than the vehicle-treated mice (significant at p < 0.05 on Day 5, and at p < 0.001 on Day 6). There were no differences in this parameter between the scopolamine-treated control group and pregabalin-treated memory-impaired mice, which indicated that pregabalin had no influence on spatial learning in this task. During the probe trial a significant difference (p < 0.05) was observed in terms of the mean number of target crossings between vehicle-treated mice and pregabalin-treated memory-impaired mice but there was no difference between the scopolamine-treated control group and mice treated with pregabalin + scopolamine. Pregabalin did not influence locomotor activity increased by scopolamine. In passive avoidance task, pregabalin reversed learning deficits induced by scopolamine. In the Morris water maze, pregabalin did not influence spatial learning deficits induced by scopolamine. These results are relevant for epileptic patients treated with pregabalin and those who use it for other therapeutic indications (anxiety, pain).

Developmental dyscalculia is related to visuo-spatial memory and inhibition impairment.

PubMed

Szucs, Denes; Devine, Amy; Soltesz, Fruzsina; Nobes, Alison; Gabriel, Florence

2013-01-01

Developmental dyscalculia is thought to be a specific impairment of mathematics ability. Currently dominant cognitive neuroscience theories of developmental dyscalculia suggest that it originates from the impairment of the magnitude representation of the human brain, residing in the intraparietal sulcus, or from impaired connections between number symbols and the magnitude representation. However, behavioral research offers several alternative theories for developmental dyscalculia and neuro-imaging also suggests that impairments in developmental dyscalculia may be linked to disruptions of other functions of the intraparietal sulcus than the magnitude representation. Strikingly, the magnitude representation theory has never been explicitly contrasted with a range of alternatives in a systematic fashion. Here we have filled this gap by directly contrasting five alternative theories (magnitude representation, working memory, inhibition, attention and spatial processing) of developmental dyscalculia in 9-10-year-old primary school children. Participants were selected from a pool of 1004 children and took part in 16 tests and nine experiments. The dominant features of developmental dyscalculia are visuo-spatial working memory, visuo-spatial short-term memory and inhibitory function (interference suppression) impairment. We hypothesize that inhibition impairment is related to the disruption of central executive memory function. Potential problems of visuo-spatial processing and attentional function in developmental dyscalculia probably depend on short-term memory/working memory and inhibition impairments. The magnitude representation theory of developmental dyscalculia was not supported. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

Spatial and Reversal Learning in the Morris Water Maze Are Largely Resistant to Six Hours of REM Sleep Deprivation Following Training

ERIC Educational Resources Information Center

Walsh, Christine M.; Booth, Victoria; Poe, Gina R.

2011-01-01

This first test of the role of REM (rapid eye movement) sleep in reversal spatial learning is also the first attempt to replicate a much cited pair of papers reporting that REM sleep deprivation impairs the consolidation of initial spatial learning in the Morris water maze. We hypothesized that REM sleep deprivation following training would impair…

Sharpening coarse-to-fine stereo vision by perceptual learning: asymmetric transfer across the spatial frequency spectrum

PubMed Central

Tran, Truyet T.; Craven, Ashley P.; Leung, Tsz-Wing; Chat, Sandy W.; Levi, Dennis M.

2016-01-01

Neurons in the early visual cortex are finely tuned to different low-level visual features, forming a multi-channel system analysing the visual image formed on the retina in a parallel manner. However, little is known about the potential ‘cross-talk’ among these channels. Here, we systematically investigated whether stereoacuity, over a large range of target spatial frequencies, can be enhanced by perceptual learning. Using narrow-band visual stimuli, we found that practice with coarse (low spatial frequency) targets substantially improves performance, and that the improvement spreads from coarse to fine (high spatial frequency) three-dimensional perception, generalizing broadly across untrained spatial frequencies and orientations. Notably, we observed an asymmetric transfer of learning across the spatial frequency spectrum. The bandwidth of transfer was broader when training was at a high spatial frequency than at a low spatial frequency. Stereoacuity training is most beneficial when trained with fine targets. This broad transfer of stereoacuity learning contrasts with the highly specific learning reported for other basic visual functions. We also revealed strategies to boost learning outcomes ‘beyond-the-plateau’. Our investigations contribute to understanding the functional properties of the network subserving stereovision. The ability to generalize may provide a key principle for restoring impaired binocular vision in clinical situations. PMID:26909178

Effect of intranasal manganese administration on neurotransmission and spatial learning in rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Blecharz-Klin, Kamilla; Piechal, Agnieszka; Joniec-Maciejak, Ilona

2012-11-15

The effect of intranasal manganese chloride (MnCl{sub 2}·4H{sub 2}O) exposure on spatial learning, memory and motor activity was estimated in Morris water maze task in adult rats. Three-month-old male Wistar rats received for 2 weeks MnCl{sub 2}·4H{sub 2}O at two doses the following: 0.2 mg/kg b.w. (Mn0.2) or 0.8 mg/kg b.w. (Mn0.8) per day. Control (Con) and manganese-exposed groups were observed for behavioral performance and learning in water maze. ANOVA for repeated measurements did not show any significant differences in acquisition in the water maze between the groups. However, the results of the probe trial on day 5, exhibited spatialmore » memory deficits following manganese treatment. After completion of the behavioral experiment, the regional brain concentrations of neurotransmitters and their metabolites were determined via HPLC in selected brain regions, i.e. prefrontal cortex, hippocampus and striatum. ANOVA demonstrated significant differences in the content of monoamines and metabolites between the treatment groups compared to the controls. Negative correlations between platform crossings on the previous platform position in Southeast (SE) quadrant during the probe trial and neurotransmitter turnover suggest that impairment of spatial memory and cognitive performance after manganese (Mn) treatment is associated with modulation of the serotonergic, noradrenergic and dopaminergic neurotransmission in the brain. These findings show that intranasally applied Mn can impair spatial memory with significant changes in the tissue level and metabolism of monoamines in several brain regions. -- Highlights: ► Intranasal exposure to manganese in rats impairs spatial memory in the water maze. ► Regional changes in levels of neurotransmitters in the brain have been identified. ► Cognitive disorder correlates with modulation of 5-HT, NA and DA neurotransmission.« less

[Nphe1]-Nociceptin (1-13)-NH2, a nociceptin receptor antagonist, reverses nociceptin-induced spatial memory impairments in the Morris water maze task in rats

PubMed Central

Redrobe, J P; Calo, G; Guerrini, R; Regoli, D; Quirion, R

2000-01-01

The present study was undertaken to investigate the effects of the novel nociceptin receptor antagonist, [Nphe1]-Nociceptin (1-13)-NH2 (bilateral intrahippocampal injection, 50 nmole rat−1) on purported nociceptin-induced (bilateral intrahippocampal injection, 5 nmole rat−1) deficits in spatial learning in the rat Morris water maze task. In addition, experiments were performed in an ‘open field' to investigate possible peptide-induced changes in exploratory behaviour. Nociceptin significantly impaired the ability of the animal to locate the hidden platform throughout training (P<0.001 versus control group). Pretreatment with [Nphe1]-Nociceptin (1-13)-NH2 significantly blocked nociceptin-induced impairment of spatial learning (P<0.001 versus nociceptin group). A probe trial revealed that vehicle-treated animals spent more time in the quadrant that had previously contained the hidden platform, whereas nociceptin-treated animals did not spend more time in any one quadrant. Learning impairments were not attributable to non-specific deficits in motor performance or change in exploratory behaviour. Taken together, our results reveal that [Nphe1]-Nociceptin (1-13)-NH2 represents an effective and useful in vivo antagonist at the nociceptin receptors involved in learning and memory. PMID:11090110

Presence of lacunar infarctions is associated with the spatial navigation impairment in patients with mild cognitive impairment: a DTI study

PubMed Central

Liu, Qing-Ping; He, Wen-Wen; Ding, Hong; Nedelska, Zuzana; Hort, Jakub; Zhang, Bing; Xu, Yun

2016-01-01

Lacunar cerebral infarction (LI) is one of risk factors of vascular dementia and correlates with progression of cognitive impairment including the executive functions. However, little is known on spatial navigation impairment and its underlying microstructural alteration of white matter in patients with LI and with or without mild cognitive impairment (MCI). Our aim was to investigate whether the spatial navigation impairment correlated with the white matter integrity in LI patients with MCI (LI-MCI). Thirty patients with LI were included in the study and were divided into LI-MCI (n=17) and non MCI (LI-Non MCI) groups (n=13) according neuropsychological tests.The microstructural integrity of white matter was assessed by calculating a fractional anisotropy (FA) and mean diffusivity (MD) from diffusion tensor imaging (DTI) scans. The spatial navigation accuracy, separately evaluated as egocentric and allocentric, was assessed by a computerized human analogue of the Morris Water Maze tests Amunet. LI-MCI performed worse than the CN and LI-NonMCI groups on egocentric and delayed spatial navigation subtests. LI-MCI patients have spatial navigation deficits. The microstructural abnormalities in diffuse brain regions, including hippocampus, uncinate fasciculus and other brain regions may contribute to the spatial navigation impairment in LI-MCI patients at follow-up. PMID:27861154

Maternal chewing during prenatal stress ameliorates stress-induced hypomyelination, synaptic alterations, and learning impairment in mouse offspring.

PubMed

Suzuki, Ayumi; Iinuma, Mitsuo; Hayashi, Sakurako; Sato, Yuichi; Azuma, Kagaku; Kubo, Kin-Ya

2016-11-15

Maternal chewing during prenatal stress attenuates both the development of stress-induced learning deficits and decreased cell proliferation in mouse hippocampal dentate gyrus. Hippocampal myelination affects spatial memory and the synaptic structure is a key mediator of neuronal communication. We investigated whether maternal chewing during prenatal stress ameliorates stress-induced alterations of hippocampal myelin and synapses, and impaired development of spatial memory in adult offspring. Pregnant mice were divided into control, stress, and stress/chewing groups. Stress was induced by placing mice in a ventilated restraint tube, and was initiated on day 12 of pregnancy and continued until delivery. Mice in the stress/chewing group were given a wooden stick to chew during restraint. In 1-month-old pups, spatial memory was assessed in the Morris water maze, and hippocampal oligodendrocytes and synapses in CA1 were assayed by immunohistochemistry and electron microscopy. Prenatal stress led to impaired learning ability, and decreased immunoreactivity of myelin basic protein (MBP) and 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) in the hippocampal CA1 in adult offspring. Numerous myelin sheath abnormalities were observed. The G-ratio [axonal diameter to axonal fiber diameter (axon plus myelin sheath)] was increased and postsynaptic density length was decreased in the hippocampal CA1 region. Maternal chewing during stress attenuated the prenatal stress-induced impairment of spatial memory, and the decreased MBP and CNPase immunoreactivity, increased G-ratios, and decreased postsynaptic-density length in the hippocampal CA1 region. These findings suggest that chewing during prenatal stress in dams could be an effective coping strategy to prevent hippocampal behavioral and morphologic impairments in their offspring. Copyright © 2016 Elsevier B.V. All rights reserved.

7,8-dihydroxyflavone, a TrkB receptor agonist, blocks long-term spatial memory impairment caused by immobilization stress in rats.

PubMed

Andero, Raül; Daviu, Núria; Escorihuela, Rosa Maria; Nadal, Roser; Armario, Antonio

2012-03-01

Post-traumatic stress disorder (PTSD) patients show cognitive deficits, but it is unclear whether these are a consequence of the pathology or a pre-existing factor of vulnerability to PTSD. Animal models may help to demonstrate whether or not exposure to certain stressors can actually induce long-lasting (LL; days) impairment of hippocampus-dependent memory tasks and to characterize neurobiological mechanisms. Adult male rats were exposed to 2-h immobilization on boards (IMO), a severe stressor, and spatial learning in the Morris water maze (MWM) was studied days later. Exposure to IMO did not modify learning or short-term memory in the MWM when learning started 3 or 9 days after IMO, but stressed rats did show impaired long-term memory at both times, in accordance with the severity of the stressor. New treatments to prevent PTSD symptoms are needed. Thus, considering the potential protective role of brain-derived neurotrophic factor (BDNF) on hippocampal function, 7,8-dihydroxyflavone (7,8-DHF), a recently characterized agonist of the BDNF receptor TrkB, was given before or after IMO in additional experiments. Again, exposure to IMO resulted in LL deficit in long-term memory, and such impairment was prevented by the administration of 7,8-DHF either 2 h prior IMO or 8 h after the termination of IMO. The finding that IMO-induced impairment of spatial memory was prevented by pharmacological potentiation of TrkB pathway with 7,8-DHF even when the drug was given 8 h after IMO suggests that IMO-induced impairment is likely to be a LL process that is strongly dependent on the integrity of the BDNF-TrkB system and is susceptible to poststress therapeutic interventions. 7,8-DHF may represent a new therapeutic approach for early treatment of subjects who have suffered traumatic experiences. Copyright © 2010 Wiley Periodicals, Inc.

Reduced mastication stimulates impairment of spatial memory and degeneration of hippocampal neurons in aged SAMP8 mice.

PubMed

Onozuka, M; Watanabe, K; Mirbod, S M; Ozono, S; Nishiyama, K; Karasawa, N; Nagatsu, I

1999-04-24

The involvement of reduced mastication in senile dementia was evaluated by examining the effect of cutting off the upper molars (molarless) on spatial memory and numbers of hippocampal neurons in aged SAMP8 mice. Molarless mice showed a decrease in both learning ability in a water maze and neuron density in the hippocampal CA1 region compared with control mice. These changes increased the longer the molarless condition persisted. The data suggest a possible link between reduced mastication and hippocampal neuron loss that may be one risk factor for senile impairment of spatial memory. Copyright 1999 Elsevier Science B.V.

Exposure to radiation accelerates normal brain aging and produces deficits in spatial learning and memory

NASA Astrophysics Data System (ADS)

Shukitt-Hale, B.; Casadesus, G.; Carey, A.; Rabin, B. M.; Joseph, J. A.

Previous studies have shown that radiation exposure, particularly to particles of high energy and charge (HZE particles), produces deficits in spatial learning and memory. These adverse behavioral effects are similar to those seen in aged animals. It is possible that these shared effects may be produced by the same mechanism; oxidative stress damage to the central nervous system caused by an increased release of reactive oxygen species is likely responsible for the deficits seen in aging and following irradiation. Both aged and irradiated rats display cognitive impairment in tests of spatial learning and memory such as the Morris water maze and the radial arm maze. These rats have decrements in the ability to build spatial representations of the environment and they utilize non-spatial strategies to solve tasks. Furthermore, they show a lack of spatial preference, due to a decline in the ability to process or retain place (position of a goal with reference to a "map" provided by the configuration of numerous cues in the environment) information. These declines in spatial memory occur in measures dependent on both reference and working memory, and in the flexibility to reset mental images. These results show that irradiation with high-energy particles produces age-like decrements in cognitive behavior that may impair the ability of astronauts to perform critical tasks during long-term space travel beyond the magnetosphere. Supported by NASA Grants NAG9-1190 and NAG9-1529

Studying on Borrowed Time: How Does Testing Impair New Learning?

ERIC Educational Resources Information Center

Davis, Sara D.; Chan, Jason C. K.

2015-01-01

Retrieving studied materials often enhances subsequent learning of new materials (Pastötter & Bäuml, 2014). However, retrieval has also been shown to impair new learning (Finn & Roediger, 2013). In this article, we attempted to determine when retrieval enhances and when it impairs new learning. We argue that testing impairs new learning…

Effect of low frequency electrical stimulation on seizure-induced short- and long-term impairments in learning and memory in rats.

PubMed

Esmaeilpour, Khadijeh; Sheibani, Vahid; Shabani, Mohammad; Mirnajafi-Zadeh, Javad

2017-01-01

Kindled seizures can impair learning and memory. In the present study the effect of low-frequency electrical stimulation (LFS) on kindled seizure-induced impairment in spatial learning and memory was investigated and followed up to one month. Animals were kindled by electrical stimulation of hippocampal CA1 area in a semi-rapid manner (12 stimulations per day). One group of animals received four trials of LFS at 30s, 6h, 24h, and 30h following the last kindling stimulation. Each LFS trial was consisted of 4 packages at 5min intervals. Each package contained 200 monophasic square wave pulses of 0.1ms duration at 1Hz. The Open field, Morris water maze, and novel object recognition tests were done 48h, 1week, 2weeks, and one month after the last kindling stimulation respectively. Kindled animals showed a significant impairment in learning and memory compared to control rats. LFS decreased the kindling-induced learning and memory impairments at 24h and one week following its application, but not at 2week or 1month after kindling. In the group of animals that received the same 4 trials of LFS again one week following the last kindling stimulation, the improving effect of LFS was observed even after one month. Obtained results showed that application of LFS in fully kindled animals has a long-term improving effect on spatial learning and memory. This effect can remain for a long duration (one month in this study) by increasing the number of applied LFS. Copyright © 2016 Elsevier Inc. All rights reserved.

Negative reinforcement impairs overnight memory consolidation.

PubMed

Stamm, Andrew W; Nguyen, Nam D; Seicol, Benjamin J; Fagan, Abigail; Oh, Angela; Drumm, Michael; Lundt, Maureen; Stickgold, Robert; Wamsley, Erin J

2014-11-01

Post-learning sleep is beneficial for human memory. However, it may be that not all memories benefit equally from sleep. Here, we manipulated a spatial learning task using monetary reward and performance feedback, asking whether enhancing the salience of the task would augment overnight memory consolidation and alter its incorporation into dreaming. Contrary to our hypothesis, we found that the addition of reward impaired overnight consolidation of spatial memory. Our findings seemingly contradict prior reports that enhancing the reward value of learned information augments sleep-dependent memory processing. Given that the reward followed a negative reinforcement paradigm, consolidation may have been impaired via a stress-related mechanism. © 2014 Stamm et al.; Published by Cold Spring Harbor Laboratory Press.

Sex-specific impairment of spatial memory in rats following a reminder of predator stress.

PubMed

Burke, Hanna M; Robinson, Cristina M; Wentz, Bethany; McKay, Jerel; Dexter, Kyle W; Pisansky, Julia M; Talbot, Jeffery N; Zoladz, Phillip R

2013-07-01

It has been suggested that cognitive impairments exhibited by people with post-traumatic stress disorder (PTSD) result from intrusive, flashback memories transiently interfering with ongoing cognitive processing. Researchers have further speculated that females are more susceptible to developing PTSD because they form stronger traumatic memories than males, hence females may be more sensitive to the negative effects of intrusive memories on cognition. We have examined how the reminder of a naturalistic stress experience would affect rat spatial memory and if sex was a contributing factor to such effects. Male and female Sprague-Dawley rats were exposed, without contact, to an adult female cat for 30 min. Five weeks later, the rats were trained to locate a hidden platform in the radial-arm water maze and given a single long-term memory test trial 24 h later. Before long-term memory testing, the rats were given a 30-min reminder of the cat exposure experienced 5 weeks earlier. The results indicated that the stress reminder impaired spatial memory in the female rats only. Control manipulations revealed that this effect was not attributable to the original cat exposure adversely impacting learning that occurred 5 weeks later, or to merely exposing rats to a novel environment or predator-related cues immediately before testing. These findings provide evidence that the reminder of a naturalistic stressful experience can impair cognitive processing in rats; moreover, since female rats were more susceptible to the memory-impairing effects of the stress reminder, the findings could lend insight into the existing sex differences in susceptibility to PTSD.

Spatial learning while navigating with severely degraded viewing: The role of attention and mobility monitoring

PubMed Central

Rand, Kristina M.; Creem-Regehr, Sarah H.; Thompson, William B.

2015-01-01

The ability to navigate without getting lost is an important aspect of quality of life. In five studies, we evaluated how spatial learning is affected by the increased demands of keeping oneself safe while walking with degraded vision (mobility monitoring). We proposed that safe low-vision mobility requires attentional resources, providing competition for those needed to learn a new environment. In Experiments 1 and 2 participants navigated along paths in a real-world indoor environment with simulated degraded vision or normal vision. Memory for object locations seen along the paths was better with normal compared to degraded vision. With degraded vision, memory was better when participants were guided by an experimenter (low monitoring demands) versus unguided (high monitoring demands). In Experiments 3 and 4, participants walked while performing an auditory task. Auditory task performance was superior with normal compared to degraded vision. With degraded vision, auditory task performance was better when guided compared to unguided. In Experiment 5, participants performed both the spatial learning and auditory tasks under degraded vision. Results showed that attention mediates the relationship between mobility-monitoring demands and spatial learning. These studies suggest that more attention is required and spatial learning is impaired when navigating with degraded viewing. PMID:25706766

Rhinal and Dorsolateral Prefrontal Cortex Lesions Produce Selective Impairments in Object and Spatial Learning and Memory in Canines

PubMed Central

Christie, Lori-Ann; Saunders, Richard C.; Kowalska, Danuta, M.; MacKay, William A.; Head, Elizabeth; Cotman, Carl W.; Milgram, Norton W.

2014-01-01

To examine the effects of rhinal and dorsolateral prefrontal cortex lesions on object and spatial recognition memory in canines, we used a protocol in which both an object (delayed non-matching to sample, or DNMS) and a spatial (delayed non-matching to position or DNMP) recognition task were administered daily. The tasks used similar procedures such that only the type of stimulus information to be remembered differed. Rhinal cortex (RC) lesions produced a selective deficit on the DNMS task, both in retention of the task rules at short delays and in object recognition memory. By contrast, performance on the DNMP task remained intact at both short and long delay intervals in RC animals. Subjects who received dorsolateral prefrontal cortex (dlPFC) lesions were impaired on a spatial task at a short, 5-sec delay, suggesting disrupted retention of the general task rules, however, this impairment was transient; long-term spatial memory performance was unaffected in dlPFC subjects. The present results provide support for the involvement of the RC in object, but not visuospatial, processing and recognition memory, whereas the dlPFC appears to mediate retention of a non-matching rule. These findings support theories of functional specialization within the medial temporal lobe and frontal cortex and suggest that rhinal and dorsolateral prefrontal cortices in canines are functionally similar to analogous regions in other mammals. PMID:18792072

Exposure to swainsonine impairs adult neurogenesis and spatial learning and memory.

PubMed

Wang, Jiutao; Song, Lingzhen; Zhang, Qi; Zhang, Wei; An, Lei; Zhang, Yamei; Tong, Dewen; Zhao, Baoyu; Chen, Shulin; Zhao, Shanting

2015-01-05

Swainsonine (SW) is an indolizidine triol plant alkaloid isolated from the species Astragalus, colloquially termed locoweed. Ingestion induces severe neurological symptoms of livestock and wildlife, including ataxia, trembling, exaggerated fright reactions. Toxicity to the central and peripheral nervous system is caused by inhibition of lysosomal a-mannosidase (AMA) and accumulation of intracellular oligosaccharide. However, the effects of SW on adult neurogenesis and cognition have remained unclear. Therefore, the present study was conducted to examine the effects of SW on adult neurogenesis and learning as well as memory performance in adult mice. SW (10μg/mL in drinking water) was administered orally to mice for 4 weeks. Our results showed that SW reduced proliferation and survival of neural progenitor cells (NPCs) in culture, and in the hippocampus of adult mice. In addition, exposure to SW led to down-regulation of doublecortin (DCX) and synaptophysin (SYP) in the hippocampus. However, caspase 3 and glial fibrillary acidic protein (GFAP) levels were significantly increased in SW-treated mice. Finally, SW-treated mice exhibited deficits in hippocampus-dependent spatial learning and memory. Our findings suggest that SW affects adult neurogenesis and cognitive function. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

N-methyl-d-aspartate receptors, learning and memory: chronic intraventricular infusion of the NMDA receptor antagonist d-AP5 interacts directly with the neural mechanisms of spatial learning.

PubMed

Morris, R G M; Steele, R J; Bell, J E; Martin, S J

2013-03-01

Three experiments were conducted to contrast the hypothesis that hippocampal N-methyl-d-aspartate (NMDA) receptors participate directly in the mechanisms of hippocampus-dependent learning with an alternative view that apparent impairments of learning induced by NMDA receptor antagonists arise because of drug-induced neuropathological and/or sensorimotor disturbances. In experiment 1, rats given a chronic i.c.v. infusion of d-AP5 (30 mm) at 0.5 μL/h were selectively impaired, relative to aCSF-infused animals, in place but not cued navigation learning when they were trained during the 14-day drug infusion period, but were unimpaired on both tasks if trained 11 days after the minipumps were exhausted. d-AP5 caused sensorimotor disturbances in the spatial task, but these gradually worsened as the animals failed to learn. Histological assessment of potential neuropathological changes revealed no abnormalities in d-AP5-treated rats whether killed during or after chronic drug infusion. In experiment 2, a deficit in spatial learning was also apparent in d-AP5-treated rats trained on a spatial reference memory task involving two identical but visible platforms, a task chosen and shown to minimise sensorimotor disturbances. HPLC was used to identify the presence of d-AP5 in selected brain areas. In Experiment 3, rats treated with d-AP5 showed a delay-dependent deficit in spatial memory in the delayed matching-to-place protocol for the water maze. These data are discussed with respect to the learning mechanism and sensorimotor accounts of the impact of NMDA receptor antagonists on brain function. We argue that NMDA receptor mechanisms participate directly in spatial learning. © 2013 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

Ego depletion impairs implicit learning.

PubMed

Thompson, Kelsey R; Sanchez, Daniel J; Wesley, Abigail H; Reber, Paul J

2014-01-01

Implicit skill learning occurs incidentally and without conscious awareness of what is learned. However, the rate and effectiveness of learning may still be affected by decreased availability of central processing resources. Dual-task experiments have generally found impairments in implicit learning, however, these studies have also shown that certain characteristics of the secondary task (e.g., timing) can complicate the interpretation of these results. To avoid this problem, the current experiments used a novel method to impose resource constraints prior to engaging in skill learning. Ego depletion theory states that humans possess a limited store of cognitive resources that, when depleted, results in deficits in self-regulation and cognitive control. In a first experiment, we used a standard ego depletion manipulation prior to performance of the Serial Interception Sequence Learning (SISL) task. Depleted participants exhibited poorer test performance than did non-depleted controls, indicating that reducing available executive resources may adversely affect implicit sequence learning, expression of sequence knowledge, or both. In a second experiment, depletion was administered either prior to or after training. Participants who reported higher levels of depletion before or after training again showed less sequence-specific knowledge on the post-training assessment. However, the results did not allow for clear separation of ego depletion effects on learning versus subsequent sequence-specific performance. These results indicate that performance on an implicitly learned sequence can be impaired by a reduction in executive resources, in spite of learning taking place outside of awareness and without conscious intent.

Ego Depletion Impairs Implicit Learning

PubMed Central

Thompson, Kelsey R.; Sanchez, Daniel J.; Wesley, Abigail H.; Reber, Paul J.

2014-01-01

Implicit skill learning occurs incidentally and without conscious awareness of what is learned. However, the rate and effectiveness of learning may still be affected by decreased availability of central processing resources. Dual-task experiments have generally found impairments in implicit learning, however, these studies have also shown that certain characteristics of the secondary task (e.g., timing) can complicate the interpretation of these results. To avoid this problem, the current experiments used a novel method to impose resource constraints prior to engaging in skill learning. Ego depletion theory states that humans possess a limited store of cognitive resources that, when depleted, results in deficits in self-regulation and cognitive control. In a first experiment, we used a standard ego depletion manipulation prior to performance of the Serial Interception Sequence Learning (SISL) task. Depleted participants exhibited poorer test performance than did non-depleted controls, indicating that reducing available executive resources may adversely affect implicit sequence learning, expression of sequence knowledge, or both. In a second experiment, depletion was administered either prior to or after training. Participants who reported higher levels of depletion before or after training again showed less sequence-specific knowledge on the post-training assessment. However, the results did not allow for clear separation of ego depletion effects on learning versus subsequent sequence-specific performance. These results indicate that performance on an implicitly learned sequence can be impaired by a reduction in executive resources, in spite of learning taking place outside of awareness and without conscious intent. PMID:25275517

PKA-CREB-BDNF signaling pathway mediates propofol-induced long-term learning and memory impairment in hippocampus of rats.

PubMed

Zhong, Yu; Chen, Jing; Li, Li; Qin, Yi; Wei, Yi; Pan, Shining; Jiang, Yage; Chen, Jialin; Xie, Yubo

2018-04-20

Studies have found that propofol can induce widespread neuroapoptosis in developing brains, which leads to cause long-term learning and memory abnormalities. However, the specific cellular and molecular mechanisms underlying propofol-induced neuroapoptosis remain elusive. The aim of the present study was to explore the role of PKA-CREB-BDNF signaling pathway in propofol-induced long-term learning and memory impairment during brain development. Seven-day-old rats were randomly assigned to control, intralipid and three treatment groups (n = 5). Rats in control group received no treatment. Intralipid (10%, 10 mL/kg) for vehicle control and different dosage of propofol for three treatment groups (50, 100 and 200 mg/kg) were administered intraperitoneally. FJB staining, immunohistochemistry analysis for neuronal nuclei antigen and transmission electron microscopy were used to detect neuronal apoptosis and structure changes. MWM test examines the long-term spatial learning and memory impairment. The expression of PKA, pCREB and BDNF was quantified using western blots. Propofol induced significant increase of FJB-positive cells and decrease of PKA, pCREB and BDNF protein levels in the immature brain of P7 rats. Using the MWM test, propofol-treated rats demonstrated long-term spatial learning and memory impairment. Moreover, hippocampal NeuN-positive cell loss, long-lasting ultrastructural abnormalities of the neurons and synapses, and long-term down-regulation of PKA, pCREB and BDNF protein expression in adult hippocampus were also found. Our results indicated that neonatal propofol exposure can significantly result in long-term learning and memory impairment in adulthood. The possible mechanism involved in the propofol-induced neuroapoptosis was related to down-regulation of PKA-CREB-BDNF signaling pathway. Copyright © 2018. Published by Elsevier B.V.

Learning to echolocate in sighted people: a correlational study on attention, working memory and spatial abilities.

PubMed

Ekkel, M R; van Lier, R; Steenbergen, B

2017-03-01

Echolocation can be beneficial for the orientation and mobility of visually impaired people. Research has shown considerable individual differences for acquiring this skill. However, individual characteristics that affect the learning of echolocation are largely unknown. In the present study, we examined individual factors that are likely to affect learning to echolocate: sustained and divided attention, working memory, and spatial abilities. To that aim, sighted participants with normal hearing performed an echolocation task that was adapted from a previously reported size-discrimination task. In line with existing studies, we found large individual differences in echolocation ability. We also found indications that participants were able to improve their echolocation ability. Furthermore, we found a significant positive correlation between improvement in echolocation and sustained and divided attention, as measured in the PASAT. No significant correlations were found with our tests regarding working memory and spatial abilities. These findings may have implications for the development of guidelines for training echolocation that are tailored to the individual with a visual impairment.

Acute administration of THC impairs spatial but not associative memory function in zebrafish.

PubMed

Ruhl, Tim; Prinz, Nicole; Oellers, Nadine; Seidel, Nathan Ian; Jonas, Annika; Albayram, Onder; Bilkei-Gorzo, Andras; von der Emde, Gerhard

2014-10-01

The present study examined the effect of acute administration of endocannabinoid receptor CB1 ligand ∆-9-tetrahydrocannabinol (THC) on intracellular signalling in the brain and retrieval from two different memory systems in the zebrafish (Danio rerio). First, fish were treated with THC and changes in the phosphorylation level of mitogen-activated protein (MAP) kinases Akt and Erk in the brain were determined 1 h after drug treatment. Next, animals of a second group learned in a two-alternative choice paradigm to discriminate between two colours, whereas a third group solved a spatial cognition task in an open-field maze by use of an ego-allocentric strategy. After memory acquisition and consolidation, animals were pharmacologically treated using the treatment regime as in the first group and then tested again for memory retrieval. We found an enhanced Erk but not Akt phosphorylation suggesting that THC treatment specifically activated Erk signalling in the zebrafish telencephalon. While CB1 agonist THC did not affect behavioural performance of animals in the colour discrimination paradigm, spatial memory was significantly impaired. The effect of THC on spatial learning is probably specific, since neither motor activity nor anxiety-related behaviour was influenced by the drug treatment. That indicates a striking influence of the endocannabinoid system (ECS) on spatial cognition in zebrafish. The results are very coincident with reports on mammals, demonstrating that the ECS is functional highly conserved during vertebrate evolution. We further conclude that the zebrafish provides a promising model organism for ongoing research on the ECS.

The chemotherapeutic agent paclitaxel selectively impairs reversal learning while sparing prior learning, new learning and episodic memory.

PubMed

Panoz-Brown, Danielle; Carey, Lawrence M; Smith, Alexandra E; Gentry, Meredith; Sluka, Christina M; Corbin, Hannah E; Wu, Jie-En; Hohmann, Andrea G; Crystal, Jonathon D

2017-10-01

Chemotherapy is widely used to treat patients with systemic cancer. The efficacy of cancer therapies is frequently undermined by adverse side effects that have a negative impact on the quality of life of cancer survivors. Cancer patients who receive chemotherapy often experience chemotherapy-induced cognitive impairment across a variety of domains including memory, learning, and attention. In the current study, the impact of paclitaxel, a taxane derived chemotherapeutic agent, on episodic memory, prior learning, new learning, and reversal learning were evaluated in rats. Neurogenesis was quantified post-treatment in the dentate gyrus of the same rats using immunostaining for 5-Bromo-2'-deoxyuridine (BrdU) and Ki67. Paclitaxel treatment selectively impaired reversal learning while sparing episodic memory, prior learning, and new learning. Furthermore, paclitaxel-treated rats showed decreases in markers of hippocampal cell proliferation, as measured by markers of cell proliferation assessed using immunostaining for Ki67 and BrdU. This work highlights the importance of using multiple measures of learning and memory to identify the pattern of impaired and spared aspects of chemotherapy-induced cognitive impairment. Copyright © 2017 Elsevier Inc. All rights reserved.

Spatial learning impairment in prepubertal guinea pigs prenatally exposed to the organophosphorus pesticide chlorpyrifos: Toxicological implications

PubMed Central

Mamczarz, Jacek; Pescrille, Joseph D.; Gavrushenko, Lisa; Burke, Richard D.; Fawcett, William P.; DeTolla, Louis J.; Chen, Hegang; Pereira, Edna F.R.; Albuquerque, Edson X.

2017-01-01

Exposure of the developing brain to chlorpyrifos (CPF), an organophosphorus (OP) pesticide used extensively in agriculture worldwide, has been associated with increased prevalence of cognitive deficits in children, particularly boys. The present study was designed to test the hypothesis that cognitive deficits induced by prenatal exposure to sub-acute doses of CPF can be reproduced in precocial small species. To address this hypothesis, pregnant guinea pigs were injected daily with CPF (25 mg/kg, s.c.) or vehicle (peanut oil) for 10 days starting on presumed gestation day (GD) 53–55. Offspring were born around GD 65, weaned on postnatal day (PND) 20, and subjected to behavioral tests starting around PND 30. On the day of birth, butyrylcholinesterase (BuChE), an OP bioscavenger used as a biomarker of OP exposures, and acetylcholinesterase (AChE), a major molecular target of OP compounds, were significantly inhibited in the blood of CPF-exposed offspring. In their brains, BuChE, but not AChE, was significantly inhibited. Prenatal CPF exposure had no significant effect on locomotor activity or on locomotor habituation, a form of non-associative memory assessed in open fields. Spatial navigation in the Morris water maze (MWM) was found to be sexually dimorphic among guinea pigs, with males outperforming females. Prenatal CPF exposure impaired spatial learning more significantly among male than female guinea pigs and, consequently, reduced the sexual dimorphism of the task. The results presented here, which strongly support the test hypothesis, reveal that the guinea pig is a valuable animal model for preclinical assessment of the developmental neurotoxicity of OP pesticides. These findings are far reaching as they lay the groundwork for future studies aimed at identifying therapeutic interventions to treat and/or prevent the neurotoxic effects of CPF in the developing brain. PMID:27296654

[GLIATILIN CORRECTION OF WORKING AND REFERENCE SPATIAL MEMORY IMPAIRMENT IN AGED RATS].

PubMed

Tyurenkov, I N; Volotova, E V; Kurkin, D V

2015-01-01

This work was aimed at evaluating the influence of gliatilin administration on the spatial memory in aged rats. Cognitive function and spatial memory in animals was evaluated using radial (8-beam) maze test. Errors of working spatial memory and reference memory were used as indicators of impaired cognitive function. It was found that aged (24-month) rats compared with younger (6-months) age group exhibited cognitive impairment, as manifested by deterioration of short- and long-term memory processes. Course administration of gliatilin in rats of the older age group at a dose of 100 mg/kg resulted in significant improvement of the working and reference spatial memory in aged rats.

Communication Skills and Learning in Impaired Individuals

ERIC Educational Resources Information Center

Eliöz, Murat

2016-01-01

The purpose of this study is to compare the communication skills of individuals with different disabilities with athletes and sedentary people and to examine their learning abilities which influence the development of communication. A total of 159 male subjects 31 sedentary, 30 visually impaired, 27 hearing impaired, 40 physically impaired and 31…

Sodium p-Aminosalicylic Acid Reverses Sub-Chronic Manganese-Induced Impairments of Spatial Learning and Memory Abilities in Rats, but Fails to Restore γ-Aminobutyric Acid Levels.

PubMed

Li, Shao-Jun; Ou, Chao-Yan; He, Sheng-Nan; Huang, Xiao-Wei; Luo, Hai-Lan; Meng, Hao-Yang; Lu, Guo-Dong; Jiang, Yue-Ming; Vieira Peres, Tanara; Luo, Yi-Ni; Deng, Xiang-Fa

2017-04-10

Excessive manganese (Mn) exposure is not only a health risk for occupational workers, but also for the general population. Sodium para-aminosalicylic acid (PAS-Na) has been successfully used in the treatment of manganism, but the involved molecular mechanisms have yet to be determined. The present study aimed to investigate the effects of PAS-Na on sub-chronic Mn exposure-induced impairments of spatial learning and memory, and determine the possible involvements of γ-aminobutyric acid (GABA) metabolism in vivo. Sprague-Dawley male rats received daily intraperitoneal injections MnCl₂ (as 6.55 mg/kg Mn body weight, five days per week for 12 weeks), followed by daily subcutaneous injections of 100, 200, or 300 mg/kg PAS-Na for an additional six weeks. Mn exposure significantly impaired spatial learning and memory ability, as noted in the Morris water maze test, and the following PAS-Na treatment successfully restored these adverse effects to levels indistinguishable from controls. Unexpectedly, PAS-Na failed to recover the Mn-induced decrease in the overall GABA levels, although PAS-Na treatment reversed Mn-induced alterations in the enzyme activities directly responsible for the synthesis and degradation of GABA (glutamate decarboxylase and GABA-transaminase, respectively). Moreover, Mn exposure caused an increase of GABA transporter 1 (GAT-1) and decrease of GABA A receptor (GABA A ) in transcriptional levels, which could be reverted by the highest dose of 300 mg/kg PAS-Na treatment. In conclusion, the GABA metabolism was interrupted by sub-chronic Mn exposure. However, the PAS-Na treatment mediated protection from sub-chronic Mn exposure-induced neurotoxicity, which may not be dependent on the GABA metabolism.

Sodium p-Aminosalicylic Acid Reverses Sub-Chronic Manganese-Induced Impairments of Spatial Learning and Memory Abilities in Rats, but Fails to Restore γ-Aminobutyric Acid Levels

PubMed Central

Li, Shao-Jun; Ou, Chao-Yan; He, Sheng-Nan; Huang, Xiao-Wei; Luo, Hai-Lan; Meng, Hao-Yang; Lu, Guo-Dong; Jiang, Yue-Ming; Vieira Peres, Tanara; Luo, Yi-Ni; Deng, Xiang-Fa

2017-01-01

Excessive manganese (Mn) exposure is not only a health risk for occupational workers, but also for the general population. Sodium para-aminosalicylic acid (PAS-Na) has been successfully used in the treatment of manganism, but the involved molecular mechanisms have yet to be determined. The present study aimed to investigate the effects of PAS-Na on sub-chronic Mn exposure-induced impairments of spatial learning and memory, and determine the possible involvements of γ-aminobutyric acid (GABA) metabolism in vivo. Sprague-Dawley male rats received daily intraperitoneal injections MnCl2 (as 6.55 mg/kg Mn body weight, five days per week for 12 weeks), followed by daily subcutaneous injections of 100, 200, or 300 mg/kg PAS-Na for an additional six weeks. Mn exposure significantly impaired spatial learning and memory ability, as noted in the Morris water maze test, and the following PAS-Na treatment successfully restored these adverse effects to levels indistinguishable from controls. Unexpectedly, PAS-Na failed to recover the Mn-induced decrease in the overall GABA levels, although PAS-Na treatment reversed Mn-induced alterations in the enzyme activities directly responsible for the synthesis and degradation of GABA (glutamate decarboxylase and GABA-transaminase, respectively). Moreover, Mn exposure caused an increase of GABA transporter 1 (GAT-1) and decrease of GABA A receptor (GABAA) in transcriptional levels, which could be reverted by the highest dose of 300 mg/kg PAS-Na treatment. In conclusion, the GABA metabolism was interrupted by sub-chronic Mn exposure. However, the PAS-Na treatment mediated protection from sub-chronic Mn exposure-induced neurotoxicity, which may not be dependent on the GABA metabolism. PMID:28394286

Impairment of probabilistic reward-based learning in schizophrenia.

PubMed

Weiler, Julia A; Bellebaum, Christian; Brüne, Martin; Juckel, Georg; Daum, Irene

2009-09-01

Recent models assume that some symptoms of schizophrenia originate from defective reward processing mechanisms. Understanding the precise nature of reward-based learning impairments might thus make an important contribution to the understanding of schizophrenia and the development of treatment strategies. The present study investigated several features of probabilistic reward-based stimulus association learning, namely the acquisition of initial contingencies, reversal learning, generalization abilities, and the effects of reward magnitude. Compared to healthy controls, individuals with schizophrenia exhibited attenuated overall performance during acquisition, whereas learning rates across blocks were similar to the rates of controls. On the group level, persons with schizophrenia were, however, unable to learn the reversal of the initial reward contingencies. Exploratory analysis of only the subgroup of individuals with schizophrenia who showed significant learning during acquisition yielded deficits in reversal learning with low reward magnitudes only. There was further evidence of a mild generalization impairment of the persons with schizophrenia in an acquired equivalence task. In summary, although there was evidence of intact basic processing of reward magnitudes, individuals with schizophrenia were impaired at using this feedback for the adaptive guidance of behavior.

Incidental Learning of Sound Categories is Impaired in Developmental Dyslexia

PubMed Central

Gabay, Yafit; Holt, Lori L.

2015-01-01

Developmental dyslexia is commonly thought to arise from specific phonological impairments. However, recent evidence is consistent with the possibility that phonological impairments arise as symptoms of an underlying dysfunction of procedural learning. The nature of the link between impaired procedural learning and phonological dysfunction is unresolved. Motivated by the observation that speech processing involves the acquisition of procedural category knowledge, the present study investigates the possibility that procedural learning impairment may affect phonological processing by interfering with the typical course of phonetic category learning. The present study tests this hypothesis while controlling for linguistic experience and possible speech-specific deficits by comparing auditory category learning across artificial, nonlinguistic sounds among dyslexic adults and matched controls in a specialized first-person shooter videogame that has been shown to engage procedural learning. Nonspeech auditory category learning was assessed online via within-game measures and also with a post-training task involving overt categorization of familiar and novel sound exemplars. Each measure reveals that dyslexic participants do not acquire procedural category knowledge as effectively as age- and cognitive-ability matched controls. This difference cannot be explained by differences in perceptual acuity for the sounds. Moreover, poor nonspeech category learning is associated with slower phonological processing. Whereas phonological processing impairments have been emphasized as the cause of dyslexia, the current results suggest that impaired auditory category learning, general in nature and not specific to speech signals, could contribute to phonological deficits in dyslexia with subsequent negative effects on language acquisition and reading. Implications for the neuro-cognitive mechanisms of developmental dyslexia are discussed. PMID:26409017

The Impact of Residual Vision in Spatial Skills of Individuals with Visual Impairments

ERIC Educational Resources Information Center

Papadopoulos, Konstantinos; Koustriava, Eleni; Kartasidou, Lefkothea

2011-01-01

Loss of vision is believed to have a great impact on the acquisition of spatial knowledge. The aims of the present study are to examine the performance of individuals with visual impairments on spatial tasks and the impact of residual vision on processing these tasks. In all, 28 individuals with visual impairments--blindness or low…

Sex effects on spatial learning but not on spatial memory retrieval in healthy young adults.

PubMed

Piber, Dominique; Nowacki, Jan; Mueller, Sven C; Wingenfeld, Katja; Otte, Christian

2018-01-15

Sex differences have been found in spatial learning and spatial memory, with several studies indicating that males outperform females. We tested in the virtual Morris Water Maze (vMWM) task, whether sex differences in spatial cognitive processes are attributable to differences in spatial learning or spatial memory retrieval in a large student sample. We tested 90 healthy students (45 women and 45 men) with a mean age of 23.5 years (SD=3.5). Spatial learning and spatial memory retrieval were measured by using the vMWM task, during which participants had to search a virtual pool for a hidden platform, facilitated by visual cues surrounding the pool. Several learning trials assessed spatial learning, while a separate probe trial assessed spatial memory retrieval. We found a significant sex effect during spatial learning, with males showing shorter latency and shorter path length, as compared to females (all p<0.001). Yet, there was no significant sex effect in spatial memory retrieval (p=0.615). Furthermore, post-hoc analyses revealed significant sex differences in spatial search strategies (p<0.05), but no difference in the number of platform crossings (p=0.375). Our results indicate that in healthy young adults, males show faster spatial learning in a virtual environment, as compared to females. Interestingly, we found no significant sex differences during spatial memory retrieval. Our study raises the question, whether men and women use different learning strategies, which nevertheless result in equal performances of spatial memory retrieval. Copyright © 2017 Elsevier B.V. All rights reserved.

Electrical Stimulation in Hippocampus and Entorhinal Cortex Impairs Spatial and Temporal Memory.

PubMed

Goyal, Abhinav; Miller, Jonathan; Watrous, Andrew J; Lee, Sang Ah; Coffey, Tom; Sperling, Michael R; Sharan, Ashwini; Worrell, Gregory; Berry, Brent; Lega, Bradley; Jobst, Barbara C; Davis, Kathryn A; Inman, Cory; Sheth, Sameer A; Wanda, Paul A; Ezzyat, Youssef; Das, Sandhitsu R; Stein, Joel; Gorniak, Richard; Jacobs, Joshua

2018-05-09

The medial temporal lobe (MTL) is widely implicated in supporting episodic memory and navigation, but its precise functional role in organizing memory across time and space remains elusive. Here we examine the specific cognitive processes implemented by MTL structures (hippocampus and entorhinal cortex) to organize memory by using electrical brain stimulation, leveraging its ability to establish causal links between brain regions and features of behavior. We studied neurosurgical patients of both sexes who performed spatial-navigation and verbal-episodic memory tasks while brain stimulation was applied in various regions during learning. During the verbal memory task, stimulation in the MTL disrupted the temporal organization of encoded memories such that items learned with stimulation tended to be recalled in a more randomized order. During the spatial task, MTL stimulation impaired subjects' abilities to remember items located far away from boundaries. These stimulation effects were specific to the MTL. Our findings thus provide the first causal demonstration in humans of the specific memory processes that are performed by the MTL to encode when and where events occurred. SIGNIFICANCE STATEMENT Numerous studies have implicated the medial temporal lobe (MTL) in encoding spatial and temporal memories, but they have not been able to causally demonstrate the nature of the cognitive processes by which this occurs in real-time. Electrical brain stimulation is able to demonstrate causal links between a brain region and a given function with high temporal precision. By examining behavior in a memory task as subjects received MTL stimulation, we provide the first causal evidence demonstrating the role of the MTL in organizing the spatial and temporal aspects of episodic memory. Copyright © 2018 the authors 0270-6474/18/384471-11$15.00/0.

Public Computer Assisted Learning Facilities for Children with Visual Impairment: Universal Design for Inclusive Learning

ERIC Educational Resources Information Center

Siu, Kin Wai Michael; Lam, Mei Seung

2012-01-01

Although computer assisted learning (CAL) is becoming increasingly popular, people with visual impairment face greater difficulty in accessing computer-assisted learning facilities. This is primarily because most of the current CAL facilities are not visually impaired friendly. People with visual impairment also do not normally have access to…

Propofol exposure during late stages of pregnancy impairs learning and memory in rat offspring via the BDNF-TrkB signalling pathway.

PubMed

Zhong, Liang; Luo, Foquan; Zhao, Weilu; Feng, Yunlin; Wu, Liuqin; Lin, Jiamei; Liu, Tianyin; Wang, Shengqiang; You, Xuexue; Zhang, Wei

2016-10-01

The brain-derived neurotrophic factor (BDNF)-tyrosine kinase B (TrkB) (BDNF-TrkB) signalling pathway plays a crucial role in regulating learning and memory. Synaptophysin provides the structural basis for synaptic plasticity and depends on BDNF processing and subsequent TrkB signalling. Our previous studies demonstrated that maternal exposure to propofol during late stages of pregnancy impaired learning and memory in rat offspring. The purpose of this study is to investigate whether the BDNF-TrkB signalling pathway is involved in propofol-induced learning and memory impairments. Propofol was intravenously infused into pregnant rats for 4 hrs on gestational day 18 (E18). Thirty days after birth, learning and memory of offspring was assessed by the Morris water maze (MWM) test. After the MWM test, BDNF and TrkB transcript and protein levels were measured in rat offspring hippocampus tissues using real-time PCR (RT-PCR) and immunohistochemistry (IHC), respectively. The levels of phosphorylated-TrkB (phospho-TrkB) and synaptophysin were measured by western blot. It was discovered that maternal exposure to propofol on day E18 impaired spatial learning and memory of rat offspring, decreased mRNA and protein levels of BDNF and TrkB, and decreased the levels of both phospho-TrkB and synaptophysin in the hippocampus. Furthermore, the TrkB agonist 7,8-dihydroxyflavone (7,8-DHF) reversed all of the observed changes. Treatment with 7,8-DHF had no significant effects on the offspring that were not exposed to propofol. The results herein indicate that maternal exposure to propofol during the late stages of pregnancy impairs spatial learning and memory of offspring by disturbing the BDNF-TrkB signalling pathway. The TrkB agonist 7,8-DHF might be a potential therapy for learning and memory impairments induced by maternal propofol exposure. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular

Enhanced long-term and impaired short-term spatial memory in GluA1 AMPA receptor subunit knockout mice: evidence for a dual-process memory model.

PubMed

Sanderson, David J; Good, Mark A; Skelton, Kathryn; Sprengel, Rolf; Seeburg, Peter H; Rawlins, J Nicholas P; Bannerman, David M

2009-06-01

The GluA1 AMPA receptor subunit is a key mediator of hippocampal synaptic plasticity and is especially important for a rapidly-induced, short-lasting form of potentiation. GluA1 gene deletion impairs hippocampus-dependent, spatial working memory, but spares hippocampus-dependent spatial reference memory. These findings may reflect the necessity of GluA1-dependent synaptic plasticity for short-term memory of recently visited places, but not for the ability to form long-term associations between a particular spatial location and an outcome. This hypothesis is in concordance with the theory that short-term and long-term memory depend on dissociable psychological processes. In this study we tested GluA1-/- mice on both short-term and long-term spatial memory using a simple novelty preference task. Mice were given a series of repeated exposures to a particular spatial location (the arm of a Y-maze) before their preference for a novel spatial location (the unvisited arm of the maze) over the familiar spatial location was assessed. GluA1-/- mice were impaired if the interval between the trials was short (1 min), but showed enhanced spatial memory if the interval between the trials was long (24 h). This enhancement was caused by the interval between the exposure trials rather than the interval prior to the test, thus demonstrating enhanced learning and not simply enhanced performance or expression of memory. This seemingly paradoxical enhancement of hippocampus-dependent spatial learning may be caused by GluA1 gene deletion reducing the detrimental effects of short-term memory on subsequent long-term learning. Thus, these results support a dual-process model of memory in which short-term and long-term memory are separate and sometimes competitive processes.

Do Low-Effort Learning Strategies Mediate Impaired Memory in ADHD?

ERIC Educational Resources Information Center

Egeland, Jens; Johansen, Susanne Nordby; Ueland, Torill

2010-01-01

As a group, participants with attention-deficit/hyperactivity disorder (ADHD) are impaired in academic performance and learning. This may be due to a mild intellectual impairment, impaired attention, or inability to allocate sufficient effort. If the latter is the case, this should be evident in the learning strategies applied. Four indices of…

Incidental learning of sound categories is impaired in developmental dyslexia.

PubMed

Gabay, Yafit; Holt, Lori L

2015-12-01

Developmental dyslexia is commonly thought to arise from specific phonological impairments. However, recent evidence is consistent with the possibility that phonological impairments arise as symptoms of an underlying dysfunction of procedural learning. The nature of the link between impaired procedural learning and phonological dysfunction is unresolved. Motivated by the observation that speech processing involves the acquisition of procedural category knowledge, the present study investigates the possibility that procedural learning impairment may affect phonological processing by interfering with the typical course of phonetic category learning. The present study tests this hypothesis while controlling for linguistic experience and possible speech-specific deficits by comparing auditory category learning across artificial, nonlinguistic sounds among dyslexic adults and matched controls in a specialized first-person shooter videogame that has been shown to engage procedural learning. Nonspeech auditory category learning was assessed online via within-game measures and also with a post-training task involving overt categorization of familiar and novel sound exemplars. Each measure reveals that dyslexic participants do not acquire procedural category knowledge as effectively as age- and cognitive-ability matched controls. This difference cannot be explained by differences in perceptual acuity for the sounds. Moreover, poor nonspeech category learning is associated with slower phonological processing. Whereas phonological processing impairments have been emphasized as the cause of dyslexia, the current results suggest that impaired auditory category learning, general in nature and not specific to speech signals, could contribute to phonological deficits in dyslexia with subsequent negative effects on language acquisition and reading. Implications for the neuro-cognitive mechanisms of developmental dyslexia are discussed. Copyright © 2015 Elsevier Ltd. All rights

Connecting mathematics learning through spatial reasoning

NASA Astrophysics Data System (ADS)

Mulligan, Joanne; Woolcott, Geoffrey; Mitchelmore, Michael; Davis, Brent

2018-03-01

Spatial reasoning, an emerging transdisciplinary area of interest to mathematics education research, is proving integral to all human learning. It is particularly critical to science, technology, engineering and mathematics (STEM) fields. This project will create an innovative knowledge framework based on spatial reasoning that identifies new pathways for mathematics learning, pedagogy and curriculum. Novel analytical tools will map the unknown complex systems linking spatial and mathematical concepts. It will involve the design, implementation and evaluation of a Spatial Reasoning Mathematics Program (SRMP) in Grades 3 to 5. Benefits will be seen through development of critical spatial skills for students, increased teacher capability and informed policy and curriculum across STEM education.

Impaired learning of event frequencies in tone deafness

PubMed Central

Loui, Psyche; Schlaug, Gottfried

2013-01-01

Musical knowledge is ubiquitous, effortless, and implicitly acquired all over the world via exposure to musical materials in one’s culture. In contrast, one group of individuals who show insensitivity to music, specifically the inability to discriminate pitches and melodies, is the tone-deaf. In this study, we asked whether difficulties in pitch and melody discrimination among the tone-deaf could be related to learning difficulties, and, if so, what processes of learning might be affected in the tone-deaf. We investigated the learning of frequency information in a new musical system in tone-deaf individuals and matched controls. Results showed significantly impaired learning abilities in frequency matching in the tone-deaf. This impairment was positively correlated with the severity of tone deafness as assessed by the Montreal Battery for Evaluation of Amusia. Taken together, the results suggest that tone deafness is characterized by an impaired ability to acquire frequency information from pitched materials in the sound environment. PMID:22524379

Impaired learning of event frequencies in tone deafness.

PubMed

Loui, Psyche; Schlaug, Gottfried

2012-04-01

Musical knowledge is ubiquitous, effortless, and implicitly acquired all over the world via exposure to musical materials in one's culture. In contrast, one group of individuals who show insensitivity to music, specifically the inability to discriminate pitches and melodies, is the tone-deaf. In this study, we asked whether difficulties in pitch and melody discrimination among the tone-deaf could be related to learning difficulties, and, if so, what processes of learning might be affected in the tone-deaf. We investigated the learning of frequency information in a new musical system in tone-deaf individuals and matched controls. Results showed significantly impaired learning abilities in frequency matching in the tone-deaf. This impairment was positively correlated with the severity of tone deafness as assessed by the Montreal Battery for Evaluation of Amusia. Taken together, the results suggest that tone deafness is characterized by an impaired ability to acquire frequency information from pitched materials in the sound environment. © 2012 New York Academy of Sciences.

Striatal degeneration impairs language learning: evidence from Huntington's disease.

PubMed

De Diego-Balaguer, R; Couette, M; Dolbeau, G; Dürr, A; Youssov, K; Bachoud-Lévi, A-C

2008-11-01

Although the role of the striatum in language processing is still largely unclear, a number of recent proposals have outlined its specific contribution. Different studies report evidence converging to a picture where the striatum may be involved in those aspects of rule-application requiring non-automatized behaviour. This is the main characteristic of the earliest phases of language acquisition that require the online detection of distant dependencies and the creation of syntactic categories by means of rule learning. Learning of sequences and categorization processes in non-language domains has been known to require striatal recruitment. Thus, we hypothesized that the striatum should play a prominent role in the extraction of rules in learning a language. We studied 13 pre-symptomatic gene-carriers and 22 early stage patients of Huntington's disease (pre-HD), both characterized by a progressive degeneration of the striatum and 21 late stage patients Huntington's disease (18 stage II, two stage III and one stage IV) where cortical degeneration accompanies striatal degeneration. When presented with a simplified artificial language where words and rules could be extracted, early stage Huntington's disease patients (stage I) were impaired in the learning test, demonstrating a greater impairment in rule than word learning compared to the 20 age- and education-matched controls. Huntington's disease patients at later stages were impaired both on word and rule learning. While spared in their overall performance, gene-carriers having learned a set of abstract artificial language rules were then impaired in the transfer of those rules to similar artificial language structures. The correlation analyses among several neuropsychological tests assessing executive function showed that rule learning correlated with tests requiring working memory and attentional control, while word learning correlated with a test involving episodic memory. These learning impairments significantly

Ketogenic diet improves the spatial memory impairment caused by exposure to hypobaric hypoxia through increased acetylation of histones in rats.

PubMed

Zhao, Ming; Huang, Xin; Cheng, Xiang; Lin, Xiao; Zhao, Tong; Wu, Liying; Yu, Xiaodan; Wu, Kuiwu; Fan, Ming; Zhu, Lingling

2017-01-01

Exposure to hypobaric hypoxia causes neuron cell damage, resulting in impaired cognitive function. Effective interventions to antagonize hypobaric hypoxia-induced memory impairment are in urgent need. Ketogenic diet (KD) has been successfully used to treat drug-resistant epilepsy and improves cognitive behaviors in epilepsy patients and other pathophysiological animal models. In the present study, we aimed to explore the potential beneficial effects of a KD on memory impairment caused by hypobaric hypoxia and the underlying possible mechanisms. We showed that the KD recipe used was ketogenic and increased plasma levels of ketone bodies, especially β-hydroxybutyrate. The results of the behavior tests showed that the KD did not affect general locomotor activity but obviously promoted spatial learning. Moreover, the KD significantly improved the spatial memory impairment caused by hypobaric hypoxia (simulated altitude of 6000 m, 24 h). In addition, the improving-effect of KD was mimicked by intraperitoneal injection of BHB. The western blot and immunohistochemistry results showed that KD treatment not only increased the acetylated levels of histone H3 and histone H4 compared to that of the control group but also antagonized the decrease in the acetylated histone H3 and H4 when exposed to hypobaric hypoxia. Furthermore, KD-hypoxia treatment also promoted PKA/CREB activation and BDNF protein expression compared to the effects of hypoxia alone. These results demonstrated that KD is a promising strategy to improve spatial memory impairment caused by hypobaric hypoxia, in which increased modification of histone acetylation plays an important role.

Working memory contributions to reinforcement learning impairments in schizophrenia.

PubMed

Collins, Anne G E; Brown, Jaime K; Gold, James M; Waltz, James A; Frank, Michael J

2014-10-08

Previous research has shown that patients with schizophrenia are impaired in reinforcement learning tasks. However, behavioral learning curves in such tasks originate from the interaction of multiple neural processes, including the basal ganglia- and dopamine-dependent reinforcement learning (RL) system, but also prefrontal cortex-dependent cognitive strategies involving working memory (WM). Thus, it is unclear which specific system induces impairments in schizophrenia. We recently developed a task and computational model allowing us to separately assess the roles of RL (slow, cumulative learning) mechanisms versus WM (fast but capacity-limited) mechanisms in healthy adult human subjects. Here, we used this task to assess patients' specific sources of impairments in learning. In 15 separate blocks, subjects learned to pick one of three actions for stimuli. The number of stimuli to learn in each block varied from two to six, allowing us to separate influences of capacity-limited WM from the incremental RL system. As expected, both patients (n = 49) and healthy controls (n = 36) showed effects of set size and delay between stimulus repetitions, confirming the presence of working memory effects. Patients performed significantly worse than controls overall, but computational model fits and behavioral analyses indicate that these deficits could be entirely accounted for by changes in WM parameters (capacity and reliability), whereas RL processes were spared. These results suggest that the working memory system contributes strongly to learning impairments in schizophrenia. Copyright © 2014 the authors 0270-6474/14/3413747-10$15.00/0.

Working Memory Contributions to Reinforcement Learning Impairments in Schizophrenia

PubMed Central

Brown, Jaime K.; Gold, James M.; Waltz, James A.; Frank, Michael J.

2014-01-01

Previous research has shown that patients with schizophrenia are impaired in reinforcement learning tasks. However, behavioral learning curves in such tasks originate from the interaction of multiple neural processes, including the basal ganglia- and dopamine-dependent reinforcement learning (RL) system, but also prefrontal cortex-dependent cognitive strategies involving working memory (WM). Thus, it is unclear which specific system induces impairments in schizophrenia. We recently developed a task and computational model allowing us to separately assess the roles of RL (slow, cumulative learning) mechanisms versus WM (fast but capacity-limited) mechanisms in healthy adult human subjects. Here, we used this task to assess patients' specific sources of impairments in learning. In 15 separate blocks, subjects learned to pick one of three actions for stimuli. The number of stimuli to learn in each block varied from two to six, allowing us to separate influences of capacity-limited WM from the incremental RL system. As expected, both patients (n = 49) and healthy controls (n = 36) showed effects of set size and delay between stimulus repetitions, confirming the presence of working memory effects. Patients performed significantly worse than controls overall, but computational model fits and behavioral analyses indicate that these deficits could be entirely accounted for by changes in WM parameters (capacity and reliability), whereas RL processes were spared. These results suggest that the working memory system contributes strongly to learning impairments in schizophrenia. PMID:25297101

Impaired associative learning with food rewards in obese women.

PubMed

Zhang, Zhihao; Manson, Kirk F; Schiller, Daniela; Levy, Ifat

2014-08-04

Obesity is a major epidemic in many parts of the world. One of the main factors contributing to obesity is overconsumption of high-fat and high-calorie food, which is driven by the rewarding properties of these types of food. Previous studies have suggested that dysfunction in reward circuits may be associated with overeating and obesity. The nature of this dysfunction, however, is still unknown. Here, we demonstrate impairment in reward-based associative learning specific to food in obese women. Normal-weight and obese participants performed an appetitive reversal learning task in which they had to learn and modify cue-reward associations. To test whether any learning deficits were specific to food reward or were more general, we used a between-subject design in which half of the participants received food reward and the other half received money reward. Our results reveal a marked difference in associative learning between normal-weight and obese women when food was used as reward. Importantly, no learning deficits were observed with money reward. Multiple regression analyses also established a robust negative association between body mass index and learning performance in the food domain in female participants. Interestingly, such impairment was not observed in obese men. These findings suggest that obesity may be linked to impaired reward-based associative learning and that this impairment may be specific to the food domain. Copyright © 2014 Elsevier Ltd. All rights reserved.

Antidepressant suppression of non-REM sleep spindles and REM sleep impairs hippocampus-dependent learning while augmenting striatum-dependent learning.

PubMed

Watts, Alain; Gritton, Howard J; Sweigart, Jamie; Poe, Gina R

2012-09-26

Rapid eye movement (REM) sleep enhances hippocampus-dependent associative memory, but REM deprivation has little impact on striatum-dependent procedural learning. Antidepressant medications are known to inhibit REM sleep, but it is not well understood if antidepressant treatments impact learning and memory. We explored antidepressant REM suppression effects on learning by training animals daily on a spatial task under familiar and novel conditions, followed by training on a procedural memory task. Daily treatment with the antidepressant and norepinephrine reuptake inhibitor desipramine (DMI) strongly suppressed REM sleep in rats for several hours, as has been described in humans. We also found that DMI treatment reduced the spindle-rich transition-to-REM sleep state (TR), which has not been previously reported. DMI REM suppression gradually weakened performance on a once familiar hippocampus-dependent maze (reconsolidation error). DMI also impaired learning of the novel maze (consolidation error). Unexpectedly, learning of novel reward positions and memory of familiar positions were equally and oppositely correlated with amounts of TR sleep. Conversely, DMI treatment enhanced performance on a separate striatum-dependent, procedural T-maze task that was positively correlated with the amounts of slow-wave sleep (SWS). Our results suggest that learning strategy switches in patients taking REM sleep-suppressing antidepressants might serve to offset sleep-dependent hippocampal impairments to partially preserve performance. State-performance correlations support a model wherein reconsolidation of hippocampus-dependent familiar memories occurs during REM sleep, novel information is incorporated and consolidated during TR, and dorsal striatum-dependent procedural learning is augmented during SWS.

Antidepressant Suppression of Non-REM Sleep Spindles and REM Sleep Impairs Hippocampus-Dependent Learning While Augmenting Striatum-Dependent Learning

PubMed Central

Watts, Alain; Gritton, Howard J.; Sweigart, Jamie

2012-01-01

Rapid eye movement (REM) sleep enhances hippocampus-dependent associative memory, but REM deprivation has little impact on striatum-dependent procedural learning. Antidepressant medications are known to inhibit REM sleep, but it is not well understood if antidepressant treatments impact learning and memory. We explored antidepressant REM suppression effects on learning by training animals daily on a spatial task under familiar and novel conditions, followed by training on a procedural memory task. Daily treatment with the antidepressant and norepinephrine reuptake inhibitor desipramine (DMI) strongly suppressed REM sleep in rats for several hours, as has been described in humans. We also found that DMI treatment reduced the spindle-rich transition-to-REM sleep state (TR), which has not been previously reported. DMI REM suppression gradually weakened performance on a once familiar hippocampus-dependent maze (reconsolidation error). DMI also impaired learning of the novel maze (consolidation error). Unexpectedly, learning of novel reward positions and memory of familiar positions were equally and oppositely correlated with amounts of TR sleep. Conversely, DMI treatment enhanced performance on a separate striatum-dependent, procedural T-maze task that was positively correlated with the amounts of slow-wave sleep (SWS). Our results suggest that learning strategy switches in patients taking REM sleep-suppressing antidepressants might serve to offset sleep-dependent hippocampal impairments to partially preserve performance. State–performance correlations support a model wherein reconsolidation of hippocampus-dependent familiar memories occurs during REM sleep, novel information is incorporated and consolidated during TR, and dorsal striatum-dependent procedural learning is augmented during SWS. PMID:23015432

Racial stereotypes impair flexibility of emotional learning

PubMed Central

Kubota, Jennifer T.; Li, Jian; Coelho, Cesar A.O.; Phelps, Elizabeth A.

2016-01-01

Flexibility of associative learning can be revealed by establishing and then reversing cue-outcome discriminations. Here, we used functional MRI to examine whether neurobehavioral correlates of reversal-learning are impaired in White and Asian volunteers when initial learning involves fear-conditioning to a racial out-group. For one group, the picture of a Black male was initially paired with shock (threat) and a White male was unpaired (safe). For another group, the White male was a threat and the Black male was safe. These associations reversed midway through the task. Both groups initially discriminated threat from safety, as expressed through skin conductance responses (SCR) and activity in the insula, thalamus, midbrain and striatum. After reversal, the group initially conditioned to a Black male exhibited impaired reversal of SCRs to the new threat stimulus (White male), and impaired reversals in the striatum, anterior cingulate cortex, midbrain and thalamus. In contrast, the group initially conditioned to a White male showed successful reversal of SCRs and successful reversal in these brain regions toward the new threat. These findings provide new evidence that an aversive experience with a racial out-group member impairs the ability to flexibly and appropriately adjust fear expression towards a new threat in the environment. PMID:27107298

Individual variations in dose response for spatial memory learning among outbred wistar rats exposed from 5 to 20 cGy of (56) Fe particles.

PubMed

Wyrobek, Andrew J; Britten, Richard A

2016-06-01

Exposures of brain tissue to ionizing radiation can lead to persistent deficits in cognitive functions and behaviors. However, little is known about the quantitative relationships between exposure dose and neurological risks, especially for lower doses and among genetically diverse individuals. We investigated the dose relationship for spatial memory learning among genetically outbred male Wistar rats exposed to graded doses of (56) Fe particles (sham, 5, 10, 15, and 20 cGy; 1 GeV/n). Spatial memory learning was assessed on a Barnes maze using REL3 ratios measured at three months after exposure. Irradiated animals showed dose-dependent declines in spatial memory learning that were fit by a linear regression (P for slope <0.0002). The irradiated animals showed significantly impaired learning at 10 cGy exposures, no detectable learning between 10 and 15 cGy, and worsened performances between 15 and 20 cGy. The proportions of poor learners and the magnitude of their impairment were fit by linear regressions with doubling doses of ∼10 cGy. In contrast, there were no detectable deficits in learning among the good learners in this dose range. Our findings suggest that genetically diverse individuals can vary substantially in their spatial memory learning, and that exposures at low doses appear to preferentially impact poor learners. This hypothesis invites future investigations of the genetic and physiological mechanisms of inter-individual variations in brain function related to spatial memory learning after low-dose HZE radiation exposures and to determine whether it also applies to physical trauma to brain tissue and exposures to chemical neurotoxicants. Environ. Mol. Mutagen. 57:331-340, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Perinatal exposure to bisphenol-A impairs spatial memory through upregulation of neurexin1 and neuroligin3 expression in male mouse brain.

PubMed

Kumar, Dhiraj; Thakur, Mahendra Kumar

2014-01-01

Bisphenol-A (BPA), a well known endocrine disruptor, impairs learning and memory in rodents. However, the underlying molecular mechanism of BPA induced impairment in learning and memory is not well known. As synaptic plasticity is the cellular basis of memory, the present study investigated the effect of perinatal exposure to BPA on the expression of synaptic proteins neurexin1 (Nrxn1) and neuroligin3 (Nlgn3), dendritic spine density and spatial memory in postnatal male mice. The pregnant mice were orally administered BPA (50 µg/kgbw/d) from gestation day (GD) 7 to postnatal day (PND) 21 and sesame oil was used as a vehicle control. In Morris water maze (MWM) test, BPA extended the escape latency time to locate the hidden platform in 8 weeks male mice. RT-PCR and Immunoblotting results showed significant upregulation of Nrxn1 and Nlgn3 expression in both cerebral cortex and hippocampus of 3 and 8 weeks male mice. This was further substantiated by in-situ hybridization and immunofluorescence techniques. BPA also significantly increased the density of dendritic spines in both regions, as analyzed by rapid Golgi staining. Thus our data suggest that perinatal exposure to BPA impairs spatial memory through upregulation of expression of synaptic proteins Nrxn1 and Nlgn3 and increased dendritic spine density in cerebral cortex and hippocampus of postnatal male mice.

Perinatal Exposure to Bisphenol-A Impairs Spatial Memory through Upregulation of Neurexin1 and Neuroligin3 Expression in Male Mouse Brain

PubMed Central

Kumar, Dhiraj; Thakur, Mahendra Kumar

2014-01-01

Bisphenol-A (BPA), a well known endocrine disruptor, impairs learning and memory in rodents. However, the underlying molecular mechanism of BPA induced impairment in learning and memory is not well known. As synaptic plasticity is the cellular basis of memory, the present study investigated the effect of perinatal exposure to BPA on the expression of synaptic proteins neurexin1 (Nrxn1) and neuroligin3 (Nlgn3), dendritic spine density and spatial memory in postnatal male mice. The pregnant mice were orally administered BPA (50 µg/kgbw/d) from gestation day (GD) 7 to postnatal day (PND) 21 and sesame oil was used as a vehicle control. In Morris water maze (MWM) test, BPA extended the escape latency time to locate the hidden platform in 8 weeks male mice. RT-PCR and Immunoblotting results showed significant upregulation of Nrxn1 and Nlgn3 expression in both cerebral cortex and hippocampus of 3 and 8 weeks male mice. This was further substantiated by in-situ hybridization and immunofluorescence techniques. BPA also significantly increased the density of dendritic spines in both regions, as analyzed by rapid Golgi staining. Thus our data suggest that perinatal exposure to BPA impairs spatial memory through upregulation of expression of synaptic proteins Nrxn1 and Nlgn3 and increased dendritic spine density in cerebral cortex and hippocampus of postnatal male mice. PMID:25330104

Frontotemporal Dementia Selectively Impairs Transitive Reasoning About Familiar Spatial Environments

PubMed Central

Vartanian, Oshin; Goel, Vinod; Tierney, Michael; Huey, Edward D.; Grafman, Jordan

2010-01-01

Although patients with frontotemporal dementia (FTD) are known to exhibit a wide range of cognitive and personality difficulties, some evidence suggests that there may be a degree of selectivity in their reasoning impairments. Based on a recent review of the neuroimaging literature on reasoning, the authors hypothesized that the presence or absence of familiar content may have a selective impact on the reasoning abilities of patients with FTD. Specifically, the authors predicted that patients with frontalvariant FTD would be more impaired when reasoning about transitive arguments involving familiar spatial environments than when reasoning about identical logical arguments involving unfamiliar spatial environments. As predicted, patients with FTD were less accurate than normal controls only when the content of arguments involved familiar spatial environments. These results indicate a degree of selectivity in the cognitive deficits of this patient population and suggest that the frontal-temporal lobe system may play a necessary role in reasoning about familiar material. PMID:19702415

Image jitter enhances visual performance when spatial resolution is impaired.

PubMed

Watson, Lynne M; Strang, Niall C; Scobie, Fraser; Love, Gordon D; Seidel, Dirk; Manahilov, Velitchko

2012-09-06

Visibility of low-spatial frequency stimuli improves when their contrast is modulated at 5 to 10 Hz compared with stationary stimuli. Therefore, temporal modulations of visual objects could enhance the performance of low vision patients who primarily perceive images of low-spatial frequency content. We investigated the effect of retinal-image jitter on word recognition speed and facial emotion recognition in subjects with central visual impairment. Word recognition speed and accuracy of facial emotion discrimination were measured in volunteers with AMD under stationary and jittering conditions. Computer-driven and optoelectronic approaches were used to induce retinal-image jitter with duration of 100 or 166 ms and amplitude within the range of 0.5 to 2.6° visual angle. Word recognition speed was also measured for participants with simulated (Bangerter filters) visual impairment. Text jittering markedly enhanced word recognition speed for people with severe visual loss (101 ± 25%), while for those with moderate visual impairment, this effect was weaker (19 ± 9%). The ability of low vision patients to discriminate the facial emotions of jittering images improved by a factor of 2. A prototype of optoelectronic jitter goggles produced similar improvement in facial emotion discrimination. Word recognition speed in participants with simulated visual impairment was enhanced for interjitter intervals over 100 ms and reduced for shorter intervals. Results suggest that retinal-image jitter with optimal frequency and amplitude is an effective strategy for enhancing visual information processing in the absence of spatial detail. These findings will enable the development of novel tools to improve the quality of life of low vision patients.

Indoor Spatial Updating With Impaired Vision

PubMed Central

Legge, Gordon E.; Granquist, Christina; Baek, Yihwa; Gage, Rachel

2016-01-01

Purpose Spatial updating is the ability to keep track of position and orientation while moving through an environment. We asked how normally sighted and visually impaired subjects compare in spatial updating and in estimating room dimensions. Methods Groups of 32 normally sighted, 16 low-vision, and 16 blind subjects estimated the dimensions of six rectangular rooms. Updating was assessed by guiding the subjects along three-segment paths in the rooms. At the end of each path, they estimated the distance and direction to the starting location, and to a designated target. Spatial updating was tested in five conditions ranging from free viewing to full auditory and visual deprivation. Results The normally sighted and low-vision groups did not differ in their accuracy for judging room dimensions. Correlations between estimated size and physical size were high. Accuracy of low-vision performance was not correlated with acuity, contrast sensitivity, or field status. Accuracy was lower for the blind subjects. The three groups were very similar in spatial-updating performance, and exhibited only weak dependence on the nature of the viewing conditions. Conclusions People with a wide range of low-vision conditions are able to judge room dimensions as accurately as people with normal vision. Blind subjects have difficulty in judging the dimensions of quiet rooms, but some information is available from echolocation. Vision status has little impact on performance in simple spatial updating; proprioceptive and vestibular cues are sufficient. PMID:27978556

Indoor Spatial Updating With Impaired Vision.

PubMed

Legge, Gordon E; Granquist, Christina; Baek, Yihwa; Gage, Rachel

2016-12-01

Spatial updating is the ability to keep track of position and orientation while moving through an environment. We asked how normally sighted and visually impaired subjects compare in spatial updating and in estimating room dimensions. Groups of 32 normally sighted, 16 low-vision, and 16 blind subjects estimated the dimensions of six rectangular rooms. Updating was assessed by guiding the subjects along three-segment paths in the rooms. At the end of each path, they estimated the distance and direction to the starting location, and to a designated target. Spatial updating was tested in five conditions ranging from free viewing to full auditory and visual deprivation. The normally sighted and low-vision groups did not differ in their accuracy for judging room dimensions. Correlations between estimated size and physical size were high. Accuracy of low-vision performance was not correlated with acuity, contrast sensitivity, or field status. Accuracy was lower for the blind subjects. The three groups were very similar in spatial-updating performance, and exhibited only weak dependence on the nature of the viewing conditions. People with a wide range of low-vision conditions are able to judge room dimensions as accurately as people with normal vision. Blind subjects have difficulty in judging the dimensions of quiet rooms, but some information is available from echolocation. Vision status has little impact on performance in simple spatial updating; proprioceptive and vestibular cues are sufficient.

Toxin-Induced Experimental Models of Learning and Memory Impairment

PubMed Central

More, Sandeep Vasant; Kumar, Hemant; Cho, Duk-Yeon; Yun, Yo-Sep; Choi, Dong-Kug

2016-01-01

Animal models for learning and memory have significantly contributed to novel strategies for drug development and hence are an imperative part in the assessment of therapeutics. Learning and memory involve different stages including acquisition, consolidation, and retrieval and each stage can be characterized using specific toxin. Recent studies have postulated the molecular basis of these processes and have also demonstrated many signaling molecules that are involved in several stages of memory. Most insights into learning and memory impairment and to develop a novel compound stems from the investigations performed in experimental models, especially those produced by neurotoxins models. Several toxins have been utilized based on their mechanism of action for learning and memory impairment such as scopolamine, streptozotocin, quinolinic acid, and domoic acid. Further, some toxins like 6-hydroxy dopamine (6-OHDA), 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and amyloid-β are known to cause specific learning and memory impairment which imitate the disease pathology of Parkinson’s disease dementia and Alzheimer’s disease dementia. Apart from these toxins, several other toxins come under a miscellaneous category like an environmental pollutant, snake venoms, botulinum, and lipopolysaccharide. This review will focus on the various classes of neurotoxin models for learning and memory impairment with their specific mechanism of action that could assist the process of drug discovery and development for dementia and cognitive disorders. PMID:27598124

Toxin-Induced Experimental Models of Learning and Memory Impairment.

PubMed

More, Sandeep Vasant; Kumar, Hemant; Cho, Duk-Yeon; Yun, Yo-Sep; Choi, Dong-Kug

2016-09-01

Animal models for learning and memory have significantly contributed to novel strategies for drug development and hence are an imperative part in the assessment of therapeutics. Learning and memory involve different stages including acquisition, consolidation, and retrieval and each stage can be characterized using specific toxin. Recent studies have postulated the molecular basis of these processes and have also demonstrated many signaling molecules that are involved in several stages of memory. Most insights into learning and memory impairment and to develop a novel compound stems from the investigations performed in experimental models, especially those produced by neurotoxins models. Several toxins have been utilized based on their mechanism of action for learning and memory impairment such as scopolamine, streptozotocin, quinolinic acid, and domoic acid. Further, some toxins like 6-hydroxy dopamine (6-OHDA), 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and amyloid-β are known to cause specific learning and memory impairment which imitate the disease pathology of Parkinson's disease dementia and Alzheimer's disease dementia. Apart from these toxins, several other toxins come under a miscellaneous category like an environmental pollutant, snake venoms, botulinum, and lipopolysaccharide. This review will focus on the various classes of neurotoxin models for learning and memory impairment with their specific mechanism of action that could assist the process of drug discovery and development for dementia and cognitive disorders.

Impaired Statistical Learning in Developmental Dyslexia

PubMed Central

Thiessen, Erik D.; Holt, Lori L.

2015-01-01

Purpose Developmental dyslexia (DD) is commonly thought to arise from phonological impairments. However, an emerging perspective is that a more general procedural learning deficit, not specific to phonological processing, may underlie DD. The current study examined if individuals with DD are capable of extracting statistical regularities across sequences of passively experienced speech and nonspeech sounds. Such statistical learning is believed to be domain-general, to draw upon procedural learning systems, and to relate to language outcomes. Method DD and control groups were familiarized with a continuous stream of syllables or sine-wave tones, the ordering of which was defined by high or low transitional probabilities across adjacent stimulus pairs. Participants subsequently judged two 3-stimulus test items with either high or low statistical coherence as being the most similar to the sounds heard during familiarization. Results As with control participants, the DD group was sensitive to the transitional probability structure of the familiarization materials as evidenced by above-chance performance. However, the performance of participants with DD was significantly poorer than controls across linguistic and nonlinguistic stimuli. In addition, reading-related measures were significantly correlated with statistical learning performance of both speech and nonspeech material. Conclusion Results are discussed in light of procedural learning impairments among participants with DD. PMID:25860795

Impairments in Learning Due to Motivational Conflict: Situation Really Matters

ERIC Educational Resources Information Center

Brassler, Nina K.; Grund, Axel; Hilckmann, Kristina; Fries, Stefan

2016-01-01

Although many theories mention distractions by conflicting alternatives as a problem for self-regulation, motivational conflicts are rarely considered when explaining impairments in learning. In two studies, we investigate the assumption of motivational interference theory that students show different amounts of impairments in learning depending…

The perirhinal cortex of the rat is necessary for spatial memory retention long after but not soon after learning.

PubMed

Ramos, Juan M J; Vaquero, Joaquín M M

2005-09-15

Many observations in humans and experimental animals support the view that the hippocampus is critical immediately after learning in order for long-term memory formation to take place. However, exactly when the medial temporal cortices adjacent to the hippocampus are necessary for this process to occur normally is not yet well known. Using a spatial task, we studied whether the perirhinal cortex of rats is necessary to establish representations in long-term memory. Results showed that, in a spatial task sensitive to hippocampal lesions, control and perirhinal lesioned rats can both learn at the same rate (Experiment 1). Interestingly, a differential involvement of the perirhinal cortex in memory retention was observed as time passes after learning. Thus, 24 days following the end of learning, lesioned and control rats remembered the task perfectly as measured by a retraining test. In contrast, 74 days after the learning the perirhinal animals showed a profound impairment in the retention of the spatial information (Experiment 2). Taken together, these results suggest that the perirhinal region is critical for the formation of long-term spatial memory. However, its contribution to memory formation and retention is time-dependent, it being necessary only long after learning takes place and not during the phase immediately following acquisition.

Learning outdoors: male lizards show flexible spatial learning under semi-natural conditions

PubMed Central

Noble, Daniel W. A.; Carazo, Pau; Whiting, Martin J.

2012-01-01

Spatial cognition is predicted to be a fundamental component of fitness in many lizard species, and yet some studies suggest that it is relatively slow and inflexible. However, such claims are based on work conducted using experimental designs or in artificial contexts that may underestimate their cognitive abilities. We used a biologically realistic experimental procedure (using simulated predatory attacks) to study spatial learning and its flexibility in the lizard Eulamprus quoyii in semi-natural outdoor enclosures under similar conditions to those experienced by lizards in the wild. To evaluate the flexibility of spatial learning, we conducted a reversal spatial-learning task in which positive and negative reinforcements of learnt spatial stimuli were switched. Nineteen (32%) male lizards learnt both tasks within 10 days (spatial task mean: 8.16 ± 0.69 (s.e.) and reversal spatial task mean: 10.74 ± 0.98 (s.e.) trials). We demonstrate that E. quoyii are capable of flexible spatial learning and suggest that future studies focus on a range of lizard species which differ in phylogeny and/or ecology, using biologically relevant cognitive tasks, in an effort to bridge the cognitive divide between ecto- and endotherms. PMID:23075525

Poststroke Hemiparesis Impairs the Rate but not Magnitude of Adaptation of Spatial and Temporal Locomotor Features

PubMed Central

Savin, Douglas N.; Tseng, Shih-Chiao; Whitall, Jill; Morton, Susanne M.

2015-01-01

Background Persons with stroke and hemiparesis walk with a characteristic pattern of spatial and temporal asymmetry that is resistant to most traditional interventions. It was recently shown in nondisabled persons that the degree of walking symmetry can be readily altered via locomotor adaptation. However, it is unclear whether stroke-related brain damage affects the ability to adapt spatial or temporal gait symmetry. Objective Determine whether locomotor adaptation to a novel swing phase perturbation is impaired in persons with chronic stroke and hemiparesis. Methods Participants with ischemic stroke (14) and nondisabled controls (12) walked on a treadmill before, during, and after adaptation to a unilateral perturbing weight that resisted forward leg movement. Leg kinematics were measured bilaterally, including step length and single-limb support (SLS) time symmetry, limb angle center of oscillation, and interlimb phasing, and magnitude of “initial” and “late” locomotor adaptation rates were determined. Results All participants had similar magnitudes of adaptation and similar initial adaptation rates both spatially and temporally. All 14 participants with stroke and baseline asymmetry temporarily walked with improved SLS time symmetry after adaptation. However, late adaptation rates poststroke were decreased (took more strides to achieve adaptation) compared with controls. Conclusions Mild to moderate hemiparesis does not interfere with the initial acquisition of novel symmetrical gait patterns in both the spatial and temporal domains, though it does disrupt the rate at which “late” adaptive changes are produced. Impairment of the late, slow phase of learning may be an important rehabilitation consideration in this patient population. PMID:22367915

Reversibility of object recognition but not spatial memory impairment following binge-like alcohol exposure in rats

PubMed Central

Cippitelli, Andrea; Zook, Michelle; Bell, Lauren; Damadzic, Ruslan; Eskay, Robert L.; Schwandt, Melanie; Heilig, Markus

2010-01-01

Excessive alcohol use leads to neurodegeneration in several brain structures including the hippocampal dentate gyrus and the entorhinal cortex. Cognitive deficits that result are among the most insidious and debilitating consequences of alcoholism. The object exploration task (OET) provides a sensitive measurement of spatial memory impairment induced by hippocampal and cortical damage. In this study, we examine whether the observed neurotoxicity produced by a 4-day binge ethanol treatment results in long-term memory impairment by observing the time course of reactions to spatial change (object configuration) and non-spatial change (object recognition). Wistar rats were assessed for their abilities to detect spatial configuration in the OET at 1 week and 10 weeks following the ethanol treatment, in which ethanol groups received 9–15 g/kg/day and achieved blood alcohol levels over 300 mg/dl. At 1 week, results indicated that the binge alcohol treatment produced impairment in both spatial memory and non-spatial object recognition performance. Unlike the controls, ethanol treated rats did not increase the duration or number of contacts with the displaced object in the spatial memory task, nor did they increase the duration of contacts with the novel object in the object recognition task. After 10 weeks, spatial memory remained impaired in the ethanol treated rats but object recognition ability was recovered. Our data suggest that episodes of binge-like alcohol exposure result in long-term and possibly permanent impairments in memory for the configuration of objects during exploration, whereas the ability to detect non-spatial changes is only temporarily affected. PMID:20849966

Impairments of spatial working memory and attention following acute psychosocial stress.

PubMed

Olver, James S; Pinney, Myra; Maruff, Paul; Norman, Trevor R

2015-04-01

Few studies have investigated the effect of an acute psychosocial stress paradigm on impaired attention and working memory in humans. Further, the duration of any stress-related cognitive impairment remains unclear. The aim of this study was to examine the effect of an acute psychosocial stress paradigm, the Trier Social Stress, on cognitive function in healthy volunteers. Twenty-three healthy male and female subjects were exposed to an acute psychosocial stress task. Physiological measures (salivary cortisol, heart rate and blood pressure) and subjective stress ratings were measured at baseline, in anticipation of stress, immediately post-stress and after a period of rest. A neuropsychological test battery including spatial working memory and verbal memory was administered at each time point. Acute psychosocial stress produced significant increases in cardiovascular and subjective measures in the anticipatory and post-stress period, which recovered to baseline after rest. Salivary cortisol steadily declined over the testing period. Acute psychosocial stress impaired delayed verbal recall, attention and spatial working memory. Attention remained impaired, and delayed verbal recall continued to decline after rest. Acute psychosocial stress is associated with an impairment of a broad range of cognitive functions in humans and with prolonged abnormalities in attention and memory. Copyright © 2014 John Wiley & Sons, Ltd.

Risk factors for spatial memory impairment in patients with temporal lobe epilepsy.

PubMed

Amlerova, Jana; Laczo, Jan; Vlcek, Kamil; Javurkova, Alena; Andel, Ross; Marusic, Petr

2013-01-01

At present, the risk factors for world-centered (allocentric) navigation impairment in patients with temporal lobe epilepsy (TLE) are not known. There is some evidence on the importance of the right hippocampus but other clinical features have not been investigated yet. In this study, we used an experimental human equivalent to the Morris water maze to examine spatial navigation performance in patients with drug-refractory unilateral TLE. We included 47 left-hemisphere speech dominant patients (25 right sided; 22 left sided). The aim of our study was to identify clinical and demographic characteristics of TLE patients who performed poorly in allocentric spatial memory tests. Our results demonstrate that poor spatial navigation is significantly associated with younger age at epilepsy onset, longer disease duration, and lower intelligence level. Allocentric navigation in TLE patients was impaired irrespective of epilepsy lateralization. Good and poor navigators did not differ in their age, gender, or preoperative/postoperative status. This study provides evidence on risk factors that increase the likelihood of allocentric navigation impairment in TLE patients. The results indicate that not only temporal lobe dysfunction itself but also low general cognitive abilities may contribute to the navigation impairment. Copyright © 2012 Elsevier Inc. All rights reserved.

Working memory and reward association learning impairments in obesity.

PubMed

Coppin, Géraldine; Nolan-Poupart, Sarah; Jones-Gotman, Marilyn; Small, Dana M

2014-12-01

Obesity has been associated with impaired executive functions including working memory. Less explored is the influence of obesity on learning and memory. In the current study we assessed stimulus reward association learning, explicit learning and memory and working memory in healthy weight, overweight and obese individuals. Explicit learning and memory did not differ as a function of group. In contrast, working memory was significantly and similarly impaired in both overweight and obese individuals compared to the healthy weight group. In the first reward association learning task the obese, but not healthy weight or overweight participants consistently formed paradoxical preferences for a pattern associated with a negative outcome (fewer food rewards). To determine if the deficit was specific to food reward a second experiment was conducted using money. Consistent with Experiment 1, obese individuals selected the pattern associated with a negative outcome (fewer monetary rewards) more frequently than healthy weight individuals and thus failed to develop a significant preference for the most rewarded patterns as was observed in the healthy weight group. Finally, on a probabilistic learning task, obese compared to healthy weight individuals showed deficits in negative, but not positive outcome learning. Taken together, our results demonstrate deficits in working memory and stimulus reward learning in obesity and suggest that obese individuals are impaired in learning to avoid negative outcomes. Copyright © 2014 Elsevier Ltd. All rights reserved.

Haploinsufficiency of VGluT1 but not VGluT2 impairs extinction of spatial preference and response suppression.

PubMed

Callaerts-Vegh, Zsuzsanna; Moechars, Diederik; Van Acker, Nathalie; Daneels, Guy; Goris, Ilse; Leo, Sandra; Naert, Arne; Meert, Theo; Balschun, Detlef; D'Hooge, Rudi

2013-05-15

The excitatory neurotransmitter l-glutamate is transported into synaptic vesicles by vesicular glutamate transporters (VGluTs) to transmit glutamatergic signals. Changes in their expression have been linked to various brain disorders including schizophrenia, Parkinson's, and Alzheimer's disease. Deleting either the VGluT1 or VGluT2 gene leads to profound developmental and neurological complications and early death, but mice heterozygous for VGluT1 or VGluT2 are viable and thrive. Acquisition, retention and extinction of conditioned visuospatial and emotional responses were compared between VGluT1(+/-) and VGluT2(+/-) mice, and their wildtype littermates, using different water maze procedures, appetitive scheduled conditioning, and conditioned fear protocols. The distinct brain expression profiles of the VGluT1 and -2 isoforms particularly in telencephalic structures, such as neocortex, hippocampus and striatum, are reflected in very specific behavioral changes. VGluT2(+/-) mice were unimpaired in spatial learning tasks and fear extinction. Conversely, VGluT1(+/-) mice displayed spatial extinction learning deficits and markedly impaired fear extinction. These data indicate that VGluT1, but not VGluT2, plays a role in the neural processes underlying inhibitory learning. Copyright © 2013 Elsevier B.V. All rights reserved.

Domain-general sequence learning deficit in specific language impairment.

PubMed

Lukács, Agnes; Kemény, Ferenc

2014-05-01

Grammar-specific accounts of specific language impairment (SLI) have been challenged by recent claims that language problems are a consequence of impairments in domain-general mechanisms of learning that also play a key role in the process of language acquisition. Our studies were designed to test the generality and nature of this learning deficit by focusing on both sequential and nonsequential, and on verbal and nonverbal, domains. Twenty-nine children with SLI were compared with age-matched typically developing (TD) control children using (a) a serial reaction time task (SRT), testing the learning of motor sequences; (b) an artificial grammar learning (AGL) task, testing the extraction of regularities from auditory sequences; and (c) a weather prediction task (WP), testing probabilistic category learning in a nonsequential task. For the 2 sequence learning tasks, a significantly smaller proportion of children showed evidence of learning in the SLI than in the TD group (χ2 tests, p < .001 for the SRT task, p < .05 for the AGL task), whereas the proportion of learners on the WP task was the same in the 2 groups. The level of learning for SLI learners was comparable with that of TD children on all tasks (with great individual variation). Taken together, these findings suggest that domain-general processes of implicit sequence learning tend to be impaired in SLI. Further research is needed to clarify the relationship of deficits in implicit learning and language.

Impairments in action-outcome learning in schizophrenia.

PubMed

Morris, Richard W; Cyrzon, Chad; Green, Melissa J; Le Pelley, Mike E; Balleine, Bernard W

2018-03-03

Learning the causal relation between actions and their outcomes (AO learning) is critical for goal-directed behavior when actions are guided by desire for the outcome. This can be contrasted with habits that are acquired by reinforcement and primed by prevailing stimuli, in which causal learning plays no part. Recently, we demonstrated that goal-directed actions are impaired in schizophrenia; however, whether this deficit exists alongside impairments in habit or reinforcement learning is unknown. The present study distinguished deficits in causal learning from reinforcement learning in schizophrenia. We tested people with schizophrenia (SZ, n = 25) and healthy adults (HA, n = 25) in a vending machine task. Participants learned two action-outcome contingencies (e.g., push left to get a chocolate M&M, push right to get a cracker), and they also learned one contingency was degraded by delivery of noncontingent outcomes (e.g., free M&Ms), as well as changes in value by outcome devaluation. Both groups learned the best action to obtain rewards; however, SZ did not distinguish the more causal action when one AO contingency was degraded. Moreover, action selection in SZ was insensitive to changes in outcome value unless feedback was provided, and this was related to the deficit in AO learning. The failure to encode the causal relation between action and outcome in schizophrenia occurred without any apparent deficit in reinforcement learning. This implies that poor goal-directed behavior in schizophrenia cannot be explained by a more primary deficit in reward learning such as insensitivity to reward value or reward prediction errors.

Advanced IT Education for the Vision Impaired via e-Learning

ERIC Educational Resources Information Center

Armstrong, Helen L.

2009-01-01

Lack of accessibility in the design of e-learning courses continues to hinder students with vision impairment. E-learning materials are predominantly vision-centric, incorporating images, animation, and interactive media, and as a result students with acute vision impairment do not have equal opportunity to gain tertiary qualifications or skills…

Perceptual learning in children with visual impairment improves near visual acuity.

PubMed

Huurneman, Bianca; Boonstra, F Nienke; Cox, Ralf F A; van Rens, Ger; Cillessen, Antonius H N

2013-09-17

This study investigated whether visual perceptual learning can improve near visual acuity and reduce foveal crowding effects in four- to nine-year-old children with visual impairment. Participants were 45 children with visual impairment and 29 children with normal vision. Children with visual impairment were divided into three groups: a magnifier group (n = 12), a crowded perceptual learning group (n = 18), and an uncrowded perceptual learning group (n = 15). Children with normal vision also were divided in three groups, but were measured only at baseline. Dependent variables were single near visual acuity (NVA), crowded NVA, LH line 50% crowding NVA, number of trials, accuracy, performance time, amount of small errors, and amount of large errors. Children with visual impairment trained during six weeks, two times per week, for 30 minutes (12 training sessions). After training, children showed significant improvement of NVA in addition to specific improvements on the training task. The crowded perceptual learning group showed the largest acuity improvements (1.7 logMAR lines on the crowded chart, P < 0.001). Only the children in the crowded perceptual learning group showed improvements on all NVA charts. Children with visual impairment benefit from perceptual training. While task-specific improvements were observed in all training groups, transfer to crowded NVA was largest in the crowded perceptual learning group. To our knowledge, this is the first study to provide evidence for the improvement of NVA by perceptual learning in children with visual impairment. (http://www.trialregister.nl number, NTR2537.).

Reversibility of object recognition but not spatial memory impairment following binge-like alcohol exposure in rats.

PubMed

Cippitelli, Andrea; Zook, Michelle; Bell, Lauren; Damadzic, Ruslan; Eskay, Robert L; Schwandt, Melanie; Heilig, Markus

2010-11-01

Excessive alcohol use leads to neurodegeneration in several brain structures including the hippocampal dentate gyrus and the entorhinal cortex. Cognitive deficits that result are among the most insidious and debilitating consequences of alcoholism. The object exploration task (OET) provides a sensitive measurement of spatial memory impairment induced by hippocampal and cortical damage. In this study, we examine whether the observed neurotoxicity produced by a 4-day binge ethanol treatment results in long-term memory impairment by observing the time course of reactions to spatial change (object configuration) and non-spatial change (object recognition). Wistar rats were assessed for their abilities to detect spatial configuration in the OET at 1 week and 10 weeks following the ethanol treatment, in which ethanol groups received 9-15 g/kg/day and achieved blood alcohol levels over 300 mg/dl. At 1 week, results indicated that the binge alcohol treatment produced impairment in both spatial memory and non-spatial object recognition performance. Unlike the controls, ethanol treated rats did not increase the duration or number of contacts with the displaced object in the spatial memory task, nor did they increase the duration of contacts with the novel object in the object recognition task. After 10 weeks, spatial memory remained impaired in the ethanol treated rats but object recognition ability was recovered. Our data suggest that episodes of binge-like alcohol exposure result in long-term and possibly permanent impairments in memory for the configuration of objects during exploration, whereas the ability to detect non-spatial changes is only temporarily affected. Copyright © 2010 Elsevier Inc. All rights reserved.

Spatial Contiguity and Incidental Learning in Multimedia Environments

ERIC Educational Resources Information Center

Paek, Seungoh; Hoffman, Daniel L.; Saravanos, Antonios

2017-01-01

Drawing on dual-process theories of cognitive function, the degree to which spatial contiguity influences incidental learning outcomes was examined. It was hypothesized that spatial contiguity would mediate what was learned even in the absence of an explicit learning goal. To test this hypothesis, 149 adults completed a multimedia-related task…

Exposure to 56Fe irradiation accelerates normal brain aging and produces deficits in spatial learning and memory

NASA Astrophysics Data System (ADS)

Shukitt-Hale, Barbara; Casadesus, Gemma; Carey, Amanda N.; Rabin, Bernard M.; Joseph, James A.

Previous studies have shown that radiation exposure, particularly to particles of high energy and charge (HZE particles) such as 56Fe, produces deficits in spatial learning and memory. These adverse behavioral effects are similar to those seen in aged animals. It is possible that these shared effects may be produced by the same mechanism. For example, an increased release of reactive oxygen species, and the subsequent oxidative stress and inflammatory damage caused to the central nervous system, is likely responsible for the deficits seen in aging and following irradiation. Therefore, dietary antioxidants, such as those found in fruits and vegetables, could be used as countermeasures to prevent the behavioral changes seen in these conditions. Both aged and irradiated rats display cognitive impairment in tests of spatial learning and memory such as the Morris water maze and the radial arm maze. These rats have decrements in the ability to build spatial representations of the environment, and they utilize non-spatial strategies to solve tasks. Furthermore, they show a lack of spatial preference, due to a decline in the ability to process or retain place (position of a goal with reference to a “map” provided by the configuration of numerous cues in the environment) information. These declines in spatial memory occur in measures dependent on both reference and working memory, and in the flexibility to reset mental images. These results show that irradiation with 56Fe high-energy particles produces age-like decrements in cognitive behavior that may impair the ability of astronauts, particularly middle-aged ones, to perform critical tasks during long-term space travel beyond the magnetosphere.

Impaired implicit learning and feedback processing after stroke.

PubMed

Lam, J M; Globas, C; Hosp, J A; Karnath, H-O; Wächter, T; Luft, A R

2016-02-09

The ability to learn is assumed to support successful recovery and rehabilitation therapy after stroke. Hence, learning impairments may reduce the recovery potential. Here, the hypothesis is tested that stroke survivors have deficits in feedback-driven implicit learning. Stroke survivors (n=30) and healthy age-matched control subjects (n=21) learned a probabilistic classification task with brain activation measured using functional magnetic resonance imaging in a subset of these individuals (17 stroke and 10 controls). Stroke subjects learned slower than controls to classify cues. After being rewarded with a smiley face, they were less likely to give the same response when the cue was repeated. Stroke subjects showed reduced brain activation in putamen, pallidum, thalamus, frontal and prefrontal cortices and cerebellum when compared with controls. Lesion analysis identified those stroke survivors as learning-impaired who had lesions in frontal areas, putamen, thalamus, caudate and insula. Lesion laterality had no effect on learning efficacy or brain activation. These findings suggest that stroke survivors have deficits in reinforcement learning that may be related to dysfunctional processing of feedback-based decision-making, reward signals and working memory. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Learning temporal statistics for sensory predictions in mild cognitive impairment.

PubMed

Di Bernardi Luft, Caroline; Baker, Rosalind; Bentham, Peter; Kourtzi, Zoe

2015-08-01

Training is known to improve performance in a variety of perceptual and cognitive skills. However, there is accumulating evidence that mere exposure (i.e. without supervised training) to regularities (i.e. patterns that co-occur in the environment) facilitates our ability to learn contingencies that allow us to interpret the current scene and make predictions about future events. Recent neuroimaging studies have implicated fronto-striatal and medial temporal lobe brain regions in the learning of spatial and temporal statistics. Here, we ask whether patients with mild cognitive impairment due to Alzheimer's disease (MCI-AD) that are characterized by hippocampal dysfunction are able to learn temporal regularities and predict upcoming events. We tested the ability of MCI-AD patients and age-matched controls to predict the orientation of a test stimulus following exposure to sequences of leftwards or rightwards orientated gratings. Our results demonstrate that exposure to temporal sequences without feedback facilitates the ability to predict an upcoming stimulus in both MCI-AD patients and controls. However, our fMRI results demonstrate that MCI-AD patients recruit an alternate circuit to hippocampus to succeed in learning of predictive structures. In particular, we observed stronger learning-dependent activations for structured sequences in frontal, subcortical and cerebellar regions for patients compared to age-matched controls. Thus, our findings suggest a cortico-striatal-cerebellar network that may mediate the ability for predictive learning despite hippocampal dysfunction in MCI-AD. Copyright © 2015 Elsevier Ltd. All rights reserved.

Astrocytic expression of HIV-1 Nef impairs spatial and recognition memory

PubMed Central

Chompre, Gladys; Cruz, Emmanuel; Maldonado, Lucianette; Rivera-Amill, Vanessa; Porter, James T.; Noel, Richard J.

2012-01-01

Despite the widespread use of antiretroviral therapy that effectively limits viral replication, memory impairment remains a dilemma for HIV infected people. In the CNS, HIV infection of astrocytes leads to the production of the HIV-1 Nef protein without viral replication. Post mortem studies have found Nef expression in hippocampal astrocytes of people with HIV associated dementia suggesting that astrocytic Nef may contribute to HIV associated cognitive impairment even when viral replication is suppressed. To test whether astrocytic expression of Nef is sufficient to induce cognitive deficits, we examined the effect of implanting primary rat astrocytes expressing Nef into the hippocampus on spatial and recognition memory. Rats implanted unilaterally with astrocytes expressing Nef showed impaired novel location and novel object recognition in comparison with controls implanted with astrocytes expressing green fluorescent protein (GFP). This impairment was correlated with an increase in chemokine ligand 2 (CCL2) expression and the infiltration of peripheral macrophages into the hippocampus at the site of injection. Furthermore, the Nef exposed rats exhibited a bilateral loss of CA3 neurons. These results suggest that Nef protein expressed by the implanted astrocytes activates the immune system leading to neuronal damage and spatial and recognition memory deficits. Therefore, the continued expression of Nef by astrocytes in the absence of viral replication has the potential to contribute to HIV associated cognitive impairment. PMID:22926191

E-Learning Environment for Hearing Impaired Students

ERIC Educational Resources Information Center

Hashim, Hisyamuddin; Tasir, Zaidatun; Mohamad, Siti Khadijah

2013-01-01

The usage of technology within the educational department has become more vital by each year passing. One of the most popular technological approaches used is the e-learning environment. The usage of e-learning environment in education involves a wide range of types of students, and this includes the hearing impaired ones. Some adjustment or…

[Co-administration of RJR-2403 with low dose of 17beta-estradiol on spatial learning in ovariectomized rats].

PubMed

Fedotova, Yu O

2013-01-01

The aim of this work was to study the influence of stimulation or blockade Nalpha7-cholinoreceptors on dynamics of spatial learning in water Morris maze and on behavior in the "open field" test in adult ovariectomized (OVX) females given with a low dose of 17beta-estradiol. Agonist of Nalpha7-cholinoreceptors - RJR-2403 (1.0 mg/kg, i.p.) or antagonist of Nalpha7-cholinoreceptors - mecamylamine (1.0 mg/kg, i.p.) treated chronically (14 days) alone and in a combination with low dose of 17beta-estradiol (0.5 micro/rat, s.c.) to OVX rats. Co-administration of RJR-2403 with low dose of 17beta-estradiol completely restored impaired spatial learning in water Morris maze in OVX females. Moreover, OVX rats treated with RJR-2403 and low dose of 17beta-estradiol demonstrated increased exploratory and grooming behavior in the "open field" test. Both mecamylamine alone and in combination with low dose of 17beta-estradiol failed to influence on spatial learning and failed to modify behavior in the "open field" test in OVX rats. The results of the present study suggest a positive effect of RJR-2403 in combination with low dose of 17beta-estradiol on spatial learning at estrogen deficiency.

Modified Navigation Instructions for Spatial Navigation Assistance Systems Lead to Incidental Spatial Learning

PubMed Central

Gramann, Klaus; Hoepner, Paul; Karrer-Gauss, Katja

2017-01-01

Spatial cognitive skills deteriorate with the increasing use of automated GPS navigation and a general decrease in the ability to orient in space might have further impact on independence, autonomy, and quality of life. In the present study we investigate whether modified navigation instructions support incidental spatial knowledge acquisition. A virtual driving environment was used to examine the impact of modified navigation instructions on spatial learning while using a GPS navigation assistance system. Participants navigated through a simulated urban and suburban environment, using navigation support to reach their destination. Driving performance as well as spatial learning was thereby assessed. Three navigation instruction conditions were tested: (i) a control group that was provided with classical navigation instructions at decision points, and two other groups that received navigation instructions at decision points including either (ii) additional irrelevant information about landmarks or (iii) additional personally relevant information (i.e., individual preferences regarding food, hobbies, etc.), associated with landmarks. Driving performance revealed no differences between navigation instructions. Significant improvements were observed in both modified navigation instruction conditions on three different measures of spatial learning and memory: subsequent navigation of the initial route without navigation assistance, landmark recognition, and sketch map drawing. Future navigation assistance systems could incorporate modified instructions to promote incidental spatial learning and to foster more general spatial cognitive abilities. Such systems might extend mobility across the lifespan. PMID:28243219

Sleep disturbance induces neuroinflammation and impairment of learning and memory.

PubMed

Zhu, Biao; Dong, Yuanlin; Xu, Zhipeng; Gompf, Heinrich S; Ward, Sarah A P; Xue, Zhanggang; Miao, Changhong; Zhang, Yiying; Chamberlin, Nancy L; Xie, Zhongcong

2012-12-01

Hospitalized patients can develop cognitive function decline, the mechanisms of which remain largely to be determined. Sleep disturbance often occurs in hospitalized patients, and neuroinflammation can induce learning and memory impairment. We therefore set out to determine whether sleep disturbance can induce neuroinflammation and impairment of learning and memory in rodents. Five to 6-month-old wild-type C57BL/6J male mice were used in the studies. The mice were placed in rocking cages for 24 h, and two rolling balls were present in each cage. The mice were tested for learning and memory function using the Fear Conditioning Test one and 7 days post-sleep disturbance. Neuroinflammation in the mouse brain tissues was also determined. Of the Fear Conditioning studies at one day and 7 days after sleep disturbance, twenty-four hour sleep disturbance decreased freezing time in the context test, which assesses hippocampus-dependent learning and memory; but not the tone test, which assesses hippocampus-independent learning and memory. Sleep disturbance increased pro-inflammatory cytokine IL-6 levels and induced microglia activation in the mouse hippocampus, but not the cortex. These results suggest that sleep disturbance induces neuroinflammation in the mouse hippocampus, and impairs hippocampus-dependent learning and memory in mice. Pending further studies, these findings suggest that sleep disturbance-induced neuroinflammation and impairment of learning and memory may contribute to the development of cognitive function decline in hospitalized patients. Copyright © 2012 Elsevier Inc. All rights reserved.

Dissociation between learning and memory impairment and other sickness behaviours during simulated Mycoplasma infection in rats.

PubMed

Swanepoel, Tanya; Harvey, Brian H; Harden, Lois M; Laburn, Helen P; Mitchell, Duncan

2011-11-01

To investigate potential consequences for learning and memory, we have simulated the effects of Mycoplasma infection, in rats, by administering fibroblast-stimulating lipopepide-1 (FSL-1), a pyrogenic moiety of Mycoplasma salivarium. We measured the effects on body temperature, cage activity, food intake, and on spatial learning and memory in a Morris Water Maze. Male Sprague-Dawley rats had radio transponders implanted to measure abdominal temperature and cage activity. After recovery, rats were assigned randomly to receive intraperitoneal (I.P.) injections of FSL-1 (500 or 1000 μg kg(-1) in 1 ml kg(-1) phosphate-buffered saline; PBS) or vehicle (PBS, 1 ml kg(-1)). Body mass and food intake were measured daily. Training in the Maze commenced 18 h after injections and continued daily for four days. Spatial memory was assessed on the fifth day. In other rats, we measured concentrations of brain pro-inflammatory cytokines, interleukin (IL)-1β and IL-6, at 3 and 18 h after injections. FSL-1 administration induced a dose-dependent fever (∼1°C) for two days, lethargy (∼78%) for four days, anorexia (∼65%) for three days and body mass stunting (∼6%) for at least four days. Eighteen hours after FSL-1 administration, when concentrations of IL-1β, but not that of IL-6, were elevated in both the hypothalamus and the hippocampus, and when rats were febrile, lethargic and anorexic, learning in the Maze was unaffected. There also was no memory impairment. Our results support emerging evidence that impaired learning and memory is not inevitable during simulated infection. Copyright © 2011 Elsevier Inc. All rights reserved.

Novelty exposure overcomes foot shock-induced spatial-memory impairment by processes of synaptic-tagging in rats.

PubMed

Almaguer-Melian, William; Bergado-Rosado, Jorge; Pavón-Fuentes, Nancy; Alberti-Amador, Esteban; Mercerón-Martínez, Daymara; Frey, Julietta U

2012-01-17

Novelty processing can transform short-term into long-term memory. We propose that this memory-reinforcing effect of novelty could be explained by mechanisms outlined in the "synaptic tagging hypothesis." Initial short-term memory is sustained by a transient plasticity change at activated synapses and sets synaptic tags. These tags are later able to capture and process the plasticity-related proteins (PRPs), which are required to transform a short-term synaptic change into a long-term one. Novelty is involved in inducing the synthesis of PRPs [Moncada D, et al. (2011) Proc Natl Acad Sci USA 108:12937-12936], which are then captured by the tagged synapses, consolidating memory. In contrast to novelty, stress can impair learning, memory, and synaptic plasticity. Here, we address questions as to whether novelty-induced PRPs are able to prevent the loss of memory caused by stress and if the latter would not interact with the tag-setting process. We used water-maze (WM) training as a spatial learning paradigm to test our hypothesis. Stress was induced by a strong foot shock (FS; 5 × 1 mA, 2 s) applied 5 min after WM training. Our data show that FS reduced long-term but not short-term memory in the WM paradigm. This negative effect on memory consolidation was time- and training-dependent. Interestingly, novelty exposure prevented the stress-induced memory loss of the spatial task and increased BDNF and Arc expression. This rescuing effect was blocked by anisomycin, suggesting that WM-tagged synapses were not reset by FS and were thus able to capture the novelty-induced PRPs, re-establishing FS-impaired long-term memory.

Learning Anatomy Enhances Spatial Ability

ERIC Educational Resources Information Center

Vorstenbosch, Marc A. T. M.; Klaassen, Tim P. F. M.; Donders, A. R. T.; Kooloos, Jan G. M.; Bolhuis, Sanneke M.; Laan, Roland F. J. M.

2013-01-01

Spatial ability is an important factor in learning anatomy. Students with high scores on a mental rotation test (MRT) systematically score higher on anatomy examinations. This study aims to investigate if learning anatomy also oppositely improves the MRT-score. Five hundred first year students of medicine ("n" = 242, intervention) and…

Steroid Receptor Coactivator-1 Knockdown Decreases Synaptic Plasticity and Impairs Spatial Memory in the Hippocampus of Mice.

PubMed

Bian, Chen; Huang, Yan; Zhu, Haitao; Zhao, Yangang; Zhao, Jikai; Zhang, Jiqiang

2018-05-01

Steroids have been demonstrated to play profound roles in the regulation of hippocampal function by acting on their receptors, which need coactivators for their transcriptional activities. Previous studies have shown that steroid receptor coactivator-1 (SRC-1) is the predominant coactivator in the hippocampus, but its exact role and the underlying mechanisms remain unclear. In this study, we constructed SRC-1 RNA interference (RNAi) lentiviruses, injected them into the hippocampus of male mice, and then examined the changes in the expression of selected synaptic proteins, CA1 synapse density, postsynaptic density (PSD) thickness, and in vivo long-term potentiation (LTP). Spatial learning and memory behavior changes were investigated using the Morris water maze. We then transfected the lentiviruses into cultured hippocampal cells and examined the changes in synaptic protein and phospho-cyclic AMP response element-binding protein (pCREB) expression. The in vivo results showed that SRC-1 knockdown significantly decreased the expression of synaptic proteins and CA1 synapse density as well as PSD thickness; SRC-1 knockdown also significantly impaired in vivo LTP and disrupted spatial learning and memory. The in vitro results showed that while the expression of synaptic proteins was significantly decreased by SRC-1 knockdown, pCREB expression was also significantly decreased. The above results suggest a pivotal role of SRC-1 in the regulation of hippocampal synaptic plasticity and spatial learning and memory, strongly indicating SRC-1 may serve as a novel therapeutic target for hippocampus-dependent memory disorders. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

Cellular Basis for Learning Impairment in Fragile X Syndrome

DTIC Science & Technology

2015-08-01

the leading cause of inherited intellectual disability and results in cognitive impairment, hyperactivity , attention deficits , seizure disorders ...impairment, hyperactivity , attention deficits and seizure disorders . Previous studies using a mouse model for FXS (Fmr1- KO) have described impairments in...neurogenesis in adult fragile X mice, test fragile X mice for learning deficits in hippocampal-independent tasks, and determine how synaptic

Neurological effects of inorganic arsenic exposure: altered cysteine/glutamate transport, NMDA expression and spatial memory impairment.

PubMed

Ramos-Chávez, Lucio A; Rendón-López, Christian R R; Zepeda, Angélica; Silva-Adaya, Daniela; Del Razo, Luz M; Gonsebatt, María E

2015-01-01

Inorganic arsenic (iAs) is an important natural pollutant. Millions of individuals worldwide drink water with high levels of iAs. Chronic exposure to iAs has been associated with lower IQ and learning disabilities as well as memory impairment. iAs is methylated in tissues such as the brain generating mono and dimethylated species. iAs methylation requires cellular glutathione (GSH), which is the main antioxidant in the central nervous system (CNS). In humans, As species cross the placenta and are found in cord blood. A CD1 mouse model was used to investigate effects of gestational iAs exposure which can lead to oxidative damage, disrupted cysteine/glutamate transport and its putative impact in learning and memory. On postnatal days (PNDs) 1, 15 and 90, the expression of membrane transporters related to GSH synthesis and glutamate transport and toxicity, such as xCT, EAAC1, GLAST and GLT1, as well as LAT1, were analyzed. Also, the expression of the glutamate receptor N-methyl-D-aspartate (NMDAR) subunits NR2A and B as well as the presence of As species in cortex and hippocampus were investigated. On PND 90, an object location task was performed to associate exposure with memory impairment. Gestational exposure to iAs affected the expression of cysteine/glutamate transporters in cortex and hippocampus and induced a negative modulation of NMDAR NR2B subunit in the hippocampus. Behavioral tasks showed significant spatial memory impairment in males while the effect was marginal in females.

Neurological effects of inorganic arsenic exposure: altered cysteine/glutamate transport, NMDA expression and spatial memory impairment

PubMed Central

Ramos-Chávez, Lucio A.; Rendón-López, Christian R. R.; Zepeda, Angélica; Silva-Adaya, Daniela; Del Razo, Luz M.; Gonsebatt, María E.

2015-01-01

Inorganic arsenic (iAs) is an important natural pollutant. Millions of individuals worldwide drink water with high levels of iAs. Chronic exposure to iAs has been associated with lower IQ and learning disabilities as well as memory impairment. iAs is methylated in tissues such as the brain generating mono and dimethylated species. iAs methylation requires cellular glutathione (GSH), which is the main antioxidant in the central nervous system (CNS). In humans, As species cross the placenta and are found in cord blood. A CD1 mouse model was used to investigate effects of gestational iAs exposure which can lead to oxidative damage, disrupted cysteine/glutamate transport and its putative impact in learning and memory. On postnatal days (PNDs) 1, 15 and 90, the expression of membrane transporters related to GSH synthesis and glutamate transport and toxicity, such as xCT, EAAC1, GLAST and GLT1, as well as LAT1, were analyzed. Also, the expression of the glutamate receptor N-methyl-D-aspartate (NMDAR) subunits NR2A and B as well as the presence of As species in cortex and hippocampus were investigated. On PND 90, an object location task was performed to associate exposure with memory impairment. Gestational exposure to iAs affected the expression of cysteine/glutamate transporters in cortex and hippocampus and induced a negative modulation of NMDAR NR2B subunit in the hippocampus. Behavioral tasks showed significant spatial memory impairment in males while the effect was marginal in females. PMID:25709567

Compound danshen tablet ameliorated aβ25-35-induced spatial memory impairment in mice via rescuing imbalance between cytokines and neurotrophins.

PubMed

Teng, Yan; Zhang, Meng-Qi; Wang, Wen; Liu, Li-Tao; Zhou, Li-Ming; Miao, Shi-Kun; Wan, Li-Hong

2014-01-14

Compound Danshen Tablet (CDT), a Traditional Chinese Medicine, has recently been reported to improve spatial cognition in a rat model of Alzheimer's disease. However, in vivo neuroprotective mechanism of the CDT in models of spatial memory impairment is not yet evaluated. The present study is aimed to elucidate the cellular mechanism of CDT on Aβ25-35-induced cognitive impairment in mice. Mice were randomly divided into 5 groups: the control group (sham operated), the Aβ25-35 treated group, the positive drug group, and large and small dosage of the CDT groups, respectively. CDT was administered at a dose of 0.81 g/kg and 0.405 g/kg for 3 weeks. The mice in the positive drug group were treated with 0.4 mg/kg of Huperzine A, whereas the mice of the control and Aβ25-35 treated groups were administrated orally with equivalent saline. After 7 days of preventive treatment, mice were subjected to lateral ventricle injection of Aβ25-35 to establish the mice model of Alzheimer's disease. Spatial memory impairment was evaluated by Morris water maze test. Choline acetyltransferase (ChAT) contents in hippocampus and cortex were quantified by ELISA. The levels of cytokines, receptor of activated protein kinase C1 (RACK1) and brain-derived neurotrophic factor (BDNF) in hippocampus were measured by RT-PCR and ELISA. The results showed that Aβ25-35 caused spatial memory impairment as demonstrated by performance in the Morris water maze test. CDT was able to confer a significant improvement in spatial memory, and protect mice from Aβ25-35-induced neurotoxicity. Additionally, CDT also inhibited the increase of TNF-α and IL-6 level, and increased the expression of choline acetyltransferase (ChAT), receptor of activated protein kinase C1 (RACK1) and brain-derived neurotrophic factor (BDNF) in brain as compared to model mice. These findings strongly implicate that CDT may be a useful treatment against learning and memory deficits in mice by rescuing imbalance between cytokines

Spatial but not object memory impairments in children with fetal alcohol syndrome.

PubMed

Uecker, A; Nadel, L

1998-07-01

Behavioral dissociations on tests of cognitive abilities are powerful tools that can help define the neuropsychology of developmentally disabling conditions. Animals gestationally exposed to alcohol demonstrate spatial (place) but not object (cue) memory impairments. Whether children with fetal alcohol syndrome demonstrate a similar dissociation has received little attention. In this experiment, 30 Native American children, 15 previously identified with fetal alcohol syndrome and 15 control children, were asked to recall places and objects in a task previously shown to be sensitive to memory skills in individuals with and without mental retardation. As in animal models, children with fetal alcohol syndrome demonstrated a spatial but not an object memory impairment. A possible role for the hippocampus was discussed.

Altering spatial priority maps via reward-based learning.

PubMed

Chelazzi, Leonardo; Eštočinová, Jana; Calletti, Riccardo; Lo Gerfo, Emanuele; Sani, Ilaria; Della Libera, Chiara; Santandrea, Elisa

2014-06-18

Spatial priority maps are real-time representations of the behavioral salience of locations in the visual field, resulting from the combined influence of stimulus driven activity and top-down signals related to the current goals of the individual. They arbitrate which of a number of (potential) targets in the visual scene will win the competition for attentional resources. As a result, deployment of visual attention to a specific spatial location is determined by the current peak of activation (corresponding to the highest behavioral salience) across the map. Here we report a behavioral study performed on healthy human volunteers, where we demonstrate that spatial priority maps can be shaped via reward-based learning, reflecting long-lasting alterations (biases) in the behavioral salience of specific spatial locations. These biases exert an especially strong influence on performance under conditions where multiple potential targets compete for selection, conferring competitive advantage to targets presented in spatial locations associated with greater reward during learning relative to targets presented in locations associated with lesser reward. Such acquired biases of spatial attention are persistent, are nonstrategic in nature, and generalize across stimuli and task contexts. These results suggest that reward-based attentional learning can induce plastic changes in spatial priority maps, endowing these representations with the "intelligent" capacity to learn from experience. Copyright © 2014 the authors 0270-6474/14/348594-11$15.00/0.

Impaired Statistical Learning in Developmental Dyslexia

ERIC Educational Resources Information Center

Gabay, Yafit; Thiessen, Erik D.; Holt, Lori L.

2015-01-01

Purpose: Developmental dyslexia (DD) is commonly thought to arise from phonological impairments. However, an emerging perspective is that a more general procedural learning deficit, not specific to phonological processing, may underlie DD. The current study examined if individuals with DD are capable of extracting statistical regularities across…

Dorsal Hippocampus Function in Learning and Expressing a Spatial Discrimination

ERIC Educational Resources Information Center

White, Norman M.; Gaskin, Stephane

2006-01-01

Learning to discriminate between spatial locations defined by two adjacent arms of a radial maze in the conditioned cue preference paradigm requires two kinds of information: latent spatial learning when the rats explore the maze with no food available, and learning about food availability in two spatial locations when the rats are then confined…

Early exposure to noise followed by predator stress in adulthood impairs the rat's re-learning flexibility in Radial Arm Water Maze.

PubMed

Jauregui-Huerta, Fernando; Ruvalcaba-Delgadillo, Yaveth; Garcia-Estrada, Joaquin; Feria-Velasco, Alfredo; Ramos-Zuñiga, Rodrigo; Gonzalez-Perez, Oscar; Luquin, Sonia

2010-01-01

This study investigated the cognitive effect of chronic exposure to environmental noise on RAWM performance of juvenile rats, and the ability of adult rats exposed to a novel acute stress to perform in the RAWM as a function of whether or not they were exposed to environmental noise as juveniles. We examined the consequences of exposure to noise during the juvenile-early periadolescent period on adulthood stress response by assessing cognitive performance in the RAWM. Male rats were exposed to environmental noise during the childhood-prepubescent period (21-35 PND), and their RAWM performance was tested at the end of the exposure to noise, and then again two months later when they had to cope with a new stressful event. RAWM execution included a 3-day training phase and a reversal learning phase on day 4. Escape latency, reference memory errors and working memory errors were compared between experimental and control groups. In addition, body weight gain and serum corticosterone levels were evaluated. Stressed rats demonstrated spatial impairment, as evidenced by poor execution on day 4. This effect was significantly noticeable in the doubly stressed group. Noise annoyance was evidenced by reduced body weight gain and increased serum corticosterone levels. Our results suggest that environmental noise may produce potent stress-like effects in developing subjects that can persist into adulthood, affecting spatial learning abilities. This cognitive impairment may restrict the subject's ability to learn under a new spatial configuration.

Dizocilpine (MK-801) impairs learning in the active place avoidance task but has no effect on the performance during task/context alternation.

PubMed

Vojtechova, Iveta; Petrasek, Tomas; Hatalova, Hana; Pistikova, Adela; Vales, Karel; Stuchlik, Ales

2016-05-15

The prevention of engram interference, pattern separation, flexibility, cognitive coordination and spatial navigation are usually studied separately at the behavioral level. Impairment in executive functions is often observed in patients suffering from schizophrenia. We have designed a protocol for assessing these functions all together as behavioral separation. This protocol is based on alternated or sequential training in two tasks testing different hippocampal functions (the Morris water maze and active place avoidance), and alternated or sequential training in two similar environments of the active place avoidance task. In Experiment 1, we tested, in adult rats, whether the performance in two different spatial tasks was affected by their order in sequential learning, or by their day-to-day alternation. In Experiment 2, rats learned to solve the active place avoidance task in two environments either alternately or sequentially. We found that rats are able to acquire both tasks and to discriminate both similar contexts without obvious problems regardless of the order or the alternation. We used two groups of rats, controls and a rat model of psychosis induced by a subchronic intraperitoneal application of 0.08mg/kg of dizocilpine (MK-801), a non-competitive antagonist of NMDA receptors. Dizocilpine had no selective effect on parallel/sequential learning of tasks/contexts. However, it caused hyperlocomotion and a significant deficit in learning in the active place avoidance task regardless of the task alternation. Cognitive coordination tested by this task is probably more sensitive to dizocilpine than spatial orientation because no hyperactivity or learning impairment was observed in the Morris water maze. Copyright © 2016 Elsevier B.V. All rights reserved.

Spatial Cognition in Autism Spectrum Disorders: Superior, Impaired, or Just Intact?

ERIC Educational Resources Information Center

Edgin, Jamie O.; Pennington, Bruce F.

2005-01-01

The profile of spatial ability is of interest across autism spectrum disorders (ASD) because of reported spatial strengths in ASD and due to the recent association of Asperger's syndrome with Nonverbal Learning Disability. Spatial functions were examined in relation to two cognitive theories in autism: the central coherence and executive function…

Prenatal cocaine exposure impairs selective attention: evidence from serial reversal and extradimensional shift tasks.

PubMed

Garavan, H; Morgan, R E; Mactutus, C F; Levitsky, D A; Booze, R M; Strupp, B J

2000-08-01

This study assessed the effects of prenatal cocaine exposure on cognitive functioning, using an intravenous (IV) rodent model that closely mimics the pharmacokinetics seen in humans after smoking or IV injection and that avoids maternal stress and undernutrition. Cocaine-exposed males were significantly impaired on a 3-choice, but not 2-choice, olfactory serial reversal learning task. Both male and female cocaine-exposed rats were significantly impaired on extradimensional shift tasks that required shifting from olfactory to spatial cues; however, they showed no impairment when required to shift from spatial to olfactory cues. In-depth analyses of discrete learning phases implicated deficient selective attention as the basis of impairment in both tasks. These data provide clear evidence that prenatal cocaine exposure produces long-lasting cognitive dysfunction, but they also underscore the specificity of the impairment.

Learning by E-Learning for Visually Impaired Students: Opportunities or Again Marginalisation?

ERIC Educational Resources Information Center

Kharade, Kalpana; Peese, Hema

2012-01-01

In recent years, e-learning has become a valuable tool for an increasing number of visually impaired (VI) learners. The benefits of this technology include: (1) remote learning for VI students; (2) the possibility for teachers living far from schools or universities to provide remote instructional assistance to VI students; and (3) continuing…

Repeated mild traumatic brain injury produces neuroinflammation, anxiety-like behaviour and impaired spatial memory in mice.

PubMed

Broussard, John I; Acion, Laura; De Jesús-Cortés, Héctor; Yin, Terry; Britt, Jeremiah K; Salas, Ramiro; Costa-Mattioli, Mauro; Robertson, Claudia; Pieper, Andrew A; Arciniegas, David B; Jorge, Ricardo

2018-01-01

Repeated traumatic brain injuries (rmTBI) are frequently associated with debilitating neuropsychiatric conditions such as cognitive impairment, mood disorders, and post-traumatic stress disorder. We tested the hypothesis that repeated mild traumatic brain injury impairs spatial memory and enhances anxiety-like behaviour. We used a between groups design using single (smTBI) or repeated (rmTBI) controlled cranial closed skull impacts to mice, compared to a control group. We assessed the effects of smTBI and rmTBI using measures of motor performance (Rotarod Test [RT]), anxiety-like behaviour (Elevated Plus Maze [EPM] and Open Field [OF] tests), and spatial memory (Morris Water Maze [MWM]) within 12 days of the final injury. In separate groups of mice, astrocytosis and microglial activation were assessed 24 hours after the final injury using GFAP and IBA-1 immunohistochemistry. RmTBI impaired spatial memory in the MWM and increased anxiety-like behaviour in the EPM and OFT. In addition, rmTBI elevated GFAP and IBA-1 immunohistochemistry throughout the mouse brain. RmTBI produced astrocytosis and microglial activation, and elicited impaired spatial memory and anxiety-like behaviour. rmTBI produces acute cognitive and anxiety-like disturbances associated with inflammatory changes in brain regions involved in spatial memory and anxiety.

Damage of GABAergic neurons in the medial septum impairs spatial working memory and extinction of active avoidance: effects on proactive interference.

PubMed

Pang, Kevin C H; Jiao, Xilu; Sinha, Swamini; Beck, Kevin D; Servatius, Richard J

2011-08-01

The medial septum and diagonal band (MSDB) are important in spatial learning and memory. On the basis of the excitotoxic damage of GABAergic MSDB neurons, we have recently suggested a role for these neurons in controlling proactive interference. Our study sought to test this hypothesis in different behavioral procedures using a new GABAergic immunotoxin. GABA-transporter-saporin (GAT1-SAP) was administered into the MSDB of male Sprague-Dawley rats. Following surgery, rats were trained in a reference memory water maze procedure for 5 days, followed by a working memory (delayed match to position) water maze procedure. Other rats were trained in a lever-press avoidance procedure after intraseptal GAT1-SAP or sham surgery. Intraseptal GAT1-SAP extensively damaged GABAergic neurons while sparing most cholinergic MSDB neurons. Rats treated with GAT1-SAP were not impaired in acquiring a spatial reference memory, learning the location of the escape platform as rapidly as sham rats. In contrast, GAT1-SAP rats were slower than sham rats to learn the platform location in a delayed match to position procedure, in which the platform location was changed every day. Moreover, GAT1-SAP rats returned to previous platform locations more often than sham rats. In the active avoidance procedure, intraseptal GAT1-SAP impaired extinction but not acquisition of the avoidance response. Using a different neurotoxin and behavioral procedures than previous studies, the results of this study paint a similar picture that GABAergic MSDB neurons are important for controlling proactive interference. Copyright © 2010 Wiley-Liss, Inc.

Impairment of long-term potentiation induction is essential for the disruption of spatial memory after microwave exposure.

PubMed

Wang, Hui; Peng, Ruiyun; Zhou, Hongmei; Wang, Shuiming; Gao, Yabing; Wang, Lifeng; Yong, Zheng; Zuo, Hongyan; Zhao, Li; Dong, Ji; Xu, Xinping; Su, Zhentao

2013-12-01

To assess the impact of microwave exposure on learning and memory and to explore the underlying mechanisms. 100 Wistar rats were exposed to a 2.856 GHz pulsed microwave field at average power densities of 0 mW/cm(2), 5 mW/cm(2), 10 mW/cm(2) and 50 mW/cm(2) for 6 min. The spatial memory was assessed by the Morris Water Maze (MWM) task. An in vivo study was conducted soon after microwave exposure to evaluate the changes of population spike (PS) amplitudes of long-term potentiation (LTP) in the medial perforant path (MPP)-dentate gyrus (DG) pathway. The structure of the hippocampus was observed by the light microscopy and the transmission electron microscopy (TEM) at 7 d after microwave exposure. Our results showed that the rats exposed in 10 mW/cm(2) and 50 mW/cm(2) microwave displayed significant deficits in spatial learning and memory at 6 h, 1 d and 3 d after exposure. Decreased PS amplitudes were also found after 10 mW/cm(2) and 50 mW/cm(2) microwave exposure. In addition, varying degrees of degeneration of hippocampal neurons, decreased synaptic vesicles and blurred synaptic clefts were observed in the rats exposed in 10 mW/cm(2) and 50 mW/cm(2) microwave. Compared with the sham group, the rats exposed in 5 mW/cm(2) microwave showed no difference in the above experiments. This study suggested that impairment of LTP induction and the damages of hippocampal structure, especially changes of synapses, might contribute to cognitive impairment after microwave exposure.

Rhynchophylline suppresses soluble Aβ1-42-induced impairment of spatial cognition function via inhibiting excessive activation of extrasynaptic NR2B-containing NMDA receptors.

PubMed

Yang, Yang; Ji, Wei-Gang; Zhu, Zhi-Ru; Wu, Yu-Ling; Zhang, Zhi-Yang; Qu, Shao-Chen

2018-06-01

Rhynchophylline (RIN) is a significant active component isolated from the Chinese herbal medicine Uncaria rhynchophylla. The overproduction of soluble amyloid β protein (Aβ) oligomers in the hippocampus is closely involved in impairments in cognitive function at the early stage of Alzheimer's disease (AD). Growing evidences show that RIN possesses neuroprotective effects against Aβ-induced neurotoxicity. However, whether RIN can prevent soluble Aβ 1-42 -induced impairments in spatial cognitive function and synaptic plasticity is still unclear. Using the combined methods of behavioral tests, immunofluorescence and electrophysiological recordings, we characterized the key neuroprotective properties of RIN and its possible cellular and molecular mechanisms against soluble Aβ 1-42 -related impairments in rats. Our findings are as follows: (1) RIN efficiently rescued the soluble Aβ 1-42 -induced spatial learning and memory deficits in the Morris water maze test and prevented soluble Aβ 1-42 -induced suppression in long term potentiation (LTP) in the entorhinal cortex (EC)-dentate gyrus (DG) circuit. (2) Excessive activation of extrasynaptic GluN2B-NMDAR and subsequent Ca 2+ overload contributed to the soluble Aβ 1-42 -induced impairments in spatial cognitive function and synaptic plasticity. (3) RIN prevented Aβ 1-42 -induced excessive activation of extrasynaptic NMDARs by reducing extrasynaptic NMDARs -mediated excitatory postsynaptic currents and down regulating GluN2B-NMDAR expression in the DG region, which inhibited Aβ 1-42 -induced Ca 2+ overload mediated by extrasynanptic NMDARs. The results suggest that RIN could be an effective therapeutic candidate for cognitive impairment in AD. Copyright © 2018 Elsevier Ltd. All rights reserved.

Implicit Perceptual-Motor Skill Learning in Mild Cognitive Impairment and Parkinson's Disease

PubMed Central

Gobel, Eric W.; Blomeke, Kelsey; Zadikoff, Cindy; Simuni, Tanya; Weintraub, Sandy; Reber, Paul J.

2015-01-01

Objective Implicit skill learning is hypothesized to depend on nondeclarative memory that operates independent of the medial temporal lobe (MTL) memory system and instead depends on cortico-striatal circuits between the basal ganglia and cortical areas supporting motor function and planning. Research with the Serial Reaction Time (SRT) task suggests that patients with memory-disorders due to MTL damage exhibit normal implicit sequence learning. However, reports of intact learning rely on observations of no group differences, leading to speculation whether implicit sequence learning is fully intact in these patients. Patients with Parkinson's Disease (PD) often exhibit impaired sequence learning, but this impairment is not universally observed. Method Implicit perceptual-motor sequence learning was examined using the Serial Interception Sequence Learning (SISL) task in patients with amnestic Mild Cognitive Impairment (MCI; n=11) and patients with PD (n=15). Sequence learning in SISL is resistant to explicit learning and individually adapted task difficulty controls for baseline performance differences. Results Patients with MCI exhibited robust sequence learning, equivalent to healthy older adults (n=20), supporting the hypothesis that the MTL does not contribute to learning in this task. In contrast, the majority of patients with PD exhibited no sequence-specific learning in spite of matched overall task performance. Two patients with PD exhibited performance indicative of an explicit compensatory strategy suggesting that impaired implicit learning may lead to greater reliance on explicit memory in some individuals. Conclusion The differences in learning between patient groups provides strong evidence in favor of implicit sequence learning depending solely on intact basal ganglia function with no contribution from the MTL memory system. PMID:23688213

Implicit perceptual-motor skill learning in mild cognitive impairment and Parkinson's disease.

PubMed

Gobel, Eric W; Blomeke, Kelsey; Zadikoff, Cindy; Simuni, Tanya; Weintraub, Sandra; Reber, Paul J

2013-05-01

Implicit skill learning is hypothesized to depend on nondeclarative memory that operates independent of the medial temporal lobe (MTL) memory system and instead depends on cortico striatal circuits between the basal ganglia and cortical areas supporting motor function and planning. Research with the Serial Reaction Time (SRT) task suggests that patients with memory disorders due to MTL damage exhibit normal implicit sequence learning. However, reports of intact learning rely on observations of no group differences, leading to speculation as to whether implicit sequence learning is fully intact in these patients. Patients with Parkinson's disease (PD) often exhibit impaired sequence learning, but this impairment is not universally observed. Implicit perceptual-motor sequence learning was examined using the Serial Interception Sequence Learning (SISL) task in patients with amnestic Mild Cognitive Impairment (MCI; n = 11) and patients with PD (n = 15). Sequence learning in SISL is resistant to explicit learning and individually adapted task difficulty controls for baseline performance differences. Patients with MCI exhibited robust sequence learning, equivalent to healthy older adults (n = 20), supporting the hypothesis that the MTL does not contribute to learning in this task. In contrast, the majority of patients with PD exhibited no sequence-specific learning in spite of matched overall task performance. Two patients with PD exhibited performance indicative of an explicit compensatory strategy suggesting that impaired implicit learning may lead to greater reliance on explicit memory in some individuals. The differences in learning between patient groups provides strong evidence in favor of implicit sequence learning depending solely on intact basal ganglia function with no contribution from the MTL memory system.

Age-related impairments in active learning and strategic visual exploration.

PubMed

Brandstatt, Kelly L; Voss, Joel L

2014-01-01

Old age could impair memory by disrupting learning strategies used by younger individuals. We tested this possibility by manipulating the ability to use visual-exploration strategies during learning. Subjects controlled visual exploration during active learning, thus permitting the use of strategies, whereas strategies were limited during passive learning via predetermined exploration patterns. Performance on tests of object recognition and object-location recall was matched for younger and older subjects for objects studied passively, when learning strategies were restricted. Active learning improved object recognition similarly for younger and older subjects. However, active learning improved object-location recall for younger subjects, but not older subjects. Exploration patterns were used to identify a learning strategy involving repeat viewing. Older subjects used this strategy less frequently and it provided less memory benefit compared to younger subjects. In previous experiments, we linked hippocampal-prefrontal co-activation to improvements in object-location recall from active learning and to the exploration strategy. Collectively, these findings suggest that age-related memory problems result partly from impaired strategies during learning, potentially due to reduced hippocampal-prefrontal co-engagement.

Connecting Mathematics Learning through Spatial Reasoning

ERIC Educational Resources Information Center

Mulligan, Joanne; Woolcott, Geoffrey; Mitchelmore, Michael; Davis, Brent

2018-01-01

Spatial reasoning, an emerging transdisciplinary area of interest to mathematics education research, is proving integral to all human learning. It is particularly critical to science, technology, engineering and mathematics (STEM) fields. This project will create an innovative knowledge framework based on spatial reasoning that identifies new…

Early Life Manipulations Alter Learning and Memory in Rats

PubMed Central

Kosten, Therese A; Kim, Jeansok J; Lee, Hongjoo J.

2012-01-01

Much research shows early life manipulations have enduring behavioral, neural, and hormonal effects. However, findings of learning and memory performance vary widely across studies. We reviewed studies in which pre-weaning rat pups were exposed to stressors and tested on learning and memory tasks in adulthood. Tasks were classified as aversive conditioning, inhibitory learning, or spatial/relational memory. Variables of duration, type, and timing of neonatal manipulation and sex and strain of animals were examined to determine if any predict enhanced or impaired performance. Brief separations enhanced and prolonged separations impaired performance on spatial/relational tasks. Performance was impaired in aversive conditioning and enhanced in inhibitory learning tasks regardless of manipulation duration. Opposing effects on performance for spatial/relational memory also depended upon timing of manipulation. Enhanced performance was likely if the manipulation occurred during postnatal week 3 but performance was impaired if it was confined to the first two postnatal weeks. Thus, the relationship between early life experiences and adulthood learning and memory performance is multifaceted and decidedly task-dependent. PMID:22819985

Inhibition of Connexin43 Hemichannels Impairs Spatial Short-Term Memory without Affecting Spatial Working Memory.

PubMed

Walrave, Laura; Vinken, Mathieu; Albertini, Giulia; De Bundel, Dimitri; Leybaert, Luc; Smolders, Ilse J

2016-01-01

Astrocytes are active players in higher brain function as they can release gliotransmitters, which are essential for synaptic plasticity. Various mechanisms have been proposed for gliotransmission, including vesicular mechanisms as well as non-vesicular ones, for example by passive diffusion via connexin hemichannels (HCs). We here investigated whether interfering with connexin43 (Cx43) HCs influenced hippocampal spatial memory. We made use of the peptide Gap19 that blocks HCs but not gap junction channels and is specific for Cx43. To this end, we microinfused transactivator of transcription linked Gap19 (TAT-Gap19) into the brain ventricle of male NMRI mice and assessed spatial memory in a Y maze. We found that the in vivo blockade of Cx43 HCs did not affect the locomotor activity or spatial working memory in a spontaneous alternation Y maze task. Cx43 blockade did however significantly impair the spatial short-term memory in a delayed spontaneous alternation Y maze task. These results indicate that Cx43 HCs play a role in spatial short-term memory.

Grammar Predicts Procedural Learning and Consolidation Deficits in Children with Specific Language Impairment

PubMed Central

Hedenius, Martina; Persson, Jonas; Tremblay, Antoine; Adi-Japha, Esther; Veríssimo, João; Dye, Cristina D.; Alm, Per; Jennische, Margareta; Tomblin, J. Bruce; Ullman, Michael T.

2011-01-01

The Procedural Deficit Hypothesis (PDH) posits that Specific Language Impairment (SLI) can be largely explained by abnormalities of brain structures that subserve procedural memory. The PDH predicts impairments of procedural memory itself, and that such impairments underlie the grammatical deficits observed in the disorder. Previous studies have indeed reported procedural learning impairments in SLI, and have found that these are associated with grammatical difficulties. The present study extends this research by examining the consolidation and longer-term procedural sequence learning in children with SLI. The Alternating Serial Reaction Time (ASRT) task was given to children with SLI and typically-developing (TD) children in an initial learning session and an average of three days later to test for consolidation and longer-term learning. Although both groups showed evidence of initial sequence learning, only the TD children showed clear signs of consolidation, even though the two groups did not differ in longer-term learning. When the children were re-categorized on the basis of grammar deficits rather than broader language deficits, a clearer pattern emerged. Whereas both the grammar impaired and normal grammar groups showed evidence of initial sequence learning, only those with normal grammar showed consolidation and longer-term learning. Indeed, the grammar-impaired group appeared to lose any sequence knowledge gained during the initial testing session. These findings held even when controlling for vocabulary or a broad non-grammatical language measure, neither of which were associated with procedural memory. When grammar was examined as a continuous variable over all children, the same relationships between procedural memory and grammar, but not vocabulary or the broader language measure, were observed. Overall, the findings support and further specify the PDH. They suggest that consolidation and longer-term procedural learning are impaired in SLI, but that

Trim9 Deletion Alters the Morphogenesis of Developing and Adult-Born Hippocampal Neurons and Impairs Spatial Learning and Memory

PubMed Central

Winkle, Cortney C.; Olsen, Reid H. J.; Kim, Hyojin; Moy, Sheryl S.

2016-01-01

During hippocampal development, newly born neurons migrate to appropriate destinations, extend axons, and ramify dendritic arbors to establish functional circuitry. These developmental stages are recapitulated in the dentate gyrus of the adult hippocampus, where neurons are continuously generated and subsequently incorporate into existing, local circuitry. Here we demonstrate that the E3 ubiquitin ligase TRIM9 regulates these developmental stages in embryonic and adult-born mouse hippocampal neurons in vitro and in vivo. Embryonic hippocampal and adult-born dentate granule neurons lacking Trim9 exhibit several morphological defects, including excessive dendritic arborization. Although gross anatomy of the hippocampus was not detectably altered by Trim9 deletion, a significant number of Trim9−/− adult-born dentate neurons localized inappropriately. These morphological and localization defects of hippocampal neurons in Trim9−/− mice were associated with extreme deficits in spatial learning and memory, suggesting that TRIM9-directed neuronal morphogenesis may be involved in hippocampal-dependent behaviors. SIGNIFICANCE STATEMENT Appropriate generation and incorporation of adult-born neurons in the dentate gyrus are critical for spatial learning and memory and other hippocampal functions. Here we identify the brain-enriched E3 ubiquitin ligase TRIM9 as a novel regulator of embryonic and adult hippocampal neuron shape acquisition and hippocampal-dependent behaviors. Genetic deletion of Trim9 elevated dendritic arborization of hippocampal neurons in vitro and in vivo. Adult-born dentate granule cells lacking Trim9 similarly exhibited excessive dendritic arborization and mislocalization of cell bodies in vivo. These cellular defects were associated with severe deficits in spatial learning and memory. PMID:27147649

Impairments in Precision, Rather than Spatial Strategy, Characterize Performance on the Virtual Morris Water Maze: A Case Study

PubMed Central

Kolarik, Branden S.; Shahlaie, Kiarash; Hassan, Abdul; Borders, Alyssa A.; Kaufman, Kyle C.; Gurkoff, Gene; Yonelinas, Andy P.; Ekstrom, Arne D.

2015-01-01

Damage to the medial temporal lobes produces profound amnesia, greatly impairing the ability of patients to learn about new associations and events. While studies in rodents suggest a strong link between damage to the hippocampus and the ability to navigate using distal landmarks in a spatial environment, the connection between navigation and memory in humans remains less clear. Past studies on human navigation have provided mixed findings about whether patients with damage to the medial temporal lobes can successfully acquire and navigate new spatial environments, possibly due, in part, to issues related to patient demographics and characterization of medial temporal lobe damage. Here, we report findings from a young, high functioning patient who suffered severe medial temporal lobe damage. Although the patient is densely amnestic, her ability to acquire and utilize new, but coarse, spatial “maps” appears largely intact. Specifically, a novel computational analysis focused on the precision of her spatial search revealed a significant deficit in spatial precision rather than spatial search strategy. These findings argue that an intact hippocampus in humans is not necessary for representing multiple external landmarks during spatial navigation of new environments. We suggest instead that the human hippocampus may store and represent complex high-resolution bindings of features in the environment as part of a larger role in perception, memory, and navigation. PMID:26593960

Does Incorrect Guessing Impair Fact Learning?

ERIC Educational Resources Information Center

Kang, Sean H. K.; Pashler, Harold; Cepeda, Nicholas J.; Rohrer, Doug; Carpenter, Shana K.; Mozer, Michael C.

2011-01-01

Taking a test has been shown to produce enhanced retention of the retrieved information. On tests, however, students often encounter questions the answers for which they are unsure. Should they guess anyway, even if they are likely to answer incorrectly? Or are errors engrained, impairing subsequent learning of the correct answer? We sought to…

Changes in the Hippocampal Proteome Associated with Spatial Memory Impairment after Exposure to Low (20 cGy) Doses of 1 GeV/n 56Fe Radiation.

PubMed

Britten, Richard A; Jewell, Jessica S; Davis, Leslie K; Miller, Vania D; Hadley, Melissa M; Semmes, O John; Lonart, György; Dutta, Sucharita M

2017-03-01

Exposure to low (∼20 cGy) doses of high-energy charged (HZE) particles, such as 1 GeV/n 56 Fe, results in impaired hippocampal-dependent learning and memory (e.g., novel object recognition and spatial memory) in rodents. While these findings raise the possibility that astronauts on deep-space missions may develop cognitive deficits, not all rats develop HZE-induced cognitive impairments, even after exposure to high (200 cGy) HZE doses. The reasons for this differential sensitivity in some animals that develop HZE-induced cognitive failure remain speculative. We employed a robust quantitative mass spectrometry-based workflow, which links early-stage discovery to next-stage quantitative verification, to identify differentially active proteins/pathways in rats that developed spatial memory impairment at three months after exposure to 20 cGy of 1 GeV/n 56 Fe (20/impaired), and in those rats that managed to maintain normal cognitive performance (20/functional). Quantitative data were obtained on 665-828 hippocampal proteins in the various cohorts of rats studied, of which 580 were expressed in all groups. A total of 107 proteins were upregulated in the irradiated rats irrespective of their spatial memory performance status, which included proteins involved in oxidative damage response, calcium transport and signaling. Thirty percent (37/107) of these "radiation biomarkers" formed a functional interactome of the proteasome and the COP9 signalosome. These data suggest that there is persistent oxidative stress, ongoing autophagy and altered synaptic plasticity in the irradiated hippocampus, irrespective of the spatial memory performance status, suggesting that the ultimate phenotype may be determined by how well the hippocampal neurons compensate to the ongoing oxidative stress and associated side effects. There were 67 proteins with expression that correlated with impaired spatial memory performance. Several of the "impaired biomarkers" have been implicated in poor

Map Learning with a 3D Printed Interactive Small-Scale Model: Improvement of Space and Text Memorization in Visually Impaired Students.

PubMed

Giraud, Stéphanie; Brock, Anke M; Macé, Marc J-M; Jouffrais, Christophe

2017-01-01

Special education teachers for visually impaired students rely on tools such as raised-line maps (RLMs) to teach spatial knowledge. These tools do not fully and adequately meet the needs of the teachers because they are long to produce, expensive, and not versatile enough to provide rapid updating of the content. For instance, the same RLM can barely be used during different lessons. In addition, those maps do not provide any interactivity, which reduces students' autonomy. With the emergence of 3D printing and low-cost microcontrollers, it is now easy to design affordable interactive small-scale models (SSMs) which are adapted to the needs of special education teachers. However, no study has previously been conducted to evaluate non-visual learning using interactive SSMs. In collaboration with a specialized teacher, we designed a SSM and a RLM representing the evolution of the geography and history of a fictitious kingdom. The two conditions were compared in a study with 24 visually impaired students regarding the memorization of the spatial layout and historical contents. The study showed that the interactive SSM improved both space and text memorization as compared to the RLM with braille legend. In conclusion, we argue that affordable home-made interactive small scale models can improve learning for visually impaired students. Interestingly, they are adaptable to any teaching situation including students with specific needs.

Map Learning with a 3D Printed Interactive Small-Scale Model: Improvement of Space and Text Memorization in Visually Impaired Students

PubMed Central

Giraud, Stéphanie; Brock, Anke M.; Macé, Marc J.-M.; Jouffrais, Christophe

2017-01-01

Special education teachers for visually impaired students rely on tools such as raised-line maps (RLMs) to teach spatial knowledge. These tools do not fully and adequately meet the needs of the teachers because they are long to produce, expensive, and not versatile enough to provide rapid updating of the content. For instance, the same RLM can barely be used during different lessons. In addition, those maps do not provide any interactivity, which reduces students’ autonomy. With the emergence of 3D printing and low-cost microcontrollers, it is now easy to design affordable interactive small-scale models (SSMs) which are adapted to the needs of special education teachers. However, no study has previously been conducted to evaluate non-visual learning using interactive SSMs. In collaboration with a specialized teacher, we designed a SSM and a RLM representing the evolution of the geography and history of a fictitious kingdom. The two conditions were compared in a study with 24 visually impaired students regarding the memorization of the spatial layout and historical contents. The study showed that the interactive SSM improved both space and text memorization as compared to the RLM with braille legend. In conclusion, we argue that affordable home-made interactive small scale models can improve learning for visually impaired students. Interestingly, they are adaptable to any teaching situation including students with specific needs. PMID:28649209

Rats with ventral hippocampal damage are impaired at various forms of learning including conditioned inhibition, spatial navigation, and discriminative fear conditioning to similar contexts.

PubMed

McDonald, Robert J; Balog, R J; Lee, Justin Q; Stuart, Emily E; Carrels, Brianna B; Hong, Nancy S

2018-10-01

The ventral hippocampus (vHPC) has been implicated in learning and memory functions that seem to differ from its dorsal counterpart. The goal of this series of experiments was to provide further insight into the functional contributions of the vHPC. Our previous work implicated the vHPC in spatial learning, inhibitory learning, and fear conditioning to context. However, the specific role of vHPC on these different forms of learning are not clear. Accordingly, we assessed the effects of neurotoxic lesions of the ventral hippocampus on retention of a conditioned inhibitory association, early versus late spatial navigation in the water task, and discriminative fear conditioning to context under high ambiguity conditions. The results showed that the vHPC was necessary for the expression of conditioned inhibition, early spatial learning, and discriminative fear conditioning to context when the paired and unpaired contexts have high cue overlap. We argue that this pattern of effects, combined with previous work, suggests a key role for vHPC in the utilization of broad contextual representations for inhibition and discriminative memory in high ambiguity conditions. Copyright © 2018 Elsevier B.V. All rights reserved.

Contributions of dorsal striatal subregions to spatial alternation behavior.

PubMed

Moussa, Roula; Poucet, Bruno; Amalric, Marianne; Sargolini, Francesca

2011-07-01

Considerable evidence has shown a clear dissociation between the dorsomedial (DMS) and the dorsolateral (DLS) striatum in instrumental conditioning. In particular, DMS activity is necessary to form action-outcome associations, whereas the DLS is required for developing habitual behavior. However, few studies have investigated whether a similar dissociation exists in more complex goal-directed learning processes. The present study examined the role of the two structures in such complex learning by analyzing the effects of excitotoxic DMS and DLS lesions during the acquisition and extinction of spatial alternation behavior, in a continuous alternation T-maze task. We demonstrate that DMS and DLS lesions have opposite effects, the former impairing and the latter improving animal performance during learning and extinction. DMS lesions may impair the acquisition of spatial alternation behavior by disrupting the signal necessary to link a goal with a specific spatial sequence. In contrast, DLS lesions may accelerate goal-driven strategies by minimizing the influence of external stimuli on the response, thus increasing the impact of action-reward contingencies. Taken together, these results suggest that DMS- and DLS-mediated learning strategies develop in parallel and compete for the control of the behavioral response early in learning.

Legionella pneumophila-induced visual learning impairment reversed by anti-interleukin-1 beta.

PubMed

Gibertini, M; Newton, C; Klein, T W; Friedman, H

1995-10-01

Infecting mice with the opportunistic intracellular pathogen Legionella pneumophila markedly inhibited place learning of infected C57BL/6 mice as determined by the Morris water maze test. Mice infected with L. pneumophila evinced much less ability to learn the position of a hidden platform than did normal noninfected mice, which quickly learned the location of the hidden platform and escaped from the cool water of the pool with increasing efficiency. However, infected mice treated with anti-interleukin-1 (anti-IL-1) neutralizing antibody learned the task with about the same efficiency as the controls. When the animals were tested 1 week after learning, control animals remembered the task well and were able to escape with near maximal efficacy. On the other hand, L. pneumophila-infected mice performed as poorly after the 1 week rest as during the training period, indicating that infection blocked learning and not merely performance. Mice infected with L. pneumophila and given the antibody treatment were found to be indistinguishable from controls in that they remembered the task and escaped with good efficiency. Thus, the results of this study suggest that the pro-inflammatory cytokine, IL-1 beta, is involved, at least partly, in the attenuation of spatial navigational learning in mice infected acutely with a sublethal concentration of L. pneumophila. These results, therefore, suggest that cognitive impairment of L. pneumophila-infected mice may be related to the cytokine IL-1 beta and, furthermore, that cytokines may be related to learning and memory changes experienced by individuals suffering acute bacterial infections.

Categorical spatial memory in patients with mild cognitive impairment and Alzheimer dementia: positional versus object-location recall.

PubMed

Kessels, Roy P C; Rijken, Stefan; Joosten-Weyn Banningh, Liesbeth W A; Van Schuylenborgh-VAN Es, Nelleke; Olde Rikkert, Marcel G M

2010-01-01

Memory for object locations, as part of spatial memory function, has rarely been studied in patients with Alzheimer dementia (AD), while studies in patients with Mild Cognitive Impairment (MCI) patients are lacking altogether. The present study examined categorical spatial memory function using the Location Learning Test (LLT) in MCI patients (n = 30), AD patients (n = 30), and healthy controls (n = 40). Two scoring methods were compared, aimed at disentangling positional recall (location irrespective of object identity) and object-location binding. The results showed that AD patients performed worse than the MCI patients on the LLT, both on recall of positional information and on recall of the locations of different objects. In addition, both measures could validly discriminate between AD and MCI patients. These findings are in agreement with the notion that visual cued-recall tests may have better diagnostic value than traditional (verbal) free-recall tests in the assessment of patients with suspected MCI or AD.

Impaired early visual response modulations to spatial information in chronic schizophrenia

PubMed Central

Knebel, Jean-François; Javitt, Daniel C.; Murray, Micah M.

2011-01-01

Early visual processing stages have been demonstrated to be impaired in schizophrenia patients and their first-degree relatives. The amplitude and topography of the P1 component of the visual evoked potential (VEP) are both affected; the latter of which indicates alterations in active brain networks between populations. At least two issues remain unresolved. First, the specificity of this deficit (and suitability as an endophenotype) has yet to be established, with evidence for impaired P1 responses in other clinical populations. Second, it remains unknown whether schizophrenia patients exhibit intact functional modulation of the P1 VEP component; an aspect that may assist in distinguishing effects specific to schizophrenia. We applied electrical neuroimaging analyses to VEPs from chronic schizophrenia patients and healthy controls in response to variation in the parafoveal spatial extent of stimuli. Healthy controls demonstrated robust modulation of the VEP strength and topography as a function of the spatial extent of stimuli during the P1 component. By contrast, no such modulations were evident at early latencies in the responses from patients with schizophrenia. Source estimations localized these deficits to the left precuneus and medial inferior parietal cortex. These findings provide insights on potential underlying low-level impairments in schizophrenia. PMID:21764264

Sex-specific effects of prenatal chronic mild stress on adult spatial learning capacity and regional glutamate receptor expression profiles.

PubMed

Wang, Yan; Ma, Yuchao; Hu, Jingmin; Zhang, Xinxin; Cheng, Wenwen; Jiang, Han; Li, Min; Ren, Jintao; Zhang, Xiaosong; Liu, Mengxi; Sun, Anji; Wang, Qi; Li, Xiaobai

2016-07-01

Both animal experiments and clinical studies have demonstrated that prenatal stress can cause cognitive disorders in offspring. To explore the scope of these deficits and identify potential underlying mechanisms, we examined the spatial learning and memory performance and glutamate receptor (GluR) expression patterns of adult rats exposed to prenatal chronic mild stress (PCMS). Principal component analysis (PCA) was employed to reveal the interrelationships among spatial learning indices and GluR expression changes. Female PCMS-exposed offspring exhibited markedly impaired spatial learning and memory in the Morris water maze (MWM) task compared to control females, while PCMS-exposed males showed better initial spatial learning in the MWM compared to control males. PCMS also altered basal and post-MWM glutamate receptor expression patterns, but these effects differed markedly between sexes. Male PCMS-exposed offspring exhibited elevated basal expression of NR1, mGluR5, and mGluR2/3 in the prefrontal cortex (PFC), whereas females showed no basal expression changes. Following MWM training, PCMS-exposed males expressed higher NR1 in the PFC and mammillary body (MB), higher mGluR2/3 in PFC, and lower NR2B in the hippocampus (HIP), PFC, and MB compared to unstressed MWM-trained males. Female PCMS-exposed offspring showed strongly reduced NR1 in MB and NR2B in the HIP, PFC, and MB, and increased mGluR2/3 in PFC compared to unstressed MWM-trained females. This is the first report suggesting that NMDA subunits in the MB are involved in spatial learning. Additionally, PCA further suggests that the NR1-NR2B form is the most important for spatial memory formation. These results reveal long-term sex-specific effects of PCMS on spatial learning and memory performance in adulthood and implicate GluR expression changes within HIP, PFC, and MB as possible molecular mechanisms underlying cognitive dysfunction in offspring exposed to prenatal stress. Copyright © 2016 Elsevier Inc

Effects of alcoholic beverage treatment on spatial learning and fear memory in mice.

PubMed

Hashikawa-Hobara, Narumi; Mishima, Shuta; Nagase, Shotaro; Morita, Keishi; Otsuka, Ami; Hashikawa, Naoya

2018-04-24

Although chronic ethanol treatment is known to impair learning and memory, humans commonly consume a range of alcoholic beverages. However, the specific effects of some alcoholic beverages on behavioral performance are largely unknown. The present study compared the effects of a range of alcoholic beverages (plain ethanol solution, red wine, sake and whiskey; with a matched alcohol concentration of 10%) on learning and memory. 6-week-old C57BL6J mice were orally administered alcohol for 7 weeks. The results revealed that red wine treatment exhibited a trend toward improvement of spatial memory and advanced extinction of fear memory. Additionally, red wine treatment significantly increased mRNA levels of brain-derived neurotrophic factor (BDNF) and N-methyl-D-aspartate (NMDA) receptors in mice hippocampus. These results support previous reports that red wine has beneficial effects.

Trim9 Deletion Alters the Morphogenesis of Developing and Adult-Born Hippocampal Neurons and Impairs Spatial Learning and Memory.

PubMed

Winkle, Cortney C; Olsen, Reid H J; Kim, Hyojin; Moy, Sheryl S; Song, Juan; Gupton, Stephanie L

2016-05-04

During hippocampal development, newly born neurons migrate to appropriate destinations, extend axons, and ramify dendritic arbors to establish functional circuitry. These developmental stages are recapitulated in the dentate gyrus of the adult hippocampus, where neurons are continuously generated and subsequently incorporate into existing, local circuitry. Here we demonstrate that the E3 ubiquitin ligase TRIM9 regulates these developmental stages in embryonic and adult-born mouse hippocampal neurons in vitro and in vivo Embryonic hippocampal and adult-born dentate granule neurons lacking Trim9 exhibit several morphological defects, including excessive dendritic arborization. Although gross anatomy of the hippocampus was not detectably altered by Trim9 deletion, a significant number of Trim9(-/-) adult-born dentate neurons localized inappropriately. These morphological and localization defects of hippocampal neurons in Trim9(-/-) mice were associated with extreme deficits in spatial learning and memory, suggesting that TRIM9-directed neuronal morphogenesis may be involved in hippocampal-dependent behaviors. Appropriate generation and incorporation of adult-born neurons in the dentate gyrus are critical for spatial learning and memory and other hippocampal functions. Here we identify the brain-enriched E3 ubiquitin ligase TRIM9 as a novel regulator of embryonic and adult hippocampal neuron shape acquisition and hippocampal-dependent behaviors. Genetic deletion of Trim9 elevated dendritic arborization of hippocampal neurons in vitro and in vivo Adult-born dentate granule cells lacking Trim9 similarly exhibited excessive dendritic arborization and mislocalization of cell bodies in vivo These cellular defects were associated with severe deficits in spatial learning and memory. Copyright © 2016 the authors 0270-6474/16/364940-19$15.00/0.

Fingolimod (FTY720) attenuates social deficits, learning and memory impairments, neuronal loss and neuroinflammation in the rat model of autism.

PubMed

Wu, Hongmei; Wang, Xuelai; Gao, Jingquan; Liang, Shuang; Hao, Yanqiu; Sun, Caihong; Xia, Wei; Cao, Yonggang; Wu, Lijie

2017-03-15

To investigate the effect of FTY720 on the valproic acid (VPA) rat model of autism. As an animal model of autism, we used intraperitoneal injection of VPA on embryonic day 12.5 in Wistar rats. The pups were given FTY720 orally at doses of 0.25, 0.5 and 1mg/kg daily from postnatal day 15 to 35. Social behavior, spatial learning and memory were assessed at the end of FTY720 treatment. The histological change, oxidative stress, neuroinflammatory responses, and apoptosis-related proteins in the hippocampus were evaluated. FTY720 (1mg/kg) administration to VPA-exposed rats (1) improved social behavior, spatial learning and memory impairment; (2) resulted in a reduction in neuronal loss and apoptosis of pyramidal cells in hippocampal CA1 regions; (3) inhibited activation of microglial cells, in turn lowering the level of pro-inflammatory cytokines interleukin-1β (IL-1β) and IL-6 in the hippocampus; (4) changed Malondialdehyde (MDA) levels, Glutathione (GSH) levels, superoxide dismutase (SOD) activity and Glutathione Peroxidase (GSH-Px) activity in the hippocampus; (6) inhibited the elevated Bax and caspase-3 protein levels and enhanced the relative expression level of Bcl-2 in the hippocampus; and (7) increased phospho-Ca2+/calmodulin-dependent protein kinase II (p-CaMKII), phospho-cAMP-response element binding protein (p-CREB) and Brain Derived Neurotrophic Factor (BDNF) protein expression in the hippocampus. FTY720 rescues social deficit, spatial learning and memory impairment in VPA-exposed rats. FTY720 exerts both a direct protection for neurons and an indirect modulation of inflammation-mediated neuron loss as a possible mechanism of neuroprotection. Copyright © 2017. Published by Elsevier Inc.

Compound danshen tablet ameliorated aβ25-35-induced spatial memory impairment in mice via rescuing imbalance between cytokines and neurotrophins

PubMed Central

2014-01-01

Background Compound Danshen Tablet (CDT), a Traditional Chinese Medicine, has recently been reported to improve spatial cognition in a rat model of Alzheimer’s disease. However, in vivo neuroprotective mechanism of the CDT in models of spatial memory impairment is not yet evaluated. The present study is aimed to elucidate the cellular mechanism of CDT on Aβ25-35-induced cognitive impairment in mice. Methods Mice were randomly divided into 5 groups: the control group (sham operated), the Aβ25-35 treated group, the positive drug group, and large and small dosage of the CDT groups, respectively. CDT was administered at a dose of 0.81 g/kg and 0.405 g/kg for 3 weeks. The mice in the positive drug group were treated with 0.4 mg/kg of Huperzine A, whereas the mice of the control and Aβ25-35 treated groups were administrated orally with equivalent saline. After 7 days of preventive treatment, mice were subjected to lateral ventricle injection of Aβ25-35 to establish the mice model of Alzheimer’s disease. Spatial memory impairment was evaluated by Morris water maze test. Choline acetyltransferase (ChAT) contents in hippocampus and cortex were quantified by ELISA. The levels of cytokines, receptor of activated protein kinase C1 (RACK1) and brain-derived neurotrophic factor (BDNF) in hippocampus were measured by RT-PCR and ELISA. Results The results showed that Aβ25-35 caused spatial memory impairment as demonstrated by performance in the Morris water maze test. CDT was able to confer a significant improvement in spatial memory, and protect mice from Aβ25-35-induced neurotoxicity. Additionally, CDT also inhibited the increase of TNF-α and IL-6 level, and increased the expression of choline acetyltransferase (ChAT), receptor of activated protein kinase C1 (RACK1) and brain-derived neurotrophic factor (BDNF) in brain as compared to model mice. Conclusion These findings strongly implicate that CDT may be a useful treatment against learning and memory deficits in

A virtual reality task based on animal research – spatial learning and memory in patients after the first episode of schizophrenia

PubMed Central

Fajnerová, Iveta; Rodriguez, Mabel; Levčík, David; Konrádová, Lucie; Mikoláš, Pavol; Brom, Cyril; Stuchlík, Aleš; Vlček, Kamil; Horáček, Jiří

2014-01-01

Objectives: Cognitive deficit is considered to be a characteristic feature of schizophrenia disorder. A similar cognitive dysfunction was demonstrated in animal models of schizophrenia. However, the poor comparability of methods used to assess cognition in animals and humans could be responsible for low predictive validity of current animal models. In order to assess spatial abilities in schizophrenia and compare our results with the data obtained in animal models, we designed a virtual analog of the Morris water maze (MWM), the virtual Four Goals Navigation (vFGN) task. Methods: Twenty-nine patients after the first psychotic episode with schizophrenia symptoms and a matched group of healthy volunteers performed the vFGN task. They were required to find and remember four hidden goal positions in an enclosed virtual arena. The task consisted of two parts. The Reference memory (RM) session with a stable goal position was designed to test spatial learning. The Delayed-matching-to-place (DMP) session presented a modified working memory protocol designed to test the ability to remember a sequence of three hidden goal positions. Results: Data obtained in the RM session show impaired spatial learning in schizophrenia patients compared to the healthy controls in pointing and navigation accuracy. The DMP session showed impaired spatial memory in schizophrenia during the recall of spatial sequence and a similar deficit in spatial bias in the probe trials. The pointing accuracy and the quadrant preference showed higher sensitivity toward the cognitive deficit than the navigation accuracy. Direct navigation to the goal was affected by sex and age of the tested subjects. The age affected spatial performance only in healthy controls. Conclusions: Despite some limitations of the study, our results correspond well with the previous studies in animal models of schizophrenia and support the decline of spatial cognition in schizophrenia, indicating the usefulness of the vFGN task in

Sulforaphane attenuates postnatal proteasome inhibition and improves spatial learning in adult mice.

PubMed

Sunkaria, Aditya; Bhardwaj, Supriya; Yadav, Aarti; Halder, Avishek; Sandhir, Rajat

2018-01-01

Proteasomes are known to degrade proteins involved in various processes like metabolism, signal transduction, cell-cycle regulation, inflammation, and apoptosis. Evidence showed that protein degradation has a strong influence on developing neurons as well as synaptic plasticity. Here, we have shown that sulforaphane (SFN) could prevent the deleterious effects of postnatal proteasomal inhibition on spatial reference and working memory of adult mice. One day old Balb/c mice received intracerebroventricular injections of MG132 and SFN. Sham received an equal volume of aCSF. We observed that SFN pre-administration could attenuate MG132 mediated decrease in proteasome and calpain activities. In vitro findings revealed that SFN could induce proteasomal activity by enhancing the expression of catalytic subunit-β5. SFN pre-administration prevented the hippocampus based spatial memory impairments during adulthood, mediated by postnatal MG132 exposure. Histological examination showed deleterious effects of MG132 on pyramidal neurons and granule cell neurons in DG and CA3 sub-regions respectively. Furthermore, SFN pre-administration has shown to attenuate the effect of MG132 on proteasome subunit-β5 expression and also induce the Nrf2 nuclear translocation. In addition, SFN pre-administered mice have also shown to induce expression of pCaMKII, pCreb, and mature/pro-Bdnf, molecules which play a crucial role in spatial learning and memory consolidation. Our findings have shown that proteasomes play an important role in hippocampal synaptic plasticity during the early postnatal period and SFN pre-administration could enhance the proteasomal activity as well as improve spatial learning and memory consolidation. Copyright © 2017 Elsevier Inc. All rights reserved.

Sex-Specific Effects of Diets High in Unsaturated Fatty Acids on Spatial Learning and Memory in Guinea Pigs.

PubMed

Nemeth, Matthias; Millesi, Eva; Wagner, Karl-Heinz; Wallner, Bernard

2015-01-01

Unsaturated fatty acids (UFAs), including omega-3, omega-6 polyunsaturated and omega-9 monounsaturated fatty acids, are essential components and modulators of neuromembranes and may affect various aspects of physiology and cognition. UFAs are suggested to positively affect spatial learning and memory and also to diminish the negative consequences of physiological stress on cognitive abilities. Due to pronounced sex differences in neurophysiological functions, we hypothesize that these UFA-related effects might differ between male and female individuals. We therefore determined the effects of dietary UFAs on cognitive performances in a radial-Y-maze in male and female guinea pigs in relation to saliva cortisol concentrations, a marker for physiological stress. Animals were assigned to four treatment groups and maintained on diets enriched in either chia seeds (omega-3), walnuts (omega-6), or peanuts (omega-9), or a control diet. Female learning abilities throughout a three-day learning phase were positively affected by omega-3 and omega-9, as determined by a decreasing latency to pass the test and the number of conducted errors, while males generally showed distinct learning abilities, irrespective of the diet. A sex difference in learning performances was found in the control group, with males outperforming females, which was not detected in the UFA-supplemented groups. This was paralleled by significantly increased saliva cortisol concentrations in males throughout the cognition test compared to females. Three days after this learning phase, UFA-supplemented males and all females showed unchanged performances, while control males showed an increased latency and therefore an impaired performance. These results were corroborated by pronounced differences in the plasma UFA-status, corresponding to the different dietary treatments. Our findings indicate sex-specific effects of dietary UFAs, apparently enhancing spatial learning abilities only in females and protecting

Electric crosstalk impairs spatial resolution of multi-electrode arrays in retinal implants

NASA Astrophysics Data System (ADS)

Wilke, R. G. H.; Khalili Moghadam, G.; Lovell, N. H.; Suaning, G. J.; Dokos, S.

2011-08-01

Active multi-electrode arrays are used in vision prostheses, including optic nerve cuffs and cortical and retinal implants for stimulation of neural tissue. For retinal implants, arrays with up to 1500 electrodes are used in clinical trials. The ability to convey information with high spatial resolution is critical for these applications. To assess the extent to which spatial resolution is impaired by electric crosstalk, finite-element simulation of electric field distribution in a simplified passive tissue model of the retina is performed. The effects of electrode size, electrode spacing, distance to target cells, and electrode return configuration (monopolar, tripolar, hexagonal) on spatial resolution is investigated in the form of a mathematical model of electric field distribution. Results show that spatial resolution is impaired with increased distance from the electrode array to the target cells. This effect can be partly compensated by non-monopolar electrode configurations and larger electrode diameters, albeit at the expense of lower pixel densities due to larger covering areas by each stimulation electrode. In applications where multi-electrode arrays can be brought into close proximity to target cells, as presumably with epiretinal implants, smaller electrodes in monopolar configuration can provide the highest spatial resolution. However, if the implantation site is further from the target cells, as is the case in suprachoroidal approaches, hexagonally guarded electrode return configurations can convey higher spatial resolution. This paper was originally submitted for the special issue containing contributions from the Sixth Biennial Research Congress of The Eye and the Chip.

Is social attention impaired in schizophrenia? Gaze, but not pointing gestures, is associated with spatial attention deficits.

PubMed

Dalmaso, Mario; Galfano, Giovanni; Tarqui, Luana; Forti, Bruno; Castelli, Luigi

2013-09-01

The nature of possible impairments in orienting attention to social signals in schizophrenia is controversial. The present research was aimed at addressing this issue further by comparing gaze and arrow cues. Unlike previous studies, we also included pointing gestures as social cues, with the goal of addressing whether any eventual impairment in the attentional response was specific to gaze signals or reflected a more general deficit in dealing with social stimuli. Patients with schizophrenia or schizoaffective disorder and matched controls performed a spatial-cuing paradigm in which task-irrelevant centrally displayed gaze, pointing finger, and arrow cues oriented rightward or leftward, preceded a lateralized target requiring a simple detection response. Healthy controls responded faster to spatially congruent targets than to spatially incongruent targets, irrespective of cue type. In contrast, schizophrenic patients responded faster to spatially congruent targets than to spatially incongruent targets only for arrow and pointing finger cues. No cuing effect emerged for gaze cues. The results support the notion that gaze cuing is impaired in schizophrenia, and suggest that this deficit may not extend to all social cues.

Children with Chromosome 22q11.2 Deletion Syndrome Exhibit Impaired Spatial Working Memory

ERIC Educational Resources Information Center

Wong, Ling M.; Riggins, Tracy; Harvey, Danielle; Cabaral, Margarita; Simon, Tony J.

2014-01-01

Individuals with chromosome 22q11.2 deletion syndrome (22q11.2DS) have been shown to have impairments in processing spatiotemporal information. The authors examined whether children with 22q11.2DS exhibit impairments in spatial working memory performance due to these weaknesses, even when controlling for maintenance of attention. Children with…

delta(9)-Tetrahydrocannabinol-dependent mice undergoing withdrawal display impaired spatial memory.

PubMed

Wise, Laura E; Varvel, Stephen A; Selley, Dana E; Wiebelhaus, Jason M; Long, Kelly A; Middleton, Lisa S; Sim-Selley, Laura J; Lichtman, Aron H

2011-10-01

Cannabis users display a constellation of withdrawal symptoms upon drug discontinuation, including sleep disturbances, irritability, and possibly memory deficits. In cannabinoid-dependent rodents, the CB(1) antagonist rimonabant precipitates somatic withdrawal and enhances forskolin-stimulated adenylyl cyclase activity in cerebellum, an effect opposite that of acutely administered ∆(9)-tetrahydrocannabinol (THC), the primary constituent in cannabis. Here, we tested whether THC-dependent mice undergoing rimonabant-precipitated withdrawal display short-term spatial memory deficits, as assessed in the Morris water maze. We also evaluated whether rimonabant would precipitate adenylyl cyclase superactivation in hippocampal and cerebellar tissue from THC-dependent mice. Rimonabant significantly impaired spatial memory of THC-dependent mice at lower doses than those necessary to precipitate somatic withdrawal behavior. In contrast, maze performance was near perfect in the cued task, suggesting sensorimotor function and motivational factors were unperturbed by the withdrawal state. Finally, rimonabant increased adenylyl cyclase activity in cerebellar, but not in hippocampal, membranes. The memory disruptive effects of THC undergo tolerance following repeated dosing, while the withdrawal state leads to a rebound deficit in memory. These results establish spatial memory impairment as a particularly sensitive component of cannabinoid withdrawal, an effect that may be mediated through compensatory changes in the cerebellum.

Dissociation of spatial memory systems in Williams syndrome.

PubMed

Bostelmann, Mathilde; Fragnière, Emilie; Costanzo, Floriana; Di Vara, Silvia; Menghini, Deny; Vicari, Stefano; Lavenex, Pierre; Lavenex, Pamela Banta

2017-11-01

Williams syndrome (WS), a genetic deletion syndrome, is characterized by severe visuospatial deficits affecting performance on both tabletop spatial tasks and on tasks which assess orientation and navigation. Nevertheless, previous studies of WS spatial capacities have ignored the fact that two different spatial memory systems are believed to contribute parallel spatial representations supporting navigation. The place learning system depends on the hippocampal formation and creates flexible relational representations of the environment, also known as cognitive maps. The spatial response learning system depends on the striatum and creates fixed stimulus-response representations, also known as habits. Indeed, no study assessing WS spatial competence has used tasks which selectively target these two spatial memory systems. Here, we report that individuals with WS exhibit a dissociation in their spatial abilities subserved by these two memory systems. As compared to typically developing (TD) children in the same mental age range, place learning performance was impaired in individuals with WS. In contrast, their spatial response learning performance was facilitated. Our findings in individuals with WS and TD children suggest that place learning and response learning interact competitively to control the behavioral strategies normally used to support human spatial navigation. Our findings further suggest that the neural pathways supporting place learning may be affected by the genetic deletion that characterizes WS, whereas those supporting response learning may be relatively preserved. The dissociation observed between these two spatial memory systems provides a coherent theoretical framework to characterize the spatial abilities of individuals with WS, and may lead to the development of new learning strategies based on their facilitated response learning abilities. © 2017 Wiley Periodicals, Inc.

Effect of short- and long-term administration of baclofen on spatial learning and memory in rats.

PubMed

Holajova, M; Franek, M

2018-03-16

Baclofen is the only clinically available metabotropic GABA(B) receptor agonist. In our experiment, we tested the hypothesis that long-term baclofen administration can impair learning and memory in rats. The experiment consisted of three parts. In the first part of the study the drug was administered simultaneously with the beginning of the behavioral tests. In the second and third part of the experiment baclofen was administered daily for 14 days and for one month before the tests. In each part of the experiment, adult rats were randomly divided into four treatment groups. Three groups were given an injection of baclofen at doses of 1 mg/kg, 5 mg/kg, 10 mg/kg, while the fourth group was injected with saline. The injections were given after each session. Spatial learning and memory were tested using the Morris water maze, involving three types of tests: Acquisition, Probe, and Re-acquisition. This work reveals that baclofen did not affect spatial learning at any of the tested doses and regardless of the length of administration. Memory was observed to be affected, but only at the highest dose of baclofen and only temporarily. This conclusion is in line with previously published clinical cases.

Chronic dietary chlorpyrifos causes long-term spatial memory impairment and thigmotaxic behavior.

PubMed

López-Granero, Caridad; Ruiz-Muñoz, Ana M; Nieto-Escámez, Francisco A; Colomina, María T; Aschner, Michael; Sánchez-Santed, Fernando

2016-03-01

Little is known about the long-term effects of chronic exposure to low-level organophosphate (OP) pesticides, and the role of neurotransmitter systems, other than the cholinergic system, in mediating OP neurotoxicity. In this study, rats were administered 5mg/kg/day of chlorpyrifos (CPF) for 6 months commencing at 3-months-of-age. The animals were examined 7 months later (at 16-months-of-age) for spatial learning and memory in the Morris water maze (MWM) and locomotor activity. In addition, we assessed the chronic effects of CPF on glutamatergic and gamma-aminobutyric acid (GABAergic) function using pharmacological challenges with dizocilpine (MK801) and diazepam. Impaired performance related to altered search patterns, including thigmotaxis and long-term spatial memory was noted in the MWM in animals exposed to CPF, pointing to dietary CPF-induced behavioral disturbances, such as anxiety. Twenty-four hours after the 31st session of repeated acquisition task, 0.1mg/kg MK801, an N-methyl-d-aspartate (NMDA) antagonist was intraperitoneally (i.p.) injected for 4 consecutive days. Decreased latencies in the MWM in the control group were noted after two sessions with MK801 treatment. Once the MWM assessment was completed, animals were administered 0.1 or 0.2mg/kg of MK801 and 1 or 3mg/kg of diazepam i.p., and tested for locomotor activity. Both groups, the CPF dietary and control, displayed analogous performance in motor activity. In conclusion, our data point to a connection between the long-term spatial memory, thigmotaxic response and CPF long after the exposure ended. Copyright © 2015 Elsevier Inc. All rights reserved.

A saturation hypothesis to explain both enhanced and impaired learning with enhanced plasticity

PubMed Central

Nguyen-Vu, TD Barbara; Zhao, Grace Q; Lahiri, Subhaneil; Kimpo, Rhea R; Lee, Hanmi; Ganguli, Surya; Shatz, Carla J; Raymond, Jennifer L

2017-01-01

Across many studies, animals with enhanced synaptic plasticity exhibit either enhanced or impaired learning, raising a conceptual puzzle: how enhanced plasticity can yield opposite learning outcomes? Here, we show that the recent history of experience can determine whether mice with enhanced plasticity exhibit enhanced or impaired learning in response to the same training. Mice with enhanced cerebellar LTD, due to double knockout (DKO) of MHCI H2-Kb/H2-Db (KbDb−/−), exhibited oculomotor learning deficits. However, the same mice exhibited enhanced learning after appropriate pre-training. Theoretical analysis revealed that synapses with history-dependent learning rules could recapitulate the data, and suggested that saturation may be a key factor limiting the ability of enhanced plasticity to enhance learning. Optogenetic stimulation designed to saturate LTD produced the same impairment in WT as observed in DKO mice. Overall, our results suggest that the recent history of activity and the threshold for synaptic plasticity conspire to effect divergent learning outcomes. DOI: http://dx.doi.org/10.7554/eLife.20147.001 PMID:28234229

Analysing the physics learning environment of visually impaired students in high schools

NASA Astrophysics Data System (ADS)

Toenders, Frank G. C.; de Putter-Smits, Lesley G. A.; Sanders, Wendy T. M.; den Brok, Perry

2017-07-01

Although visually impaired students attend regular high school, their enrolment in advanced science classes is dramatically low. In our research we evaluated the physics learning environment of a blind high school student in a regular Dutch high school. For visually impaired students to grasp physics concepts, time and additional materials to support the learning process are key. Time for teachers to develop teaching methods for such students is scarce. Suggestions for changes to the learning environment and of materials used are given.

Attenuation of ketamine-induced impairment in verbal learning and memory in healthy volunteers by the AMPA receptor potentiator PF-04958242.

PubMed

Ranganathan, M; DeMartinis, N; Huguenel, B; Gaudreault, F; Bednar, M M; Shaffer, C L; Gupta, S; Cahill, J; Sherif, M A; Mancuso, J; Zumpano, L; D'Souza, D C

2017-11-01

There is a need to develop treatments for cognitive impairment associated with schizophrenia (CIAS). The significant role played by N-methyl-d-aspartate receptors (NMDARs) in both the pathophysiology of schizophrenia and in neuronal plasticity suggests that facilitation of NMDAR function might ameliorate CIAS. One strategy to correct NMDAR hypofunction is to stimulate α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) as AMPAR and NMDAR functioning are coupled and interdependent. In rats and nonhuman primates (NHP), AMPAR potentiators reduce spatial working memory deficits caused by the nonselective NMDAR antagonist ketamine. The current study assessed whether the AMPAR potentiator PF-04958242 would attenuate ketamine-induced deficits in verbal learning and memory in humans. Healthy male subjects (n=29) participated in two randomized treatment periods of daily placebo or PF-04958242 for 5 days separated by a washout period. On day 5 of each treatment period, subjects underwent a ketamine infusion for 75 min during which the effects of PF-04958242/placebo were assessed on ketamine-induced: (1) impairments in verbal learning and recall measured by the Hopkins Verbal Learning Test; (2) impairments in working memory on a CogState battery; and (3) psychotomimetic effects measured by the Positive and Negative Syndrome Scale and Clinician-Administered Dissociative Symptoms Scale. PF-04958242 significantly reduced ketamine-induced impairments in immediate recall and the 2-Back and spatial working memory tasks (CogState Battery), without significantly attenuating ketamine-induced psychotomimetic effects. There were no pharmacokinetic interactions between PF-04958242 and ketamine. Furthermore, PF-04958242 was well tolerated. 'High-impact' AMPAR potentiators like PF-04958242 may have a role in the treatment of the cognitive symptoms, but not the positive or negative symptoms, associated with schizophrenia. The excellent concordance between the

Blockade of 5-HT2A/2C-type receptors impairs learning in female rats in the course of estrous cycle.

PubMed

Fedotova, Yu O; Ordyan, N E

2010-12-01

We studied the effects of chronic administration (14 days) of agonist of 5-HT2B/2C serotonin receptors m-CPP (0.5 mg/kg subcutaneously) and agonist of 5-HT2A/2C serotonin receptors ketanserin (0.1 mg/kg intraperitoneally) on conditioned reactions in female rats in different phases of the estrous cycle. Passive avoidance (PA) paradigm and Morris water maze were used as behavioral tests. Chronic administration of m-CPP did not affect PA retrieval during the proestrus and estrus phases, but improved the dynamics of spatial learning in Morris water maze in comparison with control rats. Chronic administration of ketanserin uniformly impaired processes of spatial and nonspatial learning in female rats irrespective to the phase of the estrous cycle. A modulating role of 5-HT2A/2C and 5-HT2B/2C serotonin receptors in process of learning in female rats during the key phases of the estrous cycle was demonstrated.

Exposure to 56Fe Particles Produces Deficits in Spatial Learning and Memory in the Radial Arm Water Maze

NASA Astrophysics Data System (ADS)

Shukitt-Hale, Barbara; Miller, Marshall; Carrihill-Knoll, Kirsty; Rabin, Bernard; Joseph, James

Previous research has shown that radiation exposure, particularly to particles of high energy and charge (HZE particles) which will be encountered on long-term space missions, can adversely affect the ability of rats to perform a variety of behavioral tasks. This outcome has implications for an astronaut's ability to successfully complete requirements associated with these missions. Both aged and irradiated rats display cognitive impairment in tests of spatial learning and memory such as the Morris water maze and the radial arm maze. Therefore, in the present study, we used a combination of these two tests, the 8 arm radial water maze (RAWM), to measure spatial learning in rats which were irradiated at the NSRL with 0, 150cGy, or 200cGy of 56Fe radiation. Following irradiation the rats were shipped to the HNRCA and tested in the RAWM (2-3 months later) for 5 days, 3 trials/day. In this version of the RAWM, there were 4 hidden platforms that the rat needed to locate to successfully solve a trial. Once the rat located a platform, it was allowed to remain there for 15 sec before the platform sank, at which point the rat tried to locate the remaining ones. Reference (entering an arm that never contained the platform) and working (re-entering an arm in which the platform had already been found) memory errors were tabulated. Results showed that the irradiated rats had more reference and working memory errors while learning the maze, particularly on Day 3 of testing. Additionally, they utilized non-spatial strategies to solve the RAWM task whereas the control animals used spatial strategies. These results show that irradiation with 56Fe high-energy particles produces age-like decrements in cognitive behavior that may impair the ability of astronauts to perform critical tasks during long-term space travel beyond the magnetosphere. Supported by USDA Intramural and N.A.S.A. Grant NNX08AM66G

Selective Spatial Working Memory Impairment in a Group of Children with Mathematics Learning Disabilities and Poor Problem-Solving Skills

ERIC Educational Resources Information Center

Passolunghi, Maria Chiara; Mammarella, Irene Cristina

2012-01-01

This study examines visual and spatial working memory skills in 35 third to fifth graders with both mathematics learning disabilities (MLD) and poor problem-solving skills and 35 of their peers with typical development (TD) on tasks involving both low and high attentional control. Results revealed that children with MLD, relative to TD children,…

Clozapine blockade of MK-801-induced learning/memory impairment in the mEPM: Role of 5-HT1A receptors and hippocampal BDNF levels.

PubMed

López Hill, Ximena; Richeri, Analía; Scorza, María Cecilia

2017-10-01

Cognitive impairment associated with schizophrenia (CIAS) is highly prevalent and affects the overall functioning of patients. Clozapine (Clz), an atypical antipsychotic drug, significantly improves CIAS although the underlying mechanisms remain under study. The role of the 5-HT 1A receptor (5-HT 1A -R) in the ability of Clz to prevent the learning/memory impairment induced by MK-801 was investigated using the modified elevated plus-maze (mEPM) considering the Transfer latency (TL) as an index of spatial memory. We also investigated if changes in hippocampal brain-derived neurotrophic factor (BDNF) levels underlie the behavioral prevention induced by Clz. Clz (0.5 and 1mg/kg)- or vehicle-pretreated Wistar rats were injected with MK-801 (0.05mg/kg) or saline. TL was evaluated 35min later (TL1, acquisition session) while learning/memory performance was measured 24h (TL2, retention session) and 48h later (TL3, long-lasting effect). WAY-100635, a 5-HT 1A -R antagonist, was pre-injected (0.3mg/kg) to examine the presumed 5-HT 1A -R involvement in Clz action. At TL2, another experimental group treated with Clz and MK-801 and its respective control groups were added to measure BDNF protein levels by ELISA. TL1 and TL3 were not significantly modified by the different treatments. MK-801 increased TL2 compared to control group leading a disruption of spatial memory processing which was markedly attenuated by Clz. WAY-100635 suppressed this action supporting a relevant role of 5-HT 1A -R in the Clz mechanism of action to improve spatial memory dysfunction. Although a significant decrease of hippocampal BDNF levels underlies the learning/memory impairment induced by MK-801, this effect was not significantly prevented by Clz. Copyright © 2017 Elsevier Inc. All rights reserved.

ECT and Pronounced Impairment in Spatial Cognition: The Fallacy of Drawing Conclusions From a Single Case.

PubMed

Andrade, Chittaranjan; Prasad, Yameni; Devaraj, Aathira; Pinto, Ekta Franscina; Shukla, Lekhansh

2018-06-01

Electroconvulsive therapy (ECT) is associated with memory deficits on neuropsychological assessment. The association of ECT with nonmemory cognitive deficits has been poorly studied. We present a 40-year-old woman who showed a bizarre form of spatial cognition impairment on a subtest of the Tactual Performance Test (TPT) after recovering from depression with 6 alternate day, thrice-weekly, inpatient ECT treatments. This woman was part of a naturalistic, nonblind study that examined nonmemory cognitive deficits in antidepressant-treated depressed patients who did and did not receive ECT. The impairment was in the form of bizarrely drawn reproductions of differently shaped wooden blocks that had been presented to the patient when she was blindfolded. The impairment was still evident when she was retested (3 hours later) under substantially simplified conditions but was much attenuated approximately 2.5 weeks later. On the surface, it seems that ECT had induced severe impairment in spatial cognition and that the impairment showed the familiar pattern of attenuation with the passage of time. However, another recovered patient in the study, who did not receive ECT, also showed substantial spatial deficits on the same subtest of the TPT, and the attenuation of the deficits across time in the ECT-treated patient was probably a result of repeated exposure to the task. We suggest that not all patients who seem to experience spectacular cognitive impairment after ECT have deficits that are attributable to ECT.

Containment and Support: Core and Complexity in Spatial Language Learning.

PubMed

Landau, Barbara; Johannes, Kristen; Skordos, Dimitrios; Papafragou, Anna

2017-04-01

Containment and support have traditionally been assumed to represent universal conceptual foundations for spatial terms. This assumption can be challenged, however: English in and on are applied across a surprisingly broad range of exemplars, and comparable terms in other languages show significant variation in their application. We propose that the broad domains of both containment and support have internal structure that reflects different subtypes, that this structure is reflected in basic spatial term usage across languages, and that it constrains children's spatial term learning. Using a newly developed battery, we asked how adults and 4-year-old children speaking English or Greek distribute basic spatial terms across subtypes of containment and support. We found that containment showed similar distributions of basic terms across subtypes among all groups while support showed such similarity only among adults, with striking differences between children learning English versus Greek. We conclude that the two domains differ considerably in the learning problems they present, and that learning in and on is remarkably complex. Together, our results point to the need for a more nuanced view of spatial term learning. Copyright © 2016 Cognitive Science Society, Inc.

Development of Critical Spatial Thinking through GIS Learning

ERIC Educational Resources Information Center

Kim, Minsung; Bednarz, Robert

2013-01-01

This study developed an interview-based critical spatial thinking oral test and used the test to investigate the effects of Geographic Information System (GIS) learning on three components of critical spatial thinking: evaluating data reliability, exercising spatial reasoning, and assessing problem-solving validity. Thirty-two students at a large…

Effect of Royal Jelly on spatial learning and memory in rat model of streptozotocin-induced sporadic Alzheimer's disease

PubMed Central

Zamani, Zohre; Reisi, Parham; Alaei, Hojjatallah; Pilehvarian, Ali Asghar

2012-01-01

Background: It has been recently demonstrated that Royal jelly (RJ) has a beneficial role on neural functions. Alzheimer's disease (AD) is associated with impairments of learning and memory. Therefore, the present study was designed to examine the effect of RJ on spatial learning and memory in rats after intracerebroventricular injection of streptozotocin (icv-STZ). Materials and Methods: Rats were infused bilaterally with an icv injection of STZ, while sham rats received vehicle only. The rats were feed with RJ-contained food (3% w/w) (lyophilized RJ mixed with powdered regular food) or regular food for 10 days. Then spatial learning and memory was tested in the rats by Morris water maze test. Results: Results showed that in icv-STZ group latency and path length were increased as compared to sham group, also icv-STZ rats less remembered the target quadrant that previously the platform was located; however, these were protected significantly in STZ group that received RJ-containing food. Conclusions: Our findings support the potential neuroprotective role of RJ and its helpful effects in AD. PMID:23210085

Opposite monosynaptic scaling of BLP–vCA1 inputs governs hopefulness- and helplessness-modulated spatial learning and memory

PubMed Central

Yang, Ying; Wang, Zhi-Hao; Jin, Sen; Gao, Di; Liu, Nan; Chen, Shan-Ping; Zhang, Sinan; Liu, Qing; Liu, Enjie; Wang, Xin; Liang, Xiao; Wei, Pengfei; Li, Xiaoguang; Li, Yin; Yue, Chenyu; Li, Hong-lian; Wang, Ya-Li; Wang, Qun; Ke, Dan; Xie, Qingguo; Xu, Fuqiang; Wang, Liping; Wang, Jian-Zhi

2016-01-01

Different emotional states lead to distinct behavioural consequences even when faced with the same challenging events. Emotions affect learning and memory capacities, but the underlying neurobiological mechanisms remain elusive. Here we establish models of learned helplessness (LHL) and learned hopefulness (LHF) by exposing animals to inescapable foot shocks or with anticipated avoidance trainings. The LHF animals show spatial memory potentiation with excitatory monosynaptic upscaling between posterior basolateral amygdale (BLP) and ventral hippocampal CA1 (vCA1), whereas the LHL show memory deficits with an attenuated BLP–vCA1 connection. Optogenetic disruption of BLP–vCA1 inputs abolishes the effects of LHF and impairs synaptic plasticity. By contrast, targeted BLP–vCA1 stimulation rescues the LHL-induced memory deficits and mimics the effects of LHF. BLP–vCA1 stimulation increases synaptic transmission and dendritic plasticity with the upregulation of CREB and intrasynaptic AMPA receptors in CA1. These findings indicate that opposite excitatory monosynaptic scaling of BLP–vCA1 controls LHF- and LHL-modulated spatial memory, revealing circuit-specific mechanisms linking emotions to memory. PMID:27411738

Opposite monosynaptic scaling of BLP-vCA1 inputs governs hopefulness- and helplessness-modulated spatial learning and memory.

PubMed

Yang, Ying; Wang, Zhi-Hao; Jin, Sen; Gao, Di; Liu, Nan; Chen, Shan-Ping; Zhang, Sinan; Liu, Qing; Liu, Enjie; Wang, Xin; Liang, Xiao; Wei, Pengfei; Li, Xiaoguang; Li, Yin; Yue, Chenyu; Li, Hong-Lian; Wang, Ya-Li; Wang, Qun; Ke, Dan; Xie, Qingguo; Xu, Fuqiang; Wang, Liping; Wang, Jian-Zhi

2016-07-14

Different emotional states lead to distinct behavioural consequences even when faced with the same challenging events. Emotions affect learning and memory capacities, but the underlying neurobiological mechanisms remain elusive. Here we establish models of learned helplessness (LHL) and learned hopefulness (LHF) by exposing animals to inescapable foot shocks or with anticipated avoidance trainings. The LHF animals show spatial memory potentiation with excitatory monosynaptic upscaling between posterior basolateral amygdale (BLP) and ventral hippocampal CA1 (vCA1), whereas the LHL show memory deficits with an attenuated BLP-vCA1 connection. Optogenetic disruption of BLP-vCA1 inputs abolishes the effects of LHF and impairs synaptic plasticity. By contrast, targeted BLP-vCA1 stimulation rescues the LHL-induced memory deficits and mimics the effects of LHF. BLP-vCA1 stimulation increases synaptic transmission and dendritic plasticity with the upregulation of CREB and intrasynaptic AMPA receptors in CA1. These findings indicate that opposite excitatory monosynaptic scaling of BLP-vCA1 controls LHF- and LHL-modulated spatial memory, revealing circuit-specific mechanisms linking emotions to memory.

Later learning stages in procedural memory are impaired in children with Specific Language Impairment.

PubMed

Desmottes, Lise; Meulemans, Thierry; Maillart, Christelle

2016-01-01

According to the Procedural Deficit Hypothesis (PDH), difficulties in the procedural memory system may contribute to the language difficulties encountered by children with Specific Language Impairment (SLI). Most studies investigating the PDH have used the sequence learning paradigm; however these studies have principally focused on initial sequence learning in a single practice session. The present study sought to extend these investigations by assessing the consolidation stage and longer-term retention of implicit sequence-specific knowledge in 42 children with or without SLI. Both groups of children completed a serial reaction time task and were tested 24h and one week after practice. Results showed that children with SLI succeeded as well as children with typical development (TD) in the early acquisition stage of the sequence learning task. However, as training blocks progressed, only TD children improved their sequence knowledge while children with SLI did not appear to evolve any more. Moreover, children with SLI showed a lack of the consolidation gains in sequence knowledge displayed by the TD children. Overall, these results were in line with the predictions of the PDH and suggest that later learning stages in procedural memory are impaired in SLI. Copyright © 2015 Elsevier Ltd. All rights reserved.

Loss of EphA4 impairs short-term spatial recognition memory performance and locomotor habituation.

PubMed

Willi, R; Winter, C; Wieske, F; Kempf, A; Yee, B K; Schwab, M E; Singer, P

2012-11-01

EphA4 receptor (EphA4) tyrosine kinase is an important regulator of central nervous system development and synaptic plasticity in the mature brain, but its relevance to the control of normal behavior remains largely unexplored. This study is the first attempt to obtain a behavioral profile of constitutive homozygous and heterozygous EphA4 knockout mice. A deficit in locomotor habituation in the open field, impairment in spatial recognition in the Y-maze and reduced probability of spatial spontaneous alternation in the T-maze were identified in homozygous EphA4(-/-) mice, while heterozygo us EphA4(+/-) mice appeared normal on these tests in comparison with wild-type (WT) controls. The multiple phenotypes observed in EphA4(-/-) mice might stem from an underlying deficit in habituation learning, reflecting an elementary form of nonassociative learning that is in contrast to Pavlovian associative learning, which appeared unaffected by EphA4 disruption. A deficit in motor coordination on the accelerating rotarod was also demonstrated only in EphA4(-/-) mice--a finding in keeping with the presence of abnormal gait in EphA4(-/-) mice--although they were able to improve performance over training. There was no evidence for substantial changes in major neurochemical markers in various brain regions rich in EphA4 as shown by post-mortem analysis. This excludes the possibility of major neurochemical compensation in the brain of EphA4(-/-) mice. In summary, we have demonstrated for the first time the behavioral significance of EphA4 disruption, supporting further investigation of EphA4 as a possible target for behavioral interventions where habituation deficits are prominent. © 2012 The Authors. Genes, Brain and Behavior © 2012 Blackwell Publishing Ltd and International Behavioural and Neural Genetics Society.

Statistical word learning in children with autism spectrum disorder and specific language impairment.

PubMed

Haebig, Eileen; Saffran, Jenny R; Ellis Weismer, Susan

2017-11-01

Word learning is an important component of language development that influences child outcomes across multiple domains. Despite the importance of word knowledge, word-learning mechanisms are poorly understood in children with specific language impairment (SLI) and children with autism spectrum disorder (ASD). This study examined underlying mechanisms of word learning, specifically, statistical learning and fast-mapping, in school-aged children with typical and atypical development. Statistical learning was assessed through a word segmentation task and fast-mapping was examined in an object-label association task. We also examined children's ability to map meaning onto newly segmented words in a third task that combined exposure to an artificial language and a fast-mapping task. Children with SLI had poorer performance on the word segmentation and fast-mapping tasks relative to the typically developing and ASD groups, who did not differ from one another. However, when children with SLI were exposed to an artificial language with phonemes used in the subsequent fast-mapping task, they successfully learned more words than in the isolated fast-mapping task. There was some evidence that word segmentation abilities are associated with word learning in school-aged children with typical development and ASD, but not SLI. Follow-up analyses also examined performance in children with ASD who did and did not have a language impairment. Children with ASD with language impairment evidenced intact statistical learning abilities, but subtle weaknesses in fast-mapping abilities. As the Procedural Deficit Hypothesis (PDH) predicts, children with SLI have impairments in statistical learning. However, children with SLI also have impairments in fast-mapping. Nonetheless, they are able to take advantage of additional phonological exposure to boost subsequent word-learning performance. In contrast to the PDH, children with ASD appear to have intact statistical learning, regardless of

Possible Signaling Pathways Mediating Neuronal Calcium Sensor-1-Dependent Spatial Learning and Memory in Mice.

PubMed

Nakamura, Tomoe Y; Nakao, Shu; Nakajo, Yukako; Takahashi, Jun C; Wakabayashi, Shigeo; Yanamoto, Hiroji

2017-01-01

Intracellular Ca2+ signaling regulates diverse functions of the nervous system. Many of these neuronal functions, including learning and memory, are regulated by neuronal calcium sensor-1 (NCS-1). However, the pathways by which NCS-1 regulates these functions remain poorly understood. Consistent with the findings of previous reports, we revealed that NCS-1 deficient (Ncs1-/-) mice exhibit impaired spatial learning and memory function in the Morris water maze test, although there was little change in their exercise activity, as determined via treadmill-analysis. Expression of brain-derived neurotrophic factor (BDNF; a key regulator of memory function) and dopamine was significantly reduced in the Ncs1-/- mouse brain, without changes in the levels of glial cell-line derived neurotrophic factor or nerve growth factor. Although there were no gross structural abnormalities in the hippocampi of Ncs1-/- mice, electron microscopy analysis revealed that the density of large dense core vesicles in CA1 presynaptic neurons, which release BDNF and dopamine, was decreased. Phosphorylation of Ca2+/calmodulin-dependent protein kinase II-α (CaMKII-α, which is known to trigger long-term potentiation and increase BDNF levels, was significantly reduced in the Ncs1-/- mouse brain. Furthermore, high voltage electric potential stimulation, which increases the levels of BDNF and promotes spatial learning, significantly increased the levels of NCS-1 concomitant with phosphorylated CaMKII-α in the hippocampus; suggesting a close relationship between NCS-1 and CaMKII-α. Our findings indicate that NCS-1 may regulate spatial learning and memory function at least in part through activation of CaMKII-α signaling, which may directly or indirectly increase BDNF production.

Dorsolateral Striatal Lesions Impair Navigation Based on Landmark-Goal Vectors but Facilitate Spatial Learning Based on a "Cognitive Map"

ERIC Educational Resources Information Center

Kosaki, Yutaka; Poulter, Steven L.; Austen, Joe M.; McGregor, Anthony

2015-01-01

In three experiments, the nature of the interaction between multiple memory systems in rats solving a variation of a spatial task in the water maze was investigated. Throughout training rats were able to find a submerged platform at a fixed distance and direction from an intramaze landmark by learning a landmark-goal vector. Extramaze cues were…

[Effects of the neurogenesis stimulator Ro 25-6981 upon formation of spatial skill in adult rats depend on the term of its administration and the animals' ability to learn].

PubMed

Solov'eva, O A; Storozheva, Z I; Proshin, A T; Sherstnev, V V

2011-02-01

Effect of administration of selective N-methyl-D-aspartate (NMDA) receptor antagonist Ro 25-6981 on learning and memory in a dose which is known to stimulate neoneurogenesis was assessed in adult rats with different abilities to formation of spatial skills in different time periods after the antagonist injection. Wistar male rats were trained to find hidden platform in the Morris water maze for 5 consecutive days. Rats' learning ability for spatial skill formation was evaluated depending on platform speed achievements. In re-training sessions (cues and platform location changed), it was found that all rats received Ro 25-6981 13 days before the re-training demonstrated impaired spatial memory. At the same time the inhibitor injected 29 days before re-training selectively facilitated the formation of spatial skill in animals with initially low learning abilities.

Caloric restriction in young rats disturbs hippocampal neurogenesis and spatial learning.

PubMed

Cardoso, Armando; Marrana, Francisco; Andrade, José P

2016-09-01

It is widely known that caloric restriction (CR) has benefits on several organic systems, including the central nervous system. However, the majority of the CR studies was performed in adult animals and the information about the consequences on young populations is limited. In this study, we analyzed the effects of young-onset CR, started at 4weeks of age, in the number of neuropeptide Y (NPY)-containing neurons and in neurogenesis of the hippocampal formation, using doublecortin (DCX) and Ki67 as markers. Knowing that CR treatment could interfere with exploratory activity, anxiety, learning and memory we have analyzed the performance of the rats in the open-field, elevated plus-maze and Morris water maze tests. Animals aged 4weeks were randomly assigned to control or CR groups. Controls were maintained in the ad libitum regimen during 2months. The adolescent CR rats were fed, during 2months, with 60% of the amount of food consumed by controls. We have found that young-onset CR treatment did not affect the total number of NPY-immunopositive neurons in dentate hilus, CA3 and CA1 hippocampal subfields and did not change the exploratory activity and anxiety levels. Interestingly, we have found that young-onset CR might affect spatial learning process since those animals showed worse performance during the acquisition phase of Morris water maze. Furthermore, young-onset CR induced alterations of neurogenesis in the dentate subgranular layer that seems to underlie the impairment of spatial learning. Our data suggest that adolescent animals are vulnerable to CR treatment and that this diet is not suitable to be applied in this age phase. Copyright © 2016 Elsevier Inc. All rights reserved.

Spatial Learning and Computer Simulations in Science

ERIC Educational Resources Information Center

Lindgren, Robb; Schwartz, Daniel L.

2009-01-01

Interactive simulations are entering mainstream science education. Their effects on cognition and learning are often framed by the legacy of information processing, which emphasized amodal problem solving and conceptual organization. In contrast, this paper reviews simulations from the vantage of research on perception and spatial learning,…

Cardiovascular Fitness and Cognitive Spatial Learning in Rodents and in Humans.

PubMed

Barak, Boaz; Feldman, Noa; Okun, Eitan

2015-09-01

The association between cardiovascular fitness and cognitive functions in both animals and humans is intensely studied. Research in rodents shows that a higher cardiovascular fitness has beneficial effects on hippocampus-dependent spatial abilities, and the underlying mechanisms were largely teased out. Research into the impact of cardiovascular fitness on spatial learning in humans, however, is more limited, and involves mostly behavioral and imaging studies. Herein, we point out the state of the art in the field of spatial learning and cardiovascular fitness. The differences between the methodologies utilized to study spatial learning in humans and rodents are emphasized along with the neuronal basis of these tasks. Critical gaps in the study of spatial learning in the context of cardiovascular fitness between the two species are discussed. © The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America.

Vesicular glutamate transporter VGLUT1 has a role in hippocampal long-term potentiation and spatial reversal learning.

PubMed

Balschun, Detlef; Moechars, Diederik; Callaerts-Vegh, Zsuzsanna; Vermaercke, Ben; Van Acker, Nathalie; Andries, Luc; D'Hooge, Rudi

2010-03-01

Vesicular glutamate transporters 1 and 2 (VGLUT1, VGLUT2) show largely complementary distribution in the mature rodent brain and tend to segregate to synapses with different physiological properties. In the hippocampus, VGLUT1 is the dominate subtype in adult animals, whereas VGLUT2 is transiently expressed during early postnatal development. We generated and characterized VGLUT1 knockout mice in order to examine the functional contribution of this transporter to hippocampal synaptic plasticity and hippocampus-dependent spatial learning. Because complete deletion of VGLUT1 resulted in postnatal lethality, we used heterozygous animals for analysis. Here, we report that deletion of VGLUT1 resulted in impaired hippocampal long-term potentiation (LTP) in the CA1 region in vitro. In contrast, heterozygous VGLUT2 mice that were investigated for comparison did not show any changes in LTP. The reduced ability of VGLUT1-deficient mice to express LTP was accompanied by a specific deficit in spatial reversal learning in the water maze. Our data suggest a functional role of VGLUT1 in forms of hippocampal synaptic plasticity that are required to adapt and modify acquired spatial maps to external stimuli and changes.

Aberrant light directly impairs mood and learning through melanopsin-expressing neurons.

PubMed

LeGates, Tara A; Altimus, Cara M; Wang, Hui; Lee, Hey-Kyoung; Yang, Sunggu; Zhao, Haiqing; Kirkwood, Alfredo; Weber, E Todd; Hattar, Samer

2012-11-22

The daily solar cycle allows organisms to synchronize their circadian rhythms and sleep-wake cycles to the correct temporal niche. Changes in day-length, shift-work, and transmeridian travel lead to mood alterations and cognitive function deficits. Sleep deprivation and circadian disruption underlie mood and cognitive disorders associated with irregular light schedules. Whether irregular light schedules directly affect mood and cognitive functions in the context of normal sleep and circadian rhythms remains unclear. Here we show, using an aberrant light cycle that neither changes the amount and architecture of sleep nor causes changes in the circadian timing system, that light directly regulates mood-related behaviours and cognitive functions in mice. Animals exposed to the aberrant light cycle maintain daily corticosterone rhythms, but the overall levels of corticosterone are increased. Despite normal circadian and sleep structures, these animals show increased depression-like behaviours and impaired hippocampal long-term potentiation and learning. Administration of the antidepressant drugs fluoxetine or desipramine restores learning in mice exposed to the aberrant light cycle, suggesting that the mood deficit precedes the learning impairments. To determine the retinal circuits underlying this impairment of mood and learning, we examined the behavioural consequences of this light cycle in animals that lack intrinsically photosensitive retinal ganglion cells. In these animals, the aberrant light cycle does not impair mood and learning, despite the presence of the conventional retinal ganglion cells and the ability of these animals to detect light for image formation. These findings demonstrate the ability of light to influence cognitive and mood functions directly through intrinsically photosensitive retinal ganglion cells.

Protective effects of prescription n-3 fatty acids against impairment of spatial cognitive learning ability in amyloid β-infused rats.

PubMed

Hashimoto, Michio; Tozawa, Ryuichi; Katakura, Masanori; Shahdat, Hossain; Haque, Abdul Md; Tanabe, Yoko; Gamoh, Shuji; Shido, Osamu

2011-07-01

Deposition of amyloid β peptide (Aβ) into the brain causes cognitive impairment. We investigated whether prescription pre-administration of n-3 fatty acids improves cognitive learning ability in young rats and whether it protects against learning ability impairments in an animal model of Alzheimer's disease that was prepared by infusion of Aβ(1-40) into the cerebral ventricles of rats. Pre-administration of TAK-085 (highly purified and concentrated n-3 fatty acids containing eicosapentaenoic acid ethyl ester and docosahexaenoic acid ethyl ester) at 300 mg kg(-1) day(-1) for 12 weeks significantly reduced the number of reference memory errors in an 8-arm radial maze, suggesting that long-term administration of TAK-085 improves cognitive leaning ability in rats. After pre-administration, the control group was divided into the vehicle and Aβ-infused groups, whereas the TAK-085 pre-administration group was divided into the TAK-085 and TAK-085 + Aβ groups (TAK-085-pre-administered Aβ-infused rats). Aβ(1-40) or vehicle was infused into the cerebral ventricle using a mini osmotic pump. Pre-administration of TAK-085 to the Aβ-infused rats significantly suppressed the number of reference and working memory errors and decreased the levels of lipid peroxide and reactive oxygen species in the cerebral cortex and hippocampus of Aβ-infused rats, suggesting that TAK-085 increases antioxidative defenses. The present study suggests that long-term administration of TAK-085 is a possible therapeutic agent for protecting against Alzheimer's disease-induced learning deficiencies. This journal is © The Royal Society of Chemistry 2011

Spatial learning and psychomotor performance of C57BL/6 mice: age sensitivity and reliability of individual differences.

PubMed

de Fiebre, Nancyellen C; Sumien, Nathalie; Forster, Michael J; de Fiebre, Christopher M

2006-09-01

Two tests often used in aging research, the elevated path test and the Morris water maze test, were examined for their application to the study of brain aging in a large sample of C57BL/6JNia mice. Specifically, these studies assessed: (1) sensitivity to age and the degree of interrelatedness among different behavioral measures derived from these tests, (2) the effect of age on variation in the measurements, and (3) the reliability of individual differences in performance on the tests. Both tests detected age-related deficits in group performance that occurred independently of each other. However, analysis of data obtained on the Morris water maze test revealed three relatively independent components of cognitive performance. Performance in initial acquisition of spatial learning in the Morris maze was not highly correlated with performance during reversal learning (when mice were required to learn a new spatial location), whereas performance in both of those phases was independent of spatial performance assessed during a single probe trial administered at the end of acquisition training. Moreover, impaired performance during initial acquisition could be detected at an earlier age than impairments in reversal learning. There were modest but significant age-related increases in the variance of both elevated path test scores and in several measures of learning in the Morris maze test. Analysis of test scores of mice across repeated testing sessions confirmed reliability of the measurements obtained for cognitive and psychomotor function. Power calculations confirmed that there are sufficiently large age-related differences in elevated path test performance, relative to within age variability, to render this test useful for studies into the ability of an intervention to prevent or reverse age-related deficits in psychomotor performance. Power calculations indicated a need for larger sample sizes for detection of intervention effects on cognitive components of the

Subclinical hypothyroidism in pregnant rats impaired learning and memory of their offspring by promoting the p75NTR signal pathway.

PubMed

Zhang, Fan; Chen, Jian; Lin, Xinyue; Peng, Shiqiao; Yu, Xiaohui; Shan, Zhongyan; Teng, Weiping

2018-05-01

Maternal hypothyroidism during pregnancy can affect the neurodevelopment of their offspring. This study aimed to investigate the effects of maternal subclinical hypothyroidism (SCH) on spatial learning and memory, and its relationship with the apoptotic factors in cerebral cortex of the offspring. Female adult Wistar rats were randomly divided into three groups ( n  = 15 per group): control (CON) group, SCH group and overt hypothyroidism (OH) group. Spatial learning and memory in the offspring were evaluated by long-term potentiation (LTP) and Morris water-maze (MWM) test. The protein expression of the p75 neurotrophin receptor (p75 NTR ), phospho-c-Jun N-terminal kinase (p-JNK), the pro-apoptotic protein p53 and Bax were detected by Western blotting. The Pups in the SCH and OH groups showed longer escape latencies in the MWM and decreased field-excitatory post synaptic potentials in LTP tests compared with those in the CON group. p75 NTR , p-JNK, p53 and Bax expression levels in the cerebral cortex increased in pups in the SCH and OH groups compared with those in the CON group. Maternal SCH during pregnancy may impair spatial learning and memory in the offspring and may be associated with the increased apoptosis in the cerebral cortex. © 2018 The authors.

Modulation of spatial attention by goals, statistical learning, and monetary reward.

PubMed

Jiang, Yuhong V; Sha, Li Z; Remington, Roger W

2015-10-01

This study documented the relative strength of task goals, visual statistical learning, and monetary reward in guiding spatial attention. Using a difficult T-among-L search task, we cued spatial attention to one visual quadrant by (i) instructing people to prioritize it (goal-driven attention), (ii) placing the target frequently there (location probability learning), or (iii) associating that quadrant with greater monetary gain (reward-based attention). Results showed that successful goal-driven attention exerted the strongest influence on search RT. Incidental location probability learning yielded a smaller though still robust effect. Incidental reward learning produced negligible guidance for spatial attention. The 95 % confidence intervals of the three effects were largely nonoverlapping. To understand these results, we simulated the role of location repetition priming in probability cuing and reward learning. Repetition priming underestimated the strength of location probability cuing, suggesting that probability cuing involved long-term statistical learning of how to shift attention. Repetition priming provided a reasonable account for the negligible effect of reward on spatial attention. We propose a multiple-systems view of spatial attention that includes task goals, search habit, and priming as primary drivers of top-down attention.

Modulation of spatial attention by goals, statistical learning, and monetary reward

PubMed Central

Sha, Li Z.; Remington, Roger W.

2015-01-01

This study documented the relative strength of task goals, visual statistical learning, and monetary reward in guiding spatial attention. Using a difficult T-among-L search task, we cued spatial attention to one visual quadrant by (i) instructing people to prioritize it (goal-driven attention), (ii) placing the target frequently there (location probability learning), or (iii) associating that quadrant with greater monetary gain (reward-based attention). Results showed that successful goal-driven attention exerted the strongest influence on search RT. Incidental location probability learning yielded a smaller though still robust effect. Incidental reward learning produced negligible guidance for spatial attention. The 95 % confidence intervals of the three effects were largely nonoverlapping. To understand these results, we simulated the role of location repetition priming in probability cuing and reward learning. Repetition priming underestimated the strength of location probability cuing, suggesting that probability cuing involved long-term statistical learning of how to shift attention. Repetition priming provided a reasonable account for the negligible effect of reward on spatial attention. We propose a multiple-systems view of spatial attention that includes task goals, search habit, and priming as primary drivers of top-down attention. PMID:26105657

Nicotinic alpha 7 receptor agonists EVP-6124 and BMS-933043, attenuate scopolamine-induced deficits in visuo-spatial paired associates learning.

PubMed

Weed, Michael R; Polino, Joseph; Signor, Laura; Bookbinder, Mark; Keavy, Deborah; Benitex, Yulia; Morgan, Daniel G; King, Dalton; Macor, John E; Zaczek, Robert; Olson, Richard; Bristow, Linda J

2017-01-01

Agonists at the nicotinic acetylcholine alpha 7 receptor (nAChR α7) subtype have the potential to treat cognitive deficits in patients with Alzheimer's disease (AD) or schizophrenia. Visuo-spatial paired associates learning (vsPAL) is a task that has been shown to reliably predict conversion from mild cognitive impairment to AD in humans and can also be performed by nonhuman primates. Reversal of scopolamine-induced impairment of vsPAL performance may represent a translational approach for the development of nAChR α7 agonists. The present study investigated the effect of treatment with the acetylcholinesterase inhibitor, donepezil, or three nAChR α7 agonists, BMS-933043, EVP-6124 and RG3487, on vsPAL performance in scopolamine-treated cynomolgus monkeys. Scopolamine administration impaired vsPAL performance accuracy in a dose- and difficulty- dependent manner. The impairment of eventual accuracy, a measure of visuo-spatial learning during the task, was significantly ameliorated by treatment with donepezil (0.3 mg/kg, i.m.), EVP-6124 (0.01 mg/kg, i.m.) or BMS-933043 (0.03, 0.1 and 0.3 mg/kg, i.m.). Both nAChR α7 agonists showed inverted-U shaped dose-effect relationships with EVP-6124 effective at a single dose only whereas BMS-933043 was effective across at least a 10 fold dose/exposure range. RG3487 was not efficacious in this paradigm at the dose range examined (0.03-1 mg/kg, i.m.). These results are the first demonstration that the nAChR α7 agonists, EVP-6124 and BMS-933043, can ameliorate scopolamine-induced cognitive deficits in nonhuman primates performing the vsPAL task.

Learning strategy preference of 5XFAD transgenic mice depends on the sequence of place/spatial and cued training in the water maze task.

PubMed

Cho, Woo-Hyun; Park, Jung-Cheol; Chung, ChiHye; Jeon, Won Kyung; Han, Jung-Soo

2014-10-15

Learning strategy preference was assessed in 5XFAD mice, which carry 5 familial Alzheimer's disease (AD) mutations. Mice were sequentially trained in cued and place/spatial versions of the water maze task. After training, a strategy preference test was conducted in which mice were required to choose between the spatial location where the platform had previously been during the place/spatial training, and a visible platform in a new location. 5XFAD and non-transgenic control mice showed equivalent escape performance in both training tasks. However, in the strategy preference test, 5XFAD mice preferred a cued strategy relative to control mice. When the training sequence was presented in the reverse order (i.e., place/spatial training before cued training), 5XFAD mice showed impairments in place/spatial training, but no differences in cued training or in the strategy preference test comparing to control. Analysis of regional Aβ42 deposition in brains of 5XFAD mice showed that the hippocampus, which is involved in the place/spatial learning strategy, had the highest levels of Aβ42 and the dorsal striatum, which is involved in cued learning strategy, showed a small increase in Aβ42 levels. The effect of training protocol order on performance, and regional differences in Aβ42 deposition observed in 5XFAD mice, suggest differential functional recruitment of brain structures related to learning in healthy and AD individuals. Copyright © 2014 Elsevier B.V. All rights reserved.

Age-related similarities and differences in monitoring spatial cognition.

PubMed

Ariel, Robert; Moffat, Scott D

2018-05-01

Spatial cognitive performance is impaired in later adulthood but it is unclear whether the metacognitive processes involved in monitoring spatial cognitive performance are also compromised. Inaccurate monitoring could affect whether people choose to engage in tasks that require spatial thinking and also the strategies they use in spatial domains such as navigation. The current experiment examined potential age differences in monitoring spatial cognitive performance in a variety of spatial domains including visual-spatial working memory, spatial orientation, spatial visualization, navigation, and place learning. Younger and older adults completed a 2D mental rotation test, 3D mental rotation test, paper folding test, spatial memory span test, two virtual navigation tasks, and a cognitive mapping test. Participants also made metacognitive judgments of performance (confidence judgments, judgments of learning, or navigation time estimates) on each trial for all spatial tasks. Preference for allocentric or egocentric navigation strategies was also measured. Overall, performance was poorer and confidence in performance was lower for older adults than younger adults. In most spatial domains, the absolute and relative accuracy of metacognitive judgments was equivalent for both age groups. However, age differences in monitoring accuracy (specifically relative accuracy) emerged in spatial tasks involving navigation. Confidence in navigating for a target location also mediated age differences in allocentric navigation strategy use. These findings suggest that with the possible exception of navigation monitoring, spatial cognition may be spared from age-related decline even though spatial cognition itself is impaired in older age.

BENZODIAZEPINE-INDUCED SPATIAL LEARNING DEFICITS IN RATS ARE REGULATED BY THE DEGREE OF MODULATION OF α1 GABAA RECEPTORS

PubMed Central

Joksimović, Srđan; Divljaković, Jovana; Van Linn, Michael L.; Varagic, Zdravko; Brajković, Gordana; Milinković, Marija M.; Yin, Wenyuan; Timić, Tamara; Sieghart, Werner; Cook, James M.; Savić, Miroslav M.

2012-01-01

Despite significant advances in understanding the role of benzodiazepine (BZ)-sensitive populations of GABAA receptors, containing the α1, α2, α3 or α5 subunit, factual substrates of BZ-induced learning and memory deficits are not yet fully elucidated. It was shown that α1-subunit affinity-selective antagonist β-CCt almost completely abolished spatial learning deficits induced by diazepam (DZP) in the Morris water maze. We examined a novel, highly (105 fold) α1-subunit selective ligand - WYS8 (0.2, 1 and 10 mg/kg), on its own and in combination with the non-selective agonist DZP (2 mg/kg) or β-CCt (5 mg/kg) in the water maze in rats. The in vitro efficacy study revealed that WYS8 acts as α1-subtype selective weak partial positive modulator (40% potentiation at 100 nM). Measurement of concentrations of WYS8 and DZP in rat serum and brain tissues suggested that they did not substantially cross-influence the respective disposition. In the water maze, DZP impaired spatial learning (acquisition trials) and memory (probe trial). WYS8 caused no effect per se, did not affect the overall influence of DZP on the water-maze performance and was devoid of any activity in this task when combined with β-CCt. Nonetheless, an additional analysis of the latency to reach the platform and the total distance swam suggested that WYS8 addition attenuated the run-down of the spatial impairment induced by DZP at the end of acquisition trials. These results demonstrate a clear difference in the influence of an α1 subtype-selective antagonist and a partial agonist on the effects of DZP on the water-maze acquisition. PMID:22633616

Enhancing Spatial Resolution of Remotely Sensed Imagery Using Deep Learning

NASA Astrophysics Data System (ADS)

Beck, J. M.; Bridges, S.; Collins, C.; Rushing, J.; Graves, S. J.

2017-12-01

Researchers at the Information Technology and Systems Center at the University of Alabama in Huntsville are using Deep Learning with Convolutional Neural Networks (CNNs) to develop a method for enhancing the spatial resolutions of moderate resolution (10-60m) multispectral satellite imagery. This enhancement will effectively match the resolutions of imagery from multiple sensors to provide increased global temporal-spatial coverage for a variety of Earth science products. Our research is centered on using Deep Learning for automatically generating transformations for increasing the spatial resolution of remotely sensed images with different spatial, spectral, and temporal resolutions. One of the most important steps in using images from multiple sensors is to transform the different image layers into the same spatial resolution, preferably the highest spatial resolution, without compromising the spectral information. Recent advances in Deep Learning have shown that CNNs can be used to effectively and efficiently upscale or enhance the spatial resolution of multispectral images with the use of an auxiliary data source such as a high spatial resolution panchromatic image. In contrast, we are using both the spatial and spectral details inherent in low spatial resolution multispectral images for image enhancement without the use of a panchromatic image. This presentation will discuss how this technology will benefit many Earth Science applications that use remotely sensed images with moderate spatial resolutions.

Sharp wave ripples during learning stabilize hippocampal spatial map

PubMed Central

Roux, Lisa; Hu, Bo; Eichler, Ronny; Stark, Eran; Buzsáki, György

2017-01-01

Cognitive representation of the environment requires a stable hippocampal map but the mechanisms maintaining map representation are unknown. Because sharp wave-ripples (SPW-R) orchestrate both retrospective and prospective spatial information, we hypothesized that disrupting neuronal activity during SPW-Rs affects spatial representation. Mice learned daily a new set of three goal locations on a multi-well maze. We used closed-loop SPW-R detection at goal locations to trigger optogenetic silencing of a subset of CA1 pyramidal neurons. Control place cells (non-silenced or silenced outside SPW-Rs) largely maintained the location of their place fields after learning and showed increased spatial information content. In contrast, the place fields of SPW-R-silenced place cells remapped, and their spatial information remained unaltered. SPW-R silencing did not impact the firing rates or the proportions of place cells. These results suggest that interference with SPW-R-associated activity during learning prevents the stabilization and refinement of the hippocampal map. PMID:28394323

Smart-system of distance learning of visually impaired people based on approaches of artificial intelligence

NASA Astrophysics Data System (ADS)

Samigulina, Galina A.; Shayakhmetova, Assem S.

2016-11-01

Research objective is the creation of intellectual innovative technology and information Smart-system of distance learning for visually impaired people. The organization of the available environment for receiving quality education for visually impaired people, their social adaptation in society are important and topical issues of modern education.The proposed Smart-system of distance learning for visually impaired people can significantly improve the efficiency and quality of education of this category of people. The scientific novelty of proposed Smart-system is using intelligent and statistical methods of processing multi-dimensional data, and taking into account psycho-physiological characteristics of perception and awareness learning information by visually impaired people.

Spatial parameters at the basis of social transfer of learning.

PubMed

Lugli, Luisa; Iani, Cristina; Milanese, Nadia; Sebanz, Natalie; Rubichi, Sandro

2015-06-01

Recent research indicates that practicing on a joint spatial compatibility task with an incompatible stimulus-response mapping affects subsequent joint Simon task performance, eliminating the social Simon effect. It has been well established that in individual contexts, for transfer of learning to occur, participants need to practice an incompatible association between stimulus and response positions. The mechanisms underlying transfer of learning in joint task performance are, however, less well understood. The present study was aimed at assessing the relative contribution of 3 different spatial relations characterizing the joint practice context: stimulus-response, stimulus-participant, and participant-response relations. In 3 experiments, the authors manipulated the stimulus-response, stimulus-participant, and response-participant associations. We found that learning from the practice task did not transfer to the subsequent task when during practice stimulus-response associations were spatially incompatible and stimulus-participant associations were compatible (Experiment 1). However, a transfer of learning was evident when stimulus-participant associations were spatially incompatible. This occurred both when response-participant associations were incompatible (Experiment 2) and when they were compatible (Experiment 3). These results seem to support an agent corepresentation account of correspondence effects emerging in joint settings since they suggest that, in social contexts, critical to obtain transfer-of-learning effects is the spatial relation between stimulus and participant positions while the spatial relation between stimulus and response positions is irrelevant. (c) 2015 APA, all rights reserved).

Mechanisms of value-learning in the guidance of spatial attention.

PubMed

Anderson, Brian A; Kim, Haena

2018-05-11

The role of associative reward learning in the guidance of feature-based attention is well established. The extent to which reward learning can modulate spatial attention has been much more controversial. At least one demonstration of a persistent spatial attention bias following space-based associative reward learning has been reported. At the same time, multiple other experiments have been published failing to demonstrate enduring attentional biases towards locations at which a target, if found, yields high reward. This is in spite of evidence that participants use reward structures to inform their decisions where to search, leading some to suggest that, unlike feature-based attention, spatial attention may be impervious to the influence of learning from reward structures. Here, we demonstrate a robust bias towards regions of a scene that participants were previously rewarded for selecting. This spatial bias relies on representations that are anchored to the configuration of objects within a scene. The observed bias appears to be driven specifically by reinforcement learning, and can be observed with equal strength following non-reward corrective feedback. The time course of the bias is consistent with a transient shift of attention, rather than a strategic search pattern, and is evident in eye movement patterns during free viewing. Taken together, our findings reconcile previously conflicting reports and offer an integrative account of how learning from feedback shapes the spatial attention system. Copyright © 2018 Elsevier B.V. All rights reserved.

Using Standardized Psychometric Tests to Identify Learning Disabilities in Students with Sensorineural Hearing Impairments.

ERIC Educational Resources Information Center

Sikora, Darryn M.; Plapinger, Donald S.

1994-01-01

The use of standardized psychoeducational diagnostic instruments to identify learning disabilities was evaluated with 19 students (ages 7 to 13) with sensorineural hearing impairments. Students with hearing impairment were found to demonstrate learning disabilities with a frequency similar to that found in students with normal hearing, suggesting…

Spatial working memory interferes with explicit, but not probabilistic cuing of spatial attention

PubMed Central

Won, Bo-Yeong; Jiang, Yuhong V.

2014-01-01

Recent empirical and theoretical work has depicted a close relationship between visual attention and visual working memory. For example, rehearsal in spatial working memory depends on spatial attention, whereas adding a secondary spatial working memory task impairs attentional deployment in visual search. These findings have led to the proposal that working memory is attention directed toward internal representations. Here we show that the close relationship between these two constructs is limited to some but not all forms of spatial attention. In five experiments, participants held color arrays, dot locations, or a sequence of dots in working memory. During the memory retention interval they performed a T-among-L visual search task. Crucially, the probable target location was cued either implicitly through location probability learning, or explicitly with a central arrow or verbal instruction. Our results showed that whereas imposing a visual working memory load diminished the effectiveness of explicit cuing, it did not interfere with probability cuing. We conclude that spatial working memory shares similar mechanisms with explicit, goal-driven attention but is dissociated from implicitly learned attention. PMID:25401460

Comparison of automated home-cage monitoring systems: emphasis on feeding behaviour, activity and spatial learning following pharmacological interventions.

PubMed

Robinson, Lianne; Riedel, Gernot

2014-08-30

Different automated systems have been developed to facilitate long-term and continuous assessment of behaviours including locomotor activity, feeding behaviour and circadian activity. This study assessed the effectiveness of three different observation systems as methods for determining strain and pharmacological induced differences in locomotor activity, feeding behaviour and spatial learning. The effect of the CB1 antagonist AM251 on feeding behaviour was determined in the PhenoMaster and PhenoTyper. Next, effects of cholinergic (scopolamine) and glutamatergic (Phenylcyclidine, PCP) receptor antagonism and dopaminergic agonism (apomorphine) on activity were assessed in the PhenoTyper and IntelliCage. Finally, the IntelliCage was utilised to determine differences in activity and spatial learning of C57BL/6 and DBA/2 mouse strains following pharmacological intervention. AM251 induced a suppression of food intake, feeding behaviour and a reduction in body weight in both the PhenoTyper and PhenoMaster. Apomorphine reduced activity in both the PhenoTyper and IntelliCage. Whereas, decreased activity was evident with PCP in the PhenoTyper, but not IntelliCage and Scopolamine induced a trend towards elevated levels of activity in the IntelliCage but not PhenoTyper. Strain differences in activity and spatial learning were also evident, with increased corner visits and drug induced impairments only observed with C57BL/6 mice. The automated home cage observation systems determined similar drug and strain effects on behaviour to those observed using traditional methods. All three observation systems reported drug-induced changes in behaviour however, they differ in their application of spatial learning tasks and utilisation of single versus group housed recordings. Copyright © 2014 Elsevier B.V. All rights reserved.

First-order and higher order sequence learning in specific language impairment.

PubMed

Clark, Gillian M; Lum, Jarrad A G

2017-02-01

A core claim of the procedural deficit hypothesis of specific language impairment (SLI) is that the disorder is associated with poor implicit sequence learning. This study investigated whether implicit sequence learning problems in SLI are present for first-order conditional (FOC) and higher order conditional (HOC) sequences. Twenty-five children with SLI and 27 age-matched, nonlanguage-impaired children completed 2 serial reaction time tasks. On 1 version, the sequence to be implicitly learnt comprised a FOC sequence and on the other a HOC sequence. Results showed that the SLI group learned the HOC sequence (η p ² = .285, p = .005) but not the FOC sequence (η p ² = .099, p = .118). The control group learned both sequences (FOC η p ² = .497, HOC η p 2= .465, ps < .001). The SLI group's difficulty learning the FOC sequence is consistent with the procedural deficit hypothesis. However, the study provides new evidence that multiple mechanisms may underpin the learning of FOC and HOC sequences. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

(+/-)3,4-Methylenedioxymethamphetamine (MDMA) dose-dependently impairs spatial learning in the morris water maze after exposure of rats to different five-day intervals from birth to postnatal day twenty.

PubMed

Vorhees, Charles V; Schaefer, Tori L; Skelton, Matthew R; Grace, Curtis E; Herring, Nicole R; Williams, Michael T

2009-01-01

During postnatal days (PD) 11-20, (+/-)3,4-methylenedioxymethamphetamine (MDMA) treatment impairs egocentric and allocentric learning, and reduces spontaneous locomotor activity; however, it does not have these effects during PD 1-10. How the learning impairments relate to the stress hyporesponsive period (SHRP) is unknown. To test this association, the preweaning period was subdivided into 5-day periods from PD 1-20. Separate pups within each litter were injected subcutaneously with 0, 10, 15, 20, or 25 mg/kg MDMA x4/day on PD 1-5, 6-10, 11-15, or 16-20, and tested as adults. The 3 highest MDMA dose groups showed reduced locomotor activity during the first 10 min (of 60 min), especially in the PD 1-5 and 6-10 dosing regimens. MDMA groups in all dosing regimens showed impaired allocentric learning in the Morris water maze (on acquisition and reversal, all MDMA groups were affected; on the small platform phase, the 2 high-dose groups were affected). No effects of MDMA were found on anxiety (elevated zero maze), novel object recognition, or egocentric learning (although a nonsignificant trend was observed). The Morris maze results did not support the idea that the SHRP is critical to the effects of MDMA on allocentric learning. However, since no effects on egocentric learning were found, but were apparent after PD 11-20 treatment, the results show that these 2 forms of learning have different exposure-duration sensitivities. 2009 S. Karger AG, Basel.

Fluoxetine attenuates the impairment of spatial learning ability and prevents neuron loss in middle-aged APPswe/PSEN1dE9 double transgenic Alzheimer's disease mice.

PubMed

Ma, Jing; Gao, Yuan; Jiang, Lin; Chao, Feng-Lei; Huang, Wei; Zhou, Chun-Ni; Tang, Wei; Zhang, Lei; Huang, Chun-Xia; Zhang, Yi; Luo, Yan-Min; Xiao, Qian; Yu, Hua-Rong; Jiang, Rong; Tang, Yong

2017-04-25

Selective serotonin reuptake inhibitors (SSRIs) have been reported to increase cognitive performance in some clinical studies of Alzheimer's disease (AD). However, there is a lack of evidence supporting the efficacy of SSRIs as cognition enhancers in AD, and the role of SSRIs as a treatment for AD remains largely unclear. Here, we characterized the impact of fluoxetine (FLX), a well-known SSRI, on neurons in the dentate gyrus (DG) and in CA1 and CA3 of the hippocampus of middle-aged (16 to 17 months old) APPswe/PSEN1dE9 (APP/PS1) transgenic AD model mice. We found that intraperitoneal (i.p.) injection of FLX (10 mg/kg/day) for 5 weeks effectively alleviated the impairment of spatial learning ability in middle-aged APP/PS1 mice as evaluated using the Morris water maze. More importantly, the number of neurons in the hippocampal DG was significantly increased by FLX. Additionally, FLX reduced the deposition of beta amyloid, inhibited GSK-3β activity and increased the level of β-catenin in middle-aged APP/PS1 mice. Collectively, the results of this study indicate that FLX delayed the progression of neuronal loss in the hippocampal DG in middle-aged AD mice, and this effect may underlie the FLX-induced improvement in learning ability. FLX may therefore serve as a promising therapeutic drug for AD.

Fluoxetine attenuates the impairment of spatial learning ability and prevents neuron loss in middle-aged APPswe/PSEN1dE9 double transgenic Alzheimer's disease mice

PubMed Central

Ma, Jing; Gao, Yuan; Jiang, Lin; Chao, Feng-lei; Huang, Wei; Zhou, Chun-ni; Tang, Wei; Zhang, Lei; Huang, Chun-xia; Zhang, Yi; Luo, Yan-min; Xiao, Qian; Yu, Hua-rong; Jiang, Rong; Tang, Yong

2017-01-01

Selective serotonin reuptake inhibitors (SSRIs) have been reported to increase cognitive performance in some clinical studies of Alzheimer’s disease (AD). However, there is a lack of evidence supporting the efficacy of SSRIs as cognition enhancers in AD, and the role of SSRIs as a treatment for AD remains largely unclear. Here, we characterized the impact of fluoxetine (FLX), a well-known SSRI, on neurons in the dentate gyrus (DG) and in CA1 and CA3 of the hippocampus of middle-aged (16 to 17 months old) APPswe/PSEN1dE9 (APP/PS1) transgenic AD model mice. We found that intraperitoneal (i.p.) injection of FLX (10 mg/kg/day) for 5 weeks effectively alleviated the impairment of spatial learning ability in middle-aged APP/PS1 mice as evaluated using the Morris water maze. More importantly, the number of neurons in the hippocampal DG was significantly increased by FLX. Additionally, FLX reduced the deposition of beta amyloid, inhibited GSK-3β activity and increased the level of β-catenin in middle-aged APP/PS1 mice. Collectively, the results of this study indicate that FLX delayed the progression of neuronal loss in the hippocampal DG in middle-aged AD mice, and this effect may underlie the FLX-induced improvement in learning ability. FLX may therefore serve as a promising therapeutic drug for AD. PMID:28430602

Is Implicit Sequence Learning Impaired in Schizophrenia? A Meta-Analysis

ERIC Educational Resources Information Center

Siegert, Richard J.; Weatherall, Mark; Bell, Elliot M.

2008-01-01

Cognition in schizophrenia seems to be characterized by impaired performance on most tests of explicit or declarative learning contrasting with relatively intact performance on most tests of implicit or procedural learning. At the same time there have been conflicting results for studies that have used the Serial Reaction Time (SRT) task to…

Guidance of Spatial Attention by Incidental Learning and Endogenous Cuing

ERIC Educational Resources Information Center

Jiang, Yuhong V.; Swallow, Khena M.; Rosenbaum, Gail M.

2013-01-01

Our visual system is highly sensitive to regularities in the environment. Locations that were important in one's previous experience are often prioritized during search, even though observers may not be aware of the learning. In this study we characterized the guidance of spatial attention by incidental learning of a target's spatial probability,…

Implicit transfer of spatial structure in visuomotor sequence learning.

PubMed

Tanaka, Kanji; Watanabe, Katsumi

2014-11-01

Implicit learning and transfer in sequence learning are essential in daily life. Here, we investigated the implicit transfer of visuomotor sequences following a spatial transformation. In the two experiments, participants used trial and error to learn a sequence consisting of several button presses, known as the m×n task (Hikosaka et al., 1995). After this learning session, participants learned another sequence in which the button configuration was spatially transformed in one of the following ways: mirrored, rotated, and random arrangement. Our results showed that even when participants were unaware of the transformation rules, accuracy of transfer session in the mirrored and rotated groups was higher than that in the random group (i.e., implicit transfer occurred). Both those who noticed the transformation rules and those who did not (i.e., explicit and implicit transfer instances, respectively) showed faster performance in the mirrored sequences than in the rotated sequences. Taken together, the present results suggest that people can use their implicit visuomotor knowledge to spatially transform sequences and that implicit transfers are modulated by a transformation cost, similar to that in explicit transfer. Copyright © 2014 Elsevier B.V. All rights reserved.

Feedback-based probabilistic category learning is selectively impaired in attention/hyperactivity deficit disorder.

PubMed

Gabay, Yafit; Goldfarb, Liat

2017-07-01

Although Attention-Deficit Hyperactivity Disorder (ADHD) is closely linked to executive function deficits, it has recently been attributed to procedural learning impairments that are quite distinct from the former. These observations challenge the ability of the executive function framework solely to account for the diverse range of symptoms observed in ADHD. A recent neurocomputational model emphasizes the role of striatal dopamine (DA) in explaining ADHD's broad range of deficits, but the link between this model and procedural learning impairments remains unclear. Significantly, feedback-based procedural learning is hypothesized to be disrupted in ADHD because of the involvement of striatal DA in this type of learning. In order to test this assumption, we employed two variants of a probabilistic category learning task known from the neuropsychological literature. Feedback-based (FB) and paired associate-based (PA) probabilistic category learning were employed in a non-medicated sample of ADHD participants and neurotypical participants. In the FB task, participants learned associations between cues and outcomes initially by guessing and subsequently through feedback indicating the correctness of the response. In the PA learning task, participants viewed the cue and its associated outcome simultaneously without receiving an overt response or corrective feedback. In both tasks, participants were trained across 150 trials. Learning was assessed in a subsequent test without a presentation of the outcome or corrective feedback. Results revealed an interesting disassociation in which ADHD participants performed as well as control participants in the PA task, but were impaired compared with the controls in the FB task. The learning curve during FB training differed between the two groups. Taken together, these results suggest that the ability to incrementally learn by feedback is selectively disrupted in ADHD participants. These results are discussed in relation to both

Contribution of Brain Tissue Oxidative Damage in Hypothyroidism-associated Learning and Memory Impairments

PubMed Central

Baghcheghi, Yousef; Salmani, Hossein; Beheshti, Farimah; Hosseini, Mahmoud

2017-01-01

The brain is a critical target organ for thyroid hormones, and modifications in memory and cognition happen with thyroid dysfunction. The exact mechanisms underlying learning and memory impairments due to hypothyroidism have not been understood yet. Therefore, this review was aimed to compress the results of previous studies which have examined the contribution of brain tissues oxidative damage in hypothyroidism-associated learning and memory impairments. PMID:28584813

Implicit Learning of Viewpoint-Independent Spatial Layouts

PubMed Central

Tsuchiai, Taiga; Matsumiya, Kazumichi; Kuriki, Ichiro; Shioiri, Satoshi

2012-01-01

We usually perceive things in our surroundings as unchanged despite viewpoint changes caused by self-motion. The visual system therefore must have a function to process objects independently of viewpoint. In this study, we examined whether viewpoint-independent spatial layout can be obtained implicitly. For this purpose, we used a contextual cueing effect, a learning effect of spatial layout in visual search displays known to be an implicit effect. We investigated the transfer of the contextual cueing effect to images from a different viewpoint by using visual search displays of 3D objects. For images from a different viewpoint, the contextual cueing effect was maintained with self-motion but disappeared when the display changed without self-motion. This indicates that there is an implicit learning effect in environment-centered coordinates and suggests that the spatial representation of object layouts can be obtained and updated implicitly. We also showed that binocular disparity plays an important role in the layout representations. PMID:22740837

Impaired Expected Value Computations Coupled With Overreliance on Stimulus-Response Learning in Schizophrenia.

PubMed

Hernaus, Dennis; Gold, James M; Waltz, James A; Frank, Michael J

2018-04-03

While many have emphasized impaired reward prediction error signaling in schizophrenia, multiple studies suggest that some decision-making deficits may arise from overreliance on stimulus-response systems together with a compromised ability to represent expected value. Guided by computational frameworks, we formulated and tested two scenarios in which maladaptive representations of expected value should be most evident, thereby delineating conditions that may evoke decision-making impairments in schizophrenia. In a modified reinforcement learning paradigm, 42 medicated people with schizophrenia and 36 healthy volunteers learned to select the most frequently rewarded option in a 75-25 pair: once when presented with a more deterministic (90-10) pair and once when presented with a more probabilistic (60-40) pair. Novel and old combinations of choice options were presented in a subsequent transfer phase. Computational modeling was employed to elucidate contributions from stimulus-response systems (actor-critic) and expected value (Q-learning). People with schizophrenia showed robust performance impairments with increasing value difference between two competing options, which strongly correlated with decreased contributions from expected value-based learning (Q-learning). Moreover, a subtle yet consistent contextual choice bias for the probabilistic 75 option was present in people with schizophrenia, which could be accounted for by a context-dependent reward prediction error in the actor-critic. We provide evidence that decision-making impairments in schizophrenia increase monotonically with demands placed on expected value computations. A contextual choice bias is consistent with overreliance on stimulus-response learning, which may signify a deficit secondary to the maladaptive representation of expected value. These results shed new light on conditions under which decision-making impairments may arise. Copyright © 2018 Society of Biological Psychiatry. Published by

Active and Passive Spatial Learning in Human Navigation: Acquisition of Graph Knowledge

ERIC Educational Resources Information Center

Chrastil, Elizabeth R.; Warren, William H.

2015-01-01

It is known that active exploration of a new environment leads to better spatial learning than does passive visual exposure. We ask whether specific components of active learning differentially contribute to particular forms of spatial knowledge--the "exploration-specific learning hypothesis". Previously, we found that idiothetic…

Nicotinic alpha 7 receptor agonists EVP-6124 and BMS-933043, attenuate scopolamine-induced deficits in visuo-spatial paired associates learning

PubMed Central

Polino, Joseph; Signor, Laura; Bookbinder, Mark; Keavy, Deborah; Benitex, Yulia; Morgan, Daniel G.; King, Dalton; Macor, John E.; Zaczek, Robert; Olson, Richard; Bristow, Linda J.

2017-01-01

Agonists at the nicotinic acetylcholine alpha 7 receptor (nAChR α7) subtype have the potential to treat cognitive deficits in patients with Alzheimer’s disease (AD) or schizophrenia. Visuo-spatial paired associates learning (vsPAL) is a task that has been shown to reliably predict conversion from mild cognitive impairment to AD in humans and can also be performed by nonhuman primates. Reversal of scopolamine-induced impairment of vsPAL performance may represent a translational approach for the development of nAChR α7 agonists. The present study investigated the effect of treatment with the acetylcholinesterase inhibitor, donepezil, or three nAChR α7 agonists, BMS-933043, EVP-6124 and RG3487, on vsPAL performance in scopolamine-treated cynomolgus monkeys. Scopolamine administration impaired vsPAL performance accuracy in a dose- and difficulty- dependent manner. The impairment of eventual accuracy, a measure of visuo-spatial learning during the task, was significantly ameliorated by treatment with donepezil (0.3 mg/kg, i.m.), EVP-6124 (0.01 mg/kg, i.m.) or BMS-933043 (0.03, 0.1 and 0.3 mg/kg, i.m.). Both nAChR α7 agonists showed inverted-U shaped dose-effect relationships with EVP-6124 effective at a single dose only whereas BMS-933043 was effective across at least a 10 fold dose/exposure range. RG3487 was not efficacious in this paradigm at the dose range examined (0.03–1 mg/kg, i.m.). These results are the first demonstration that the nAChR α7 agonists, EVP-6124 and BMS-933043, can ameliorate scopolamine-induced cognitive deficits in nonhuman primates performing the vsPAL task. PMID:29261656

G protein-gated K+ channel ablation in forebrain pyramidal neurons selectively impairs fear learning

PubMed Central

Victoria, Nicole C.; de Velasco, Ezequiel Marron Fernandez; Ostrovskaya, Olga; Metzger, Stefania; Xia, Zhilian; Kotecki, Lydia; Benneyworth, Michael A.; Zink, Anastasia N.; Martemyanov, Kirill A.; Wickman, Kevin

2015-01-01

Background Cognitive dysfunction occurs in many debilitating conditions including Alzheimer’s disease, Down syndrome, schizophrenia, and mood disorders. The dorsal hippocampus is a critical locus of cognitive processes linked to spatial and contextual learning. G protein-gated inwardly rectifying K+ (GIRK/Kir3) channels, which mediate the postsynaptic inhibitory effect of many neurotransmitters, have been implicated in hippocampal-dependent cognition. Available evidence, however, derives primarily from constitutive gain-of-function models that lack cellular specificity. Methods We used constitutive and neuron-specific gene ablation models targeting an integral subunit of neuronal GIRK channels (GIRK2) to probe the impact of GIRK channels on associative learning and memory. Results Constitutive Girk2−/− mice exhibited a striking deficit in hippocampal-dependent (contextual) and hippocampal-independent (cue) fear conditioning. Mice lacking GIRK2 in GABA neurons (GAD-Cre:Girk2flox/flox mice) exhibited a clear deficit in GIRK-dependent signaling in dorsal hippocampal GABA neurons, but no evident behavioral phenotype. Mice lacking GIRK2 in forebrain pyramidal neurons (CaMKII-Cre(+):Girk2flox/flox mice) exhibited diminished GIRK-dependent signaling in dorsal, but not ventral, hippocampal pyramidal neurons. CaMKII-Cre(+):Girk2flox/flox mice also displayed a selective impairment in contextual fear conditioning, as both cue-fear and spatial learning were intact in these mice. Finally, loss of GIRK2 in forebrain pyramidal neurons correlated with enhanced long-term depression and blunted depotentiation of long-term potentiation at the Schaffer collateral/CA1 synapse in the dorsal hippocampus. Conclusions Our data suggest that GIRK channels in dorsal hippocampal pyramidal neurons are necessary for normal learning involving aversive stimuli, and support the contention that dysregulation of GIRK-dependent signaling may underlie cognitive dysfunction in some disorders. PMID

Providing Hearing-Impaired Students with Learning Care after Classes through Smart Phones and the GPRS Network

ERIC Educational Resources Information Center

Liu, Chen-Chung; Hong, Yi-Ching

2007-01-01

Although computers and network technology have been widely utilised to assist students learn, few technical supports have been developed to help hearing-impaired students learn in Taiwan. A significant challenge for teachers is to provide after-class learning care and assistance to hearing-impaired students that sustain their motivation to…

Altered spatial learning and delay discounting in a rat model of human third trimester binge ethanol exposure

PubMed Central

Bañuelos, Cristina; Gilbert, Ryan J.; Montgomery, Karienn S.; Fincher, Annette S.; Wang, Haiying; Frye, Gerald D.; Setlow, Barry; Bizon, Jennifer L.

2012-01-01

Ethanol exposure during perinatal development can cause cognitive abnormalities including difficulties in learning, attention, and memory, as well as heightened impulsivity. The purpose of this study was to assess performance in spatial learning and impulsive choice tasks in rats subjected to an intragastric intubation model of binge ethanol exposure during human third trimester-equivalent brain development. Male and female Sprague–Dawley rat pups were intubated with ethanol (5.25 g/kg/day) on postnatal days 4–9. At adolescence (between postnatal days 35–38), these rats and sham intubated within-litter controls were trained in both spatial and cued versions of the Morris water maze. A subset of the male rats was subsequently tested on a delay-discounting task to assess impulsive choice. Ethanol-exposed rats were spatially impaired relative to controls, but performed comparably to controls on the cued version of the water maze. Ethanol-exposed rats also showed greater preference for large delayed rewards on the delay discounting task, but no evidence for altered reward sensitivity or perseverative behavior. These data demonstrate that early postnatal intermittent binge-like ethanol exposure has prolonged, detrimental, but selective effects on cognition, suggesting that even relatively brief ethanol exposure late in human pregnancy can be deleterious for cognitive function. PMID:22129556

Postural Motor Learning Deficits in People With MS in Spatial but Not Temporal Control of Center of Mass.

PubMed

Gera, Geetanjali; Fling, Brett W; Van Ooteghem, Karen; Cameron, Michelle; Frank, James S; Horak, Fay B

2016-09-01

Multiple sclerosis (MS) is associated with balance deficits resulting in falls and impaired mobility. Although rehabilitation has been recommended to address these balance deficits, the extent to which people with MS can learn and retain improvements in postural responses is unknown. To determine the ability of people with MS to improve postural control with surface perturbation training. A total of 24 patients with mild MS and 14 age-matched controls underwent postural control training with a set pattern of continuous, forward-backward, sinusoidal, and surface translations provided by a force platform. Postural control was then tested the following day for retention. The primary outcome measures were the relative phase and center-of-mass (CoM) gain between the body CoM and the platform motion. People with MS demonstrated similar improvements in acquiring and retaining changes in the temporal control of the CoM despite significant deficits in postural motor performance at the baseline. Both MS and control groups learned to anticipate the pattern of forward-backward perturbations, so body CoM shifted from a phase-lag (age-matched controls [CS] = -7.1 ± 1.3; MS = -12.9 ± 1.0) toward a phase-lead (CS = -0.7 ± 1.8; MS = -6.1 ± 1.4) relationship with the surface oscillations. However, MS patients were not able to retain the changes in the spatial control of the CoM acquired during training. People with MS have the capacity to improve use of a feed-forward postural strategy with practice and retain the learned behavior for temporal not spatial control of CoM, despite their significant postural response impairments. © The Author(s) 2015.

Nerve growth factor levels and choline acetyltransferase activity in the brain of aged rats with spatial memory impairments.

PubMed

Hellweg, R; Fischer, W; Hock, C; Gage, F H; Björklund, A; Thoenen, H

1990-12-24

Nerve growth factor (NGF) and choline acetyltransferase (ChAT) activity levels were measured in 7 different brain regions in young (3-month-old) and aged (2-years-old) female Sprague-Dawley rats. Prior to analysis the spatial learning ability of the aged rats was assessed in the Morris' water maze test. In the aged rats a significant, 15-30%, increase in NGF levels was observed in 4 regions (septum, cortex, olfactory bulb and cerebellum), whereas the levels in hippocampus, striatum and the brainstem were similar to those of the young rats. The NGF changes did not correlate with the behavioral performance within the aged group. Minor 15-30%, changes in ChAT activity were observed in striatum, brainstem and cerebellum, but these changes did not correlate with the changes in NGF levels in any region. The results indicate that brain NGF levels are maintained at normal or supranormal levels in rats with severe learning and memory impairments. The results, therefore, do not support the view that the marked atrophy and cell loss in the forebrain cholinergic system that is known to occur in the behaviorally impaired aged rats is caused by a reduced availability of NGF in the cholinergic target areas. The results also indicate that the slightly increased levels of NGF are not sufficient to prevent the age-dependent atrophy of cholinergic neurons, although they might be important for the stimulation of compensatory functional changes in a situation where the system is undergoing progressive degeneration.

Aβ Damages Learning and Memory in Alzheimer's Disease Rats with Kidney-Yang Deficiency

PubMed Central

Qi, Dongmei; Qiao, Yongfa; Zhang, Xin; Yu, Huijuan; Cheng, Bin; Qiao, Haifa

2012-01-01

Previous studies demonstrated that Alzheimer's disease was considered as the consequence produced by deficiency of Kidney essence. However, the mechanism underlying the symptoms also remains elusive. Here we report that spatial learning and memory, escape, and swimming capacities were damaged significantly in Kidney-yang deficiency rats. Indeed, both hippocampal Aβ 40 and 42 increases in Kidney-yang deficiency contribute to the learning and memory impairments. Specifically, damage of synaptic plasticity is involved in the learning and memory impairment of Kidney-yang deficiency rats. We determined that the learning and memory damage in Kidney-yang deficiency due to synaptic plasticity impairment and increases of Aβ 40 and 42 was not caused via NMDA receptor internalization induced by Aβ increase. β-Adrenergic receptor agonist can rescue the impaired long-term potential (LTP) in Kidney-yang rats. Taken together, our results suggest that spatial learning and memory inhibited in Kidney-yang deficiency might be induced by Aβ increase and the decrease of β 2 receptor function in glia. PMID:22645624

Blue light filtered white light induces depression-like responses and temporary spatial learning deficits in rats.

PubMed

Meng, Qinghe; Lian, Yuzheng; Jiang, Jianjun; Wang, Wei; Hou, Xiaohong; Pan, Yao; Chu, Hongqian; Shang, Lanqin; Wei, Xuetao; Hao, Weidong

2018-04-18

Ambient light has a vital impact on mood and cognitive functions. Blue light has been previously reported to play a salient role in the antidepressant effect via melanopsin. Whether blue light filtered white light (BFW) affects mood and cognitive functions remains unclear. The present study aimed to investigate whether BFW led to depression-like symptoms and cognitive deficits including spatial learning and memory abilities in rats, and whether they were associated with the light-responsive function in retinal explants. Male Sprague-Dawley albino rats were randomly divided into 2 groups (n = 10) and treated with a white light-emitting diode (LED) light source and BFW light source, respectively, under a standard 12 : 12 h L/D condition over 30 days. The sucrose consumption test, forced swim test (FST) and the level of plasma corticosterone (CORT) were employed to evaluate depression-like symptoms in rats. Cognitive functions were assessed by the Morris water maze (MWM) test. A multi-electrode array (MEA) system was utilized to measure electro-retinogram (ERG) responses induced by white or BFW flashes. The effect of BFW over 30 days on depression-like responses in rats was indicated by decreased sucrose consumption in the sucrose consumption test, an increased immobility time in the FST and an elevated level of plasma CORT. BFW led to temporary spatial learning deficits in rats, which was evidenced by prolonged escape latency and swimming distances in the spatial navigation test. However, no changes were observed in the short memory ability of rats treated with BFW. The micro-ERG results showed a delayed implicit time and reduced amplitudes evoked by BFW flashes compared to the white flash group. BFW induces depression-like symptoms and temporary spatial learning deficits in rats, which might be closely related to the impairment of light-evoked output signals in the retina.

Maternal Exposure of Rats to Isoflurane during Late Pregnancy Impairs Spatial Learning and Memory in the Offspring by Up-Regulating the Expression of Histone Deacetylase 2.

PubMed

Luo, Foquan; Hu, Yan; Zhao, Weilu; Zuo, Zhiyi; Yu, Qi; Liu, Zhiyi; Lin, Jiamei; Feng, Yunlin; Li, Binda; Wu, Liuqin; Xu, Lin

2016-01-01

Increasing evidence indicates that most general anesthetics can harm developing neurons and induce cognitive dysfunction in a dose- and time-dependent manner. Histone deacetylase 2 (HDAC2) has been implicated in synaptic plasticity and learning and memory. Our previous results showed that maternal exposure to general anesthetics during late pregnancy impaired the offspring's learning and memory, but the role of HDAC2 in it is not known yet. In the present study, pregnant rats were exposed to 1.5% isoflurane in 100% oxygen for 2, 4 or 8 hours or to 100% oxygen only for 8 hours on gestation day 18 (E18). The offspring born to each rat were randomly subdivided into 2 subgroups. Thirty days after birth, the Morris water maze (MWM) was used to assess learning and memory in the offspring. Two hours before each MWM trial, an HDAC inhibitor (SAHA) was given to the offspring in one subgroup, whereas a control solvent was given to those in the other subgroup. The results showed that maternal exposure to isoflurane impaired learning and memory of the offspring, impaired the structure of the hippocampus, increased HDAC2 mRNA and downregulated cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) mRNA, N-methyl-D-aspartate receptor 2 subunit B (NR2B) mRNA and NR2B protein in the hippocampus. These changes were proportional to the duration of the maternal exposure to isoflurane and were reversed by SAHA. These results suggest that exposure to isoflurane during late pregnancy can damage the learning and memory of the offspring rats via the HDAC2-CREB -NR2B pathway. This effect can be reversed by HDAC2 inhibition.

Finding faults: analogical comparison supports spatial concept learning in geoscience.

PubMed

Jee, Benjamin D; Uttal, David H; Gentner, Dedre; Manduca, Cathy; Shipley, Thomas F; Sageman, Bradley

2013-05-01

A central issue in education is how to support the spatial thinking involved in learning science, technology, engineering, and mathematics (STEM). We investigated whether and how the cognitive process of analogical comparison supports learning of a basic spatial concept in geoscience, fault. Because of the high variability in the appearance of faults, it may be difficult for students to learn the category-relevant spatial structure. There is abundant evidence that comparing analogous examples can help students gain insight into important category-defining features (Gentner in Cogn Sci 34(5):752-775, 2010). Further, comparing high-similarity pairs can be especially effective at revealing key differences (Sagi et al. 2012). Across three experiments, we tested whether comparison of visually similar contrasting examples would help students learn the fault concept. Our main findings were that participants performed better at identifying faults when they (1) compared contrasting (fault/no fault) cases versus viewing each case separately (Experiment 1), (2) compared similar as opposed to dissimilar contrasting cases early in learning (Experiment 2), and (3) viewed a contrasting pair of schematic block diagrams as opposed to a single block diagram of a fault as part of an instructional text (Experiment 3). These results suggest that comparison of visually similar contrasting cases helped distinguish category-relevant from category-irrelevant features for participants. When such comparisons occurred early in learning, participants were more likely to form an accurate conceptual representation. Thus, analogical comparison of images may provide one powerful way to enhance spatial learning in geoscience and other STEM disciplines.

Elevation of endogenous anandamide impairs LTP, learning, and memory through CB1 receptor signaling in mice.

PubMed

Basavarajappa, Balapal S; Nagre, Nagaraja N; Xie, Shan; Subbanna, Shivakumar

2014-07-01

In rodents, many exogenous and endogenous cannabinoids, such as anandamide (AEA) and 2-arachidonyl glycerol (2-AG), have been shown to play an important role in certain hippocampal memory processes. However, the mechanisms by which endogenous AEA regulate this processes are not well understood. Here the effects of AEA on long-term potentiation (LTP), hippocampal-dependent learning and memory tasks, pERK1/2, pCaMKIV, and pCREB signaling events in both cannabinoid receptor type 1 (CB1R) wild-type (WT) and knockout (KO) mice were assessed following administration of URB597, an inhibitor of the fatty acid amide hydrolase (FAAH). Acute administration of URB597 enhanced AEA levels without affecting the levels of 2-AG or CB1R in the hippocampus and neocortex as compared to vehicle. In hippocampal slices, URB597 impaired LTP in CB1R WT but not in KO littermates. URB597 impaired object recognition, spontaneous alternation and spatial memory in the Y-maze test in CB1R WT mice but not in KO mice. Furthermore, URB597 enhanced ERK phosphorylation in WT without affecting total ERK levels in WT or KO mice. URB597 impaired CaMKIV and CREB phosphorylation in WT but not in KO mice. CB1R KO mice have a lower pCaMKIV/CaMKIV ratio and higher pCREB/CREB ratio as compared to WT littermates. Our results indicate that pharmacologically elevated AEA impair LTP, learning and memory and inhibit CaMKIV and CREB phosphorylation, via the activation of CB1Rs. Collectively, these findings also suggest that pharmacological elevation of AEA beyond normal concentrations is also detrimental for the underlying physiological responses. © 2014 Wiley Periodicals, Inc.

Cabri 3D - assisted collaborative learning to enhance junior high school students’ spatial ability

NASA Astrophysics Data System (ADS)

Muntazhimah; Miatun, A.

2018-01-01

The main purpose of this quasi-experimental study was to determine the enhancement of spatial ability of junior high school students who learned through Cabri-3D assisted collaborative learning. The methodology of this study was the nonequivalent group that was conducted to students of the eighth grade in a junior high school as a population. Samples consisted one class of the experimental group who studied with Cabri-3D assisted collaborative learning and one class as a control group who got regular learning activity. The instrument used in this study was a spatial ability test. Analyzing normalized gain of students’ spatial ability based on mathemathical prior knowledge (MPK) and its interactions was tested by two-way ANOVA at a significance level of 5% then continued with using Post Hoc Scheffe test. The research results showed that there was significant difference in enhancement of the spatial ability between students who learnt with Cabri 3D assisted collaborative learning and students who got regular learning, there was significant difference in enhancement of the spatial ability between students who learnt with cabri 3D assisted collaborative learning and students who got regular learning in terms of MPK and there is no significant interaction between learning (Cabri-3D assisted collaborative learning and regular learning) with students’ MPK (high, medium, and low) toward the enhancement of students’ spatial abilities. From the above findings, it can be seen that cabri-3D assisted collaborative learning could enhance spatial ability of junior high school students.

Impairments in learning by monetary rewards and alcohol-associated rewards in detoxified alcoholic patients.

PubMed

Jokisch, Daniel; Roser, Patrik; Juckel, Georg; Daum, Irene; Bellebaum, Christian

2014-07-01

Excessive alcohol consumption has been linked to structural and functional brain changes associated with cognitive, emotional, and behavioral impairments. It has been suggested that neural processing in the reward system is also affected by alcoholism. The present study aimed at further investigating reward-based associative learning and reversal learning in detoxified alcohol-dependent patients. Twenty-one detoxified alcohol-dependent patients and 26 healthy control subjects participated in a probabilistic learning task using monetary and alcohol-associated rewards as feedback stimuli indicating correct responses. Performance during acquisition and reversal learning in the different feedback conditions was analyzed. Alcohol-dependent patients and healthy control subjects showed an increase in learning performance over learning blocks during acquisition, with learning performance being significantly lower in alcohol-dependent patients. After changing the contingencies, alcohol-dependent patients exhibited impaired reversal learning and showed, in contrast to healthy controls, different learning curves for different types of rewards with no increase in performance for high monetary and alcohol-associated feedback. The present findings provide evidence that dysfunctional processing in the reward system in alcohol-dependent patients leads to alterations in reward-based learning resulting in a generally reduced performance. In addition, the results suggest that alcohol-dependent patients are, in particular, more impaired in changing an established behavior originally reinforced by high rewards. Copyright © 2014 by the Research Society on Alcoholism.

Impaired Learning of Social Compared to Monetary Rewards in Autism

PubMed Central

Lin, Alice; Rangel, Antonio; Adolphs, Ralph

2012-01-01

A leading hypothesis to explain the social dysfunction in people with autism spectrum disorders (ASD) is that they exhibit a deficit in reward processing and motivation specific to social stimuli. However, there have been few direct tests of this hypothesis to date. Here we used an instrumental reward learning task that contrasted learning with social rewards (pictures of positive and negative faces) against learning with monetary reward (winning and losing money). The two tasks were structurally identical except for the type of reward, permitting direct comparisons. We tested 10 high-functioning people with ASD (7M, 3F) and 10 healthy controls who were matched on gender, age, and education. We found no significant differences between the two groups in terms of overall ability behaviorally to discriminate positive from negative slot machines, reaction-times, and valence ratings, However, there was a specific impairment in the ASD group in learning to choose social rewards, compared to monetary rewards: they had a significantly lower cumulative number of choices of the most rewarding social slot machine, and had a significantly slower initial learning rate for the socially rewarding slot machine, compared to the controls. The findings show a deficit in reward learning in ASD that is greater for social rewards than for monetary rewards, and support the hypothesis of a disproportionate impairment in social reward processing in ASD. PMID:23060743

Ripple-triggered stimulation of the locus coeruleus during post-learning sleep disrupts ripple/spindle coupling and impairs memory consolidation.

PubMed

Novitskaya, Yulia; Sara, Susan J; Logothetis, Nikos K; Eschenko, Oxana

2016-05-01

Experience-induced replay of neuronal ensembles occurs during hippocampal high-frequency oscillations, or ripples. Post-learning increase in ripple rate is predictive of memory recall, while ripple disruption impairs learning. Ripples may thus present a fundamental component of a neurophysiological mechanism of memory consolidation. In addition to system-level local and cross-regional interactions, a consolidation mechanism involves stabilization of memory representations at the synaptic level. Synaptic plasticity within experience-activated neuronal networks is facilitated by noradrenaline release from the axon terminals of the locus coeruleus (LC). Here, to better understand interactions between the system and synaptic mechanisms underlying "off-line" consolidation, we examined the effects of ripple-associated LC activation on hippocampal and cortical activity and on spatial memory. Rats were trained on a radial maze; after each daily learning session neural activity was monitored for 1 h via implanted electrode arrays. Immediately following "on-line" detection of ripple, a brief train of electrical pulses (0.05 mA) was applied to LC. Low-frequency (20 Hz) stimulation had no effect on spatial learning, while higher-frequency (100 Hz) trains transiently blocked generation of ripple-associated cortical spindles and caused a reference memory deficit. Suppression of synchronous ripple/spindle events appears to interfere with hippocampal-cortical communication, thereby reducing the efficiency of "off-line" memory consolidation. © 2016 Novitskaya et al.; Published by Cold Spring Harbor Laboratory Press.

Ripple-triggered stimulation of the locus coeruleus during post-learning sleep disrupts ripple/spindle coupling and impairs memory consolidation

PubMed Central

Novitskaya, Yulia; Sara, Susan J.; Logothetis, Nikos K.

2016-01-01

Experience-induced replay of neuronal ensembles occurs during hippocampal high-frequency oscillations, or ripples. Post-learning increase in ripple rate is predictive of memory recall, while ripple disruption impairs learning. Ripples may thus present a fundamental component of a neurophysiological mechanism of memory consolidation. In addition to system-level local and cross-regional interactions, a consolidation mechanism involves stabilization of memory representations at the synaptic level. Synaptic plasticity within experience-activated neuronal networks is facilitated by noradrenaline release from the axon terminals of the locus coeruleus (LC). Here, to better understand interactions between the system and synaptic mechanisms underlying “off-line” consolidation, we examined the effects of ripple-associated LC activation on hippocampal and cortical activity and on spatial memory. Rats were trained on a radial maze; after each daily learning session neural activity was monitored for 1 h via implanted electrode arrays. Immediately following “on-line” detection of ripple, a brief train of electrical pulses (0.05 mA) was applied to LC. Low-frequency (20 Hz) stimulation had no effect on spatial learning, while higher-frequency (100 Hz) trains transiently blocked generation of ripple-associated cortical spindles and caused a reference memory deficit. Suppression of synchronous ripple/spindle events appears to interfere with hippocampal-cortical communication, thereby reducing the efficiency of “off-line” memory consolidation. PMID:27084931

Impairment of learning and memory performances induced by BPA: Evidences from the literature of a MoA mediated through an ED.

PubMed

Mhaouty-Kodja, Sakina; Belzunces, Luc P; Canivenc, Marie-Chantal; Schroeder, Henri; Chevrier, Cécile; Pasquier, Elodie

2018-03-29

Many rodent studies and a few non-human primate data report impairments of spatial and non-spatial memory induced by exposure to bisphenol A (BPA), which are associated with neural modifications, particularly in processes involved in synaptic plasticity. BPA-induced alterations involve disruption of the estrogenic pathway as established by reversal of BPA-induced effects with estrogenic receptor antagonist or by interference of BPA with administered estradiol in ovariectomized animals. Sex differences in hormonal impregnation during critical periods of development and their influence on maturation of learning and memory processes may explain the sexual dimorphism observed in BPA-induced effects in some studies. Altogether, these data highly support the plausibility that alteration of learning and memory and synaptic plasticity by BPA is essentially mediated by disturbance of the estrogenic pathways. As memory function in humans involves similar signaling pathways, this mode of action of BPA has the potential to alter human cognitive abilities. Copyright © 2018. Published by Elsevier B.V.

Relaxin-3 inputs target hippocampal interneurons and deletion of hilar relaxin-3 receptors in "floxed-RXFP3" mice impairs spatial memory.

PubMed

Haidar, M; Guèvremont, G; Zhang, C; Bathgate, R A D; Timofeeva, E; Smith, C M; Gundlach, A L

2017-05-01

Hippocampus is innervated by γ-aminobutyric acid (GABA) "projection" neurons of the nucleus incertus (NI), including a population expressing the neuropeptide, relaxin-3 (RLN3). In studies aimed at gaining an understanding of the role of RLN3 signaling in hippocampus via its G i/o -protein-coupled receptor, RXFP3, we examined the distribution of RLN3-immunoreactive nerve fibres and RXFP3 mRNA-positive neurons in relation to hippocampal GABA neuron populations. RLN3-positive elements were detected in close-apposition with a substantial population of somatostatin (SST)- and GABA-immunoreactive neurons, and a smaller population of parvalbumin- and calretinin-immunoreactive neurons in different hippocampal areas, consistent with the relative distribution patterns of RXFP3 mRNA and these marker transcripts. In light of the functional importance of the dentate gyrus (DG) hilus in learning and memory, and our anatomical data, we examined the possible influence of RLN3/RXFP3 signaling in this region on spatial memory. Using viral-based Cre/LoxP recombination methods and adult mice with a floxed Rxfp3 gene, we deleted Rxfp3 from DG hilar neurons and assessed spatial memory performance and affective behaviors. Following infusions of an AAV (1/2) -Cre-IRES-eGFP vector, Cre expression was observed in DG hilar neurons, including SST-positive cells, and in situ hybridization histochemistry for RXFP3 mRNA confirmed receptor depletion relative to levels in floxed-RXFP3 mice infused with an AAV (1/2) -eGFP (control) vector. RXFP3 depletion within the DG hilus impaired spatial reference memory in an appetitive T-maze task reflected by a reduced percentage of correct choices and increased time to meet criteria, relative to control. In a continuous spontaneous alternation Y-maze task, RXFP3-depleted mice made fewer alternations in the first minute, suggesting impairment of spatial working memory. However, RXFP3-depleted and control mice displayed similar locomotor activity, anxiety

Aβ25-35 injection into the temporal cortex induces chronic inflammation that contributes to neurodegeneration and spatial memory impairment in rats.

PubMed

Diaz, Alfonso; Limon, Daniel; Chávez, Raúl; Zenteno, Edgar; Guevara, Jorge

2012-01-01

Amyloid-β (Aβ)25-35 is able to cause memory impairment and neurodegenerative events. Recent evidence has shown that the injection of Aβ25-35 into the temporal cortex (TCx) of rats increases the inflammatory response; however, it is unclear how the inflammatory process could be involved in the progression of Aβ25-35 toxicity. In this study we investigated the role of inflammation in the neuronal damage and spatial memory impairment generated by Aβ25-35 in rat TCx using immunohistochemistry, ELISA, and a behavioral test in the radial maze. Our findings show that Aβ25-35 -injection into the TCx induced a reactive gliosis (GFAP and CD11b-reactivity) and an increase of pro-inflammatory cytokines (IL-1β, IL-6, IL-17, and TNF-α) in the TCx and the hippocampus at 5, 15, and 30 days after injection. Thirty days after Aβ25-35 injection, we observed that the inflammatory reaction probably contributed to increase the immunoreactivity of inducible nitric oxide synthase and nitrite levels, as well as to the loss of neurons in TCx and hippocampus. Behavioral performance showed that the neurodegeneration evoked by Aβ25-35 delayed acquisition of learning and impaired spatial memory, because the Aβ25-35-treated animals showed a greater number of errors during the task than the control group. Previous administration of an interleukin receptor antagonist (IL-1ra) (10 and 20 μg/μL, into TCx), an anti-inflammatory agent, suppressed the Aβ25-35-induced inflammatory response and neurodegeneration, as well as memory dysfunction. This study suggests that the chronic inflammatory reaction could contribute to the progression of Aβ25-35 toxicity and cause cognitive impairment.

Evaluation of Deep Learning Representations of Spatial Storm Data

NASA Astrophysics Data System (ADS)

Gagne, D. J., II; Haupt, S. E.; Nychka, D. W.

2017-12-01

The spatial structure of a severe thunderstorm and its surrounding environment provide useful information about the potential for severe weather hazards, including tornadoes, hail, and high winds. Statistics computed over the area of a storm or from the pre-storm environment can provide descriptive information but fail to capture structural information. Because the storm environment is a complex, high-dimensional space, identifying methods to encode important spatial storm information in a low-dimensional form should aid analysis and prediction of storms by statistical and machine learning models. Principal component analysis (PCA), a more traditional approach, transforms high-dimensional data into a set of linearly uncorrelated, orthogonal components ordered by the amount of variance explained by each component. The burgeoning field of deep learning offers two potential approaches to this problem. Convolutional Neural Networks are a supervised learning method for transforming spatial data into a hierarchical set of feature maps that correspond with relevant combinations of spatial structures in the data. Generative Adversarial Networks (GANs) are an unsupervised deep learning model that uses two neural networks trained against each other to produce encoded representations of spatial data. These different spatial encoding methods were evaluated on the prediction of severe hail for a large set of storm patches extracted from the NCAR convection-allowing ensemble. Each storm patch contains information about storm structure and the near-storm environment. Logistic regression and random forest models were trained using the PCA and GAN encodings of the storm data and were compared against the predictions from a convolutional neural network. All methods showed skill over climatology at predicting the probability of severe hail. However, the verification scores among the methods were very similar and the predictions were highly correlated. Further evaluations are being

Teachers' Spatial Anxiety Relates to 1st-and 2nd-Graders' Spatial Learning

ERIC Educational Resources Information Center

Gunderson, Elizabeth A.; Ramirez, Gerardo; Beilock, Sian L.; Levine, Susan C.

2013-01-01

Teachers' anxiety about an academic domain, such as math, can impact students' learning in that domain. We asked whether this relation held in the domain of spatial skill, given the importance of spatial skill for success in math and science and its malleability at a young age. We measured 1st-and 2nd-grade teachers' spatial anxiety…

Chronic administration of R-flurbiprofen attenuates learning impairments in transgenic amyloid precursor protein mice

PubMed Central

Kukar, Thomas; Prescott, Sonya; Eriksen, Jason L; Holloway, Vallie; Murphy, M Paul; Koo, Edward H; Golde, Todd E; Nicolle, Michelle M

2007-01-01

Background Long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) is associated with a reduced incidence of Alzheimer's disease (AD). We and others have shown that certain NSAIDs reduce secretion of Aβ42 in cell culture and animal models, and that the effect of NSAIDs on Aβ42 is independent of the inhibition of cyclooxygenase by these compounds. Since Aβ42 is hypothesized to be the initiating pathologic molecule in AD, the ability of these compounds to lower Aβ42 selectively may be associated with their protective effect. We have previously identified R-flurbiprofen (tarenflurbil) as a selective Aβ42 lowering agent with greatly reduced cyclooxygenase activity that shows promise for testing this hypothesis. In this study we report the effect of chronic R-flurbiprofen treatment on cognition and Aβ loads in Tg2576 APP mice. Results A four-month preventative treatment regimen with R-flurbiprofen (10 mg/kg/day) was administered to young Tg2576 mice prior to robust plaque or Aβ pathology. This treatment regimen improved spatial learning as assessed by the Morris water maze, indicated by an increased spatial bias during the third probe trial and an increased utilization of a place strategy to solve the water maze. These results are consistent with an improvement in hippocampal- and medial temporal lobe-dependent memory function. A modest, though not statistically significant, reduction in formic acid-soluble levels of Aβ was also observed. To determine if R-flurbiprofen could reverse cognitive deficits in Tg2576 mice where plaque pathology was already robust, a two-week therapeutic treatment was given to older Tg2576 mice with the same dose of R-flurbiprofen. This approach resulted in a significant decrease in Aβ plaque burden but no significant improvement in spatial learning. Conclusion We have found that chronic administration of R-flurbiprofen is able to attenuate spatial learning deficits if given prior to plaque deposition in Tg2576 mice. Given its

MEMANTINE ATTENUATES THE OKADAIC ACID INDUCED SHORT-TERM SPATIAL MEMORY IMPAIRMENT AND HIPPOCAMPAL CELL LOSS IN RATS.

PubMed

Dashniani, M; Chighladze, M; Burjanadze, M; Beselia, G; Kruashvili, L

2016-03-01

In the present study, the possible beneficial effect of memantine on the Okadaic Acid (OA) induced spatial short-term memory impairment was examined in spatial alternation task, and the neuroprotective potential of memantine on OA-induced structural changes in the hippocampus was evaluated by Nissl staining. OA was dissolved in artificial cerebrospinal fluid (aCSF) and injected intracerebroventriculary (ICV) 200 ng in a volume of 10 μl bilaterally. Vehicle control received aCSF ICV bilaterally. Control and OA injected rats were divided into 2 subgroups injected i.p. with saline or memantine (5 mg/kg). Memantine or saline were given daily for 13 days starting from the day of OA injection. Behavioral study showed that bilateral ICV microinjection of OA induced impairment in spatial short-term memory. Nissl staining in the present study showed that the ICV microinjection of OA significantly decreased the number of surviving pyramidal neurons in the CA1 region of the hippocampus. Chronic administration of memantine effectively attenuated OA induced spatial short-term memory impairment and the OA-induced neuropathological changes in the hippocampus. Therefore, ICV injection of OA can be used as an experimental model to study mechanisms of neurodegeneration and define novel therapeutics targets for AD pathology.

Spatial working memory interferes with explicit, but not probabilistic cuing of spatial attention.

PubMed

Won, Bo-Yeong; Jiang, Yuhong V

2015-05-01

Recent empirical and theoretical work has depicted a close relationship between visual attention and visual working memory. For example, rehearsal in spatial working memory depends on spatial attention, whereas adding a secondary spatial working memory task impairs attentional deployment in visual search. These findings have led to the proposal that working memory is attention directed toward internal representations. Here, we show that the close relationship between these 2 constructs is limited to some but not all forms of spatial attention. In 5 experiments, participants held color arrays, dot locations, or a sequence of dots in working memory. During the memory retention interval, they performed a T-among-L visual search task. Crucially, the probable target location was cued either implicitly through location probability learning or explicitly with a central arrow or verbal instruction. Our results showed that whereas imposing a visual working memory load diminished the effectiveness of explicit cuing, it did not interfere with probability cuing. We conclude that spatial working memory shares similar mechanisms with explicit, goal-driven attention but is dissociated from implicitly learned attention. (c) 2015 APA, all rights reserved).

Dorsolateral prefrontal lesions do not impair tests of scene learning and decision-making that require frontal–temporal interaction

PubMed Central

Baxter, Mark G; Gaffan, David; Kyriazis, Diana A; Mitchell, Anna S

2008-01-01

Theories of dorsolateral prefrontal cortex (DLPFC) involvement in cognitive function variously emphasize its involvement in rule implementation, cognitive control, or working and/or spatial memory. These theories predict broad effects of DLPFC lesions on tests of visual learning and memory. We evaluated the effects of DLPFC lesions (including both banks of the principal sulcus) in rhesus monkeys on tests of scene learning and strategy implementation that are severely impaired following crossed unilateral lesions of frontal cortex and inferotemporal cortex. Dorsolateral lesions had no effect on learning of new scene problems postoperatively, or on the implementation of preoperatively acquired strategies. They were also without effect on the ability to adjust choice behaviour in response to a change in reinforcer value, a capacity that requires interaction between the amygdala and frontal lobe. These intact abilities following DLPFC damage support specialization of function within the prefrontal cortex, and suggest that many aspects of memory and strategic and goal-directed behaviour can survive ablation of this structure. PMID:18702721

D1 Receptor Activation in the Mushroom Bodies Rescues Sleep Loss Induced Learning Impairments in Drosophila

PubMed Central

Seugnet, Laurent; Suzuki, Yasuko; Vine, Lucy; Gottschalk, Laura; Shaw, Paul J

2008-01-01

Background Extended wakefulness disrupts acquisition of short term memories in mammals. However, the underlying molecular mechanisms triggered by extended waking and restored by sleep are unknown. Moreover, the neuronal circuits that depend on sleep for optimal learning remain unidentified. Results Learning was evaluated using Aversive Phototaxic Suppression (APS). In this task, flies learn to avoid light that is paired with an aversive stimulus (quinine /humidity). We demonstrate extensive homology in sleep deprivation induced learning impairment between flies and humans. Both 6 h and 12 h of sleep deprivation are sufficient to impair learning in Canton-S (Cs) flies. Moreover, learning is impaired at the end of the normal waking-day in direct correlation with time spent awake. Mechanistic studies indicate that this task requires intact mushroom bodies (MBs) and requires the Dopamine D1-like receptor (dDA1). Importantly, sleep deprivation induced learning impairments could be rescued by targeted gene expression of the dDA1 receptor to the MBs. Conclusion These data provide direct evidence that extended wakefulness disrupts learning in Drosophila. These results demonstrate that it is possible to prevent the effects of sleep deprivation by targeting a single neuronal structure and identify cellular and molecular targets adversely affected by extended waking in a genetically tractable model organism. PMID:18674913

Ageing and spatial reversal learning in humans: findings from a virtual water maze.

PubMed

Schoenfeld, R; Foreman, N; Leplow, B

2014-08-15

Deterioration in spatial memory with normal ageing is well accepted. Animal research has shown spatial reversal learning to be most vulnerable to pathological changes in the brain, but this has never been tested in humans. We studied ninety participants (52% females, 20-80 yrs) in a virtual water maze with a reversal learning procedure. Neuropsychological functioning, mood and personality were assessed to control moderator effects. For data analysis, participants were subdivided post hoc into groups aged 20-24, 25-34, 35-44, 45-64 and 65-80 yrs. Initial spatial learning occurred in all age groups but 65-80-yrs-olds never reached the level of younger participants. When tested for delayed recall of spatial memory, younger people frequented the target area but those over 65 yrs did not. In spatial reversal learning, age groups over 45 yrs were deficient and the 65-80-yrs-olds showed no evidence of reversal. Spatial measures were associated with neuropsychological functioning. Extraversion and measures of depression moderated the age effect on the learning index with older introverted and non-depressed individuals showing better results. Measures of anxiety moderated the age effect on reversal learning with older people having higher anxiety scores showing a preserved reversal learning capability. Results confirmed age to be a major factor in spatial tasks but further showed neuropsychological functioning, psycho-affective determinants and personality traits to be significant predictors of individual differences. Copyright © 2014 Elsevier B.V. All rights reserved.

Nondeclarative learning in children with specific language impairment: predicting regularities in the visuomotor, phonological, and cognitive domains.

PubMed

Mayor-Dubois, C; Zesiger, P; Van der Linden, M; Roulet-Perez, E

2014-01-01

Ullman (2004) suggested that Specific Language Impairment (SLI) results from a general procedural learning deficit. In order to test this hypothesis, we investigated children with SLI via procedural learning tasks exploring the verbal, motor, and cognitive domains. Results showed that compared with a Control Group, the children with SLI (a) were unable to learn a phonotactic learning task, (b) were able but less efficiently to learn a motor learning task and (c) succeeded in a cognitive learning task. Regarding the motor learning task (Serial Reaction Time Task), reaction times were longer and learning slower than in controls. The learning effect was not significant in children with an associated Developmental Coordination Disorder (DCD), and future studies should consider comorbid motor impairment in order to clarify whether impairments are related to the motor rather than the language disorder. Our results indicate that a phonotactic learning but not a cognitive procedural deficit underlies SLI, thus challenging Ullmans' general procedural deficit hypothesis, like a few other recent studies.

Learning impairment in honey bees caused by agricultural spray adjuvants.

PubMed

Ciarlo, Timothy J; Mullin, Christopher A; Frazier, James L; Schmehl, Daniel R

2012-01-01

Spray adjuvants are often applied to crops in conjunction with agricultural pesticides in order to boost the efficacy of the active ingredient(s). The adjuvants themselves are largely assumed to be biologically inert and are therefore subject to minimal scrutiny and toxicological testing by regulatory agencies. Honey bees are exposed to a wide array of pesticides as they conduct normal foraging operations, meaning that they are likely exposed to spray adjuvants as well. It was previously unknown whether these agrochemicals have any deleterious effects on honey bee behavior. An improved, automated version of the proboscis extension reflex (PER) assay with a high degree of trial-to-trial reproducibility was used to measure the olfactory learning ability of honey bees treated orally with sublethal doses of the most widely used spray adjuvants on almonds in the Central Valley of California. Three different adjuvant classes (nonionic surfactants, crop oil concentrates, and organosilicone surfactants) were investigated in this study. Learning was impaired after ingestion of 20 µg organosilicone surfactant, indicating harmful effects on honey bees caused by agrochemicals previously believed to be innocuous. Organosilicones were more active than the nonionic adjuvants, while the crop oil concentrates were inactive. Ingestion was required for the tested adjuvant to have an effect on learning, as exposure via antennal contact only induced no level of impairment. A decrease in percent conditioned response after ingestion of organosilicone surfactants has been demonstrated here for the first time. Olfactory learning is important for foraging honey bees because it allows them to exploit the most productive floral resources in an area at any given time. Impairment of this learning ability may have serious implications for foraging efficiency at the colony level, as well as potentially many social interactions. Organosilicone spray adjuvants may therefore contribute to the

Learning Impairment in Honey Bees Caused by Agricultural Spray Adjuvants

PubMed Central

Ciarlo, Timothy J.; Mullin, Christopher A.; Frazier, James L.; Schmehl, Daniel R.

2012-01-01

Background Spray adjuvants are often applied to crops in conjunction with agricultural pesticides in order to boost the efficacy of the active ingredient(s). The adjuvants themselves are largely assumed to be biologically inert and are therefore subject to minimal scrutiny and toxicological testing by regulatory agencies. Honey bees are exposed to a wide array of pesticides as they conduct normal foraging operations, meaning that they are likely exposed to spray adjuvants as well. It was previously unknown whether these agrochemicals have any deleterious effects on honey bee behavior. Methodology/Principal Findings An improved, automated version of the proboscis extension reflex (PER) assay with a high degree of trial-to-trial reproducibility was used to measure the olfactory learning ability of honey bees treated orally with sublethal doses of the most widely used spray adjuvants on almonds in the Central Valley of California. Three different adjuvant classes (nonionic surfactants, crop oil concentrates, and organosilicone surfactants) were investigated in this study. Learning was impaired after ingestion of 20 µg organosilicone surfactant, indicating harmful effects on honey bees caused by agrochemicals previously believed to be innocuous. Organosilicones were more active than the nonionic adjuvants, while the crop oil concentrates were inactive. Ingestion was required for the tested adjuvant to have an effect on learning, as exposure via antennal contact only induced no level of impairment. Conclusions/Significance A decrease in percent conditioned response after ingestion of organosilicone surfactants has been demonstrated here for the first time. Olfactory learning is important for foraging honey bees because it allows them to exploit the most productive floral resources in an area at any given time. Impairment of this learning ability may have serious implications for foraging efficiency at the colony level, as well as potentially many social interactions

Learning efficient visual search for stimuli containing diagnostic spatial configurations and color-shape conjunctions.

PubMed

Reavis, Eric A; Frank, Sebastian M; Tse, Peter U

2018-04-12

Visual search is often slow and difficult for complex stimuli such as feature conjunctions. Search efficiency, however, can improve with training. Search for stimuli that can be identified by the spatial configuration of two elements (e.g., the relative position of two colored shapes) improves dramatically within a few hundred trials of practice. Several recent imaging studies have identified neural correlates of this learning, but it remains unclear what stimulus properties participants learn to use to search efficiently. Influential models, such as reverse hierarchy theory, propose two major possibilities: learning to use information contained in low-level image statistics (e.g., single features at particular retinotopic locations) or in high-level characteristics (e.g., feature conjunctions) of the task-relevant stimuli. In a series of experiments, we tested these two hypotheses, which make different predictions about the effect of various stimulus manipulations after training. We find relatively small effects of manipulating low-level properties of the stimuli (e.g., changing their retinotopic location) and some conjunctive properties (e.g., color-position), whereas the effects of manipulating other conjunctive properties (e.g., color-shape) are larger. Overall, the findings suggest conjunction learning involving such stimuli might be an emergent phenomenon that reflects multiple different learning processes, each of which capitalizes on different types of information contained in the stimuli. We also show that both targets and distractors are learned, and that reversing learned target and distractor identities impairs performance. This suggests that participants do not merely learn to discriminate target and distractor stimuli, they also learn stimulus identity mappings that contribute to performance improvements.

Rats with hippocampal lesion show impaired learning and memory in the ziggurat task: a new task to evaluate spatial behavior.

PubMed

Faraji, Jamshid; Lehmann, Hugo; Metz, Gerlinde A; Sutherland, Robert J

2008-05-16

Spatial tasks are widely used to determine the function of limbic system structures in rats. The present study used a new task designed to evaluate spatial behavior, the ziggurat task (ZT), to examine the performance of rats with widespread hippocampal damage induced by N-methyl-d-aspartic acid (NMDA). The task consisted of an open field containing 16 identical ziggurats (pyramid shaped towers) arranged at equal distances. One of the ziggurats was baited with a food reward. The task required rats to navigate through the open field by using a combination of distal and/or proximal cues in order to locate the food reward. The ability to acquire and recall the location of the goal (baited) ziggurat was tested in consecutive training sessions of eight trials per day for 10 days. The location of the goal ziggurat was changed every second day, requiring the rats to learn a total of five different locations. Several parameters, including latency to find the target, distance traveled, the number of visits to non-baited ziggurats (errors), and the number of returns were used as indices of learning and memory. Control rats showed a significant decrease in distance traveled and reduced latency in locating the goal ziggurat across trials and days, suggesting that they learned and remembered the location of the goal ziggurat. Interestingly, the hippocampal-damaged group moved significantly faster, and traveled longer distances compared to the control group. Significant differences were observed between these groups with respect to the number of errors and returns on test days. Day 11 served as probe day, in which no food reward was given. The controls spent more time searching for the food in the previous training quadrant compared to the hippocampal group. The findings demonstrate that the ZT is a sensitive and efficient dry task for measuring hippocampus-dependent spatial performance in rats requiring little training and not associated with some of the disadvantages of water

Spatial cognition and sexually dimorphic synaptic plasticity balance impairment in rats with chronic prenatal ethanol exposure.

PubMed

An, Lei; Zhang, Tao

2013-11-01

Prenatal ethanol exposure can lead to long-lasting impairments in the ability of rats to process spatial information, as well as produce long-lasting deficits in long-term potentiation (LTP), a biological model of learning and memory processing. The present study aimed to examine the sexually dimorphic effects of chronic prenatal ethanol exposure (CPEE) on behavior cognition and synaptic plasticity balance (SPB), and tried to understand a possible mechanism by evaluating the alternation of SPB. The animal model was produced by ethanol exposure throughout gestational period with 4 g/kg bodyweight. Offspring of both male and female were selected and studied on postnatal days 36. Subsequently, the data showed that chronic ethanol exposure resulted in birth weight reduction, losing bodyweight gain, microcephaly and hippocampus weight retardation. In Morris water maze (MWM) test, escape latencies were significantly higher in CPEE-treated rats than that in control ones. They also spent much less time in the target quadrant compared to that of control animals in the probe phase. In addition, it was found that there was a more severe impairment in females than that in males after CPEE treatment. Electrophysiological studies showed that CPEE considerably inhibited hippocampal LTP and facilitated depotentiation in males, while significantly enhanced LTP and suppressed depotentiation in females. A novel index, developed by us, showed that the action of CPEE on SPB was more sensitive in females than that in males, suggesting that it might be an effective index to distinguish the difference of SPB impairment between males and females. Copyright © 2013 Elsevier B.V. All rights reserved.

Concord grape juice reverses the age-related impairment in latent learning in rats.

PubMed

Smith, Jessica M; Stouffer, Eric M

2014-02-01

Two experiments were conducted to determine if dietary supplementation with Concord grape juice could reverse the latent learning impairment normally observed in middle-aged male rats. Both experiments utilized the latent cue preference (LCP) task, in which water-replete rats sample water in one compartment of a three-compartment box, and are subsequently given a compartment preference test when water-deprived to determine if they remember the compartment cue previously associated with water. In the first experiment, 40 male Sprague-Dawley rats (9, 10, 11, or 12 months old) were used to determine the age of onset of the impairment. In the second experiment, 24 male Sprague-Dawley rats (11 months old) were given daily access (10 ml/day) to 50% Concord grape juice, 50% white grape juice, or a calorically-equivalent sugar solution daily for 5 weeks prior to training. The first experiment revealed that the latent learning impairment begins to manifest at 10 months of age in the male rats and is fully present at 11 months. The second experiment showed that rats that consumed the 50% Concord grape juice for 5 weeks beginning at 11 months of age showed intact latent learning in the LCP task, while rats that consumed the other two supplements showed the normal impairment on the LCP task. These results indicate that daily supplementation with Concord grape juice was able to reverse the latent learning impairment normally seen in middle-aged male rats. This reversal is most likely due to the presence of flavonoids in Concord grape juice.

Visible spatial contiguity of social information and reward affects social learning in brown capuchins (Sapajus apella) and children (Homo sapiens).

PubMed

Wood, Lara A; Whiten, Andrew

2017-11-01

Animal social learning is typically studied experimentally by the presentation of artificial foraging tasks. Although productive, results are often variable even for the same species. We present and test the hypothesis that one cause of variation is that spatial distance between rewards and the means of reward release causes conflicts for participants' attentional focus. We investigated whether spatial contiguity between a visible reward and the means of release would affect behavioral responses that evidence social learning, testing 21 brown capuchins ( Sapajus apella ), a much-studied species with variant evidence for social learning, and one hundred eighty 2- to 4-year-old human children ( Homo sapiens ), a benchmark species known for a strong social learning disposition. Participants were presented with a novel transparent apparatus where a reward was either proximal or distal to a demonstrated means of releasing it. A distal reward location decreased attention toward the location of the demonstration and impaired subsequent success in gaining rewards. Generally, the capuchins produced the alternative method to that demonstrated, whereas children copied the method demonstrated, although a distal reward location reduced copying in younger children. We conclude that some design features in common social learning tasks may significantly degrade the evidence for social learning. We have demonstrated this for 2 different primates but suggest that it is a significant factor to control for in social learning research across all taxa. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Are visual cues helpful for virtual spatial navigation and spatial memory in patients with mild cognitive impairment or Alzheimer's disease?

PubMed

Cogné, Mélanie; Auriacombe, Sophie; Vasa, Louise; Tison, François; Klinger, Evelyne; Sauzéon, Hélène; Joseph, Pierre-Alain; N Kaoua, Bernard

2018-05-01

To evaluate whether visual cues are helpful for virtual spatial navigation and memory in Alzheimer's disease (AD) and patients with mild cognitive impairment (MCI). 20 patients with AD, 18 patients with MCI and 20 age-matched healthy controls (HC) were included. Participants had to actively reproduce a path that included 5 intersections with one landmark at each intersection that they had seen previously during a learning phase. Three cueing conditions for navigation were offered: salient landmarks, directional arrows and a map. A path without additional visual stimuli served as control condition. Navigation time and number of trajectory mistakes were recorded. With the presence of directional arrows, no significant difference was found between groups concerning the number of trajectory mistakes and navigation time. The number of trajectory mistakes did not differ significantly between patients with AD and patients with MCI on the path with arrows, the path with salient landmarks and the path with a map. There were significant correlations between the number of trajectory mistakes under the arrow condition and executive tests, and between the number of trajectory mistakes under the salient landmark condition and memory tests. Visual cueing such as directional arrows and salient landmarks appears helpful for spatial navigation and memory tasks in patients with AD and patients with MCI. This study opens new research avenues for neuro-rehabilitation, such as the use of augmented reality in real-life settings to support the navigational capabilities of patients with MCI and patients with AD. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

(-)Epigallocatechin-3-gallate decreases the stress-induced impairment of learning and memory in rats.

PubMed

Soung, Hung-Sheng; Wang, Mao-Hsien; Tseng, Hsiang-Chien; Fang, Hsu-Wei; Chang, Kuo-Chi

2015-08-18

Stress induces reactive oxygen species (ROS) and causes alterations in brain cytoarchitecture and cognition. Green tea has potent antioxidative properties especially the tea catechin (-) epigallocatechin-3-gallate (EGCG). These powerful antioxidative properties are able to protect against various oxidative damages. In this study we investigated the impact of stress on rats' locomotor activity, learning and memory. Many tea catechins, including EGCG, were examined for their possible therapeutic effects in treating stress-induced impairment. Our results indicated that locomotor activity was decreased, and the learning and memory were impaired in stressed rats (SRs). EGCG treatment was able to prevent the decreased locomotor activity as well as improve the learning and memory in SRs. EGCG treatment was also able to reduce the increased oxidative status in SRs' hippocampi. The above results suggest a therapeutic effect of EGCG in treating stress-induced impairment of learning and memory, most likely by means of its powerful antioxidative properties. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Ginsenoside Rb1 improves spatial learning and memory by regulation of cell genesis in the hippocampal subregions of rats.

PubMed

Liu, Lei; Hoang-Gia, Trinh; Wu, Hui; Lee, Mi-Ra; Gu, Lijuan; Wang, Chunyan; Yun, Beom-Sik; Wang, Qijun; Ye, Shengquan; Sung, Chang-Keun

2011-03-25

Ginsenoside Rb1 (Rb1) is known to improve learning and memory in hippocampus-dependent tasks. However, the cellular mechanism remains unknown. Cell genesis in hippocampus is involved in spatial learning and memory. In the present study, Rb1 was orally administrated to adult rats for 30days. The behavioral training tests indicated that Rb1 improved spatial cognitive performance of rats in Morris water maze (MWM). Furthermore, we investigated the effects of Rb1 on cell genesis in adult rats' hippocampus, using thymidine analog bromodeoxyuridine (BrdU) as a marker for dividing cells. It has been shown that hippocampal cell genesis can be influenced by several factors such as learning and exercise. In order to avoid the effects of the interfering factors, only the rats treated with Rb1 without training in MWM were used to investigate cell genesis in hippocampus. When BrdU was given to the rats 30days prior to being killed, it was shown that oral administration of Rb1 significantly increased cell survival in dentate gyrus and hippocampal subregion CA3. However, when BrdU was injected 2h prior to sacrifice, the results indicated that Rb1 had no significant influence on cell proliferation in the hippocampal subregions. Thus, an increase of cell survival in hippocampus stimulated by Rb1 may be one of the mechanisms by which ginseng facilitates spatial learning and memory. Our study also indicates that Rb1 may be developed as a therapeutic agent for patients with memory impairment. Copyright © 2011 Elsevier B.V. All rights reserved.

Isorhynchophylline improves learning and memory impairments induced by D-galactose in mice.

PubMed

Xian, Yan-Fang; Su, Zi-Ren; Chen, Jian-Nan; Lai, Xiao-Ping; Mao, Qing-Qiu; Cheng, Christopher H K; Ip, Siu-Po; Lin, Zhi-Xiu

2014-10-01

Isorhynchophylline (IRN), an alkaloid isolated from Uncaria rhynchophylla, has been reported to improve cognitive impairment induced by beta-amyloid in rats. However, whether IRN could also ameliorate the D-galactose (D-gal)-induced mouse memory deficits is still not clear. In the present study, we aimed to investigate whether IRN had potential protective effect against the D-gal-induced cognitive deficits in mice. Mice were given a subcutaneous injection of D-gal (100mg/kg) and orally administered IRN (20 or 40mg/kg) daily for 8weeks, followed by assessing spatial learning and memory function by the Morris water maze test. The results showed that IRN significantly improved spatial learning and memory function in the D-gal-treated mice. In the mechanistic studies, IRN significantly increased the level of glutathione (GSH) and the activities of superoxide dismutase (SOD) and catalase (CAT), while decreased the level of malondialdehyde (MDA) in the brain tissues of the D-gal-treated mice. Moreover, IRN (20 or 40mg/kg) significantly inhibited the production of prostaglandin E 2 (PGE2) and nitric oxide (NO), and the mRNA expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS), as well as the activation of nuclear factor kappa B (NF-κB) in the brain tissues of D-gal-treated mice. Our results amply demonstrated that IRN was able to ameliorate cognitive deficits induced by D-gal in mice, and the observed cognition-improving action may be mediated, at least in part, through enhancing the antioxidant status and anti-inflammatory effect of brain tissues via NFκB signaling. Copyright © 2014 Elsevier Ltd. All rights reserved.

Think3d!: Improving Mathematics Learning through Embodied Spatial Training

ERIC Educational Resources Information Center

Burte, Heather; Gardony, Aaron L.; Hutton, Allyson; Taylor, Holly A.

2017-01-01

Spatial thinking skills positively relate to Science, Technology, Engineering, and Math (STEM) outcomes, but spatial training is largely absent in elementary school. Elementary school is a time when children develop foundational cognitive skills that will support STEM learning throughout their education. Spatial thinking should be considered a…

Extensive Lesions of Cholinergic Basal Forebrain Neurons Do Not Impair Spatial Working Memory

ERIC Educational Resources Information Center

Vuckovich, Joseph A.; Semel, Mara E.; Baxter, Mark G.

2004-01-01

A recent study suggests that lesions to all major areas of the cholinergic basal forebrain in the rat (medial septum, horizontal limb of the diagonal band of Broca, and nucleus basalis magnocellularis) impair a spatial working memory task. However, this experiment used a surgical technique that may have damaged cerebellar Purkinje cells. The…

Multiple Learning Strategies Project. Small Engine Repair. Visually Impaired.

ERIC Educational Resources Information Center

Foster, Don; And Others

This instructional package designed for visually impaired students, focuses on the vocational area of small engine repair. Contained in this document are forty learning modules organized into fourteen units: engine block; starters; fuel tank, lines, filters and pumps; carburetors; electrical; test equipment; motorcycle; machining; tune-ups; short…

Learning trajectories for speech motor performance in children with specific language impairment.

PubMed

Richtsmeier, Peter T; Goffman, Lisa

2015-01-01

Children with specific language impairment (SLI) often perform below expected levels, including on tests of motor skill and in learning tasks, particularly procedural learning. In this experiment we examined the possibility that children with SLI might also have a motor learning deficit. Twelve children with SLI and thirteen children with typical development (TD) produced complex nonwords in an imitation task. Productions were collected across three blocks, with the first and second blocks on the same day and the third block one week later. Children's lip movements while producing the nonwords were recorded using an Optotrak camera system. Movements were then analyzed for production duration and stability. Movement analyses indicated that both groups of children produced shorter productions in later blocks (corroborated by an acoustic analysis), and the rate of change was comparable for the TD and SLI groups. A nonsignificant trend for more stable productions was also observed in both groups. SLI is regularly accompanied by a motor deficit, and this study does not dispute that. However, children with SLI learned to make more efficient productions at a rate similar to their peers with TD, revealing some modification of the motor deficit associated with SLI. The reader will learn about deficits commonly associated with specific language impairment (SLI) that often occur alongside the hallmark language deficit. The authors present an experiment showing that children with SLI improved speech motor performance at a similar rate compared to typically developing children. The implication is that speech motor learning is not impaired in children with SLI. Copyright © 2015 Elsevier Inc. All rights reserved.

Mild cognitive impairment affects motor control and skill learning.

PubMed

Wu, Qiaofeng; Chan, John S Y; Yan, Jin H

2016-02-01

Mild cognitive impairment (MCI) is a transitional phase between normal cognitive aging and dementia. As the world population is aging rapidly, more MCI patients will be identified, posing significant problems to society. Normal aging is associated with cognitive and motor decline, and MCI brings additional impairments. Compared to healthy older adults, MCI patients show poorer motor control in a variety of tasks. Efficient motor control and skill learning are essential for occupational and leisure purposes; degradation of motor behaviors in MCI patients often adversely affects their health and quality of life. In this article, we first define MCI and describe its pathology and neural correlates. After this, we review cognitive changes and motor control and skill learning in normal aging. This section is followed by a discussion of MCI-related degradation of motor behaviors. Finally, we propose that multicomponent interventions targeting both cognitive and motor domains can improve MCI patients' motor functions. Future research directions are also raised.

Effects of genistein in the maternal diet on reproductive development and spatial learning in male rats.

PubMed

Ball, Evan R; Caniglia, Mary Kay; Wilcox, Jenna L; Overton, Karla A; Burr, Marra J; Wolfe, Brady D; Sanders, Brian J; Wisniewski, Amy B; Wrenn, Craige C

2010-03-01

Endocrine disruptors, chemicals that disturb the actions of endogenous hormones, have been implicated in birth defects associated with hormone-dependent development. Phytoestrogens are a class of endocrine disruptors found in plants. In the current study we examined the effects of exposure at various perinatal time periods to genistein, a soy phytoestrogen, on reproductive development and learning in male rats. Dams were fed genistein-containing (5 mg/kg feed) food during both gestation and lactation, during gestation only, during lactation only, or during neither period. Measures of reproductive development and body mass were taken in the male offspring during postnatal development, and learning and memory performance was assessed in adulthood. Genistein exposure via the maternal diet decreased body mass in the male offspring of dams fed genistein during both gestation and lactation, during lactation only, but not during gestation only. Genistein decreased anogenital distance when exposure was during both gestation and lactation, but there was no effect when exposure was limited to one of these time periods. Similarly, spatial learning in the Morris water maze was impaired in male rats exposed to genistein during both gestation and lactation, but not in rats exposed during only one of these time periods. There was no effect of genistein on cued or contextual fear conditioning. In summary, the data indicate that exposure to genistein through the maternal diet significantly impacts growth in male offspring if exposure is during lactation. The effects of genistein on reproductive development and spatial learning required exposure throughout the pre- and postnatal periods. Copyright 2009 Elsevier Inc. All rights reserved.

Reward-Based Spatial Learning in Teens With Bulimia Nervosa.

PubMed

Cyr, Marilyn; Wang, Zhishun; Tau, Gregory Z; Zhao, Guihu; Friedl, Eve; Stefan, Mihaela; Terranova, Kate; Marsh, Rachel

2016-11-01

To assess the functioning of mesolimbic and fronto-striatal areas involved in reward-based spatial learning in teenaged girls with bulimia nervosa (BN) that might be involved in the development and maintenance of maladaptive behaviors characteristic of the disorder. We compared functional magnetic resonance imaging blood oxygen level-dependent response in 27 adolescent girls with BN to that of 27 healthy, age-matched control participants during a reward-based learning task that required learning to use extra-maze cues to navigate a virtual 8-arm radial maze to find hidden rewards. We compared groups in their patterns of brain activation associated with reward-based spatial learning versus a control condition in which rewards were unexpected because they were allotted pseudo-randomly to experimentally prevent learning. Both groups learned to navigate the maze to find hidden rewards, but group differences in brain activity associated with maze navigation and reward processing were detected in the fronto-striatal regions and right anterior hippocampus. Unlike healthy adolescents, those with BN did not engage the right inferior frontal gyrus during maze navigation, activated the right anterior hippocampus during the receipt of unexpected rewards (control condition), and deactivated the left superior frontal gyrus and right anterior hippocampus during expected reward receipt (learning condition). These patterns of hippocampal activation in the control condition were significantly associated with the frequency of binge-eating episodes. Adolescents with BN displayed abnormal functioning of the anterior hippocampus and fronto-striatal regions during reward-based spatial learning. These findings suggest that an imbalance in control and reward circuits may arise early in the course of BN. Clinical trial registration information-An fMRI Study of Self-Regulation in Adolescents With Bulimia Nervosa; https://clinicaltrials.gov/; NCT00345943. Copyright © 2016 American Academy

Reward-Based Spatial Learning in Teens With Bulimia Nervosa

PubMed Central

Cyr, Marilyn; Wang, Zhishun; Tau, Gregory Z.; Zhao, Guihu; Friedl, Eve; Stefan, Mihaela; Terranova, Kate; Marsh, Rachel

2016-01-01

Objective To assess the functioning of mesolimbic and fronto-striatal areas involved in reward-based spatial learning in teenaged girls with bulimia nervosa (BN) that might be involved in the development and maintenance of maladaptive behaviors characteristic of the disorder. Method We compared functional magnetic resonance imaging blood oxygen level dependent response in 27 adolescent girls with BN to that of 27 healthy, age-matched control participants during a reward-based learning task that required learning to use extra-maze cues to navigate a virtual 8-arm radial maze to find hidden rewards. We compared groups in their patterns of brain activation associated with reward-based spatial learning versus a control condition in which rewards were unexpected because they were allotted pseudo-randomly to experimentally prevent learning. Results Both groups learned to navigate the maze to find hidden rewards, but group differences in brain activity associated with maze navigation and reward processing were detected in fronto-striatal regions and right anterior hippocampus. Unlike healthy adolescents, those with BN did not engage right inferior frontal gyrus during maze navigation, activated right anterior hippocampus during the receipt of unexpected rewards (control condition), and deactivated left superior frontal gyrus and right anterior hippocampus during expected reward receipt (learning condition). These patterns of hippocampal activation in the control condition were significantly associated with the frequency of binge-eating episodes. Conclusion Adolescents with BN displayed abnormal functioning of anterior hippocampus and fronto-striatal regions during reward-based spatial learning. These findings suggest that an imbalance in control and reward circuits may arise early in the course of BN. Clinical trial registration information An fMRI Study of Self-regulation in Adolescents With Bulimia Nervosa; https://clinicaltrials.gov/ct2/show/NCT00345943; NCT00345943

Trainable Mentally Impaired/Severely Multiply Impaired/Autistic Impaired/Severely Mentally Impaired. Product Evaluation Report 1989-1990.

ERIC Educational Resources Information Center

Claus, Richard N.; And Others

The evaluation report describes special education services provided to trainable mentally impaired (TMI), autistic impaired (AI), severely multiply impaired (SXI), and severely mentally impaired (SMI) students at and through the Melvin G. Millet Learning Center (Bridgeport, Michigan). The eight program components are described individually and…

Risperidone reverses the spatial object recognition impairment and hippocampal BDNF-TrkB signalling system alterations induced by acute MK-801 treatment

PubMed Central

Chen, Guangdong; Lin, Xiaodong; Li, Gongying; Jiang, Diego; Lib, Zhiruo; Jiang, Ronghuan; Zhuo, Chuanjun

2017-01-01

The aim of the present study was to investigate the effects of a commonly-used atypical antipsychotic, risperidone, on alterations in spatial learning and in the hippocampal brain-derived neurotrophic factor (BDNF)-tyrosine receptor kinase B (TrkB) signalling system caused by acute dizocilpine maleate (MK-801) treatment. In experiment 1, adult male Sprague-Dawley rats subjected to acute treatment of either low-dose MK801 (0.1 mg/kg) or normal saline (vehicle) were tested for spatial object recognition and hippocampal expression levels of BDNF, TrkB and the phophorylation of TrkB (p-TrkB). We found that compared to the vehicle, MK-801 treatment impaired spatial object recognition of animals and downregulated the expression levels of p-TrkB. In experiment 2, MK-801- or vehicle-treated animals were further injected with risperidone (0.1 mg/kg) or vehicle before behavioural testing and sacrifice. Of note, we found that risperidone successfully reversed the deleterious effects of MK-801 on spatial object recognition and upregulated the hippocampal BDNF-TrkB signalling system. Collectively, the findings suggest that cognitive deficits from acute N-methyl-D-aspartate receptor blockade may be associated with the hypofunction of hippocampal BDNF-TrkB signalling system and that risperidone was able to reverse these alterations. PMID:28451387

Structural and functional neuroplasticity in human learning of spatial routes.

PubMed

Keller, Timothy A; Just, Marcel Adam

2016-01-15

Recent findings with both animals and humans suggest that decreases in microscopic movements of water in the hippocampus reflect short-term neuroplasticity resulting from learning. Here we examine whether such neuroplastic structural changes concurrently alter the functional connectivity between hippocampus and other regions involved in learning. We collected both diffusion-weighted images and fMRI data before and after humans performed a 45min spatial route-learning task. Relative to a control group with equal practice time, there was decreased diffusivity in the posterior-dorsal dentate gyrus of the left hippocampus in the route-learning group accompanied by increased synchronization of fMRI-measured BOLD signal between this region and cortical areas, and by changes in behavioral performance. These concurrent changes characterize the multidimensionality of neuroplasticity as it enables human spatial learning. Copyright © 2015 Elsevier Inc. All rights reserved.

Protective effects of physical exercise on MDMA-induced cognitive and mitochondrial impairment.

PubMed

Taghizadeh, Ghorban; Pourahmad, Jalal; Mehdizadeh, Hajar; Foroumadi, Alireza; Torkaman-Boutorabi, Anahita; Hassani, Shokoufeh; Naserzadeh, Parvaneh; Shariatmadari, Reyhaneh; Gholami, Mahdi; Rouini, Mohammad Reza; Sharifzadeh, Mohammad

2016-10-01

Debate continues about the effect of 3, 4-methylenedioxymethamphetamine (MDMA) on cognitive and mitochondrial function through the CNS. It has been shown that physical exercise has an important protective effect on cellular damage and death. Therefore, we investigated the effect of physical exercise on MDMA-induced impairments of spatial learning and memory as well as MDMA effects on brain mitochondrial function in rats. Male wistar rats underwent short-term (2 weeks) or long-term (4 weeks) treadmill exercise. After completion of exercise duration, acquisition and retention of spatial memory were evaluated by Morris water maze (MWM) test. Rats were intraperitoneally (I.P) injected with MDMA (5, 10, and 15mg/kg) 30min before the first training trial in 4 training days of MWM. Different parameters of brain mitochondrial function were measured including the level of ROS production, mitochondrial membrane potential (MMP), mitochondrial swelling, mitochondrial outermembrane damage, the amount of cytochrome c release from the mitochondria, and ADP/ATP ratio. MDMA damaged the spatial learning and memory in a dose-dependent manner. Brain mitochondria isolated from the rats treated with MDMA showed significant increase in ROS formation, collapse of MMP, mitochondrial swelling, and outer membrane damage, cytochrome c release from the mitochondria, and finally increased ADP/ATP ratio. This study also found that physical exercise significantly decreased the MDMA-induced impairments of spatial learning and memory and also mitochondrial dysfunction. The results indicated that MDMA-induced neurotoxicity leads to brain mitochondrial dysfunction and subsequent oxidative stress is followed by cognitive impairments. However, physical exercise could reduce these deleterious effects of MDMA through protective effects on brain mitochondrial function. Copyright © 2016 Elsevier Inc. All rights reserved.

Spatial features of synaptic adaptation affecting learning performance.

PubMed

Berger, Damian L; de Arcangelis, Lucilla; Herrmann, Hans J

2017-09-08

Recent studies have proposed that the diffusion of messenger molecules, such as monoamines, can mediate the plastic adaptation of synapses in supervised learning of neural networks. Based on these findings we developed a model for neural learning, where the signal for plastic adaptation is assumed to propagate through the extracellular space. We investigate the conditions allowing learning of Boolean rules in a neural network. Even fully excitatory networks show very good learning performances. Moreover, the investigation of the plastic adaptation features optimizing the performance suggests that learning is very sensitive to the extent of the plastic adaptation and the spatial range of synaptic connections.

Route Learning Impairment in Temporal Lobe Epilepsy

PubMed Central

Bell, Brian D.

2012-01-01

Memory impairment on neuropsychological tests is relatively common in temporal lobe epilepsy (TLE) patients. But memory rarely has been evaluated in more naturalistic settings. This study assessed TLE (n = 19) and control (n = 32) groups on a real-world route learning (RL) test. Compared to the controls, the TLE group committed significantly more total errors across the three RL test trials. RL errors correlated significantly with standardized auditory and visual memory and visual-perceptual test scores in the TLE group. In the TLE subset for whom hippocampal data were available (n = 14), RL errors also correlated significantly with left hippocampal volume. This is one of the first studies to demonstrate real-world memory impairment in TLE patients and its association with both mesial temporal lobe integrity and standardized memory test performance. The results support the ecological validity of clinical neuropsychological assessment. PMID:23041173

Spatial release of cognitive load measured in a dual-task paradigm in normal-hearing and hearing-impaired listeners.

PubMed

Xia, Jing; Nooraei, Nazanin; Kalluri, Sridhar; Edwards, Brent

2015-04-01

This study investigated whether spatial separation between talkers helps reduce cognitive processing load, and how hearing impairment interacts with the cognitive load of individuals listening in multi-talker environments. A dual-task paradigm was used in which performance on a secondary task (visual tracking) served as a measure of the cognitive load imposed by a speech recognition task. Visual tracking performance was measured under four conditions in which the target and the interferers were distinguished by (1) gender and spatial location, (2) gender only, (3) spatial location only, and (4) neither gender nor spatial location. Results showed that when gender cues were available, a 15° spatial separation between talkers reduced the cognitive load of listening even though it did not provide further improvement in speech recognition (Experiment I). Compared to normal-hearing listeners, large individual variability in spatial release of cognitive load was observed among hearing-impaired listeners. Cognitive load was lower when talkers were spatially separated by 60° than when talkers were of different genders, even though speech recognition was comparable in these two conditions (Experiment II). These results suggest that a measure of cognitive load might provide valuable insight into the benefit of spatial cues in multi-talker environments.

Dynamic Assessment of Word Learning Skills: Identifying Language Impairment in Bilingual Children

ERIC Educational Resources Information Center

Kapantzoglou, Maria; Restrepo, M. Adelaida; Thompson, Marilyn S.

2012-01-01

Purpose: Bilingual children are often diagnosed with language impairment, although they may simply have fewer opportunities to learn English than English-speaking monolingual children. This study examined whether dynamic assessment (DA) of word learning skills is an effective method for identifying bilingual children with primary language…

"I know your name, but not your number"--Patients with verbal short-term memory deficits are impaired in learning sequences of digits.

PubMed

Bormann, Tobias; Seyboth, Margret; Umarova, Roza; Weiller, Cornelius

2015-06-01

Studies on verbal learning in patients with impaired verbal short-term memory (vSTM) have revealed dissociations among types of verbal information. Patients with impaired vSTM are able to learn lists of known words but fail to acquire new word forms. This suggests that vSTM is involved in new word learning. The present study assessed both new word learning and the learning of digit sequences in two patients with impaired vSTM. In two experiments, participants were required to learn people's names, ages and professions, or their four digit 'phone numbers'. The STM patients were impaired on learning unknown family names and phone numbers, but managed to acquire other verbal information. In contrast, a patient with a severe verbal episodic memory impairment was impaired across information types. These results indicate verbal STM involvement in the learning of digit sequences. Copyright © 2015 Elsevier Ltd. All rights reserved.

Continuous manganese delivery via osmotic pumps for manganese-enhanced mouse MRI does not impair spatial learning but leads to skin ulceration.

PubMed

Vousden, Dulcie A; Cox, Elizabeth; Allemang-Grand, Rylan; Laliberté, Christine; Qiu, Lily R; Lindenmaier, Zsuzsa; Nieman, Brian J; Lerch, Jason P

2018-06-01

Manganese-enhanced magnetic resonance imaging (MEMRI) is a widely used technique in rodent neuroimaging studies. Traditionally, Mn 2+ is delivered to animals via a systemic injection; however, this can lead to toxic effects at high doses. Recent studies have shown that subcutaneously implanted mini-osmotic pumps can be used to continuously deliver manganese chloride (MnCl 2 ), and that they produce satisfactory contrast while circumventing many of the toxic side effects. However, neither the time-course of signal enhancement nor the effect of continuous Mn 2+ delivery on behaviour, particularly learning and memory, have been well-characterized. Here, we investigated the effect of MnCl 2 dose and route of administration on a) spatial learning in the Morris Water Maze and b) tissue signal enhancement in the mouse brain. Even as early as 3 days after pump implantation, infusion of 25-50 mg/kg/day MnCl 2 via osmotic pump produced signal enhancement as good as or better than that achieved 24 h after a single 50 mg/kg intraperitoneal injection. Neither route of delivery nor MnCl 2 dose adversely affected spatial learning and memory on the water maze. However, especially at higher doses, mice receiving MnCl 2 via osmotic pumps developed skin ulceration which limited the imaging window. With these findings, we provide recommendations for route and dose of MnCl 2 to use for different study designs. Copyright © 2018 Elsevier Inc. All rights reserved.

Modulation of GSK-3β/β-Catenin Signaling Contributes to Learning and Memory Impairment in a Rat Model of Depression.

PubMed

Hui, Jiaojie; Zhang, Jianping; Pu, Mengjia; Zhou, Xingliang; Dong, Liang; Mao, Xuqiang; Shi, Guofeng; Zou, Jian; Wu, Jingjing; Jiang, Dongmei; Xi, Guangjun

2018-04-23

It is widely accepted that cognitive processes, such as learning and memory, are affected in depression, but the molecular mechanisms underlying the interactions of these 2 disorders are not clearly understood. Recently, glycogen synthase kinase-3 beta (GSK-3β)/β-catenin signaling was shown to play an important role in the regulation of learning and memory. The present study used a rat model of depression, chronic unpredictable stress, to determine whether hippocampal GSK-3β/β-catenin signaling was involved in learning and memory alterations. Our results demonstrated that chronic unpredictable stress had a dramatic influence on spatial cognitive performance in the Morris water maze task and reduced the phosphorylation of Ser9 of GSK-3β as well as the total and nuclear levels of β-catenin in the hippocampus. Inhibition of GSK3β by SB216763 significantly ameliorated the cognitive deficits induced by chronic unpredictable stress, while overexpression of GSK3β by AAV-mediated gene transfer significantly decreased cognitive performance in adult rats. In addition, chronic unpredictable stress exposure increased the expression of the canonical Wnt antagonist Dkk-1. Furthermore, chronic administration of corticosterone significantly increased Dkk-1 expression, decreased the phosphorylation of Ser9 of GSK-3β, and resulted in the impairment of hippocampal learning and memory. Our results indicate that impairment of learning and memory in response to chronic unpredictable stress may be attributed to the dysfunction of GSK-3β/β-catenin signaling mediated by increased glucocorticoid signaling via Dkk-1.

Calcium sensor regulation of the CaV2.1 Ca2+ channel contributes to long-term potentiation and spatial learning.

PubMed

Nanou, Evanthia; Scheuer, Todd; Catterall, William A

2016-11-15

Many forms of short-term synaptic plasticity rely on regulation of presynaptic voltage-gated Ca 2+ type 2.1 (Ca V 2.1) channels. However, the contribution of regulation of Ca V 2.1 channels to other forms of neuroplasticity and to learning and memory are not known. Here we have studied mice with a mutation (IM-AA) that disrupts regulation of Ca V 2.1 channels by calmodulin and related calcium sensor proteins. Surprisingly, we find that long-term potentiation (LTP) of synaptic transmission at the Schaffer collateral-CA1 synapse in the hippocampus is substantially weakened, even though this form of synaptic plasticity is thought to be primarily generated postsynaptically. LTP in response to θ-burst stimulation and to 100-Hz tetanic stimulation is much reduced. However, a normal level of LTP can be generated by repetitive 100-Hz stimulation or by depolarization of the postsynaptic cell to prevent block of NMDA-specific glutamate receptors by Mg 2+ The ratio of postsynaptic responses of NMDA-specific glutamate receptors to those of AMPA-specific glutamate receptors is decreased, but the postsynaptic current from activation of NMDA-specific glutamate receptors is progressively increased during trains of stimuli and exceeds WT by the end of 1-s trains. Strikingly, these impairments in long-term synaptic plasticity and the previously documented impairments in short-term synaptic plasticity in IM-AA mice are associated with pronounced deficits in spatial learning and memory in context-dependent fear conditioning and in the Barnes circular maze. Thus, regulation of Ca V 2.1 channels by calcium sensor proteins is required for normal short-term synaptic plasticity, LTP, and spatial learning and memory in mice.

The Learning Disabled, Hearing Impaired Students: Reality, Myth, or Overextension?

ERIC Educational Resources Information Center

Laughton, Joan

1989-01-01

This paper focuses on definitions, incidence, and characteristics of the multihandicapping condition known as "learning disabled, hearing impaired," in order to provide a means of identifying these children and determining whether or not they require different teaching strategies. (JDD)

Neurobiological and Endocrine Correlates of Individual Differences in Spatial Learning Ability

PubMed Central

Sandi, Carmen; Cordero, M. Isabel; Merino, José J.; Kruyt, Nyika D.; Regan, Ciaran M.; Murphy, Keith J.

2004-01-01

The polysialylated neural cell adhesion molecule (PSA-NCAM) has been implicated in activity-dependent synaptic remodeling and memory formation. Here, we questioned whether training-induced modulation of PSA-NCAM expression might be related to individual differences in spatial learning abilities. At 12 h posttraining, immunohistochemical analyses revealed a learning-induced up-regulation of PSA-NCAM in the hippocampal dentate gyrus that was related to the spatial learning abilities displayed by rats during training. Specifically, a positive correlation was found between latency to find the platform and subsequent activated PSA levels, indicating that greater induction of polysialylation was observed in rats with the slower acquisition curve. At posttraining times when no learning-associated activation of PSA was observed, no such correlation was found. Further experiments revealed that performance in the massed water maze training is related to a pattern of spatial learning and memory abilities, and to learning-related glucocorticoid responsiveness. Taken together, our findings suggest that the learning-related neural circuits of fast learners are better suited to solving the water maze task than those of slow learners, the latter relying more on structural reorganization to form memory, rather than the relatively economic mechanism of altering synaptic efficacy that is likely used by the former. PMID:15169853

Neurobiological and endocrine correlates of individual differences in spatial learning ability.

PubMed

Sandi, Carmen; Cordero, M Isabel; Merino, José J; Kruyt, Nyika D; Regan, Ciaran M; Murphy, Keith J

2004-01-01

The polysialylated neural cell adhesion molecule (PSA-NCAM) has been implicated in activity-dependent synaptic remodeling and memory formation. Here, we questioned whether training-induced modulation of PSA-NCAM expression might be related to individual differences in spatial learning abilities. At 12 h posttraining, immunohistochemical analyses revealed a learning-induced up-regulation of PSA-NCAM in the hippocampal dentate gyrus that was related to the spatial learning abilities displayed by rats during training. Specifically, a positive correlation was found between latency to find the platform and subsequent activated PSA levels, indicating that greater induction of polysialylation was observed in rats with the slower acquisition curve. At posttraining times when no learning-associated activation of PSA was observed, no such correlation was found. Further experiments revealed that performance in the massed water maze training is related to a pattern of spatial learning and memory abilities, and to learning-related glucocorticoid responsiveness. Taken together, our findings suggest that the learning-related neural circuits of fast learners are better suited to solving the water maze task than those of slow learners, the latter relying more on structural reorganization to form memory, rather than the relatively economic mechanism of altering synaptic efficacy that is likely used by the former.

Verbal learning and memory impairments in posttraumatic stress disorder: the role of encoding strategies.

PubMed

Johnsen, Grethe E; Asbjørnsen, Arve E

2009-01-30

The present study examined mechanisms underlying verbal memory impairments in patients with posttraumatic stress disorder (PTSD). Earlier studies have reported that the verbal learning and memory alterations in PTSD are related to impaired encoding, but the use of encoding and organizational strategies in patients with PTSD has not been fully explored. This study examined organizational strategies in 21 refugees/immigrants exposed to war and political violence who fulfilled DSM-IV criteria for chronic PTSD compared with a control sample of 21 refugees/immigrants with similar exposure, but without PTSD. The California Verbal Learning Test was administered to examine differences in organizational strategies and memory. The semantic clustering score was slightly reduced in both groups, but the serial cluster score was significantly impaired in the PTSD group and they also reported more items from the recency region of the list. In addition, intrusive errors were significantly increased in the PTSD group. The data support an assumption of changed memory strategies in patients with PTSD associated with a specific impairment in executive control. However, memory impairment and the use of ineffective learning strategies may not be related to PTSD symptomatology only, but also to self-reported symptoms of depression and general distress.

Statistical Learning in Specific Language Impairment: A Meta-Analysis

ERIC Educational Resources Information Center

Lammertink, Imme; Boersma, Paul; Wijnen, Frank; Rispens, Judith

2017-01-01

Purpose: The current meta-analysis provides a quantitative overview of published and unpublished studies on statistical learning in the auditory verbal domain in people with and without specific language impairment (SLI). The database used for the meta-analysis is accessible online and open to updates (Community-Augmented Meta-Analysis), which…

Diagnosing a Learning Disability in a Hearing-Impaired Child.

ERIC Educational Resources Information Center

Plapinger, Donald; Sikora, Darryn

1990-01-01

This paper presents a case study that used an interdisciplinary diagnostic approach to determine whether a hearing-impaired nine-year-old child had a learning disability and to determine the type of disability. The assessment included medical examination, gross and fine motor skills, psychological functioning, mental processing and achievement,…

Spatial context learning survives interference from working memory load

PubMed Central

Vickery, Timothy J.; Sussman, Rachel S.; Jiang, Yuhong V.

2010-01-01

The human visual system is constantly confronted with an overwhelming amount of information, only a subset of which can be processed in complete detail. Attention and implicit learning are two important mechanisms that optimize vision. This study addresses the relationship between these two mechanisms. Specifically we ask: Is implicit learning of spatial context affected by the amount of working memory load devoted to an irrelevant task? We tested observers in visual search tasks where search displays occasionally repeated. Observers became faster searching repeated displays than unrepeated ones, showing contextual cueing. We found that the size of contextual cueing was unaffected by whether observers learned repeated displays under unitary attention or when their attention was divided using working memory manipulations. These results held when working memory was loaded by colors, dot patterns, individual dot locations, or multiple potential targets. We conclude that spatial context learning is robust to interference from manipulations that limit the availability of attention and working memory. PMID:20853996

Working Memory Functioning in Children with Learning Disorders and Specific Language Impairment

ERIC Educational Resources Information Center

Schuchardt, Kirsten; Bockmann, Ann-Katrin; Bornemann, Galina; Maehler, Claudia

2013-01-01

Purpose: On the basis of Baddeley's working memory model (1986), we examined working memory functioning in children with learning disorders with and without specific language impairment (SLI). We pursued the question whether children with learning disorders exhibit similar working memory deficits as children with additional SLI. Method: In…

Cognitive deficits are a matter of emotional context: inflexible strategy use mediates context-specific learning impairments in OCD.

PubMed

Zetsche, Ulrike; Rief, Winfried; Westermann, Stefan; Exner, Cornelia

2015-01-01

The present study examines the interplay between cognitive deficits and emotional context in obsessive-compulsive disorder (OCD) and social phobia (SP). Specifically, this study examines whether the inflexible use of efficient learning strategies in an emotional context underlies impairments in probabilistic classification learning (PCL) in OCD, and whether PCL impairments are specific to OCD. Twenty-three participants with OCD, 30 participants with SP and 30 healthy controls completed a neutral and an OCD-specific PCL task. OCD participants failed to adopt efficient learning strategies and showed fewer beneficial strategy switches than controls only in an OCD-specific context, but not in a neutral context. Additionally, OCD participants did not show any explicit memory impairments. Number of beneficial strategy switches in the OCD-specific task mediated the difference in PCL performance between OCD and control participants. Individuals with SP were impaired in both PCL tasks. In contrast to neuropsychological models postulating general cognitive impairments in OCD, the present findings suggest that it is the interaction between cognition and emotion that is impaired in OCD. Specifically, activated disorder-specific fears may impair the flexible adoption of efficient learning strategies and compromise otherwise unimpaired PCL. Impairments in PCL are not specific to OCD.

Sex and boldness explain individual differences in spatial learning in a lizard.

PubMed

Carazo, Pau; Noble, Daniel W A; Chandrasoma, Dani; Whiting, Martin J

2014-05-07

Understanding individual differences in cognitive performance is a major challenge to animal behaviour and cognition studies. We used the Eastern water skink (Eulamprus quoyii) to examine associations between exploration, boldness and individual variability in spatial learning, a dimension of lizard cognition with important bearing on fitness. We show that males perform better than females in a biologically relevant spatial learning task. This is the first evidence for sex differences in learning in a reptile, and we argue that it is probably owing to sex-specific selective pressures that may be widespread in lizards. Across the sexes, we found a clear association between boldness after a simulated predatory attack and the probability of learning the spatial task. In contrast to previous studies, we found a nonlinear association between boldness and learning: both 'bold' and 'shy' behavioural types were more successful learners than intermediate males. Our results do not fit with recent predictions suggesting that individual differences in learning may be linked with behavioural types via high-low-risk/reward trade-offs. We suggest the possibility that differences in spatial cognitive performance may arise in lizards as a consequence of the distinct environmental variability and complexity experienced by individuals as a result of their sex and social tactics.

Effects of harmine, an acetylcholinesterase inhibitor, on spatial learning and memory of APP/PS1 transgenic mice and scopolamine-induced memory impairment mice.

PubMed

He, Dandan; Wu, Hui; Wei, Yue; Liu, Wei; Huang, Fei; Shi, Hailian; Zhang, Beibei; Wu, Xiaojun; Wang, Changhong

2015-12-05

Harmine, a β-carboline alkaloid present in Peganum harmala with a wide spectrum of pharmacological activities, has been shown to exert strong inhibition against acetylcholinesterase in vitro. However, whether it can rescue the impaired cognition has not been elucidated yet. In current study, we examined its effects on scopolamine-induced memory impairment mice and APP/PS1 transgenic mice, one of the models for Alzheimer's disease, using Morris Water Maze test. In addition, whether harmine could penetrate blood brain barrier, interact with and inhibit acetylcholinesterase, and activate downstream signaling network was also investigated. Our results showed that harmine (20mg/kg) administered by oral gavage for 2 weeks could effectively enhance the spatial cognition of C57BL/6 mice impaired by intraperitoneal injection of scopolamine (1mg/kg). Meanwhile, long-term consumption of harmine (20mg/kg) for 10 weeks also slightly benefited the impaired memory of APP/PS1 mice. Furthermore, harmine could pass through blood brain barrier, penetrate into the brain parenchyma shortly after oral administration, and modulate the expression of Egr-1, c-Jun and c-Fos. Molecular docking assay disclosed that harmine molecule could directly dock into the catalytic active site of acetylcholinesterase, which was partially confirmed by its in vivo inhibitory activity on acetylcholinesterase. Taken together, all these results suggested that harmine could ameliorate impaired memory by enhancement of cholinergic neurotransmission via inhibiting the activity of acetylcholinesterase, which may contribute to its clinical use in the therapy of neurological diseases characterized with acetylcholinesterase deficiency. Copyright © 2015 Elsevier B.V. All rights reserved.

Early developmental bisphenol-A exposure sex-independently impairs spatial memory by remodeling hippocampal dendritic architecture and synaptic transmission in rats

NASA Astrophysics Data System (ADS)

Liu, Zhi-Hua; Ding, Jin-Jun; Yang, Qian-Qian; Song, Hua-Zeng; Chen, Xiang-Tao; Xu, Yi; Xiao, Gui-Ran; Wang, Hui-Li

2016-08-01

Bisphenol-A (BPA, 4, 4‧-isopropylidene-2-diphenol), a synthetic xenoestrogen that widely used in the production of polycarbonate plastics, has been reported to impair hippocampal development and function. Our previous study has shown that BPA exposure impairs Sprague-Dawley (SD) male hippocampal dendritic spine outgrowth. In this study, the sex-effect of chronic BPA exposure on spatial memory in SD male and female rats and the related synaptic mechanism were further investigated. We found that chronic BPA exposure impaired spatial memory in both SD male and female rats, suggesting a dysfunction of hippocampus without gender-specific effect. Further investigation indicated that BPA exposure causes significant impairment of dendrite and spine structure, manifested as decreased dendritic complexity, dendritic spine density and percentage of mushroom shaped spines in hippocampal CA1 and dentate gyrus (DG) neurons. Furthermore, a significant reduction in Arc expression was detected upon BPA exposure. Strikingly, BPA exposure significantly increased the mIPSC amplitude without altering the mEPSC amplitude or frequency, accompanied by increased GABAARβ2/3 on postsynaptic membrane in cultured CA1 neurons. In summary, our study indicated that Arc, together with the increased surface GABAARβ2/3, contributed to BPA induced spatial memory deficits, providing a novel molecular basis for BPA achieved brain impairment.

Developing Effective Learning Material to Students with Hearing Impairment (HI) through ODL in Zimbabwe

ERIC Educational Resources Information Center

Mpofu, John; Chimhenga, Sylod; Mafa, Onias

2013-01-01

Students with Hearing Impairment (HI) are experiencing learning problems in most institutions of Higher Learning in Zimbabwe. Access to colleges and universities is limited and where they are accepted, there are no facilities to cater for their needs, hence there is need to develop learning materials that enable these students to learn effectively…

The reduced serum free triiodothyronine and increased dorsal hippocampal SNAP-25 and Munc18-1 had existed in middle-aged CD-1 mice with mild spatial cognitive impairment.

PubMed

Cao, Lei; Jiang, Wei; Wang, Fang; Yang, Qi-Gang; Wang, Chao; Chen, Yong-Ping; Chen, Gui-Hai

2013-12-02

Changes of synaptic proteins in highlighted brain regions and decreased serum thyroid hormones (THs) have been implied in age-related learning and memory decline. Previously, we showed significant pairwise correlations among markedly impaired spatial learning and memory ability, decreased serum free triiodothyronine (FT3) and increased hippocampal SNAP-25 and Munc18-1 in old Kunming mice. However, whether these changes and the correlations occur in middle-age mice remains unclear. Since this age is one of the best stages to study age-related cognitive decline, we explored the spatial learning and memory ability, serum THs, cerebral SNAP-25 and Munc18-1 levels and their relationships of middle-aged mice in this study. The learning and memory abilities of 35 CD-1 mice (19 mice aged 6 months and 16 mice aged 12 months) were measured with a radial six-arm water maze (RAWM). The SNAP-25 and Munc18-1 levels were semi-quantified by Western blotting and the serum THs were detected by radioimmunoassay. The results showed the middle-aged mice had decreased serum FT3, increased dorsal hippocampal (DH) SNAP-25 and Munc18-1, and many or long number of errors and latency in both learning and memory phases of the RAWM. The Pearson's correlation test showed that the DH SANP-25 and Munc18-1 levels were positively correlated with the number of errors and latency in learning phases of the RAWM. Meanwhile, the DH SANP-25 and Munc18-1 levels negatively correlated with the serum FT3 level. These results suggested that reduced FT3 with increased DH SNAP-25 and Munc18-1 levels might be involved in the spatial learning ability decline in the middle-aged mice. © 2013 Elsevier B.V. All rights reserved.

Active and Passive Spatial Learning in Human Navigation: Acquisition of Survey Knowledge

ERIC Educational Resources Information Center

Chrastil, Elizabeth R.; Warren, William H.

2013-01-01

It seems intuitively obvious that active exploration of a new environment would lead to better spatial learning than would passive visual exposure. It is unclear, however, which components of active learning contribute to spatial knowledge, and previous literature is decidedly mixed. This experiment tests the contributions of 4 components to…

A Cognitive Component Analysis Approach for Developing Game-Based Spatial Learning Tools

ERIC Educational Resources Information Center

Hung, Pi-Hsia; Hwang, Gwo-Jen; Lee, Yueh-Hsun; Su, I-Hsiang

2012-01-01

Spatial ability has been recognized as one of the most important factors affecting the mathematical performance of students. Previous studies on spatial learning have mainly focused on developing strategies to shorten the problem-solving time of learners for very specific learning tasks. Such an approach usually has limited effects on improving…

Serial-order learning impairment and hypersensitivity-to-interference in dyscalculia.

PubMed

De Visscher, Alice; Szmalec, Arnaud; Van Der Linden, Lize; Noël, Marie-Pascale

2015-11-01

In the context of heterogeneity, the different profiles of dyscalculia are still hypothetical. This study aims to link features of mathematical difficulties to certain potential etiologies. First, we wanted to test the hypothesis of a serial-order learning deficit in adults with dyscalculia. For this purpose we used a Hebb repetition learning task. Second, we wanted to explore a recent hypothesis according to which hypersensitivity-to-interference hampers the storage of arithmetic facts and leads to a particular profile of dyscalculia. We therefore used interfering and non-interfering repeated sequences in the Hebb paradigm. A final test was used to assess the memory trace of the non-interfering sequence and the capacity to manipulate it. In line with our predictions, we observed that people with dyscalculia who show good conceptual knowledge in mathematics but impaired arithmetic fluency suffer from increased sensitivity-to-interference compared to controls. Secondly, people with dyscalculia who show a deficit in a global mathematical test suffer from a serial-order learning deficit characterized by a slow learning and a quick degradation of the memory trace of the repeated sequence. A serial-order learning impairment could be one of the explanations for a basic numerical deficit, since it is necessary for the number-word sequence acquisition. Among the different profiles of dyscalculia, this study provides new evidence and refinement for two particular profiles. Copyright © 2015 Elsevier B.V. All rights reserved.

Reinforcement Learning in Young Adults with Developmental Language Impairment

ERIC Educational Resources Information Center

Lee, Joanna C.; Tomblin, J. Bruce

2012-01-01

The aim of the study was to examine reinforcement learning (RL) in young adults with developmental language impairment (DLI) within the context of a neurocomputational model of the basal ganglia-dopamine system (Frank, Seeberger, & O'Reilly, 2004). Two groups of young adults, one with DLI and the other without, were recruited. A probabilistic…

On the role of working memory in spatial contextual cueing.

PubMed

Travis, Susan L; Mattingley, Jason B; Dux, Paul E

2013-01-01

The human visual system receives more information than can be consciously processed. To overcome this capacity limit, we employ attentional mechanisms to prioritize task-relevant (target) information over less relevant (distractor) information. Regularities in the environment can facilitate the allocation of attention, as demonstrated by the spatial contextual cueing paradigm. When observers are exposed repeatedly to a scene and invariant distractor information, learning from earlier exposures enhances the search for the target. Here, we investigated whether spatial contextual cueing draws on spatial working memory resources and, if so, at what level of processing working memory load has its effect. Participants performed 2 tasks concurrently: a visual search task, in which the spatial configuration of some search arrays occasionally repeated, and a spatial working memory task. Increases in working memory load significantly impaired contextual learning. These findings indicate that spatial contextual cueing utilizes working memory resources.

History of Reading Struggles Linked to Enhanced Learning in Low Spatial Frequency Scenes

PubMed Central

Schneps, Matthew H.; Brockmole, James R.; Sonnert, Gerhard; Pomplun, Marc

2012-01-01

People with dyslexia, who face lifelong struggles with reading, exhibit numerous associated low-level sensory deficits including deficits in focal attention. Countering this, studies have shown that struggling readers outperform typical readers in some visual tasks that integrate distributed information across an expanse. Though such abilities would be expected to facilitate scene memory, prior investigations using the contextual cueing paradigm failed to find corresponding advantages in dyslexia. We suggest that these studies were confounded by task-dependent effects exaggerating known focal attention deficits in dyslexia, and that, if natural scenes were used as the context, advantages would emerge. Here, we investigate this hypothesis by comparing college students with histories of severe lifelong reading difficulties (SR) and typical readers (TR) in contexts that vary attention load. We find no differences in contextual-cueing when spatial contexts are letter-like objects, or when contexts are natural scenes. However, the SR group significantly outperforms the TR group when contexts are low-pass filtered natural scenes [F(3, 39) = 3.15, p<.05]. These findings suggest that perception or memory for low spatial frequency components in scenes is enhanced in dyslexia. These findings are important because they suggest strengths for spatial learning in a population otherwise impaired, carrying implications for the education and support of students who face challenges in school. PMID:22558210

History of reading struggles linked to enhanced learning in low spatial frequency scenes.

PubMed

Schneps, Matthew H; Brockmole, James R; Sonnert, Gerhard; Pomplun, Marc

2012-01-01

People with dyslexia, who face lifelong struggles with reading, exhibit numerous associated low-level sensory deficits including deficits in focal attention. Countering this, studies have shown that struggling readers outperform typical readers in some visual tasks that integrate distributed information across an expanse. Though such abilities would be expected to facilitate scene memory, prior investigations using the contextual cueing paradigm failed to find corresponding advantages in dyslexia. We suggest that these studies were confounded by task-dependent effects exaggerating known focal attention deficits in dyslexia, and that, if natural scenes were used as the context, advantages would emerge. Here, we investigate this hypothesis by comparing college students with histories of severe lifelong reading difficulties (SR) and typical readers (TR) in contexts that vary attention load. We find no differences in contextual-cueing when spatial contexts are letter-like objects, or when contexts are natural scenes. However, the SR group significantly outperforms the TR group when contexts are low-pass filtered natural scenes [F(3, 39) = 3.15, p<.05]. These findings suggest that perception or memory for low spatial frequency components in scenes is enhanced in dyslexia. These findings are important because they suggest strengths for spatial learning in a population otherwise impaired, carrying implications for the education and support of students who face challenges in school.

How Students with Hearing Impairments: Can Learn and Flourish in Your Music Classroom

ERIC Educational Resources Information Center

Butler, Maureen

2004-01-01

Activities in music class allow students, especially students with hearing impairments, to explore new means of expression and to enhance existing ones. Additional benefits may include increases in auditory awareness, cognitive ability, attention span, memory recall, and vocabulary. Students with hearing impairments can learn and flourish in music…

Using ICT at an Open Distance Learning (ODL) Institution in South Africa: The Learning Experiences of Students with Visual Impairments

ERIC Educational Resources Information Center

Mokiwa, S. A.; Phasha, T. N.

2012-01-01

For students with visual impairments, Information and Communication Technology (ICT) has become an important means through which they can learn and access learning materials at various levels of education. However, their learning experiences in using such form of technologies have been rarely documented, thus suggests society's lack of…

Guidance of spatial attention by incidental learning and endogenous cuing

PubMed Central

Jiang, Yuhong V.; Swallow, Khena M.; Rosenbaum, Gail M.

2012-01-01

Our visual system is highly sensitive to regularities in the environment. Locations that were important in one’s previous experience are often prioritized during search, even though observers may not be aware of the learning. In this study we characterized the guidance of spatial attention by incidental learning of a target’s spatial probability, and examined the interaction between endogenous cuing and probability cuing. Participants searched for a target (T) among distractors (L’s). The target was more often located in one region of the screen than in others. We found that search RT was faster when the target appeared in the high-frequency region rather than the low-frequency regions. This difference increased when there were more items on the display, suggesting that probability cuing guides spatial attention. Additional data indicated that on their own, probability cuing and endogenous cuing (e.g., a central arrow that predicted a target’s location) were similarly effective at guiding attention. However, when both cues were presented at once, probability cuing was largely eliminated. Thus, although both incidental learning and endogenous cuing can effectively guide attention, endogenous cuing takes precedence over incidental learning. PMID:22506784

Unilateral lesion of dorsal hippocampus in adult rats impairs contralateral long-term potentiation in vivo and spatial memory in the early postoperative phase.

PubMed

Li, Hongjie; Wu, Xiaoyan; Bai, Yanrui; Huang, Yan; He, Wenting; Dong, Zhifang

2012-05-01

It is well documented that bilateral hippocampal lesions or unilateral hippocampal lesion at birth causes impairment of contralateral LTP and long-term memory. However, effects of unilateral hippocampal lesion in adults on contralateral in vivo LTP and memory are not clear. We here examined the influence of unilateral electrolytic dorsal hippocampal lesion in adult rats on contralateral LTP in vivo and spatial memory during different postoperative phases. We found that acute unilateral hippocampal lesion had no effect on contralateral LTP. However, contralateral LTP was impaired at 1 week after lesion, and was restored to the control level at postoperative week 4. Similarly, spatial memory was also impaired at postoperative week 1, and was restored at postoperative week 4. In addition, the rats at postoperative week 1 showed stronger spatial exploratory behavior in a novel open-field environment. The sham operation had no effects on contralateral LTP, spatial memory and exploration at either postoperative week 1 or week 4. These results suggest that unilateral dorsal hippocampal lesion in adult rats causes transient contralateral LTP impairment and spatial memory deficit. Copyright © 2012 Elsevier B.V. All rights reserved.

Mice lacking hippocampal left-right asymmetry show non-spatial learning deficits.

PubMed

Shimbo, Akihiro; Kosaki, Yutaka; Ito, Isao; Watanabe, Shigeru

2018-01-15

Left-right asymmetry is known to exist at several anatomical levels in the brain and recent studies have provided further evidence to show that it also exists at a molecular level in the hippocampal CA3-CA1 circuit. The distribution of N-methyl-d-aspartate (NMDA) receptor NR2B subunits in the apical and basal synapses of CA1 pyramidal neurons is asymmetrical if the input arrives from the left or right CA3 pyramidal neurons. In the present study, we examined the role of hippocampal asymmetry in cognitive function using β2-microglobulin knock-out (β2m KO) mice, which lack hippocampal asymmetry. We tested β2m KO mice in a series of spatial and non-spatial learning tasks and compared the performances of β2m KO and C57BL6/J wild-type (WT) mice. The β2m KO mice appeared normal in both spatial reference memory and spatial working memory tasks but they took more time than WT mice in learning the two non-spatial learning tasks (i.e., a differential reinforcement of lower rates of behavior (DRL) task and a straight runway task). The β2m KO mice also showed less precision in their response timing in the DRL task and showed weaker spontaneous recovery during extinction in the straight runway task. These results indicate that hippocampal asymmetry is important for certain characteristics of non-spatial learning. Copyright © 2017 Elsevier B.V. All rights reserved.

Linking memory and language: Evidence for a serial-order learning impairment in dyslexia.

PubMed

Bogaerts, Louisa; Szmalec, Arnaud; Hachmann, Wibke M; Page, Mike P A; Duyck, Wouter

2015-01-01

The present study investigated long-term serial-order learning impairments, operationalized as reduced Hebb repetition learning (HRL), in people with dyslexia. In a first multi-session experiment, we investigated both the persistence of a serial-order learning impairment as well as the long-term retention of serial-order representations, both in a group of Dutch-speaking adults with developmental dyslexia and in a matched control group. In a second experiment, we relied on the assumption that HRL mimics naturalistic word-form acquisition and we investigated the lexicalization of novel word-forms acquired through HRL. First, our results demonstrate that adults with dyslexia are fundamentally impaired in the long-term acquisition of serial-order information. Second, dyslexic and control participants show comparable retention of the long-term serial-order representations in memory over a period of 1 month. Third, the data suggest weaker lexicalization of newly acquired word-forms in the dyslexic group. We discuss the integration of these findings into current theoretical views of dyslexia. Copyright © 2015 Elsevier Ltd. All rights reserved.