Elevations of Endogenous Kynurenic Acid Produce Spatial Working Memory Deficits

PubMed Central

Chess, Amy C.; Simoni, Michael K.; Alling, Torey E.; Bucci, David J.

2007-01-01

Kynurenic acid (KYNA) is a tryptophan metabolite that is synthesized and released by astrocytes and acts as a competitive antagonist of the glycine site of N-methyl-D-aspartate receptors at high concentrations and as a noncompetitive antagonist of the α7-nicotinic acetylcholine receptor at low concentrations. The discovery of increased cortical KYNA levels in schizophrenia prompted the hypothesis that elevated KYNA concentration may underlie the working memory dysfunction observed in this population that has been attributed to altered glutamatergic and/or cholinergic transmission. The present study investigated the effect of elevated endogenous KYNA on spatial working memory function in rats. Increased KYNA levels were achieved with intraperitoneal administration of kynurenine (100 mg/kg), the precursor of KYNA synthesis. Rats were treated with either kynurenine or a vehicle solution prior to testing in a radial arm maze task at various delays. Elevations of endogenous KYNA resulted in increased errors in the radial arm maze. In separate experiments, assessment of locomotor activity in an open field and latency to retrieve food reward from one of the maze arms ruled out the possibility that deficits in the maze were attributable to altered locomotor activity or motivation to consume food. These results provide evidence that increased KYNA levels produce spatial working memory deficits and are among the first to demonstrate the influence of glia-derived molecules on cognitive function. The implications for psychopathological conditions such as schizophrenia are discussed. PMID:16920787

Hippocampal activation during the recall of remote spatial memories in radial maze tasks.

PubMed

Schlesiger, Magdalene I; Cressey, John C; Boublil, Brittney; Koenig, Julie; Melvin, Neal R; Leutgeb, Jill K; Leutgeb, Stefan

2013-11-01

Temporally graded retrograde amnesia is observed in human patients with medial temporal lobe lesions as well as in animal models of medial temporal lobe lesions. A time-limited role for these structures in memory recall has also been suggested by the observation that the rodent hippocampus and entorhinal cortex are activated during the retrieval of recent but not of remote memories. One notable exception is the recall of remote memories for platform locations in the water maze, which requires an intact hippocampus and results in hippocampal activation irrespective of the age of the memory. These findings raise the question whether the hippocampus is always involved in the recall of spatial memories or, alternatively, whether it might be required for procedural computations in the water maze task, such as for calculating a path to a hidden platform. We performed spatial memory testing in radial maze tasks to distinguish between these possibilities. Radial maze tasks require a choice between spatial locations on a center platform and thus have a lesser requirement for navigation than the water maze. However, we used a behavioral design in the radial maze that retained other aspects of the standard water maze task, such as the use of multiple start locations and retention testing in a single trial. Using the immediate early gene c-fos as a marker for neuronal activation, we found that all hippocampal subregions were more activated during the recall of remote compared to recent spatial memories. In areas CA3 and CA1, activation during remote memory testing was higher than in rats that were merely reexposed to the testing environment after the same time interval. Conversely, Fos levels in the dentate gyrus were increased after retention testing to the extent that was also observed in the corresponding exposure control group. This pattern of hippocampal activation was also obtained in a second version of the task that only used a single start arm instead of multiple start arms. The CA3 and CA1 activation during remote memory recall is consistent with the interpretation that an older memory might require increased pattern completion and/or relearning after longer time intervals. Irrespective of whether the hippocampus is required for remote memory recall, the hippocampus might engage in computations that either support recall of remote memories or that update remote memories. Copyright © 2013 Elsevier Inc. All rights reserved.

An Exploration Based Cognitive Bias Test for Mice: Effects of Handling Method and Stereotypic Behaviour.

PubMed

Novak, Janja; Bailoo, Jeremy D; Melotti, Luca; Rommen, Jonas; Würbel, Hanno

2015-01-01

Behavioural tests to assess affective states are widely used in human research and have recently been extended to animals. These tests assume that affective state influences cognitive processing, and that animals in a negative affective state interpret ambiguous information as expecting a negative outcome (displaying a negative cognitive bias). Most of these tests however, require long discrimination training. The aim of the study was to validate an exploration based cognitive bias test, using two different handling methods, as previous studies have shown that standard tail handling of mice increases physiological and behavioural measures of anxiety compared to cupped handling. Therefore, we hypothesised that tail handled mice would display a negative cognitive bias. We handled 28 female CD-1 mice for 16 weeks using either tail handling or cupped handling. The mice were then trained in an eight arm radial maze, where two adjacent arms predicted a positive outcome (darkness and food), while the two opposite arms predicted a negative outcome (no food, white noise and light). After six days of training, the mice were also given access to the four previously unavailable intermediate ambiguous arms of the radial maze and tested for cognitive bias. We were unable to validate this test, as mice from both handling groups displayed a similar pattern of exploration. Furthermore, we examined whether maze exploration is affected by the expression of stereotypic behaviour in the home cage. Mice with higher levels of stereotypic behaviour spent more time in positive arms and avoided ambiguous arms, displaying a negative cognitive bias. While this test needs further validation, our results indicate that it may allow the assessment of affective state in mice with minimal training-a major confound in current cognitive bias paradigms.

An Exploration Based Cognitive Bias Test for Mice: Effects of Handling Method and Stereotypic Behaviour

PubMed Central

Novak, Janja; Bailoo, Jeremy D.; Melotti, Luca; Rommen, Jonas; Würbel, Hanno

2015-01-01

Behavioural tests to assess affective states are widely used in human research and have recently been extended to animals. These tests assume that affective state influences cognitive processing, and that animals in a negative affective state interpret ambiguous information as expecting a negative outcome (displaying a negative cognitive bias). Most of these tests however, require long discrimination training. The aim of the study was to validate an exploration based cognitive bias test, using two different handling methods, as previous studies have shown that standard tail handling of mice increases physiological and behavioural measures of anxiety compared to cupped handling. Therefore, we hypothesised that tail handled mice would display a negative cognitive bias. We handled 28 female CD-1 mice for 16 weeks using either tail handling or cupped handling. The mice were then trained in an eight arm radial maze, where two adjacent arms predicted a positive outcome (darkness and food), while the two opposite arms predicted a negative outcome (no food, white noise and light). After six days of training, the mice were also given access to the four previously unavailable intermediate ambiguous arms of the radial maze and tested for cognitive bias. We were unable to validate this test, as mice from both handling groups displayed a similar pattern of exploration. Furthermore, we examined whether maze exploration is affected by the expression of stereotypic behaviour in the home cage. Mice with higher levels of stereotypic behaviour spent more time in positive arms and avoided ambiguous arms, displaying a negative cognitive bias. While this test needs further validation, our results indicate that it may allow the assessment of affective state in mice with minimal training—a major confound in current cognitive bias paradigms. PMID:26154309

Inference Based on Transitive Relation in Tree Shrews ("Tupaia belangeri") and Rats ("Rattus norvegicus") on a Spatial Discrimination Task

ERIC Educational Resources Information Center

Takahashi, Makoto; Ushitani, Tomokazu; Fujita, Kazuo

2008-01-01

Six tree shrews and 8 rats were tested for their ability to infer transitively in a spatial discrimination task. The apparatus was a semicircular radial-arm maze with 8 arms labeled A through H. In Experiment 1, the animals were first trained in sequence on 4 discriminations to enter 1 of the paired adjacent arms, AB, BC, CD, and DE, with right…

Spatial memory: a Rosetta stone for rat and human hippocampal discourse: Theoretical comment on Goodrich-Hunsaker and Hopkins (2010).

PubMed

Sutherland, Robert J

2010-06-01

The article by Goodrich-Hunsaker and Hopkins (2010, this issue) takes up an important place among in the recent contributions on the role of the hippocampus in memory. They evaluate the effect of bilateral damage to the hippocampus on performance by human participants in a virtual 8-arm radial maze. The hippocampal damage appears to be highly selective and nearly complete. Exactly as with selective hippocampal damage in rats, the human participants showed a deficit in accurately choosing rewarded versus never-rewarded arms and a deficit in avoiding reentering recently visited arms. The results are triply significant: (1) They provide good support for the idea that the wealth of neurobiological information, from network to synapse to gene, on spatial memory in the rat may apply as a whole to the human hippocampal memory system; (2) They affirm the utility of human virtual task models of rat spatial memory tasks; (3) They support one interpretation of the dampening of the hippocampal functional MRI (fMRI) blood oxygen level-dependent (BOLD) signal during performance of the virtual radial arm maze observed by Astur et al. (2005).

Rapid learning of magnetic compass direction by C57BL/6 mice in a 4-armed 'plus' water maze.

PubMed

Phillips, John B; Youmans, Paul W; Muheim, Rachel; Sloan, Kelly A; Landler, Lukas; Painter, Michael S; Anderson, Christopher R

2013-01-01

Magnetoreception has been demonstrated in all five vertebrate classes. In rodents, nest building experiments have shown the use of magnetic cues by two families of molerats, Siberian hamsters and C57BL/6 mice. However, assays widely used to study rodent spatial cognition (e.g. water maze, radial arm maze) have failed to provide evidence for the use of magnetic cues. Here we show that C57BL/6 mice can learn the magnetic direction of a submerged platform in a 4-armed (plus) water maze. Naïve mice were given two brief training trials. In each trial, a mouse was confined to one arm of the maze with the submerged platform at the outer end in a predetermined alignment relative to magnetic north. Between trials, the training arm and magnetic field were rotated by 180(°) so that the mouse had to swim in the same magnetic direction to reach the submerged platform. The directional preference of each mouse was tested once in one of four magnetic field alignments by releasing it at the center of the maze with access to all four arms. Equal numbers of responses were obtained from mice tested in the four symmetrical magnetic field alignments. Findings show that two training trials are sufficient for mice to learn the magnetic direction of the submerged platform in a plus water maze. The success of these experiments may be explained by: (1) absence of alternative directional cues (2), rotation of magnetic field alignment, and (3) electromagnetic shielding to minimize radio frequency interference that has been shown to interfere with magnetic compass orientation of birds. These findings confirm that mice have a well-developed magnetic compass, and give further impetus to the question of whether epigeic rodents (e.g., mice and rats) have a photoreceptor-based magnetic compass similar to that found in amphibians and migratory birds.

Rapid Learning of Magnetic Compass Direction by C57BL/6 Mice in a 4-Armed ‘Plus’ Water Maze

PubMed Central

Phillips, John B.; Youmans, Paul W.; Muheim, Rachel; Sloan, Kelly A.; Landler, Lukas; Painter, Michael S.; Anderson, Christopher R.

2013-01-01

Magnetoreception has been demonstrated in all five vertebrate classes. In rodents, nest building experiments have shown the use of magnetic cues by two families of molerats, Siberian hamsters and C57BL/6 mice. However, assays widely used to study rodent spatial cognition (e.g. water maze, radial arm maze) have failed to provide evidence for the use of magnetic cues. Here we show that C57BL/6 mice can learn the magnetic direction of a submerged platform in a 4-armed (plus) water maze. Naïve mice were given two brief training trials. In each trial, a mouse was confined to one arm of the maze with the submerged platform at the outer end in a predetermined alignment relative to magnetic north. Between trials, the training arm and magnetic field were rotated by 180° so that the mouse had to swim in the same magnetic direction to reach the submerged platform. The directional preference of each mouse was tested once in one of four magnetic field alignments by releasing it at the center of the maze with access to all four arms. Equal numbers of responses were obtained from mice tested in the four symmetrical magnetic field alignments. Findings show that two training trials are sufficient for mice to learn the magnetic direction of the submerged platform in a plus water maze. The success of these experiments may be explained by: (1) absence of alternative directional cues (2), rotation of magnetic field alignment, and (3) electromagnetic shielding to minimize radio frequency interference that has been shown to interfere with magnetic compass orientation of birds. These findings confirm that mice have a well-developed magnetic compass, and give further impetus to the question of whether epigeic rodents (e.g., mice and rats) have a photoreceptor-based magnetic compass similar to that found in amphibians and migratory birds. PMID:24023673

How Bumblebees First Find Flowers: Habituation of Visual Pattern Preferences, Spontaneous Recovery, and Dishabituation

ERIC Educational Resources Information Center

Plowright, C. M. S.; Simonds, V. M.; Butler, M. A.

2006-01-01

Two experiments examined the exploratory behaviour of flower-naive bumblebees. Bees were tested four times in a 12-arm radial arm maze in which they never received reward. Patterned and unpatterned stimuli were presented at the end of each corridor and the choices of the bees were recorded. We examined the effects of two variables, time and the…

Septal serotonin depletion in rats facilitates working memory in the radial arm maze and increases hippocampal high-frequency theta activity.

PubMed

López-Vázquez, Miguel Ángel; López-Loeza, Elisa; Lajud Ávila, Naima; Gutiérrez-Guzmán, Blanca Erika; Hernández-Pérez, J Jesús; Reyes, Yoana Estrada; Olvera-Cortés, María Esther

2014-07-05

Hippocampal theta activity, which is strongly modulated by the septal medial/Broca׳s diagonal band neurons, has been linked to information processing of the hippocampus. Serotonin from the medial raphe nuclei desynchronises hippocampal theta activity, whereas inactivation or a lesion of this nucleus induces continuous and persistent theta activity in the hippocampus. Hippocampal serotonin depletion produces an increased expression of high-frequency theta activity concurrent with the facilitation of place learning in the Morris maze. The medial septum-diagonal band of Broca complex (MS/DBB) has been proposed as a key structure in the serotonin modulation of theta activity. We addressed whether serotonin depletion of the MS/DBB induces changes in the characteristics of hippocampal theta activity and whether the depletion is associated with learning in a working memory spatial task in the radial arm maze. Sprague Dawley rats were depleted of 5HT with the infusion of 5,7-dihydroxytriptamine (5,7-DHT) in MS/DBB and were subsequently trained in the standard test (win-shift) in the radial arm, while the CA1 EEG activity was simultaneously recorded through telemetry. The MS/DBB serotonin depletion induced a low level of expression of low-frequency (4.5-6.5Hz) and a higher expression of high-frequency (6.5-9.5Hz) theta activity concomitant to a minor number of errors committed by rats on the working memory test. Thus, the depletion of serotonin in the MS/DBB caused a facilitator effect on working memory and a predominance of high-frequency theta activity. Copyright © 2014 Elsevier B.V. All rights reserved.

Methylphenidate improves performance on the radial arm maze in periadolescent rats

PubMed Central

Dow-Edwards, Diana L.; Weedon, Jeremy C.; Hellmann, Esther

2008-01-01

Methylphenidate (Ritalin; MPD) is one of the most commonly prescribed drugs in childhood and adolescence and many clinical studies have documented its efficacy. Due to the limitations of conducting invasive research in humans, animal models can be beneficial for studying drug effects. However, few animal studies have demonstrated the effects of methylphenidate on cognitive processes. The objective of this study was to find a dose of methylphenidate that was effective in improving performance on a spatial working memory cognitive task when administered orally to periadolescent rats. Therefore, we dosed subjects with methylphenidate at 1 or 3 mg/kg/day via gastric intubation from postnatal day 22 to 59 and assessed the effects of the drug on performance on the radial arm maze each day. To enhance performance overall, a second experiment was conducted where the subjects were moderately food restricted (to 90% of the free-feeding weight). Results of Experiment 1 show that during the first week of testing only the 3mg/kg MPD-treated males showed improved performance (entries prior to repeated entry) when ad-lib fed and housed in pairs while the same dose significantly improved performance in both males and females under conditions of food-restriction and individual housing in Experiment 2. MPD also produced a pattern of increased errors and arms entered during the first week, especially in Experiment 2. MPD increased locomotor activity when tested at postnatal day 60 in both experiments. The data suggest that 3mg/kg oral methylphenidate improves performance on a spatial cognitive task only early in treatment in the rat. While males show improvement under conditions of both high and low motivation, females only show MPD effects when highly motivated. Hypothetically, methylphenidate may improve radial arm maze performance through increased attention and improved spatial working memory and/or alterations in locomotion, reactivity to novelty or anxiety. Regardless, the study supports the utility of the rat as a suitable model to examine the effects of low dose oral MPD. PMID:18538539

A dissociation of dorso-lateral striatum and amygdala function on the same stimulus-response habit task.

PubMed

McDonald, R J; Hong, N S

2004-01-01

This experiment tested the idea that the amygdala-based learning and memory system covertly acquires a stimulus-reward (stimulus-outcome) association during acquisition of a stimulus-response (S-R) habit task developed for the eight-arm radial maze. Groups of rats were given dorso-lateral striatal or amygdala lesions and then trained on the S-R habit task on the eight-arm radial maze. Rats with neurotoxic damage to the dorso-lateral striatum were severely impaired on the acquisition of the S-R habit task but showed a conditioned-cue preference for the stimulus reinforced during S-R habit training. Rats with neurotoxic damage to the amygdala were able to acquire the S-R habit task but did not show a conditioned-cue preference for the stimulus reinforced during S-R habit training. This pattern of results represents a dissociation of learning and memory functions of the dorsal striatum and amygdala on the same task.

A Virtual Radial Arm Maze for the Study of Multiple Memory Systems in a Functional Magnetic Resonance Imaging Environment

PubMed Central

Xu, Dongrong; Hao, Xuejun; Wang, Zhishun; Duan, Yunsuo; Liu, Feng; Marsh, Rachel; Yu, Shan; Peterson, Bradley S.

2015-01-01

An increasing number of functional brain imaging studies are employing computer-based virtual reality (VR) to study changes in brain activity during the performance of high-level psychological and cognitive tasks. We report the development of a VR radial arm maze that adapts for human use in a scanning environment with the same general experimental design of behavioral tasks as that has been used with remarkable effectiveness for the study of multiple memory systems in rodents. The software platform is independent of specific computer hardware and operating systems, as we aim to provide shared access to this technology by the research community. We hope that doing so will provide greater standardization of software platform and study paradigm that will reduce variability and improve the comparability of findings across studies. We report the details of the design and implementation of this platform and provide information for downloading of the system for demonstration and research applications. PMID:26366052

Working and reference memory across the estrous cycle of rat: a long-term study in gonadally intact females.

PubMed

Pompili, Assunta; Tomaz, Carlos; Arnone, Benedetto; Tavares, Maria Clotilde; Gasbarri, Antonella

2010-11-12

The results of many studies conducted over the past two decades suggested a role of estrogen on mammal's ability to learn and remember. In the present paper, we analyzed the influence that the endogenous fluctuation of estrogen, naturally present across the different phases of estrous cycle of female rats, can exert over the performance of tasks utilized to assess memory. In particular, we analyzed the performances in an eight arms radial maze task, dependent upon working memory, and in a water maze (WM) task, dependent upon spatial reference memory. The water maze is aversively motivated by the desire to escape onto a safe platform, whereas the radial arm maze (RAM) is motivated by food reward. The difference in reinforcement may affect the speed of learning, the strategy adopted and the necessity for accurate navigation. Therefore, coherent results obtained through the two different tasks can be due to mnemonic factors. The study was conducted during a long period of time, 14 months, utilizing gonadally intact females, without pharmacological and surgical treatments. In order to evaluate the post-acquisition phase we first trained the animals to reach the criterion in performing tasks, and then we submitted them to experimental phase. Our results show that estrogen can have an effect on memory processes, and that this effect may be different in relation to different kinds of memory. In fact, in our study, estrogen selectively improved working memory, but not reference memory, during post-acquisition performance of a RAM task with four baited and four un-baited arms. Moreover, WM performances showed that estrogen have a negative effect on spatial reference memory. (c) 2010 Elsevier B.V. All rights reserved.

Effect of "enriched environment" during development on adult rat behavior and response to the dopamine receptor agonist apomorphine.

PubMed

Hoffmann, L C; Schütte, S R M; Koch, M; Schwabe, K

2009-02-18

Enriched housing conditions (enriched environment, EE) during development has been shown to influence adult rat behavior and transmitter systems, especially dopamine function. We were interested in how different degrees of enrichment during development would affect adult rats' behavior and response to dopamine receptor challenge. Two groups of male Wistar rats (n=11-12) were raised under two different degrees of EE, i.e. "high enriched" and "low enriched" groups. A third group was kept under standard conditions and served as "non-enriched" control. As adults, rats were tested for anxiety (elevated plus-maze), for spatial learning (four-arm-baited eight-arm radial maze), and for motivation (breakpoint of the progressive ratio test). Finally, locomotor activity (activity box) and sensorimotor gating (prepulse inhibition (PPI) of the acoustic startle response (ASR)) were tested with and without challenge with the dopamine receptor agonist apomorphine. The time spent on the open or enclosed arms of the elevated plus-maze did not differ between groups, but the high enriched group showed higher rearing activity on the open arms. The breakpoint did not differ between groups. Learning and memory in the radial maze task only differed on the first few trials, but high enriched rats run faster compared with the other groups. In contrast, in the activity box enriched groups were less active, but apomorphine had the highest effect. Between groups, no difference in PPI and startle amplitude was found, but in the high and low EE group startle amplitude was enhanced after administration of apomorphine, while the PPI deficit induced by this drug was not different between groups. Altogether, we found no evidence that different amounts of environmental enrichment without differences in social EE affect rats' cognitive, emotional or motivational behavior. However, motor activity seems to be enhanced when rats are behaviorally or pharmacologically challenged by dopamine receptor agonists.

Sex differences in chronic stress effects on cognition in rodents

PubMed Central

Luine, Victoria; Gomez, Juan; Beck, Kevin; Bowman, Rachel

2016-01-01

Chronic stress causes deleterious changes in physiological function in systems ranging from neural cells in culture to laboratory rodents, sub-human primates and humans. It is notable, however, that the vast majority of research in this area has been conducted in males. In this review, we provide information about chronic stress effects on cognition in female rodents and contrast it with responses in male rodents. In general, females show cognitive resilience to chronic stressors which impair male cognitive function using spatial tasks including the radial arm maze, radial arm water maze, Morris water maze, Y-maze and object placement. Moreover, stress often enhances female performance in some of these cognitive tasks. Memory in females is not affected by stress in non-spatial memory tasks like recognition memory and temporal order recognition memory while males show impaired memory following stress. We discuss possible bases for these sex-dependent differences including the use of different strategies by the sexes to solve cognitive tasks. Whether the sex differences result from changes in non-mnemonic factors is also considered. Sex-dependent differences in alcohol and drug influences on stress responses are also described. Finally, the role of neurally derived estradiol in driving sex differences and providing resilience to stress in females is shown. The importance of determining the nature and extent of sex differences in stress responses is that such differences may provide vital information for understanding why some stress related diseases have different incidence rates between the sexes and for developing novel therapeutic treatments. PMID:27566290

Cognitive and behavioral evaluation of nutritional interventions in rodent models of brain aging and dementia

PubMed Central

Wahl, Devin; Coogan, Sean CP; Solon-Biet, Samantha M; de Cabo, Rafael; Haran, James B; Raubenheimer, David; Cogger, Victoria C; Mattson, Mark P; Simpson, Stephen J; Le Couteur, David G

2017-01-01

Evaluation of behavior and cognition in rodent models underpins mechanistic and interventional studies of brain aging and neurodegenerative diseases, especially dementia. Commonly used tests include Morris water maze, Barnes maze, object recognition, fear conditioning, radial arm water maze, and Y maze. Each of these tests reflects some aspects of human memory including episodic memory, recognition memory, semantic memory, spatial memory, and emotional memory. Although most interventional studies in rodent models of dementia have focused on pharmacological agents, there are an increasing number of studies that have evaluated nutritional interventions including caloric restriction, intermittent fasting, and manipulation of macronutrients. Dietary interventions have been shown to influence various cognitive and behavioral tests in rodents indicating that nutrition can influence brain aging and possibly neurodegeneration. PMID:28932108

Sex differences in chronic stress effects on cognition in rodents.

PubMed

Luine, Victoria; Gomez, Juan; Beck, Kevin; Bowman, Rachel

2017-01-01

Chronic stress causes deleterious changes in physiological function in systems ranging from neural cells in culture to laboratory rodents, sub-human primates and humans. It is notable, however, that the vast majority of research in this area has been conducted in males. In this review, we provide information about chronic stress effects on cognition in female rodents and contrast it with responses in male rodents. In general, females show cognitive resilience to chronic stressors which impair male cognitive function using spatial tasks including the radial arm maze, radial arm water maze, Morris water maze, Y-maze and object placement. Moreover, stress often enhances female performance in some of these cognitive tasks. Memory in females is not affected by stress in non-spatial memory tasks like recognition memory and temporal order recognition memory while males show impaired memory following stress. We discuss possible bases for these sex-dependent differences including the use of different strategies by the sexes to solve cognitive tasks. Whether the sex differences result from changes in non-mnemonic factors is also considered. Sex-dependent differences in alcohol and drug influences on stress responses are also described. Finally, the role of neurally derived estradiol in driving sex differences and providing resilience to stress in females is shown. The importance of determining the nature and extent of sex differences in stress responses is that such differences may provide vital information for understanding why some stress related diseases have different incidence rates between the sexes and for developing novel therapeutic treatments. Copyright © 2016 Elsevier Inc. All rights reserved.

Memory systems in the rat: effects of reward probability, context, and congruency between working and reference memory.

PubMed

Roberts, William A; Guitar, Nicole A; Marsh, Heidi L; MacDonald, Hayden

2016-05-01

The interaction of working and reference memory was studied in rats on an eight-arm radial maze. In two experiments, rats were trained to perform working memory and reference memory tasks. On working memory trials, they were allowed to enter four randomly chosen arms for reward in a study phase and then had to choose the unentered arms for reward in a test phase. On reference memory trials, they had to learn to visit the same four arms on the maze on every trial for reward. Retention was tested on working memory trials in which the interval between the study and test phase was 15 s, 15 min, or 30 min. At each retention interval, tests were performed in which the correct WM arms were either congruent or incongruent with the correct RM arms. Both experiments showed that congruency interacted with retention interval, yielding more forgetting at 30 min on incongruent trials than on congruent trials. The effect of reference memory strength on the congruency effect was examined in Experiment 1, and the effect of associating different contexts with working and reference memory on the congruency effect was studied in Experiment 2.

The Preference for Symmetry in Flower-Naive and Not-so-Naive Bumblebees

ERIC Educational Resources Information Center

Plowright, C. M. S.; Evans, S. A.; Leung, J. Chew; Collin, C. A.

2011-01-01

Truly flower-naive bumblebees, with no prior rewarded experience for visits on any visual patterns outside the colony, were tested for their choice of bilaterally symmetric over asymmetric patterns in a radial-arm maze. No preference for symmetry was found. Prior training with rewarded black and white disks did, however, lead to a significant…

Pre-training in a radial arm maze abolished anxiety and impaired habituation in C57BL6/J mice treated with dizocilpine.

PubMed

Abuhamdah, R M; Hussain, M D; Chazot, P L; Ennaceur, A

2016-10-01

Familiarity can imply a reduction of fear and anxiety, which may render learning and memory performance insensitive to NMDA receptor antagonism. Our previous study indicates that MK-801 (dizocilpine), NMDA antagonist, increased anxiety and prevented the acquisition of a spatial memory task. Here, we examined whether MK-801 will produce anxiety in mice that were familiar with the test environment. Male C57BL/6J mice were exposed, one session a day for 7days, to a 3D maze, which consisted of nine arms attached to upward inclined bridges radiating from a nonagonal platform. In this maze, high anxiety mice avoid the arms in the first sessions. One group of mice received saline (SAL) while a second group received MK-801 (MKD1), both on day one. A third group received saline in the first 3 sessions, and MK 801 in subsequent sessions (MKD4). Saline and MK-801 (0.1mg/kg) were administered intraperitoneally 30min before the test. MKD4 mice demonstrated an increase in bridge and arm visits, and reached arm/bridge entries ratio close to 1 in session 5. SAL mice also crossed frequently onto the arms, and reached a comparable ratio, but this was achieved with a lower number of arm visits. MKD1 mice demonstrated a reduced number of arm visits in each session compared to SAL and MKD4 mice. Dizocilpine produced anxiety in mice treated from day 1 of the test, but not in those treated from day 4. It also impaired habituation in animals familiar with the test environment; it produced sustained non-habituating hyperactivity. Copyright © 2016 Elsevier Inc. All rights reserved.

Spatial Memory in Rats after 25 Hours

ERIC Educational Resources Information Center

Crystal, Jonathon D.; Babb, Stephanie J.

2008-01-01

We investigated the time course of spatial-memory decay in rats using an eight-arm radial maze. It is well established that performance remains high with retention intervals as long as 4 h, but declines to chance with a 24-h retention interval (Beatty, W. W., & Shavalia, D. A. (1980b). Spatial memory in rats: time course of working memory and…

Prefrontal Cortical GABA Modulation of Spatial Reference and Working Memory

PubMed Central

Auger, Meagan L.

2015-01-01

Background: Dysfunction in prefrontal cortex (PFC) GABA transmission has been proposed to contribute to cognitive dysfunction in schizophrenia, yet how this system regulates different cognitive and mnemonic functions remains unclear. Methods: We assessed the effects of pharmacological reduction of GABAA signaling in the medial PFC of rats on spatial reference/working memory using different versions of the radial-arm maze task. We used a massed-trials procedure to probe how PFC GABA regulates susceptibility to proactive interference. Male rats were well-trained to retrieve food from the same 4 arms of an 8-arm maze, receiving 5 trials/day (1–2min intervals). Results: Infusions of the GABAA receptor antagonist bicuculline (12.5–50ng) markedly increased working and reference memory errors and response latencies. Similar treatments also impaired short-term memory on an 8-baited arm task. These effects did not appear to be due to increased susceptibility to proactive interference. In contrast, PFC inactivation via infusion of GABA agonists baclofen/muscimol did not affect reference/working memory. In comparison to the pronounced effects on the 8-arm maze tasks, PFC GABAA antagonism only causes a slight and transient decrease in accuracy on a 2-arm spatial discrimination. Conclusions: These findings demonstrate that prefrontal GABA hypofunction severely disrupts spatial reference and short-term memory and that disinhibition of the PFC can, in some instances, perturb memory processes not normally dependent on the frontal lobes. Moreover, these impairments closely resemble those observed in schizophrenic patients, suggesting that perturbation in PFC GABA signaling may contribute to these types of cognitive deficits associated with the disorder. PMID:25552433

Where Have I Been? Where Should I Go? Spatial Working Memory on a Radial Arm Maze in a Rat Model of Depression

PubMed Central

Richter, Sophie Helene; Zeuch, Benjamin; Lankisch, Katja; Gass, Peter; Durstewitz, Daniel; Vollmayr, Barbara

2013-01-01

Disturbances in cognitive functioning are among the most debilitating problems experienced by patients with major depression. Investigations of these deficits in animals help to extend and refine our understanding of human emotional disorder, while at the same time providing valid tools to study higher executive functions in animals. We employ the “learned helplessness” genetic rat model of depression in studying working memory using an eight arm radial maze procedure with temporal delay. This so-called delayed spatial win-shift task consists of three phases, training, delay and test, requiring rats to hold information on-line across a retention interval and making choices based on this information in the test phase. According to a 2×2 factorial design, working memory performance of thirty-one congenitally helpless (cLH) and non-helpless (cNLH) rats was tested on eighteen trials, additionally imposing two different delay durations, 30 s and 15 min, respectively. While not observing a general cognitive deficit in cLH rats, the delay length greatly influenced maze performance. Notably, performance was most impaired in cLH rats tested with the shorter 30 s delay, suggesting a stress-related disruption of attentional processes in rats that are more sensitive to stress. Our study provides direct animal homologues of clinically important measures in human research, and contributes to the non-invasive assessment of cognitive deficits associated with depression. PMID:23614050

Prefrontal cortical GABA modulation of spatial reference and working memory.

PubMed

Auger, Meagan L; Floresco, Stan B

2014-10-31

Dysfunction in prefrontal cortex (PFC) GABA transmission has been proposed to contribute to cognitive dysfunction in schizophrenia, yet how this system regulates different cognitive and mnemonic functions remains unclear. We assessed the effects of pharmacological reduction of GABAA signaling in the medial PFC of rats on spatial reference/working memory using different versions of the radial-arm maze task. We used a massed-trials procedure to probe how PFC GABA regulates susceptibility to proactive interference. Male rats were well-trained to retrieve food from the same 4 arms of an 8-arm maze, receiving 5 trials/day (1-2 min intervals). Infusions of the GABAA receptor antagonist bicuculline (12.5-50 ng) markedly increased working and reference memory errors and response latencies. Similar treatments also impaired short-term memory on an 8-baited arm task. These effects did not appear to be due to increased susceptibility to proactive interference. In contrast, PFC inactivation via infusion of GABA agonists baclofen/muscimol did not affect reference/working memory. In comparison to the pronounced effects on the 8-arm maze tasks, PFC GABAA antagonism only causes a slight and transient decrease in accuracy on a 2-arm spatial discrimination. These findings demonstrate that prefrontal GABA hypofunction severely disrupts spatial reference and short-term memory and that disinhibition of the PFC can, in some instances, perturb memory processes not normally dependent on the frontal lobes. Moreover, these impairments closely resemble those observed in schizophrenic patients, suggesting that perturbation in PFC GABA signaling may contribute to these types of cognitive deficits associated with the disorder. © The Author 2014. Published by Oxford University Press on behalf of CINP.

Nigella sativa Oil Enhances the Spatial Working Memory Performance of Rats on a Radial Arm Maze

PubMed Central

Sahak, Mohamad Khairul Azali; Mohamed, Abdul Majid; Hashim, Noor Hashida; Hasan Adli, Durriyyah Sharifah

2013-01-01

Nigella sativa, an established historical and religion-based remedy for a wide range of health problems, is a herbal medicine known to have antioxidant and neuroprotective effects. This present study investigated the effect of Nigella sativa oil (NSO) administration on the spatial memory performance (SMP) of male adult rats using eight-arm radial arm maze (RAM). Twelve Sprague Dawley rats (7–9 weeks old) were force-fed daily with 6.0 μL/100 g body weight of Nigella sativa oil (NSO group; n = 6) or 0.1 mL/100 g body weight of corn oil (control) (CO group; n = 6) for a period of 20 consecutive weeks. For each weekly evaluation of SMP, one day food-deprived rats were tested by allowing each of them 3 minutes to explore the RAM for food as their rewards. Similar to the control group, the SMP of the treated group was not hindered, as indicated by the establishment of the reference and working memory components of the spatial memory. The results demonstrated that lesser mean numbers of error were observed for the NSO-treated group in both parameters as compared to the CO-treated group. NSO could therefore enhance the learning and memory abilities of the rats; there was a significant decrease in the overall mean number of working memory error (WME) in the NSO-treated group. PMID:24454487

A Distributed Model for Mobile Robot Environment-Learning and Navigation

DTIC Science & Technology

1990-05-01

are unex- pectedly removed, the bats continue to navigate around, as if they continue to be present [ Gallistel 89]. This behavior indicates the...itself ( Gallistel 80]. 11.2.2 Bees The behavior of bees has been intriguing biologists, behaviorists, and ethol- ogists for centuries. Bee hives...corresponding to their previous length [ Gallistel 80]. In experiments with rotated radial mazes, rats enter already sampled arms without realizing the

Effect of acute pesticide exposure on bee spatial working memory using an analogue of the radial-arm maze

NASA Astrophysics Data System (ADS)

Samuelson, Elizabeth E. W.; Chen-Wishart, Zachary P.; Gill, Richard J.; Leadbeater, Ellouise

2016-12-01

Pesticides, including neonicotinoids, typically target pest insects by being neurotoxic. Inadvertent exposure to foraging insect pollinators is usually sub-lethal, but may affect cognition. One cognitive trait, spatial working memory, may be important in avoiding previously-visited flowers and other spatial tasks such as navigation. To test this, we investigated the effect of acute thiamethoxam exposure on spatial working memory in the bumblebee Bombus terrestris, using an adaptation of the radial-arm maze (RAM). We first demonstrated that bumblebees use spatial working memory to solve the RAM by showing that untreated bees performed significantly better than would be expected if choices were random or governed by stereotyped visitation rules. We then exposed bees to either a high sub-lethal positive control thiamethoxam dose (2.5 ng-1 bee), or one of two low doses (0.377 or 0.091 ng-1) based on estimated field-realistic exposure. The high dose caused bees to make more and earlier spatial memory errors and take longer to complete the task than unexposed bees. For the low doses, the negative effects were smaller but statistically significant, and dependent on bee size. The spatial working memory impairment shown here has the potential to harm bees exposed to thiamethoxam, through possible impacts on foraging efficiency or homing.

Effects of tobacco smoke constituents, anabasine and anatabine, on memory and attention in female rats.

PubMed

Levin, Edward D; Hao, Ian; Burke, Dennis A; Cauley, Marty; Hall, Brandon J; Rezvani, Amir H

2014-10-01

Nicotine has been well characterized to improve memory and attention. Nicotine is the primary, but not only neuroactive compound in tobacco. Other tobacco constituents such as anabasine and anatabine also have agonist actions on nicotinic receptors. The current study investigated the effects of anabasine and anatabine on memory and attention. Adult female Sprague-Dawley rats were trained on a win-shift spatial working and reference memory task in the 16-arm radial maze or a visual signal detection operant task to test attention. Acute dose-effect functions of anabasine and anatabine over two orders of magnitude were evaluated for both tasks. In the radial-arm maze memory test, anabasine but not anatabine significantly reduced the memory impairment caused by the NMDA antagonist dizocilpine (MK-801). In the signal detection attentional task, anatabine but not anabasine significantly attenuated the attentional impairment caused by dizocilpine. These studies show that non-nicotine nicotinic agonists in tobacco, similar to nicotine, can significantly improve memory and attentional function. Both anabasine and anatabine produced cognitive improvement, but their effectiveness differed with regard to memory and attention. Follow-up studies with anabasine and anatabine are called for to determine their efficacy as therapeutics for memory and attentional dysfunction. © The Author(s) 2014.

Learning about cognition risk with the radial-arm maze in the developmental neurotoxicology battery.

PubMed

Levin, Edward D

2015-01-01

Cognitive dysfunction has been found in epidemiological studies to be among the most sensitive impairments associated with developmental exposure to a variety of environmental contaminants from heavy metals to polyhalogenated hydrocarbons and pesticides. These chemicals have been also shown to impair cognitive function after developmental exposure in experimental animal models. The radial-arm maze (RAM) has proven to be a sensitive and reliable way to assess both learning and memory in a variety of species, most often in rats and mice. The RAM is a very adaptable test method that takes advantage of rodents' instinct to explore new places in the environment to forage. That is, rodents do not need to be trained to run through the maze; they will normally do this from the initial session of testing. Training with differential reinforcement for arm choices provides a more rigorous test of learning and memory. The RAM is quite adaptable for assessing various aspects of cognition. Although the RAM has been mostly used to assess spatial learning and memory, it can be configured to assess non-spatial memory as well. Both working and reference memory can be easily distinguished. The RAM can be run with both appetitive (food reinforced) and aversive (water escape) motivators. The RAM has been found to be sensitive to a wide variety of developmental toxicants including heavy metals such as mercury and pesticides such as chlorpyrifos. There is an extremely rich literature especially with rats showing the effects of many types of brain lesions and drug effects so that the participation of a wide variety of neural systems in RAM performance is known. These systems, notably the hippocampus and frontal cortex, and acetylcholine and glutamate neurotransmitter systems, are the same neural systems that have been shown in humans to be critical for learning and memory. This considerably aids the interpretation of neurobehavioral toxicity studies. Copyright © 2015 Elsevier Inc. All rights reserved.

Release from proactive interference in rat spatial working memory.

PubMed

Roberts, William A; MacDonald, Hayden; Brown, Lyn; Macpherson, Krista

2017-09-01

A three-phase procedure was used to produce proactive interference (PI) in one trial on an eight-arm radial maze. Rats were forced to enter four arms for reward on an initial interference phase, to then enter the four remaining arms on a target phase, and to then choose among all eight arms on a retention test, with only the arms not visited in the target phase containing reward. Control trials involved only the target phase and the retention test. Lower accuracy was found on PI trials than on control trials, but performance on PI trials significantly exceeded chance, showing some retention of target memories. Changes in temporal and reward variables between the interference, target, and retention test phases showed release from PI, but changes in context and pattern of arm entry did not. It is suggested that the release from PI paradigm can be used to understand spatial memory encoding in rats and other species.

Chronic administration of cardanol (ginkgol) extracted from ginkgo biloba leaves and cashew nutshell liquid improves working memory-related learning in rats.

PubMed

Tobinaga, Seisho; Hashimoto, Michio; Utsunomiya, Iku; Taguchi, Kyoji; Nakamura, Morihiko; Tsunematsu, Tokugoro

2012-01-01

Cardanol (ginkgol) extracted from Ginkgo biloba leaves and cashew nutshell liquid enhances the growth of NSC-34 immortalized motor neuron-like cells and, when chronically administered to young rats, improves working memory-related learning ability as assessed by eight-arm radial maze tasks. These findings suggest that cardanol is one of the components in Ginkgo biloba leaves that improves cognitive learning ability.

Robust training attenuates TBI-induced deficits in reference and working memory on the radial 8-arm maze

PubMed Central

Sebastian, Veronica; Diallo, Aissatou; Ling, Douglas S. F.; Serrano, Peter A.

2013-01-01

Globally, it is estimated that nearly 10 million people sustain severe brain injuries leading to hospitalization and/or death every year. Amongst survivors, traumatic brain injury (TBI) results in a wide variety of physical, emotional and cognitive deficits. The most common cognitive deficit associated with TBI is memory loss, involving impairments in spatial reference and working memory. However, the majority of research thus far has characterized the deficits associated with TBI on either reference or working memory systems separately, without investigating how they interact within a single task. Thus, we examined the effects of TBI on short-term working and long-term reference memory using the radial 8-arm maze (RAM) with a sequence of four baited and four unbaited arms. Subjects were given 10 daily trials for 6 days followed by a memory retrieval test 2 weeks after training. Multiple training trials not only provide robust training, but also test the subjects' ability to frequently update short-term memory while learning the reference rules of the task. Our results show that TBI significantly impaired short-term working memory function on previously acquired spatial information but has little effect on long-term reference memory. Additionally, TBI significantly increased working memory errors during acquisition and reference memory errors during retention testing 2 weeks later. With a longer recovery period after TBI, the robust RAM training mitigated the reference memory deficit in retention but not the short-term working memory deficit during acquisition. These results identify the resiliency and vulnerabilities of short-term working and long-term reference memory to TBI in the context of robust training. The data highlight the role of cognitive training and other behavioral remediation strategies implicated in attenuating deficits associated with TBI. PMID:23653600

Frontal cortex and hippocampus neurotransmitter receptor complex level parallels spatial memory performance in the radial arm maze.

PubMed

Shanmugasundaram, Bharanidharan; Sase, Ajinkya; Miklosi, András G; Sialana, Fernando J; Subramaniyan, Saraswathi; Aher, Yogesh D; Gröger, Marion; Höger, Harald; Bennett, Keiryn L; Lubec, Gert

2015-08-01

Several neurotransmitter receptors have been proposed to be involved in memory formation. However, information on receptor complexes (RCs) in the radial arm maze (RAM) is missing. It was therefore the aim of this study to determine major neurotransmitter RCs levels that are modulated by RAM training because receptors are known to work in homo-or heteromeric assemblies. Immediate early gene Arc expression was determined by immunohistochemistry to show if prefrontal cortices (PFC) and hippocampi were activated following RAM training as these regions are known to be mainly implicated in spatial memory. Twelve rats per group, trained and untrained in the twelve arm RAM were used, frontal cortices and hippocampi were taken, RCs in membrane protein were quantified by blue-native PAGE immunoblotting. RCs components were characterised by co-immunoprecipitation followed by mass spectrometrical analysis and by the use of the proximity ligation assay. Arc expression was significantly higher in PFC of trained as compared to untrained rats whereas it was comparable in hippocampi. Frontal cortical levels of RCs containing AMPA receptors GluA1, GluA2, NMDA receptors GluN1 and GluN2A, dopamine receptor D1, acetylcholine nicotinic receptor alpha 7 (nAChR-α7) and hippocampal levels of RCs containing D1, GluN1, GluN2B and nAChR-α7 were increased in the trained group; phosphorylated dopamine transporter levels were decreased in the trained group. D1 and GluN1 receptors were shown to be in the same complex. Taken together, distinct RCs were paralleling performance in the RAM which is relevant for interpretation of previous and design of future work on RCs in memory studies. Copyright © 2015 Elsevier B.V. All rights reserved.

Delay-dependent working memory impairment in young-adult and aged 5-HT1BKO mice as assessed in a radial-arm water maze.

PubMed

Wolff, Mathieu; Benhassine, Narimane; Costet, Pierre; Hen, Rene; Segu, Louis; Buhot, Marie-Christine

2003-01-01

Serotonin (5-HT) plays a modulatory role in mnemonic functions, especially by interacting with the cholinergic system. The 5-HT1B receptor is a key target of this interaction. The 5-HT1B receptor knockout mice were found previously to exhibit a facilitation in hippocampal-dependent spatial reference memory learning. In the present study, we submitted mice to a delayed spatial working memory task, allowing the introduction of various delays between an exposure trial and a test trial. The 5-HT1BKO and wild-type mice learned the task in a radial-arm water maze (returning to the most recent presented arm containing the escape platform), and exhibited a high level of performance at delays of 0 and 5 min. However, at the delay of 60 min, only 5-HT1BKO mice exhibited an impairment. At a delay of 90 min, all mice were impaired. Treatment by scopolamine (0.8 mg/kg) induced the same pattern of performance in wild type as did the mutation for short (5 min, no impairment) and long (60 min, impairment) delays. The 22-month-old wild-type and knockout mice exhibited an impairment at short delays (5 and 15 min). The effect of the mutation affected both young-adult and aged mice at delays of 15, 30, and 60 min. Neurobiological data show that stimulation of the 5-HT1B receptor inhibits the release of acetylcholine in the hippocampus, but stimulates this in the frontal cortex. This dual function might, at least in part, explain the opposite effect of the mutation on reference memory (facilitation) and delay-dependent working memory (impairment). These results support the idea that cholinergic-serotonergic interactions play an important role in memory processes.

Memory-enhancing activities of the aqueous extract of Albizia adianthifolia leaves in the 6-hydroxydopamine-lesion rodent model of Parkinson’s disease

PubMed Central

2014-01-01

Background Albizia adianthifolia (Schumach.) W. Wright (Fabaceae) is a traditional herb largely used in the African traditional medicine as analgesic, purgative, anti-inflammatory, antioxidant, antimicrobial and memory-enhancer drug. This study was undertaken in order to evaluate the possible cognitive-enhancing and antioxidative effects of the aqueous extract of A. adianthifolia leaves in the 6-hydroxydopamine-lesion rodent model of Parkinson’s disease. Methods The effect of the aqueous extract of A. adianthifolia leaves (150 and 300 mg/kg, orally, daily, for 21 days) on spatial memory performance was assessed using Y-maze and radial arm-maze tasks, as animal models of spatial memory. Pergolide - induced rotational behavior test was employed to validate unilateral damage to dopamine nigrostriatal neurons. Also, in vitro antioxidant activity was assessed through the estimation of total flavonoid and total phenolic contents along with determination of free radical scavenging activity. Statistical analyses were performed using two-way analysis of variance (ANOVA). Significant differences were determined by Tukey’s post hoc test. F values for which p < 0.05 were regarded as statistically significant. Pearson’s correlation coefficient and regression analysis were used in order to evaluate the association between behavioral parameters and net rotations in rotational behavior test. Results The 6-OHDA-treated rats exhibited the following: decrease of spontaneous alternations percentage within Y-maze task and increase of working memory errors and reference memory errors within radial arm maze task. Administration of the aqueous extract of A. adianthifolia leaves significantly improved these parameters, suggesting positive effects on spatial memory formation. Also, the aqueous extract of A. adianthifolia leaves showed potent in vitro antioxidant activity. Furthermore, in vivo evaluation, the aqueous extract of A. adianthifolia leaves attenuated the contralateral rotational asymmetry observed by pergolide challenge in 6-OHDA-treated rats. Conclusions Taken together, our results suggest that the aqueous extract of A. adianthifolia leaves possesses antioxidant potential and might provide an opportunity for management neurological abnormalities in Parkinson’s disease conditions. PMID:24884469

Attenuation of social interaction-associated ultrasonic vocalizations and spatial working memory performance in rats exposed to chronic unpredictable stress.

PubMed

Riaz, Muhammad S; Bohlen, Martin O; Gunter, Barak W; Quentin, Henry; Stockmeier, Craig A; Paul, Ian A

2015-12-01

Exposure to unpredictable chronic mild stress (CUS) is a commonly used protocol in rats that is reported to evoke antidepressant-reversible behaviors such as loss of preference for a sweetened water solution which is taken as an analog of the anhedonia seen in major depression. However, the induction of anhedonic-like behavior by chronic mild stress, gauged by an animal's preference for sucrose solution, is not fully reproducible and consistent across laboratories. In this study, we compared a widely used behavioral marker of anhedonia - the sucrose preference test, with another phenotypic marker of emotional valence, social interaction-associated ultrasonic vocalizations as well as a marker of an anxiety-like phenotype, novelty-suppressed feeding, and cognitive performance in the eight arm radial maze task in adult male Sprague-Dawley rats. Chronic four-week exposure to unpredictable mild stressors resulted in 1) attenuation of social interaction-associated ultrasonic vocalizations 2) attenuation of spatial memory performance on the radial arm maze 3) attenuation of body weight gain and 4) increased latency to feed in a novelty-suppressed feeding task. However, chronic exposure to CUS did not result in any significant change in sucrose preference at one-week and three-week intervals. Our results argue for the utility of ultrasonic vocalizations in a social interaction context as a comparable alternative or adjunct to the sucrose preference test in determining the efficacy of CUS to generate an anhedonic-like phenotypic state. Copyright © 2015 Elsevier Inc. All rights reserved.

Cognitive deficits induced by 56Fe radiation exposure

NASA Technical Reports Server (NTRS)

Shukitt-Hale, B.; Casadesus, G.; Cantuti-Castelvetri, I.; Rabin, B. M.; Joseph, J. A.

2003-01-01

Exposing rats to particles of high energy and charge (e.g., 56Fe) disrupts neuronal systems and the behaviors mediated by them; these adverse behavioral and neuronal effects are similar to those seen in aged animals. Because cognition declines with age, and our previous study showed that radiation disrupted Morris water maze spatial learning and memory performance, the present study used an 8-arm radial maze (RAM) to further test the cognitive behavioral consequences of radiation exposure. Control rats or rats exposed to whole-body irradiation with 1.0 Gy of 1 GeV/n high-energy 56Fe particles (delivered at the alternating gradient synchrotron at Brookhaven National Laboratory) were tested nine months following exposure. Radiation adversely affected RAM performance, and the changes seen parallel those of aging. Irradiated animals entered baited arms during the first 4 choices significantly less than did controls, produced their first error sooner, and also tended to make more errors as measured by re-entries into non-baited arms. 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. Published by Elsevier Science Ltd on behalf of COSPAR.

Unaltered radial maze performance and brain acetylcholine of the endothelial nitric oxide synthase knockout mouse.

PubMed

Dere, E; Frisch, C; De Souza Silva, M A; Gödecke, A; Schrader, J; Huston, J P

2001-01-01

Proceeding from previous findings of a beneficial effect of endothelial nitric oxide synthase (eNOS) gene inactivation on negatively reinforced water maze performance, we asked whether this improvement in place learning capacities also holds for a positively reinforced radial maze task. Unlike its beneficial effects on the water maze task, eNOS gene inactivation did not facilitate radial maze performance. The acquisition performance over the days of place learning did not differ between eNOS knockout (eNOS-/-) and wild-type mice (eNOS+/+). eNOS-/- mice displayed a slight and eNOS+/+ mice a more severe working memory deficit in the place learning version of the radial maze compared to the genetic background C57BL/6 strain. Possible differential effects of eNOS inactivation, related to differences in reinforcement contingencies between the Morris water maze and radial maze tasks, behavioral strategy requirements, or to different emotional and physiological concomitants inherent in the two tasks are discussed. These task-unique characteristics might be differentially affected by the reported anxiogenic and hypertensional effects of eNOS gene inactivation. Post-mortem determination of acetylcholine concentrations in diverse brain structures revealed that acetylcholine and choline contents were not different between eNOS-/- and eNOS+/+ mice, but were increased in eNOS+/+ mice compared to C57BL/6 mice in the frontal cortex. Our findings demonstrate that phenotyping of learning and memory capacities should not rely on one learning task only, but should include tasks employing both negative and positive reinforcement contingencies in order to allow valid statements regarding differences in learning capacities between rodent strains.

Sleep Enhances Recognition Memory for Conspecifics as Bound into Spatial Context

PubMed Central

Sawangjit, Anuck; Kelemen, Eduard; Born, Jan; Inostroza, Marion

2017-01-01

Social memory refers to the fundamental ability of social species to recognize their conspecifics in quite different contexts. Sleep has been shown to benefit consolidation, especially of hippocampus-dependent episodic memory whereas effects of sleep on social memory are less well studied. Here, we examined the effect of sleep on memory for conspecifics in rats. To discriminate interactions between the consolidation of social memory and of spatial context during sleep, adult Long Evans rats performed on a social discrimination task in a radial arm maze. The Learning phase comprised three 10-min sampling sessions in which the rats explored a juvenile rat presented at a different arm of the maze in each session. Then the rats were allowed to sleep (n = 18) or stayed awake (n = 18) for 120 min. During the following 10-min Test phase, the familiar juvenile rat (of the Learning phase) was presented along with a novel juvenile rat, each rat at an opposite arm of the maze. Significant social recognition memory, as indicated by preferential exploration of the novel over the familiar conspecific, occurred only after post-learning sleep, but not after wakefulness. Sleep, compared with wakefulness, significantly enhanced social recognition during the first minute of the Test phase. However, memory expression depended on the spatial configuration: Significant social recognition memory emerged only after sleep when the rat encountered the novel conspecific at a place different from that of the familiar juvenile in the last sampling session before sleep. Though unspecific retrieval-related effects cannot entirely be excluded, our findings suggest that sleep, rather than independently enhancing social and spatial aspects of memory, consolidates social memory by acting on an episodic representation that binds the memory of the conspecific together with the spatial context in which it was recently encountered. PMID:28270755

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.

Pharmacological validation of in-silico guided novel nootropic potential of Achyranthes aspera L.

PubMed

Gawande, Dinesh Yugraj; Goel, Rajesh Kumar

2015-12-04

Achyranthes aspera (A. aspera) has been used as a brain tonic in folk medicine. Although, ethnic use of medicinal plant has been basis for drug discovery from medicinal plants, but the available in-silico tools can be useful to find novel pharmacological uses of medicinal plants beyond their ethnic use. To validate in-silico prediction for novel nootropic effect of A. aspera by employing battery of tests in mice. Phytoconstituents of A. aspera reported in Dictionary of Natural Product were subjected to in-silico prediction using PASS and Pharmaexpert. The nootropic activity predicted for A. aspera was assessed using radial arm maze, passive shock avoidance and novel object recognition tests in mice. After behavioral evaluation animals were decapitated and their brains were collected and stored for estimation of glutamate levels and acetylcholinesterase activity. In-silico activity spectrum for majority of A. aspera phytoconstituents exhibited excellent prediction score for nootropic activity of this plant. A. aspera extract treatment significantly improved the learning and memory as evident by decreased working memory errors, reference memory errors and latency time in radial arm maze, step through latency in passive shock avoidance and increased recognition index in novel object recognition were observed, moreover significantly enhanced glutamate levels and reduced acetylcholinesterase activity in hippocampus and cortex were observed as compared to the saline treated group. In-silico and in-vivo results suggest that A. aspera plant may improve the learning and memory by modulating the brain glutamatergic and cholinergic neurotransmission. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Vitamin E can improve behavioral tests impairment, cell loss, and dendrite changes in rats' medial prefrontal cortex induced by acceptable daily dose of aspartame.

PubMed

Rafati, Ali; Noorafshan, Ali; Jahangir, Mahboubeh; Hosseini, Leila; Karbalay-Doust, Saied

2018-01-01

Aspartame is an artificial sweetener used in about 6000 sugar-free products. Aspartame consumption could be associated with various neurological disorders. This study aimed to evaluate the effect of aspartame onmedial Prefrontal Cortex (mPFC) as well as neuroprotective effects of vitamin E. The rats were divided into seven groups, including distilled water, corn oil, vitamin E (100mg/kg/day), and low (acceptable daily dose) and high doses of aspartame (40 and 200mg/kg/day) respectively, with or without vitamin E consumption, for 8 weeks. Behavioral tests were recorded and the brain was prepared for stereological assessments. Novel objects test and eight-arm radial maze showed impairmentoflong- and short-termmemoriesin aspartame groups. Besides, mPFC volume, infralimbic volume, neurons number, glial cells number, dendrites length per neuron,and number of spines per dendrite length were decreased by 7-61% in the rats treated with aspartame. However, neurons' number, glial cells number, and rats' performance in eight-arm radial mazes were improved by concomitant consumption of vitamin E and aspartame. Yet, the mPFC volume and infralimbic cortex were protected only in the rats receiving the low dose of aspartame+vitamin E. On the other hand, dendrites length, spines number,and novel object recognition were not protected by treatment with vitamin E+aspartame. The acceptable daily dose or higher doses of aspartame could induce memory impairments and cortical cells loss in mPFC. However, vitamin E could ameliorate some of these changes. Copyright © 2017 Elsevier GmbH. All rights reserved.

Oxidative stress induced NMDA receptor alteration leads to spatial memory deficits in temporal lobe epilepsy: ameliorative effects of Withania somnifera and Withanolide A.

PubMed

Soman, Smijin; Korah, P K; Jayanarayanan, S; Mathew, Jobin; Paulose, C S

2012-09-01

In the present study we investigate the effect of Withania somnifera (WS) root extract and Withanolide A (WA) in restoring spatial memory deficit by inhibiting oxidative stress induced alteration in glutamergic neurotransmission. We demonstrate significant cellular loss in hippocampus of epileptic rats, visualized through decreased TOPRO stained neurons. Impaired spatial memory was observed in epileptic rats after Radial arm maze test. Treatment with WS and WA has resulted in increased number of TOPRO stained neurons. Enhanced performance of epileptic rats treated with WS and WA was observed in Radial arm maze test. The antioxidant activity of WS and WA was studied using superoxide dismutase (SOD) and Catalase (CAT) assays in the hippocampus of experimental rats. The SOD activity and CAT activity decreased significantly in epileptic group, treatment with WS and WA significantly reversed the enzymatic activities to near control. Real time gene expression studies of SOD and GPx showed significant up-regulation in epileptic group compared to control. Treatment with WS and WA showed significant reversal to near control. Lipid peroxidation quantified using TBARS assay, significantly increased in epileptic rats. Treatment with WS and WA showed significant reversal to near control. NMDA receptor expression decreased in epileptic rats. The treatment with WS and WA resulted in physiological expression of NMDA receptors. This data suggests that oxidative stress effects membrane constitution resulting in decreased NMDA receptor density leading to impaired spatial memory. Treatment with WS and WA has ameliorated spatial memory deficits by enhancing antioxidant system and restoring altered NMDA receptor density.

Highly stabilized curcumin nanoparticles tested in an in vitro blood-brain barrier model and in Alzheimer's disease Tg2576 mice.

PubMed

Cheng, Kwok Kin; Yeung, Chin Fung; Ho, Shuk Wai; Chow, Shing Fung; Chow, Albert H L; Baum, Larry

2013-04-01

The therapeutic effects of curcumin in treating Alzheimer's disease (AD) depend on the ability to penetrate the blood-brain barrier. The latest nanoparticle technology can help to improve the bioavailability of curcumin, which is affected by the final particle size and stability. We developed a stable curcumin nanoparticle formulation to test in vitro and in AD model Tg2576 mice. Flash nanoprecipitation of curcumin, polyethylene glycol-polylactic acid co-block polymer, and polyvinylpyrrolidone in a multi-inlet vortex mixer, followed by freeze drying with β-cyclodextrin, produced dry nanocurcumin with mean particle size <80 nm. Nanocurcumin powder, unformulated curcumin, or placebo was orally administered to Tg2576 mice for 3 months. Before and after treatment, memory was measured by radial arm maze and contextual fear conditioning tests. Nanocurcumin produced significantly (p=0.04) better cue memory in the contextual fear conditioning test than placebo and tendencies toward better working memory in the radial arm maze test than ordinary curcumin (p=0.14) or placebo (p=0.12). Amyloid plaque density, pharmacokinetics, and Madin-Darby canine kidney cell monolayer penetration were measured to further understand in vivo and in vitro mechanisms. Nanocurcumin produced significantly higher curcumin concentration in plasma and six times higher area under the curve and mean residence time in brain than ordinary curcumin. The P(app) of curcumin and tetrahydrocurcumin were 1.8×10(-6) and 1.6×10(-5)cm/s, respectively, for nanocurcumin. Our novel nanocurcumin formulation produced highly stabilized nanoparticles with positive treatment effects in Tg2576 mice.

A Novel Heterocyclic Compound CE-104 Enhances Spatial Working Memory in the Radial Arm Maze in Rats and Modulates the Dopaminergic System

PubMed Central

Aher, Yogesh D.; Subramaniyan, Saraswathi; Shanmugasundaram, Bharanidharan; Sase, Ajinkya; Saroja, Sivaprakasam R.; Holy, Marion; Höger, Harald; Beryozkina, Tetyana; Sitte, Harald H.; Leban, Johann J.; Lubec, Gert

2016-01-01

Various psychostimulants targeting monoamine neurotransmitter transporters (MATs) have been shown to rescue cognition in patients with neurological disorders and improve cognitive abilities in healthy subjects at low doses. Here, we examined the effects upon cognition of a chemically synthesized novel MAT inhibiting compound 2-(benzhydrylsulfinylmethyl)-4-methylthiazole (named as CE-104). The efficacy of CE-104 in blocking MAT [dopamine transporter (DAT), serotonin transporter (SERT), and norepinephrine transporter] was determined using in vitro neurotransmitter uptake assay. The effect of the drug at low doses (1 and 10 mg/kg) on spatial memory was studied in male rats in the radial arm maze (RAM). Furthermore, the dopamine receptor and transporter complex levels of frontal cortex (FC) tissue of trained and untrained animals treated either with the drug or vehicle were quantified on blue native PAGE (BN-PAGE). The drug inhibited dopamine (IC50: 27.88 μM) and norepinephrine uptake (IC50: 160.40 μM), but had a negligible effect on SERT. In the RAM, both drug-dose groups improved spatial working memory during the performance phase of RAM as compared to vehicle. BN-PAGE Western blot quantification of dopamine receptor and transporter complexes revealed that D1, D2, D3, and DAT complexes were modulated due to training and by drug effects. The drug’s ability to block DAT and its influence on DAT and receptor complex levels in the FC is proposed as a possible mechanism for the observed learning and memory enhancement in the RAM. PMID:26941626

Altitude acclimatization improves submaximal cognitive performance in mice and involves an imbalance of the cholinergic system.

PubMed

Guerra-Narbona, R; Delgado-García, J M; López-Ramos, J C

2013-06-15

The aim of this work was to reveal a hypothetical improvement of cognitive abilities in animals acclimatized to altitude and performing under ground level conditions, when looking at submaximal performance, once seen that it was not possible when looking at maximal scores. We modified contrasted cognitive tasks (object recognition, operant conditioning, eight-arm radial maze, and classical conditioning of the eyeblink reflex), increasing their complexity in an attempt to find performance differences in acclimatized animals vs. untrained controls. In addition, we studied, through immunohistochemical quantification, the expression of choline acetyltransferase and acetyl cholinesterase, enzymes involved in the synthesis and degradation of acetylcholine, in the septal area, piriform and visual cortexes, and the hippocampal CA1 area of animals submitted to acute hypobaric hypoxia, or acclimatized to this simulated altitude, to find a relationship between the cholinergic system and a cognitive improvement due to altitude acclimatization. Results showed subtle improvements of the cognitive capabilities of acclimatized animals in all of the tasks when performed under ground-level conditions (although not before 24 h), in the three tasks used to test explicit memory (object recognition, operant conditioning in the Skinner box, and eight-arm radial maze) and (from the first conditioning session) in the classical conditioning task used to evaluate implicit memory. An imbalance of choline acetyltransferase/acetyl cholinesterase expression was found in acclimatized animals, mainly 24 h after the acclimatization period. In conclusion, altitude acclimatization improves cognitive capabilities, in a process parallel to an imbalance of the cholinergic system.

Analysis of behavioral asymmetries in the elevated plus-maze and in the T-maze.

PubMed

Schwarting, Rainer K W; Borta, Andreas

2005-02-15

When studying functional asymmetries in normal laboratory rats, several behavioral tests have been applied and proven their utility, including turning in rotometers or open-fields, handedness in paw usage, T-maze alternation, and others. Here, we analyzed male Wistar rats in two tests, namely the elevated plus-maze and the T-maze. In these tests, behavioral asymmetries are rather likely to occur, since the animals have to show several types of turns towards the left or right when ambulating through these environments. In a first study using the plus-maze, we provide detailed data on (A) the types of turns which the animals showed when changing their direction within arms (i.e., 180 degrees turns), and (B) the types of turns when proceeding from one arm to an adjacent one (i.e., 90 degrees turns). With respect to asymmetry, we found moderate biases in favor of the right. On the 1st day of plus-maze testing, there was a trend for more rightward turns within arms. On the 2nd day of testing, there was a trend for turns towards the right when alternating between arms of the plus-maze. In a 2nd study, we asked for asymmetries in the plus-maze in animals, which had been treated acutely with the psychostimulatory amphetamine analogue 3,4-methylene-dioxymethamphetamine (MDMA). Psychostimulants drugs, especially amphetamine, have repeatedly been used before in work on functional asymmetry, since they can enhance or reveal asymmetries in normal rats. MDMA had dose-dependent effects on activity, which affected turns within arms, and turns between arms; however, there was only sparse evidence with respect to asymmetry. Interestingly, and if at all, asymmetry was in favor of the right. Finally, we present data for behavior in the T-maze, where we used a spontaneous test version, that is, the animals could explore the maze but had no task to solve. Asymmetries were measured as turns within the start arm (180 degrees), and as left- or rightward turns between arms (90 degrees ) at the T-point of the maze. In both measures, we again obtained evidence for asymmetries in favor of the right. This work supports previous studies showing that the T-maze is suitable to analyze behavioral asymmetries in rats. In addition, it provides new evidence with respect to the elevated plus-maze, indicating that this standard tool of anxiety research may also be useful in research on behavioral asymmetries and their underlying brain mechanisms. Behavioral biases in favor of the right, as shown here, have often been reported before, especially with Wistar rats. Such biases should be taken into account, since they can serve as an approach to study brain/behavior relationships, and since they may affect the outcome of physiological manipulations or behavioral trainings.

Evaluation of the rewarding properties of nicotine and caffeine by implementation of a five-choice conditioned place preference task in zebrafish.

PubMed

Faillace, M P; Pisera-Fuster, A; Bernabeu, R

2018-06-08

The rewarding properties of drugs in zebrafish can be studied using the conditioned place preference (CPP) paradigm. Most devices that have been used for CPP consist of two-half tanks with or without a central chamber. Here we evaluated the rewarding effects of nicotine and caffeine using a tank with five arms distributed radially from a central chamber that we have denoted Fish Tank Radial Maze (FTRM). Zebrafish were trained to associate nicotine or caffeine with a coloured arm. In testing sessions to assess CPP induction, between two and five different arms were available to explore. We found that when offering the two arms, one of them associated to the drug mediating conditioning for 14 days, zebrafish showed nicotine-induced CPP but not caffeine-induced CPP. When zebrafish had the option to explore drug-paired arms together with new coloured arms as putative distractors, the nicotine-CPP strength was maintained for at least three days. The presence of novel environments induced caffeine-CPP, which was still positive after three days of testing sessions. Complementary behavioural data supported these findings. Nicotine-CPP was prevented by the histone deacetylase inhibitor phenylbutyrate administered during conditioning; however, there were no effects on caffeine-CPP. The specific acetylation of lysine 9 in histone 3 (H3-K9) was increased in nicotine-conditioned zebrafish brains. This study suggests that novel environmental cues facilitate drug-environment associations, and hence, the use of drugs of abuse. Copyright © 2018 Elsevier Inc. All rights reserved.

Excitotoxic lesions of the infralimbic, but not prelimbic cortex facilitate reversal of appetitive discriminative context conditioning: the role of the infralimbic cortex in context generalization

PubMed Central

Ashwell, Rachel; Ito, Rutsuko

2014-01-01

The prelimbic and infralimbic regions of the rat medial prefrontal cortex (mPFC) are important components of the limbic cortico-striatal circuit, receiving converging projections from the hippocampus (HPC) and amygdala. Mounting evidence points to these regions having opposing roles in the regulation of the expression of contextual fear and context-induced cocaine-seeking. To investigate this functional differentiation in motivated behavior further, this study employed a novel radial maze task previously shown to be dependent on the integrity of the hippocampus and its functional connection to the nucleus accumbens (NAc) shell, to investigate the effects of selective excitotoxic lesions of the prelimbic (PL) and infralimbic (IL) upon the spatial contextual control over reward learning. To this end, rats were trained to develop discriminative responding towards a reward-associated discrete cue presented in three out of six spatial locations (3 arms out of 6 radial maze arms), and to avoid the same discrete cue presented in the other three spatial locations. Once acquired, the reward contingencies of the spatial locations were reversed, such that responding to the cue presented in a previously rewarded location was no longer rewarded. Furthermore, the acquisition of spatial learning was probed separately using conditioned place preference (CPP) and the monitoring of arm selection at the beginning of each training session. Lesions of the PL transiently attenuated the acquisition of the initial cue approach training and spatial learning, while leaving reversal learning intact. In contrast, IL lesions led to a significantly superior performance of spatial context-dependent discriminative cue approach and reversal learning, in the absence of a significant preference for the new reward-associated spatial locations. These results indicate that the PL and IL have functionally dissociative, and potentially opposite roles in the regulation of spatial contextual control over appetitive learning. PMID:24616678

Long-term effects of chronic intermittent ethanol exposure in adolescent and adult rats: radial-arm maze performance and operant food reinforced responding.

PubMed

Risher, Mary-Louise; Fleming, Rebekah L; Boutros, Nathalie; Semenova, Svetlana; Wilson, Wilkie A; Levin, Edward D; Markou, Athina; Swartzwelder, H Scott; Acheson, Shawn K

2013-01-01

Adolescence is not only a critical period of late-stage neurological development in humans, but is also a period in which ethanol consumption is often at its highest. Given the prevalence of ethanol use during this vulnerable developmental period we assessed the long-term effects of chronic intermittent ethanol (CIE) exposure during adolescence, compared to adulthood, on performance in the radial-arm maze (RAM) and operant food-reinforced responding in male rats. Male Sprague Dawley rats were exposed to CIE (or saline) and then allowed to recover. Animals were then trained in either the RAM task or an operant task using fixed- and progressive- ratio schedules. After baseline testing was completed all animals received an acute ethanol challenge while blood ethanol levels (BECs) were monitored in a subset of animals. CIE exposure during adolescence, but not adulthood decreased the amount of time that animals spent in the open portions of the RAM arms (reminiscent of deficits in risk-reward integration) and rendered animals more susceptible to the acute effects of an ethanol challenge on working memory tasks. The operant food reinforced task showed that these effects were not due to altered food motivation or to differential sensitivity to the nonspecific performance-disrupting effects of ethanol. However, CIE pre-treated animals had lower BEC levels than controls during the acute ethanol challenges indicating persistent pharmacokinetic tolerance to ethanol after the CIE treatment. There was little evidence of enduring effects of CIE alone on traditional measures of spatial and working memory. These effects indicate that adolescence is a time of selective vulnerability to the long-term effects of repeated ethanol exposure on neurobehavioral function and acute ethanol sensitivity. The positive and negative findings reported here help to further define the nature and extent of the impairments observed after adolescent CIE and provide direction for future research.

Toward early estimation and treatment of addiction vulnerability: radial arm maze and N-acetyl cysteine before cocaine sensitization or nicotine self-administration in neonatal ventral hippocampal lesion rats.

PubMed

Rao, Kalyan N; Sentir, Alena M; Engleman, Eric A; Bell, Richard L; Hulvershorn, Leslie A; Breier, Alan; Chambers, R Andrew

2016-12-01

Prefrontal cortical (PFC)-hippocampal-striatal circuits, interconnected via glutamatergic signaling, are dysfunctional in mental illnesses that involve addiction vulnerability. In healthy and neurodevelopmentally altered rats, we examined how Radial Arm Maze (RAM) performance estimates addiction vulnerability, and how starting a glutamatergic modulating agent, N-acetyl cysteine (NAC) in adolescence alters adult mental illness and/or addiction phenotypes. Rats with neonatal ventral hippocampal lesions (NVHL) vs. SHAM-operated controls were randomized to NAC vs. saline in adolescence followed by cognitive testing (RAM) in early adulthood and then cocaine behavioral sensitization (experiment 1; n = 80) or nicotine self-administration (experiment 2; n = 12). In experiment 1, NVHL rats showed over-consumption of food (Froot-Loops (FL)) baiting the RAM with poor working memory (low-arm entries to repeat (ETR)), producing an elevated FL to ETR ratio ("FLETR"; p < 0.001). FLETR was the best linear estimator (compared to FL or ETR) of magnitude of long-term cocaine sensitization (R 2  = 0.14, p < 0.001). NAC treatment did not alter FL, ETR, FLETR, or cocaine sensitization. In experiment 2, FLETR also significantly and uniquely correlated with subsequent drug seeking during nicotine-induced reinstatement after extinction of nicotine self-administration (R 2  = 0.47, p < 0.01). NAC did not alter RAM performance, but significantly reversed NVHL-induced increases in nicotine seeking during extinction and reinstatement. These findings demonstrate the utility of animal models of mental illness with addiction vulnerability for developing novel diagnostic measures of PFC-hippocampal-striatal circuit dysfunction that may reflect addiction risk. Such tests may direct pharmacological treatments prior to adulthood and addictive drug exposure, to prevent or treat adult addictions.

Modified radial v/s biatrial maze for atrial fibrillation in rheumatic valvular heart surgery.

PubMed

Sayed, Sajid A; Katewa, Ashish; Srivastava, Vivek; Jana, Sujit; Patwardhan, Anil M

2014-01-01

Atrial fibrillation (AF) is commonest sustained atrial arrhythmia producing high morbidity. Although Cox's Maze III procedure cures AF in majority, reduced atrial transport function (ATF) is a concern. Radial approach with ablation lines radial from sinus node towards atrioventricular annulii and parallel to atrial coronary arteries, has shown better ATF. Single blind open randomized prospective study of 80 patients was undertaken in two groups (40 each) of modified Cox's maze III and modified radial approach, to evaluate conversion to normal sinus rhythm (NSR) and ATF. Patients undergoing surgery for rheumatic valvular heart disease with continuous AF were prospectively randomized. Ablation lines were created with radiofrequency (RF) bipolar coagulation with cryoablation for the isthmal lesions and coronary sinus. Results were compared at 6 months and ATF was evaluated by atrial filling fraction (AFF) and A/E ratio on echocardiography. The rate of conversion to NSR in both groups was statistically insignificant by Fisher's exact test (p > 0.05). ATF was better in modified radial approach compared to modified Cox's Maze III (A/E compared by unpaired t test:0.52 ± 0.08 v/s 0.36 ± 0.10; p < 0.05. AFF compared using Mann Whitney U test: median AFF for radial group was 23 v/s 20 for biatrial group; p < 0.05). In patients with AF undergoing rheumatic valvular surgery, radiofrequency radial approach is as effective as modified Cox's maze III for conversion to NSR with better atrial transport function. Copyright © 2014 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.

Models of anxiety: responses of mice to novelty and open spaces in a 3D maze.

PubMed

Ennaceur, A; Michalikova, S; van Rensburg, R; Chazot, P L

2006-11-01

The present report describes the emotional responses of different strains of mice to exposure to a novel open space model of anxiety using a 3D spatial navigation task. The 3D maze is modification of the radial maze with flexible arms that can be raised above or lowered below the horizontal level of a central platform. To access the arms animals need to cross a bridge linking the arms to the central platform. In this model, mice are exposed to novelty in an unfamiliar open space setting with no safe alternative. Fear from novelty is compounded with the need to explore. The drive to escape and the drive to approach are intermingled making this open space model radically different from the current models of anxiety which provide animals with the choice between safe and anxiogenic spaces. In a series of experiments, we examined the behaviour of different groups of mice from C57, C3H, CD1 and Balb/c strains. In the first experiment, different groups of C57 mice were tested in one of the three arms configurations. In the second experiment, C57 mice were compared to C3H mice. In the third experiment, C57 mice were compared to CD1 and Balb/c mice in the raised arm configuration over three successive sessions. In the fourth experiment, we examined the behaviour of C57 mice in the lowered arm configuration with an open and an enclosed central. In the final experiment, we examined the difference between C57 and C3H mice of both genders. Using several spatio-temporal parameters of the transition responses between central platform, bridges and arms, we have been able to show consistent results demonstrating significant differences between C57 and C3H mice, and between Balb/c and both C57 and CD1 mice. C3H appear more anxious than C57 mice, and Balb/c mice seem more anxious than C57 and CD1 mice. We also observed significant differences between sexes in C3H mice but not in C57 mice. C3H male mice appear more anxious than C3H female mice and than both C57 male and female mice. In the lowered arm configuration with an enclosed central platform, C57 mice took longer time to make a first entry to an arm, made more visits to bridges before first entry to an arm and required longer time between re-entries to arms, spent longer time on the central platform and shorter time on arms compared to mice in the other arm configurations. They also made frequent entries to the centre and bridges compared to mice in the lowered arm with an open central platform. These results demonstrate not only the sensitivity of the parameters of the test but also the consistencies and concordances of the results which make this 3D maze a valuable new tool in the study of the underlying neural mechanisms of anxiety responses in addition to learning and memory, and in assessing the effects of potential anxiolytic drugs. In this report we examine methodological issues related to the design of animal behavioural paradigms and question the value and the construct validity of the current models of human anxiety.

A test of the reward-value hypothesis.

PubMed

Smith, Alexandra E; Dalecki, Stefan J; Crystal, Jonathon D

2017-03-01

Rats retain source memory (memory for the origin of information) over a retention interval of at least 1 week, whereas their spatial working memory (radial maze locations) decays within approximately 1 day. We have argued that different forgetting functions dissociate memory systems. However, the two tasks, in our previous work, used different reward values. The source memory task used multiple pellets of a preferred food flavor (chocolate), whereas the spatial working memory task provided access to a single pellet of standard chow-flavored food at each location. Thus, according to the reward-value hypothesis, enhanced performance in the source memory task stems from enhanced encoding/memory of a preferred reward. We tested the reward-value hypothesis by using a standard 8-arm radial maze task to compare spatial working memory accuracy of rats rewarded with either multiple chocolate or chow pellets at each location using a between-subjects design. The reward-value hypothesis predicts superior accuracy for high-valued rewards. We documented equivalent spatial memory accuracy for high- and low-value rewards. Importantly, a 24-h retention interval produced equivalent spatial working memory accuracy for both flavors. These data are inconsistent with the reward-value hypothesis and suggest that reward value does not explain our earlier findings that source memory survives unusually long retention intervals.

Dietary uridine enhances the improvement in learning and memory produced by administering DHA to gerbils.

PubMed

Holguin, Sarah; Martinez, Joseph; Chow, Camille; Wurtman, Richard

2008-11-01

This study examined the effects on cognitive behaviors of giving normal adult gerbils three compounds, normally in the circulation, which interact to increase brain phosphatides, synaptic proteins, dendritic spines, and neurotransmitter release. Animals received supplemental uridine (as its monophosphate, UMP; 0.5%) and choline (0.1%) via the diet, and docosahexaenoic acid (DHA; 300 mg/kg/day) by gavage, for 4 wk, and then throughout the subsequent period of behavioral training and testing. As shown previously, giving all three compounds caused highly significant (P<0.001) increases in total brain phospholipids and in each major phosphatide; giving DHA or UMP (plus choline) produced smaller increases in some of the phosphatides. DHA plus choline improved performance on the four-arm radial maze, T-maze, and Y-maze tests; coadministering UMP further enhanced these increases. (Uridine probably acts by generating both CTP, which can be limiting in phosphatide synthesis, and UTP, which activates P2Y receptors coupled to neurite outgrowth and protein synthesis. All three compounds also act by enhancing the substrate-saturation of phosphatide-synthesizing enzymes.) These findings demonstrate that a treatment that increases synaptic membrane content can enhance cognitive functions in normal animals.

Intact working memory in the absence of forebrain neuronal glycine transporter 1

PubMed Central

Dubroqua, Sylvain; Serrano, Lucas; Boison, Detlev; Feldon, Joram; Gargiulo, Pascual A.; Yee, Benjamin K.

2012-01-01

Glycine transporter 1 (GlyT1) is a potential pharmacological target to ameliorate memory deficits attributable to N-methyl-d-aspartate receptor (NMDAR) hypofunction. Disruption of glycine-reuptake near excitatory synapses is expected to enhance NMDAR function by increasing glycine-B site occupancy. Genetic models with conditional GlyT1 deletion restricted to forebrain neurons have yielded several promising promnesic effects, yet its impact on working memory function remains essentially unanswered because a previous attempt had yielded un-interpretable outcomes. The present study clarified this important outstanding lacuna using a within-subject multi-paradigm approach. Here, a consistent lack of effects was convincingly demonstrated across three working memory test paradigms – the radial arm maze, the cheeseboard maze, and the water maze. These null outcomes contrasted with the phenotype of enhanced working memory performance seen in mutant mice with GlyT1 deletion extended to cortical/hippocampal glial cells. It follows that glial-based GlyT1 might be more closely linked to the modulation of working memory function, and raises the possibility that neuronal and glial GlyT1 may regulate cognitive functions via dissociable mechanisms. PMID:22342492

Disruption of hippocampus-regulated behavioural and cognitive processes by heterozygous constitutive deletion of SynGAP.

PubMed

Muhia, Mary; Yee, Benjamin K; Feldon, Joram; Markopoulos, Foivos; Knuesel, Irene

2010-02-01

The brain-specific Ras/Rap-GTPase activating protein (SynGAP) is a prime candidate linking N-methyl-d-aspartate receptors to the regulation of the ERK/MAP kinase signalling cascade, suggested to be essential for experience-dependent synaptic plasticity. Here, we evaluated the behavioural phenotype of SynGAP heterozygous knockout mice (SG(+/-)), expressing roughly half the normal levels of SynGAP. In the cognitive domain, SG(+/-) mice demonstrated severe working and reference memory deficits in the radial arm maze task, a mild impairment early in the transfer test of the water maze task, and a deficiency in spontaneous alternation in an elevated T-maze. In the non-cognitive domain, SG(+/-) mice were hyperactive in the open field and appeared less anxious in the elevated plus maze test. In contrast, object recognition memory performance was not impaired in SG(+/-) mice. The reduction in SynGAP thus resulted in multiple behavioural traits suggestive of aberrant cognitive and non-cognitive processes normally mediated by the hippocampus. Immunohistochemical evaluation further revealed a significant reduction in calbindin-positive interneurons in the hippocampus and doublecortin-positive neurons in the dentate gyrus of adult SG(+/-) mice. Heterozygous constitutive deletion of SynGAP is therefore associated with notable behavioural as well as morphological phenotypes indicative of hippocampal dysfunction. Any suggestion of a possible causal link between them however remains a matter for further investigation.

Chronic infusion of GABA and saline into the nucleus basalis magnocellularis of rats: II. Cognitive impairments.

PubMed

Majchrzak, M; Brailowsky, S; Will, B

1990-02-12

In order to assess sensorimotor and/or cognitive modifications following chronic inhibition of nucleus basalis magnocellularis (NBM) neurons, rats trained in two radial maze paradigms (the classical version of the test and a modified version introducing a one-hour delay between the fourth and the fifth choice) received chronic infusion of gamma-aminobutyric acid (GABA) into the NBM area. GABA (10 and 50 micrograms/microliters/h) was infused for 3 days into the NBM contralateral to their preferred turning direction in the radial maze. Simultaneously, saline (NaCl 0.9%; 1 microliter/h) was infused into the contralateral NBM. GABA and saline infusions were alternated for the subsequent 3-day period. One week later, we investigated the rats' ability to learn a multiple trial passive avoidance task. At the dose of 50 micrograms/microliters, GABA infusion produced (1) a turning bias ipsilateral to the side first infused with GABA, (2) transitory cognitive impairments in radial maze tasks and (3) a deficit in the acquisition of the passive avoidance task. At the dose of 10 micrograms/microliters, the same behavioral deficits were observed except that (1) the turning bias was reversed by the contralateral GABA infusion and (2) cognitive impairments in the radial maze were observed only when a delay was inserted between the fourth and the fifth choice. Histologically, we found a dose-dependent gliosis in the NBM area first infused with GABA. These data suggest a reactivity of the NBM to GABAergic manipulations and the intervention of this structure in both sensorimotor and cognitive processes involved in the radial maze paradigms.

Radial Maze Analog for Pigeons: Evidence for Flexible Coding Strategies May Result from Faulty Assumptions

ERIC Educational Resources Information Center

Gipson, Cassandra D.; DiGian, Kelly A.; Miller, Holly C.; Zentall, Thomas R.

2008-01-01

Previous research with the radial maze has found evidence that rats can remember both places that they have already been (retrospective coding) and places they have yet to visit (prospective coding; Cook, R. G., Brown, M. F., & Riley, D. A. (1985). Flexible memory processing by rats: Use of prospective and retrospective information in the radial…

MK-801 increases the baseline level of anxiety in mice introduced to a spatial memory task without prior habituation.

PubMed

Ennaceur, A; Michalikova, S; van Rensburg, R; Chazot, P L

2011-01-01

C57BL/6J mice were introduced to a nine arm radial maze without prior habituation and trained in the acquisition of a working memory task in 16 sessions, one session per day. In this maze mice need to climb onto an upward inclined bridge in order to reach and cross onto an arm. They received in each session an i.p. injection of MK-801 (0.1 mg/kg) 30 min before training or immediately after training. MK-801 pre-treated mice made significantly more entries onto the bridges, fewer entries onto the arms and took significantly longer time to make a first arm visit compared to saline and MK-801 post-treated mice during the first 3 session blocks (4 sessions per block). These results indicate that MK-801 induced anxiety which was extended throughout the first 3 session blocks. MK-801 pre-treated mice made also significantly more errors and required more sessions to reach the criterion compared to saline and MK-801 post-treated mice. Administration of MK-801 after training did not affect the acquisition of the task. The present results indicate that MK-801 pre-treatment impaired the acquisition of a spatial task and this can be accounted for by its effect on the baseline level of anxiety which was elevated. The introduction of mice to the acquisition of the task without prior habituation demonstrates that a drug treatment can affect learning and memory by increasing and/or prolonging anxiety. Such effect may be confounded with learning and memory performance and not detected with pre-habituation training procedures, particularly when the number of sessions is determined a-priori. Copyright © 2011 Elsevier Ltd. All rights reserved.

The VMAT-2 inhibitor tetrabenazine alters effort-related decision making as measured by the T-maze barrier choice task: reversal with the adenosine A2A antagonist MSX-3 and the catecholamine uptake blocker bupropion.

PubMed

Yohn, Samantha E; Thompson, Christian; Randall, Patrick A; Lee, Christie A; Müller, Christa E; Baqi, Younis; Correa, Mercè; Salamone, John D

2015-04-01

Depressed people show effort-related motivational symptoms, such as anergia, retardation, lassitude, and fatigue. Animal tests can model these motivational symptoms, and the present studies characterized the effort-related effects of the vesicular monoamine transport (VMAT-2) inhibitor tetrabenazine. Tetrabenazine produces depressive symptoms in humans and, at low doses, preferentially depletes dopamine. The current studies investigated the effects of tetrabenazine on effort-based decision making using the T-maze barrier task. Rats were tested in a T-maze in which the choice arms of the maze contain different reinforcement densities, and under some conditions, a vertical barrier was placed in the high-density arm to provide an effort-related challenge. The first experiment assessed the effects of tetrabenazine under different maze conditions: a barrier in the arm with 4 food pellets and 2 pellets in the no barrier arm (4-2 barrier), 4 pellets in one arm and 2 pellets in the other with no barrier in either arm (no barrier), and 4 pellets in the barrier arm with no pellets in the other (4-0 barrier). Tetrabenazine (0.25-0.75 mg/kg IP) decreased selection of the high cost/high reward arm when the barrier was present, but had no effect on choice under the no barrier and 4-0 barrier conditions. The effects of tetrabenazine on barrier climbing in the 4-2 condition were reversed by the adenosine A2A antagonist MSX-3 and the catecholamine uptake inhibitor and antidepressant bupropion. These studies have implications for the development of animal models of the motivational symptoms of depression and other disorders.

Influence of spatial and temporal manipulations on the anxiolytic efficacy of chlordiazepoxide in mice previously exposed to the elevated plus-maze.

PubMed

Holmes, A; Rodgers, R J

1999-11-01

It has been widely reported that the anxiolytic efficacy of benzodiazepines in the elevated plus-maze test is abolished in subjects (rats or mice) that have been given a single prior undrugged experience of the test apparatus. The present series of experiments was designed to further characterise the key experiential determinants of this intriguing phenomenon in Swiss Webster mice. Using a standard 5 min test duration for both trials, Experiment 1 confirmed the anxiolytic efficacy of chlordiazepoxide (CDP; 5-20 mg/kg) in mice naive to the plus-maze, but a virtual elimination of drug effects in animals that had been pre-exposed to the maze 24 h earlier. Experiments 2 and 3 demonstrated that, while extending the duration of initial exposure to 10 min did not prevent the loss of CDP (10 mg/kg) efficacy in a standard-duration second trial, increasing the duration of both trials reinstated an anxiolytic profile for the compound. Finally, although trial 1 confinement to an open arm did not compromise CDP efficacy when animals were subsequently allowed to freely explore the maze (Experiment 4), closed arm confinement during initial exposure abolished the drug's anxiolytic action upon retest (Experiment 5). In contrast to previous findings in rats, these data suggest that the experientially induced loss of benzodiazepine efficacy in the mouse plus-maze depends rather critically upon prior discovery and exploration of relatively safe areas of the maze (i.e. closed arms). Results are discussed in relation to the hypothesis that the absence of an anxiolytic response to benzodiazepines in plus-maze-experienced subjects reflects the acquisition of an open arm phobia during trial 1.

Cerebellar contribution to spatial event processing: involvement in procedural and working memory components.

PubMed

Mandolesi, L; Leggio, M G; Graziano, A; Neri, P; Petrosini, L

2001-12-01

Spatial function is one of the cognitive functions altered in the presence of cerebellar lesions. We investigated the cerebellar contribution to the acquisition of spatial procedural and working memory components by means of a radial maze. To establish whether a cerebellar lesion would cause a deficit in solving the radial maze, a first experiment was carried out by using a full-baited maze procedure in different experimental groups, with or without cerebellar lesion and with or without pretraining. Non-pretrained hemicerebellectomized (HCbed) animals exhibited impaired performances in all (motor, spatial and procedural) task aspects. Pre-trained HCbed animals performed similarly to control animals in the task aspects linked to the processing of spatial and procedural factors. To distinguish procedural from working memory components, a forced-choice paradigm of the radial maze was used in the second experiment. Non-pretrained HCbed rats continued to make a lot of errors and show severe perseverative tendencies, already observed in the first experiment, supporting a specific cerebellar role in acquiring new behaviours and in modifying them in relation to the context. Interestingly, hindered from putting the acquired explorative patterns into action and compelled to use only working memory abilities, the pretrained HCbed group exhibited a dramatic worsening of performance. In conclusion, the present findings demonstrate that cerebellar damage induces a specific behaviour in radial maze tasks, characterized by an inflexible use of the procedures (if indeed any procedure was acquired before the lesion) and by a severe impairment in working memory processes.

The shift from a response strategy to object-in-place strategy during learning is accompanied by a matching shift in neural firing correlates in the hippocampus.

PubMed

Lee, Inah; Kim, Jangjin

2010-08-01

Hippocampal-dependent tasks often involve specific associations among stimuli (including egocentric information), and such tasks are therefore prone to interference from irrelevant task strategies before a correct strategy is found. Using an object-place paired-associate task, we investigated changes in neural firing patterns in the hippocampus in association with a shift in strategy during learning. We used an object-place paired-associate task in which a pair of objects was presented in two different arms of a radial maze. Each object was associated with reward only in one of the arms, thus requiring the rats to consider both object identity and its location in the maze. Hippocampal neurons recorded in CA1 displayed a dynamic transition in their firing patterns during the acquisition of the task across days, and this corresponded to a shift in strategy manifested in behavioral data. Specifically, before the rats learned the task, they chose an object that maintained a particular egocentric relationship with their body (response strategy) irrespective of the object identity. However, as the animal acquired the task, it chose an object according to both its identity and the associated location in the maze (object-in-place strategy). We report that CA1 neurons in the hippocampus changed their prospective firing correlates according to the dominant strategy (i.e., response versus object-in-place strategy) employed at a given stage of learning. The results suggest that neural firing pattern in the hippocampus is heavily influenced by the task demand hypothesized by the animal and the firing pattern changes flexibly as the perceived task demand changes.

Hippocampal activation and memory performance in schizophrenia depend on strategy use in a virtual maze.

PubMed

Wilkins, Leanne K; Girard, Todd A; Herdman, Katherine A; Christensen, Bruce K; King, Jelena; Kiang, Michael; Bohbot, Veronique D

2017-10-30

Different strategies may be spontaneously adopted to solve most navigation tasks. These strategies are associated with dissociable brain systems. Here, we use brain-imaging and cognitive tasks to test the hypothesis that individuals living with Schizophrenia Spectrum Disorders (SSD) have selective impairment using a hippocampal-dependent spatial navigation strategy. Brain activation and memory performance were examined using functional magnetic resonance imaging (fMRI) during the 4-on-8 virtual maze (4/8VM) task, a human analog of the rodent radial-arm maze that is amenable to both response-based (egocentric or landmark-based) and spatial (allocentric, cognitive mapping) strategies to remember and navigate to target objects. SSD (schizophrenia and schizoaffective disorder) participants who adopted a spatial strategy performed more poorly on the 4/8VM task and had less hippocampal activation than healthy comparison participants using either strategy as well as SSD participants using a response strategy. This study highlights the importance of strategy use in relation to spatial cognitive functioning in SSD. Consistent with a selective-hippocampal dependent deficit in SSD, these results support the further development of protocols to train impaired hippocampal-dependent abilities or harness non-hippocampal dependent intact abilities. Copyright © 2017 Elsevier B.V. All rights reserved.

Does Chronic Unpredictable Stress during Adolescence Affect Spatial Cognition in Adulthood?

PubMed

Chaby, Lauren E; Sheriff, Michael J; Hirrlinger, Amy M; Lim, James; Fetherston, Thomas B; Braithwaite, Victoria A

2015-01-01

Spatial abilities allow animals to retain and cognitively manipulate information about their spatial environment and are dependent upon neural structures that mature during adolescence. Exposure to stress in adolescence is thought to disrupt neural maturation, possibly compromising cognitive processes later in life. We examined whether exposure to chronic unpredictable stress in adolescence affects spatial ability in late adulthood. We evaluated spatial learning, reference and working memory, as well as long-term retention of visuospatial cues using a radial arm water maze. We found that stress in adolescence decreased the rate of improvement in spatial learning in adulthood. However, we found no overall performance impairments in adult reference memory, working memory, or retention caused by adolescent-stress. Together, these findings suggest that adolescent-stress may alter the strategy used to solve spatial challenges, resulting in performance that is more consistent but is not refined by incorporating available spatial information. Interestingly, we also found that adolescent-stressed rats showed a shorter latency to begin the water maze task when re-exposed to the maze after an overnight delay compared with control rats. This suggests that adolescent exposure to reoccurring stressors may prepare animals for subsequent reoccurring challenges. Overall, our results show that stress in adolescence does not affect all cognitive processes, but may affect cognition in a context-dependent manner.

Does Chronic Unpredictable Stress during Adolescence Affect Spatial Cognition in Adulthood?

PubMed Central

Chaby, Lauren E.; Sheriff, Michael J.; Hirrlinger, Amy M.; Lim, James; Fetherston, Thomas B.; Braithwaite, Victoria A.

2015-01-01

Spatial abilities allow animals to retain and cognitively manipulate information about their spatial environment and are dependent upon neural structures that mature during adolescence. Exposure to stress in adolescence is thought to disrupt neural maturation, possibly compromising cognitive processes later in life. We examined whether exposure to chronic unpredictable stress in adolescence affects spatial ability in late adulthood. We evaluated spatial learning, reference and working memory, as well as long-term retention of visuospatial cues using a radial arm water maze. We found that stress in adolescence decreased the rate of improvement in spatial learning in adulthood. However, we found no overall performance impairments in adult reference memory, working memory, or retention caused by adolescent-stress. Together, these findings suggest that adolescent-stress may alter the strategy used to solve spatial challenges, resulting in performance that is more consistent but is not refined by incorporating available spatial information. Interestingly, we also found that adolescent-stressed rats showed a shorter latency to begin the water maze task when re-exposed to the maze after an overnight delay compared with control rats. This suggests that adolescent exposure to reoccurring stressors may prepare animals for subsequent reoccurring challenges. Overall, our results show that stress in adolescence does not affect all cognitive processes, but may affect cognition in a context-dependent manner. PMID:26580066

Behavioral deficits and cholinergic pathway abnormalities in male Sanfilippo B mice.

PubMed

Kan, Shih-Hsin; Le, Steven Q; Bui, Quang D; Benedict, Braeden; Cushman, Jesse; Sands, Mark S; Dickson, Patricia I

2016-10-01

Sanfilippo B syndrome is a progressive neurological disorder caused by inability to catabolize heparan sulfate glycosaminoglycans. We studied neurobehavior in male Sanfilippo B mice and heterozygous littermate controls from 16 to 20 weeks of age. Affected mice showed reduced anxiety, with a decrease in the number of stretch-attend postures during the elevated plus maze (p=0.001) and an increased tendency to linger in the center of an open field (p=0.032). Water maze testing showed impaired spatial learning, with reduced preference for the target quadrant (p=0.01). In radial arm maze testing, affected mice failed to achieve above-chance performance in a win-shift working memory task (t-test relative to 50% chance: p=0.289), relative to controls (p=0.037). We found a 12.4% reduction in mean acetylcholinesterase activity (p<0.001) and no difference in choline acetyltransferase activity or acetylcholine in whole brain of affected male animals compared to controls. Cholinergic pathways are affected in adult-onset dementias, including Alzheimer disease. Our results suggest that male Sanfilippo B mice display neurobehavioral deficits at a relatively early age, and that as in adult dementias, they may display deficits in cholinergic pathways. Copyright © 2016 Elsevier B.V. All rights reserved.

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…

Spatial Memory in the Progeny of Rats Subjected to Different Types of Experimental Preeclampsia.

PubMed

Perfilova, V N; Zhakupova, G A; Lashchenova, L I; Lebedeva, S A; Tyurenkov, I N

2016-09-01

Spatial memory was studied in 2-month-old offspring of rats subjected to different types of experimental preeclampsia (replacement of drinking water with 1.8% NaCl from day 1 to 21 of gestation or intraperitoneal administration of non-selective NO-synthase inhibitor L-NAME to pregnant rats in a daily dose of 25 mg/kg for 7 days on gestation days 14-20). Spatial memory was evaluated in an elevated 8-arm radial maze. Both types of experimental preeclampsia impaired spatial (long-term and short-term) memory and can be used in the development of drugs correcting negative effects of this pregnancy complication on memory.

Characterization of the rat exploratory behavior in the elevated plus-maze with Markov chains.

PubMed

Tejada, Julián; Bosco, Geraldine G; Morato, Silvio; Roque, Antonio C

2010-11-30

The elevated plus-maze is an animal model of anxiety used to study the effect of different drugs on the behavior of the animal. It consists of a plus-shaped maze with two open and two closed arms elevated 50cm from the floor. The standard measures used to characterize exploratory behavior in the elevated plus-maze are the time spent and the number of entries in the open arms. In this work, we use Markov chains to characterize the exploratory behavior of the rat in the elevated plus-maze under three different conditions: normal and under the effects of anxiogenic and anxiolytic drugs. The spatial structure of the elevated plus-maze is divided into squares, which are associated with states of a Markov chain. By counting the frequencies of transitions between states during 5-min sessions in the elevated plus-maze, we constructed stochastic matrices for the three conditions studied. The stochastic matrices show specific patterns, which correspond to the observed behaviors of the rat under the three different conditions. For the control group, the stochastic matrix shows a clear preference for places in the closed arms. This preference is enhanced for the anxiogenic group. For the anxiolytic group, the stochastic matrix shows a pattern similar to a random walk. Our results suggest that Markov chains can be used together with the standard measures to characterize the rat behavior in the elevated plus-maze. Copyright © 2010 Elsevier B.V. All rights reserved.

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. PMID:27806864

Sheep laterality.

PubMed

Anderson, Dean M; Murray, Leigh W

2013-01-01

Turning preferences among 309 white-faced ewes were individually evaluated in an enclosed, artificially lit T-maze, followed by each ewe choosing either a right or left return alley to return to peers. Data recorded included time in the start box, time in the T-maze, exit arm chosen to leave the T-maze, and return alley. Right and left arms of the T-maze were chosen 65.7% and 34.3% of the time, respectively, while right and left return alleys were chosen 32.4% and 67.6%, respectively. Exit arm and return alley were not independently chosen (p <.0001), with observed counts being higher than expected under independence when ewes made the same choice for exit and alley (RR or LL turn patterns) and being lower than expected for alternating choices (RL or LR). Out of the 309 ewes, 28.2% and 30.1% chose RR and LL turn patterns, respectively, while 37.5% chose the RL turn pattern, but only 13 (4.2%) chose the LR turning pattern. Overall, ewes that initially turned right when presented a second turning opportunity had a slight preference to alternate their turning direction, while ewes that initially turned left tended to continue turning left when given another chance to turn. Exit arm and return alley laterality was not related (α =.05) to time of day the test was administered, ewe's age or genetics, most recent liveweight, or most recent shorn fleece weight. The mean time spent in the start box (21 s) was not related to exit arm (p =.947) or return alley (p =.779). Mean time (15 s) spent in the T-maze was not related to exit arm (p =.086) or return alley (p =.952). More research will be required to understand sheep turning laterality and how it can impact working facilities and research equipment.

Small-scale spatial cognition in pigeons.

PubMed

Cheng, Ken; Spetch, Marcia L; Kelly, Debbie M; Bingman, Verner P

2006-05-01

Roberts and Van Veldhuizen's [Roberts, W.A., Van Veldhuizen, N., 1985. Spatial memory in pigeons on the radial maze. J. Exp. Psychol.: Anim. Behav. Proc. 11, 241-260] study on pigeons in the radial maze sparked research on landmark use by pigeons in lab-based tasks as well as variants of the radial-maze task. Pigeons perform well on open-field versions of the radial maze, with feeders scattered on the laboratory floor. Pigeons can also be trained to search precisely for buried food. The search can be based on multiple landmarks, but is sometimes controlled by just one or two landmarks, with the preferred landmarks varying across individuals. Findings are similar in landmark-based searching on a computer monitor and on a lab floor, despite many differences between the two kinds of tasks. A number of general learning principles are found in landmark-based searching, such as cue competition, generalization and peak shift, and selective attention. Pigeons also learn the geometry of the environment in which they are searching. Neurophysiological studies have implicated the hippocampal formation (HF) in avian spatial cognition, with the right hippocampus hypothesized to play a more important role in the spatial recognition of goal locations. Most recently, single-cell recording from the pigeon's hippocampal formation has revealed cells with different properties from the classic 'place' cells of rats, as well as differences in the two sides of the hippocampus.

Effects of Astaxanthin and Docosahexaenoic-Acid-Acylated Astaxanthin on Alzheimer's Disease in APP/PS1 Double-Transgenic Mice.

PubMed

Che, Hongxia; Li, Qian; Zhang, Tiantian; Wang, Dandan; Yang, Lu; Xu, Jie; Yanagita, Teruyoshi; Xue, Changhu; Chang, Yaoguang; Wang, Yuming

2018-05-16

Alzheimer's disease (AD) is a progressive neurodegenerative disorder with the characteristics of senile plaques, neuroinflammation, neurofibrillary tangles, and destruction of synapse structure stability. Previous studies have verified the protective effects of astaxanthin (AST). However, whether synthesized docosahexaenoic-acid-acylated AST diesters (AST-DHA) could delay AD pathogenesis remains unclear. In the present study, APP/PSEN1 (APP/PS1) double-transgenic mice were administrated with AST and AST-DHA for 2 months. The results of radial 8-arm maze and Morris water maze tests showed that AST-DHA exerted more significant effects than AST in enhancing learning and memory levels of APP/PS1 mice. Further mechanical studies suggested that AST-DHA was superior to AST in regulating the parameters of oxidative stress, reducing tau hyperphosphorylation, suppressing neuroinflammation, and regulating inflammasome expression and activation in APP/PS1 mice. The findings suggested that AST-DHA attenuated cognitive disorders by reducing pathological features in APP/PS1 mice, suggesting that AST-DHA might be a potential therapeutic agent for AD.

Corticosterone response to the plus-maze: high correlation with risk assessment in rats and mice.

PubMed

Rodgers, R J; Haller, J; Holmes, A; Halasz, J; Walton, T J; Brain, P F

Exposure to the elevated plus-maze induces behavioural and physiological effects in rodents consistent with fear/anxiety. Maze-naive animals display high levels of risk assessment towards the open arms, and explore these areas less extensively than other parts of the maze while, immediately following the test, pain latencies, skin conductance levels, and plasma corticosterone titres (CORT) are significantly elevated. Although previous research has suggested a link between the plasma CORT response and open-arm exploration, significant elevations in CORT have also been found with restricted exposure to the closed arms. The present study employed ethological measures in an attempt to further characterise the relationship between behavioural and CORT responses to this widely used animal model of anxiety. Our results confirm that, relative to home-cage controls, 5-min exposure to the plus-maze significantly increases plasma CORT levels in test-naive male Wistar rats and male Swiss-Webster mice. Furthermore, in both species, the CORT response was found to be highly correlated with measures of risk assessment (mice: rs = +0.87; rats: rs = +0.58), but not with measures of open-arm activity (entries, time), general locomotor activity, rearing, or head dipping. Findings are discussed in relation to the functional significance of risk assessment in potentially dangerous situations and the potential involvement of glucocorticoids in this process. All rights reserved.

Melatonin administration impairs visuo-spatial performance and inhibits neocortical long-term potentiation in rats.

PubMed

Soto-Moyano, Rubén; Burgos, Héctor; Flores, Francisco; Valladares, Luis; Sierralta, Walter; Fernández, Victor; Pérez, Hernán; Hernández, Paula; Hernández, Alejandro

2006-10-01

Melatonin has been shown to inhibit long-term potentiation (LTP) in hippocampal slices of rats. Since LTP may be one of the main mechanisms by which memory traces are encoded and stored in the central nervous system, it is possible that melatonin could modulate cognitive performance by interfering with the cellular and/or molecular mechanisms involved in LTP. We investigated in rats the effects of intraperitoneally-administered melatonin (0.1, 1 and 10 mg/kg), its saline-ethanol solvent, or saline alone, on the acquisition of visuo-spatial memory as well as on the ability of the cerebral cortex to develop LTP in vivo. Visuo-spatial performance was assessed daily in rats, for 10 days, in an 8-arm radial maze, 30 min after they received a single daily dose of melatonin. Visual cortex LTP was determined in sodium pentobarbital anesthetized rats (65 mg/kg i.p.), by potentiating transcallosal evoked responses with a tetanizing train (312 Hz, 500 ms duration) 30 min after administration of a single dose of melatonin. Results showed that melatonin impaired visuo-spatial performance in rats, as revealed by the greater number of errors committed and time spent to solve the task in the radial maze. Melatonin also prevented the induction of neocortical LTP. It is concluded that melatonin, at the doses utilized in this study, could alter some forms of neocortical plasticity involved in short- and long-term visuo-spatial memories in rats.

Effects of testosterone on spatial learning and memory in adult male rats

PubMed Central

Spritzer, Mark D.; Daviau, Emily D.; Coneeny, Meagan K.; Engelman, Shannon M.; Prince, W. Tyler; Rodriguez-Wisdom, Karlye N.

2011-01-01

A male advantage over females for spatial tasks has been well documented in both humans and rodents, but it remains unclear how the activational effects of testosterone influence spatial ability in males. In a series of experiments, we tested how injections of testosterone influenced the spatial working and reference memory of castrated male rats. In the eight-arm radial maze, testosterone injections (0.500 mg/rat) reduced the number of working memory errors during the early blocks of testing but had no effect on the number of reference memory errors relative to the castrated control group. In a reference memory version of the Morris water maze, injections of a wide range of testosterone doses (0.0625-1.000 mg/rat) reduced path lengths to the hidden platform, indicative of improved spatial learning. This improved learning was independent of testosterone dose, with all treatment groups showing better performance than the castrated control males. Furthermore, this effect was only observed when rats were given testosterone injections starting seven days prior to water maze testing and not when injections were given only on the testing days. We also observed that certain doses of testosterone (0.250 and 1.000 mg/rat) increased perseverative behavior in a reversal-learning task. Finally, testosterone did not have a clear effect on spatial working memory in the Morris water maze, although intermediate doses seemed to optimize performance. Overall, the results indicate that testosterone can have positive activational effects on spatial learning and memory, but the duration of testosterone replacement and the nature of the spatial task modify these effects. PMID:21295035

Comparative evaluation of ethanolic extracts of Bacopa monnieri, Evolvulus alsinoides, Tinospora cordifolia and their combinations on cognitive functions in rats.

PubMed

Gupta, Avneet; Raj, Hem; Karchuli, Manvender Singh; Upmanyu, Neeraj

2013-12-01

The effects of ethanolic extracts of whole plants of Bacopa monnieri (BME), Evolvulus alsinoides (EAE), Tinospora cordifolia (TCE) and their combinations in equal proportion [CEP-1 (BME+EAE), CEP-2 (BME+TCE), CEP-3 (EAE+TCE) and CEP-4 (BME+EAE+TCE)] were tested in amnesic rats using Radial arm maze task performance (RAM) and Barnes maze test at 200 mg/kg p.o. The latency to find food and target hole was observed in RAM and Barnes maze respectively. Cognitive dysfunction was induced by scopolamine (0.3 mg/kg i.p.) treatment. BME, EAE, TCE and their combinations of equal proportion (CEPs) showed significant decrease in latency to find food and target hole in RAM and Barnes maze respectively. Inter comparison among single extract alone treated groups revealed that BME treated animals showed significant difference as compared to EAE and TCE treated animals. All combinations of equal proportion (CEPs) of these extracts showed significant difference in latency to find food and target hole as compared to single extracts treated animals. CEP-1 showed significantly better effect as compared to CEP-2 and CEP-3. Significant difference in latency to find food and target hole was also present between CEP-2 and CEP-3. Effect of CEP-4 was found to be significantly better than CEP-1, CEP-2 and CEP-3 treated rats in both models. From present investigation, it was concluded that ethanolic extract of Bacopa monnieri, Evolvulus alsinoides and Tinospora cordifolia provided better nootropic effect when used in combination.

The impact of multiple memory formation on dendritic complexity in the hippocampus and anterior cingulate cortex assessed at recent and remote time points

PubMed Central

Wartman, Brianne C.; Holahan, Matthew R.

2014-01-01

Consolidation processes, involving synaptic and systems level changes, are suggested to stabilize memories once they are formed. At the synaptic level, dendritic structural changes are associated with long-term memory storage. At the systems level, memory storage dynamics between the hippocampus and anterior cingulate cortex (ACC) may be influenced by the number of sequentially encoded memories. The present experiment utilized Golgi-Cox staining and neuron reconstruction to examine recent and remote structural changes in the hippocampus and ACC following training on three different behavioral procedures. Rats were trained on one hippocampal-dependent task only (a water maze task), two hippocampal-dependent tasks (a water maze task followed by a radial arm maze task), or one hippocampal-dependent and one non-hippocampal-dependent task (a water maze task followed by an operant conditioning task). Rats were euthanized recently or remotely. Brains underwent Golgi-Cox processing and neurons were reconstructed using Neurolucida software (MicroBrightField, Williston, VT, USA). Rats trained on two hippocampal-dependent tasks displayed increased dendritic complexity compared to control rats, in neurons examined in both the ACC and hippocampus at recent and remote time points. Importantly, this behavioral group showed consistent, significant structural differences in the ACC compared to the control group at the recent time point. These findings suggest that taxing the demand placed upon the hippocampus, by training rats on two hippocampal-dependent tasks, engages synaptic and systems consolidation processes in the ACC at an accelerated rate for recent and remote storage of spatial memories. PMID:24795581

An automated Y-maze based on a reduced instruction set computer (RISC) microcontroller for the assessment of continuous spontaneous alternation in rats.

PubMed

Heredia-López, Francisco J; Álvarez-Cervera, Fernando J; Collí-Alfaro, José G; Bata-García, José L; Arankowsky-Sandoval, Gloria; Góngora-Alfaro, José L

2016-12-01

Continuous spontaneous alternation behavior (SAB) in a Y-maze is used for evaluating working memory in rodents. Here, the design of an automated Y-maze equipped with three infrared optocouplers per arm, and commanded by a reduced instruction set computer (RISC) microcontroller is described. The software was devised for recording only true entries and exits to the arms. Experimental settings are programmed via a keyboard with three buttons and a display. The sequence of arm entries and the time spent in each arm and the neutral zone (NZ) are saved as a text file in a non-volatile memory for later transfer to a USB flash memory. Data files are analyzed with a program developed under LabVIEW® environment, and the results are exported to an Excel® spreadsheet file. Variables measured are: latency to exit the starting arm, sequence and number of arm entries, number of alternations, alternation percentage, and cumulative times spent in each arm and NZ. The automated Y-maze accurately detected the SAB decrease produced in rats by the muscarinic antagonist trihexyphenidyl, and its reversal by caffeine, having 100 % concordance with the alternation percentages calculated by two trained observers who independently watched videos of the same experiments. Although the values of time spent in the arms and NZ measured by the automated system had small discrepancies with those calculated by the observers, Bland-Altman analysis showed 95 % concordance in three pairs of comparisons, while in one it was 90 %, indicating that this system is a reliable and inexpensive alternative for the study of continuous SAB in rodents.

Mathematical methods to model rodent behavior in the elevated plus-maze.

PubMed

Arantes, Rafael; Tejada, Julián; Bosco, Geraldine G; Morato, Silvio; Roque, Antonio C

2013-11-15

The elevated plus maze is a widely used experimental test to study anxiety-like rodent behavior. It is made of four arms, two open and two closed, connected at a central area forming a plus shaped maze. The whole apparatus is elevated 50 cm from the floor. The anxiety of the animal is usually assessed by the number of entries and duration of stay in each arm type during a 5-min period. Different mathematical methods have been proposed to model the mechanisms that control the animal behavior in the maze, such as factor analysis, statistical inference on Markov chains and computational modeling. In this review we discuss these methods and propose possible extensions of them as a direction for future research. Copyright © 2013 Elsevier B.V. All rights reserved.

Effect of Exposure to Lithium-Paired or Amphetamine-Paired Saccharin Solution on Open Arm Avoidance in an Elevated Plus Maze

ERIC Educational Resources Information Center

Rana, Shadna A.; Parker, Linda A.

2006-01-01

Recent evidence suggests that drug-induced conditioned taste avoidance may be mediated by conditioned fear (e.g., Parker, 2003). The experiments reported here evaluated the effect of exposure to a drug-paired flavor on open arm exploration in an elevated plus maze (EPM), a measure of fear. When rats were tested on a familiar (trial 2) EPM, but not…

Individual differences in the elevated plus-maze and the forced swim test.

PubMed

Estanislau, Celio; Ramos, Anna Carolina; Ferraresi, Paula Daniele; Costa, Naiara Fernanda; de Carvalho, Heloisa Maria Cotta Pires; Batistela, Silmara

2011-01-01

The elevated plus-maze is an apparatus composed of enclosed and open (elevated) arms and time spent in the open arms by a rat can be increased/decreased by anxiolytic/anxiogenic agents. In the forced swim test, floating behavior is used as an index of behavioral despair and can be decreased by antidepressant agents. As the comorbidity between anxiety and depression is a remarkable issue in human behavioral disorders, a possible relationship between the behaviors seen in the cited tests is of great relevance. In the present study, fifty-four male rats (Rattus norvegicus) were submitted to a plus-maze session and to a 2-day forced swim protocol. According to their time in the open arms, they were divided into three groups: Low Open, Medium Open and High Open. Some plus-maze measures were found to be coherent with time in the open arms and are suggested to also be reliable anxiety indexes. In the forced swim test, the Low Open group showed decreases in floating duration from forced swim Session 1 to Session 2, an alteration opposite to that observed in the other groups (particularly, the Medium Open group). The Low Open group also showed increases in floating latency, again in sharp contrast with the alteration found in the other groups. Accordingly, positive and negative correlation were found between time in the open arms and floating duration and latency, respectively. Results are compared to previous studies and mediation of the effect by reactivity to aversive stimulation or alterations induced by open arm exposure is discussed. Copyright © 2010 Elsevier B.V. All rights reserved.

Relations between open-field, elevated plus-maze, and emergence tests as displayed by C57/BL6J and BALB/c mice.

PubMed

Lalonde, R; Strazielle, C

2008-06-15

The relations between open-field, elevated plus-maze, and emergence tests were examined in two strains of mice. In the open-field, C57BL/6J mice had more ambulatory movements and rears but not stereotyped movements relative to BALB/c. In addition, C57BL/6J mice entered more often than BALB/c into enclosed and open arms of the elevated plus-maze. When placed inside a large enclosure, C57BL/6J mice emerged more quickly than BALB/c from a small toy object. In the entire series of mice, ambulation and rears in the open-field were linearly correlated with open and enclosed arm visits in the elevated plus-maze. Ambulatory movements and rears were also correlated with emergence latencies. In contrast, stereotyped movements were correlated with emergence latencies, but not with any elevated plus-maze value. These results specify the extent and limits of association between the three tests.

Lewis and Fischer 344 rats as a model for genetic differences in spatial learning and memory: Cocaine effects.

PubMed

Fole, Alberto; Miguéns, Miguel; Morales, Lidia; González-Martín, Carmen; Ambrosio, Emilio; Del Olmo, Nuria

2017-06-02

Lewis (LEW) and Fischer 344 (F344) rats are considered a model of genetic vulnerability to drug addiction. We previously showed important differences in spatial learning and memory between them, but in contrast with previous experiments demonstrating cocaine-induced enhanced learning in Morris water maze (MWM) highly demanding tasks, the eight-arm radial maze (RAM) performance was not modified either in LEW or F344 rats after chronic cocaine treatment. In the present work, chronically cocaine-treated LEW and F344 adult rats have been evaluated in learning and memory performance using the Y-maze, two RAM protocols that differ in difficulty, and a reversal protocol that tests cognitive flexibility. After one of the RAM protocols, we quantified dendritic spine density in hippocampal CA1 neurons and compared it to animals treated with cocaine but not submitted to RAM. LEW cocaine treated rats showed a better performance in the Y maze than their saline counterparts, an effect that was not evident in the F344 strain. F344 rats significantly took more time to learn the RAM task and made a greater number of errors than LEW animals in both protocols tested, whereas cocaine treatment induced deleterious effects in learning and memory in the highly difficult protocol. Moreover, hippocampal spine density was cocaine-modulated in LEW animals whereas no effects were found in F344 rats. We propose that differences in addictive-like behavior between LEW and F344 rats could be related to differences in hippocampal learning and memory processes that could be on the basis of individual vulnerability to cocaine addiction. Copyright © 2017 Elsevier Inc. All rights reserved.

Spatial problem-solving in a wheel-shaped maze: quantitative and qualitative analyses of the behavioural changes following damage to the hippocampus in the rat.

PubMed

Buhot, M C; Chapuis, N; Scardigli, P; Herrmann, T

1991-07-01

The behaviour of sham-operated rats and rats with damage to the dorsal hippocampus was compared in a complex spatial problem-solving task using a 'hub-spoke-rim' wheel type maze. Compared to the classical Olton 8-arm radial maze and Morris water maze, this apparatus presents the animal with a series of possible alternative routes both direct and indirect to the goal (food). The task included 3 main stages: exploration, feeding and testing, as do the classic problem-solving tasks. During exploration, hippocampal rats were found to be more active than sham rats. Nevertheless, they displayed habituation and a relatively efficient circumnavigation, though, in both cases, different from those of sham rats. During test trials, hippocampal rats were characterized as being less accurate, making more errors than sham rats. Nevertheless, both groups increased their accuracy of first choices over trials. The qualitative analyses of test trial performance indicated that hippocampal rats were less accurate in terms of the initial error's deviation from the goal, and less efficient in terms of corrective behaviour than sham rats which used either the periphery or the spokes to attain economically the goal. Surprisingly, hippocampal rats were not limited to a taxon type orientation but learned to use the periphery, a tendency which developed over time. Seemingly, for sham rats, the problem-solving process took the form of updating information during transit. For hippocampal rats, the use of periphery reflected both an ability to discriminate its usefulness in reaching the goal via a taxis type behaviour, and some sparing of ability to generalize the closeness and the location of the goal. These results, especially the strategic correction patterns, are discussed in the light of Sutherland and Rudy's 'configurational association theory'.

Radial arm strike rail

DOEpatents

McKeown, Mark H.; Beason, Steven C.

1991-01-01

The radial arm strike rail assembly is a system for measurement of bearings, directions, and stereophotography for geologic mapping, particularly where magnetic compasses are not appropriate. The radial arm, pivoting around a shaft axis, provides a reference direction determination for geologic mapping and bearing or direction determination. The centerable and levelable pedestal provide a base for the radial arm strike rail and the telescoping camera pedestal. The telescoping feature of the radial arm strike rail allows positioning the end of the rail for strike direction or bearing measurement with a goniometer.

Antiamnesic and Antioxidants Effects of Ferulago angulata Essential Oil Against Scopolamine-Induced Memory Impairment in Laboratory Rats.

PubMed

Hritcu, Lucian; Bagci, Eyup; Aydin, Emel; Mihasan, Marius

2015-09-01

Ferulago angulata (Apiaceae) is a shrub indigenous to western Iran, Turkey and Iraq. In traditional medicine, F. angulata is recommended for treating digestive pains, hemorrhoids, snake bite, ulcers and as sedative. In the present study, the effects of inhaled F. angulata essential oil (1 and 3%, daily, for 21 days) on spatial memory performance were assessed in scopolamine-treated rats. Scopolamine-induced memory impairments were observed, as measured by the Y-maze and radial arm-maze tasks. Decreased activities of superoxide dismutase, glutathione peroxidase and catalase along with increase of acetylcholinesterase activity and decrease of total content of reduced glutathione were observed in the rat hippocampal homogenates of scopolamine-treated animals as compared with control. Production of protein carbonyl and malondialdehyde significantly increased in the rat hippocampal homogenates of scopolamine-treated animals as compared with control, as a consequence of impaired antioxidant enzymes activities. Additionally, in scopolamine-treated rats exposure to F. angulata essential oil significantly improved memory formation and decreased oxidative stress, suggesting memory-enhancing and antioxidant effects. Therefore, our results suggest that multiple exposures to F. angulata essential oil ameliorate scopolamine-induced spatial memory impairment by attenuation of the oxidative stress in the rat hippocampus.

Behavioral assays with mouse models of Alzheimer’s disease: practical considerations and guidelines

PubMed Central

Puzzo, Daniela; Lee, Linda; Palmeri, Agostino; Calabrese, Giorgio; Arancio, Ottavio

2014-01-01

In Alzheimer’s disease (AD) basic research and drug discovery, mouse models are essential resources for uncovering biological mechanisms, validating molecular targets and screening potential compounds. Both transgenic and non-genetically modified mouse models enable access to different types of AD-like pathology in vivo. Although there is a wealth of genetic and biochemical studies on proposed AD pathogenic pathways, as a disease that centrally features cognitive failure, the ultimate readout for any interventions should be measures of learning and memory. This is particularly important given the lack of knowledge on disease etiology – assessment by cognitive assays offers the advantage of targeting relevant memory systems without requiring assumptions about pathogenesis. A multitude of behavioral assays are available for assessing cognitive functioning in mouse models, including ones specific for hippocampal-dependent learning and memory. Here we review the basics of available transgenic and non-transgenic AD mouse models and detail three well-established behavioral tasks commonly used for testing hippocampal-dependent cognition in mice – contextual fear conditioning, radial arm water maze and Morris water maze. In particular, we discuss the practical considerations, requirements and caveats of these behavioral testing paradigms. PMID:24462904

Naringenin improves learning and memory in an Alzheimer's disease rat model: Insights into the underlying mechanisms.

PubMed

Ghofrani, Saeed; Joghataei, Mohammad-Taghi; Mohseni, Simin; Baluchnejadmojarad, Tourandokht; Bagheri, Maryam; Khamse, Safoura; Roghani, Mehrdad

2015-10-05

Alzheimer's disease (AD) is one of the prevalent neurological disorders of the central nervous system hallmarked by increased beta-amyloid (Aβ) deposition and ensuing learning and memory deficit. In the present study, the beneficial effect of naringenin on improvement of learning and memory was evaluated in an Alzheimer's disease rat model. The Aβ-injected rats showed a lower alternation score in Y-maze task, impairment of retention and recall capability in passive avoidance test, and lower correct choices and higher errors in radial arm maze (RAM) task as compared to sham group in addition to enhanced oxidative stress and apoptosis. Naringenin, but not a combination of naringenin and fulvestrant (an estrogenic receptor antagonist) significantly improved the performance of Aβ-injected rats in passive avoidance and RAM tasks. Naringenin pretreatment of Aβ-injected rats also lowered hippocampal malondialdehyde (MDA) with no significant effect on nitrite and superoxide dismutase (SOD) activity in addition to lowering apoptosis. These results suggest naringenin pretreatment attenuates Aβ-induced impairment of learning and memory through mitigation of lipid peroxidation and apoptosis and its beneficial effect is somewhat mediated via estrogenic pathway. Copyright © 2015 Elsevier B.V. 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 of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

Spatial memory deficit and neurodegeneration induced by the direct injection of okadaic acid into the hippocampus in rats.

PubMed

He, J; Yamada, K; Zou, L B; Nabeshima, T

2001-01-01

We investigated the effects of okadaic acid (OA), a specific inhibitor of protein phosphatases 1 and 2A, on spatial memory and neuronal survival in rats. Rats were initially trained on a spatial memory task in an eight arm radial maze. Spatial reference and working memory was impaired 1 day after the unilateral microinjection of OA into the dorsal hippocampus. The impairment was transient, and had disappeared by the following day. In contrast, neurodegeneration induced by OA was persistent and extended to the contralateral side 13 days after the injection. These results suggest that OA causes spatial memory impairment and neurodegeneration when injected directly into the hippocampus. Our findings also indicate dissociation between memory impairment and neurodegeneration induced by OA.

Anxiolytic effects of environmental enrichment attenuate sex-related anxiogenic effects of scopolamine in rats.

PubMed

Hughes, Robert N; Otto, Maria T

2013-01-10

In groups of four same-sexed animals, PVG/c hooded rats were housed for 4.5 months in standard or enriched cages containing several objects that could be explored and manipulated. On separate occasions, each rat then experienced two consecutive daily trials in an open field, a light-dark box or a Y maze with arm inserts that enabled an acquisition trial comprising one black and one white arm to be changed for a retention trial consisting of two black arms. Before their trials in the open field and light-dark box, and following each acquisition trial in the Y maze, the rats received an intraperitoneal injection of 2 mg/kg scopolamine or isotonic saline. In the open field, enrichment led to higher levels of ambulation, walking, rearing and occupancy of the center of the apparatus and shorter emergence latencies from the dark into the light compartment of the light-dark box accompanied by more entries of this compartment. Enrichment also increased entries of and time spent in the changed (or novel) Y-maze arm only for male rats treated with scopolamine. The drug decreased rearing and increased grooming in the open field as well as increasing emergence latencies and decreasing entries of and the time spent on the light compartment of the light-dark box. The main results were interpreted as enrichment having attenuated anxiogenic effects of the behavioral testing and the action of scopolamine for male (but not female) rats in their choices of the novel arm in the Y maze. Copyright © 2012 Elsevier Inc. All rights reserved.

Spatial Working Memory Deficits in Male Rats Following Neonatal Hypoxic Ischemic Brain Injury Can Be Attenuated by Task Modifications

PubMed Central

Smith, Amanda L.; Hill, Courtney A.; Alexander, Michelle; Szalkowski, Caitlin E.; Chrobak, James J.; Rosenkrantz, Ted S.; Fitch, R. Holly

2014-01-01

Hypoxia-ischemia (HI; reduction in blood/oxygen supply) is common in infants with serious birth complications, such as prolonged labor and cord prolapse, as well as in infants born prematurely (<37 weeks gestational age; GA). Most often, HI can lead to brain injury in the form of cortical and subcortical damage, as well as later cognitive/behavioral deficits. A common domain of impairment is working memory, which can be associated with heightened incidence of developmental disorders. To further characterize these clinical issues, the current investigation describes data from a rodent model of HI induced on postnatal (P)7, an age comparable to a term (GA 36–38) human. Specifically, we sought to assess working memory using an eight-arm radial water maze paradigm. Study 1 used a modified version of the paradigm, which requires a step-wise change in spatial memory via progressively more difficult tasks, as well as multiple daily trials for extra learning opportunity. Results were surprising and revealed a small HI deficit only for the final and most difficult condition, when a delay before test trial was introduced. Study 2 again used the modified radial arm maze, but presented the most difficult condition from the start, and only one daily test trial. Here, results were expected and revealed a robust and consistent HI deficit across all weeks. Combined results indicate that male HI rats can learn a difficult spatial working memory task if it is presented in a graded multi-trial format, but performance is poor and does not appear to remediate if the task is presented with high initial memory demand. Male HI rats in both studies displayed impulsive characteristics throughout testing evidenced as reduced choice latencies despite more errors. This aspect of behavioral results is consistent with impulsiveness as a core symptom of ADHD—a diagnosis common in children with HI insult. Overall findings suggest that task specific behavioral modifications are crucial to accommodating memory deficits in children suffering from cognitive impairments following neonatal HI. PMID:24961760

Dentate network activity is necessary for spatial working memory by supporting CA3 sharp-wave ripple generation and prospective firing of CA3 neurons.

PubMed

Sasaki, Takuya; Piatti, Verónica C; Hwaun, Ernie; Ahmadi, Siavash; Lisman, John E; Leutgeb, Stefan; Leutgeb, Jill K

2018-02-01

Complex spatial working memory tasks have been shown to require both hippocampal sharp-wave ripple (SWR) activity and dentate gyrus (DG) neuronal activity. We therefore asked whether DG inputs to CA3 contribute to spatial working memory by promoting SWR generation. Recordings from DG and CA3 while rats performed a dentate-dependent working memory task on an eight-arm radial maze revealed that the activity of dentate neurons and the incidence rate of SWRs both increased during reward consumption. We then found reduced reward-related CA3 SWR generation without direct input from dentate granule neurons. Furthermore, CA3 cells with place fields in not-yet-visited arms preferentially fired during SWRs at reward locations, and these prospective CA3 firing patterns were more pronounced for correct trials and were dentate-dependent. These results indicate that coordination of CA3 neuronal activity patterns by DG is necessary for the generation of neuronal firing patterns that support goal-directed behavior and memory.

Relations between open-field, elevated plus-maze, and emergence tests in C57BL/6J and BALB/c mice injected with GABA- and 5HT-anxiolytic agents.

PubMed

Lalonde, Robert; Strazielle, Catherine

2010-06-01

Two 5HT(1A) receptor agonists and chlordiazepoxide were examined in open-field, elevated plus maze, and emergence tests. At doses with no effect in the open-field, chlordiazepoxide increased open and open/total arm visits as well as open arm duration in the elevated plus maze, whereas 5HT(1A) receptor agonists showed an anxiolytic response on a single measure. The anxiolytic action of chlordiazepoxide was limited to the less active BALB/c strain. Unlike the 5HT(1A) receptor agonists, chlordiazepoxide was also anxiolytic in the emergence test, once again only in BALB/c and not C57BL/6J mice. Significant correlations were found between emergence latencies and specific indicators of anxiety in the elevated plus-maze in chlordiazepoxide-treated but not in mice treated with buspirone and 8-OH-DPAT. These results indicate that elevated plus-maze and emergence tests depend on benzodiazepine receptors. In contrast, 5HT(1A) receptor agonists were ineffective in the emergence test and no correlation was found between emergence latencies and specific indicators of anxiety in the elevated plus-maze. Though superficially similar, the emergence test seems to tap into a partially separate facet of anxiety.

Role of hippocampus in polymodal-cue guided tasks in rats.

PubMed

Miniaci, Maria Concetta; Lippiello, Pellegrino; Monda, Marcellino; Scotto, Pietro

2016-09-01

To examine how signals from different sensory modalities are integrated to generate an appropriate goal-oriented behavior, we trained rats in an eight-arm radial maze to visit a cue arm provided with intramaze cues from different sensory modalities, i.e. visual, tactile and auditory, in order to obtain a reward. When the same rats were then examined on test trials in which the cue arm contained one of the stimuli that the animals were trained with (i.e. light, sound or rough sheet), they showed a significant impairment with respect to the performance on the polymodal-cue task. The contribution of the dorsal hippocampus to the acquisition and retention of polymodal-cue guided task was also examined. We found that rats with dorsal hippocampal lesions before training showed a significant deficit in the acquisition of polymodal-cue oriented task that improved with overtraining. The selective lesion of the dorsal hippocampus after training disrupted memory retention, but the animals' performance improved following retraining of the polymodal task. All hippocampal lesioned rats displayed an impaired performance on the unimodal test. These findings suggest that the dorsal hippocampus contributes to the processing of multimodal sensory information for the associative memory formation and consolidation. Copyright © 2016 Elsevier B.V. All rights reserved.

Continuous recognition of spatial and nonspatial stimuli in hippocampal-lesioned rats.

PubMed

Jackson-Smith, P; Kesner, R P; Chiba, A A

1993-03-01

The present experiments compared the performance of hippocampal-lesioned rats to control rats on a spatial continuous recognition task and an analogous nonspatial task with similar processing demands. Daily sessions for Experiment 1 involved sequential presentation of individual arms on a 12-arm radial maze. Each arm contained a Froot Loop reinforcement the first time it was presented, and latency to traverse the arm was measured. A subset of the arms were repeated, but did not contain reinforcement. Repeated arms were presented with lags ranging from 0 to 6 (0 to 6 different arm presentations occurred between the first and the repeated presentation). Difference scores were computed by subtracting the latency on first presentations from the latency on repeated presentations, and these scores were high in all rats prior to surgery, with a decreasing function across lag. There were no differences in performance following cortical control or sham surgery. However, there was a total deficit in performance following large electrolytic lesions of the hippocampus. The second experiment employed the same continuous recognition memory procedure, but used three-dimensional visual objects (toys, junk items, etc., in various shapes, sizes, and textures) as stimuli on a flat runway. As in Experiment 1, the stimuli were presented successively and latency to run to and move the object was measured. Objects were repeated with lags ranging from 0 to 4. Performance on this task following surgery did not differ from performance prior to surgery for either the control group or the hippocampal lesion group. These results provide support for Kesner's attribute model of hippocampal function in that the hippocampus is assumed to mediate data-based memory for spatial locations, but not three-dimensional visual objects.

Sheep laterality

USDA-ARS?s Scientific Manuscript database

Turning preferences among 309 white-faced ewes were individually evaluated in an enclosed, artificially lighted, T-maze, followed by each ewe choosing either a right or left return alley to return to peers. Data recorded included time in the start box, time in the T-maze, exit arm chosen to leave th...

Cognitive-enhancing and antioxidant activities of the aqueous extract from Markhamia tomentosa (Benth.) K. Schum. stem bark in a rat model of scopolamine.

PubMed

Ionita, Radu; Postu, Paula Alexandra; Beppe, Galba Jean; Mihasan, Marius; Petre, Brindusa Alina; Hancianu, Monica; Cioanca, Oana; Hritcu, Lucian

2017-03-28

Plants of the genus Markhamia have been traditionally used by different tribes in various parts of West African countries, including Cameroun. Markhamia tomentosa (Benth.) K. Schum. (Bignoniaceae) is used as an antimalarial, anti-inflammatory, analgesic, antioxidant and anti-Alzheimer agent. The current study was undertaken in order to investigate its anti-amnesic and antioxidant potential on scopolamine-induced cognitive impairment and to determine its possible mechanism of action. Rats were pretreated with the aqueous extract (50 and 200 mg/kg, p.o.), for 10 days, and received a single injection of scopolamine (0.7 mg/kg, i.p.) before training in Y-maze and radial arm-maze tests. The biochemical parameters in the rat hippocampus were also assessed to explore oxidative status. Statistical analyses were performed using two-way ANOVA followed by Tukey's post hoc test. F values for which p < 0.05 were regarded as statistically significant. In the scopolamine-treated rats, the aqueous extract improved memory in behavioral tests and decreased the oxidative stress in the rat hippocampus. Also, the aqueous extract exhibited anti-acetylcholinesterase activity. These results suggest that the aqueous extract ameliorates scopolamine-induced spatial memory impairment by attenuation of the oxidative stress in the rat hippocampus.

Effects of chronic scopolamine administration on spatial working memory and hippocampal receptors related to learning.

PubMed

Doguc, Duygu K; Delibas, Namik; Vural, Huseyin; Altuntas, Irfan; Sutcu, Recep; Sonmez, Yonca

2012-12-01

Scopolamine has been used in neuropsychopharmacology as a standard drug that leads to symptoms mimicking cognitive deficits seen during the aging process in healthy humans and animals. Scopolamine is known to be a nonselective muscarinic receptor blocker, but its chronic effect on the expression of certain hippocampal receptors is not clear. The aim of the present study was to determine the effect of chronic scopolamine administration on hippocampal receptor expression and spatial working memory in two different learning tasks, the water maze and the eight-arm radial maze. Male rats (8-12 months) were trained in both tasks. Subsequently, different groups received physiological saline or 0.1, 0.8, or 2 mg/kg scopolamine hydrobromide, respectively, for 15 days. After drug administration, the rats were retested for both tasks, and hippocampal expressions of NR2A, NR2B, nAChRα7, and mAChRM1 receptors were assessed by western blotting analysis. In both tasks, the spatial working memory was decreased dose dependently in all groups compared with the control group. In terms of receptor expressions, 0.8 and 2 mg/kg scopolamine administration significantly decreased NR2A protein expression, which corroborates suggestions of an interaction between cholinergic and glutamatergic receptors in the hippocampus.

Effects of the Methanolic Extract of Vitellaria paradoxa Stem Bark Against Scopolamine-Induced Cognitive Dysfunction and Oxidative Stress in the Rat Hippocampus.

PubMed

Foyet, Harquin Simplice; Asongalem, Acha Emmanuel; Oben, Eyong Kenneth; Cioanca, Oana; Hancianu, Monica; Hritcu, Lucian

2016-10-01

Vitellaria paradoxa C.F. Gaertn (Sapotaceae) is a perennial three which naturally grows in the northern part of Cameroon. It has been traditionally used in the Cameroonian folk medicine for treating inflammation and pain. In the present study, we evaluate the possible anti-amnesic and antioxidative effects of the methanolic extract of V. paradoxa stem bark in an Alzheimer's disease (AD) rat model of scopolamine. Rats received a single injection of scopolamine (1.5 mg/kg) before behavioral testing and were treated with the methanolic extract (25 and 50 mg/kg), daily, for eight continuous days. Also, the antioxidant activity in the hippocampus was assessed using the total content of reduced glutathione and malondialdehyde levels. The scopolamine-treated rats exhibited the following: decrease of exploratory time and discrimination index within the novel object recognition test, decrease of spontaneous alternations percentage within Y-maze task, and increase of working memory errors, reference memory errors, and time taken to consume all five baits within radial arm-maze task. Administration of the methanolic extract significantly improved these parameters, suggesting positive effects on memory formation processes and antioxidant potential. Our results suggest that the methanolic extract ameliorates scopolamine-induced memory impairment by attenuation of the oxidative stress in the rat hippocampus.

Reduced cognitive function, increased blood-brain-barrier transport and inflammatory responses, and altered brain metabolites in LDLr -/-and C57BL/6 mice fed a western diet

PubMed Central

Lee, Linda L.; Puchowicz, Michelle; Golub, Mari S.; Befroy, Douglas E.; Wilson, Dennis W.; Anderson, Steven; Cline, Gary; Bini, Jason; Borkowski, Kamil; Knotts, Trina A.; Rutledge, John C.

2018-01-01

Recent work suggests that diet affects brain metabolism thereby impacting cognitive function. Our objective was to determine if a western diet altered brain metabolism, increased blood-brain barrier (BBB) transport and inflammation, and induced cognitive impairment in C57BL/6 (WT) mice and low-density lipoprotein receptor null (LDLr -/-) mice, a model of hyperlipidemia and cognitive decline. We show that a western diet and LDLr -/- moderately influence cognitive processes as assessed by Y-maze and radial arm water maze. Also, western diet significantly increased BBB transport, as well as microvessel factor VIII in LDLr -/- and microglia IBA1 staining in WT, both indicators of activation and neuroinflammation. Interestingly, LDLr -/- mice had a significant increase in 18F- fluorodeoxyglucose uptake irrespective of diet and brain 1H-magnetic resonance spectroscopy showed increased lactate and lipid moieties. Metabolic assessments of whole mouse brain by GC/MS and LC/MS/MS showed that a western diet altered brain TCA cycle and β-oxidation intermediates, levels of amino acids, and complex lipid levels and elevated proinflammatory lipid mediators. Our study reveals that the western diet has multiple impacts on brain metabolism, physiology, and altered cognitive function that likely manifest via multiple cellular pathways. PMID:29444171

Lactuca capensis reverses memory deficits in Aβ1-42-induced an animal model of Alzheimer's disease.

PubMed

Postu, Paula Alexandra; Noumedem, Jaures A K; Cioanca, Oana; Hancianu, Monica; Mihasan, Marius; Ciorpac, Mitica; Gorgan, Dragos Lucian; Petre, Brindusa Alina; Hritcu, Lucian

2018-01-01

We investigated the neuropharmacological effects of the methanolic extract from Lactuca capensis Thunb. leaves (100 and 200 mg/kg) for 21 days on memory impairment in an Alzheimer's disease (AD) rat model produced by direct intraventricular delivery of amyloid-β1-42 (Aβ1-42). Behavioural assays such as Y-maze and radial arm maze test were used for assessing memory performance. Aβ1-42 decreased cognitive performance in the behavioural tests which were ameliorated by pre-treatment with the methanolic extract. Acetylcholinesterase activity and oxidant-antioxidant balance in the rat hippocampus were abnormally altered by Aβ1-42 treatment while these deficits were recovered by pre-treatment with the methanolic extract. In addition, rats were given Aβ1-42 exhibited in the hippocampus decreased brain-derived neurotrophic factor (BDNF) mRNA copy number and increased IL-1β mRNA copy number which was reversed by the methanolic extract administration. These findings suggest that the methanolic extract could be a potent neuropharmacological agent against dementia via modulating cholinergic activity, increasing of BDNF levels and promoting antioxidant action in the rat hippocampus. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Spatial memory and hippocampal plasticity are differentially sensitive to the availability of choline in adulthood as a function of choline supply in utero

PubMed Central

Wong-Goodrich, Sarah J.E.; Glenn, Melissa J.; Mellott, Tiffany J.; Blusztajn, Jan K.; Meck, Warren H.; Williams, Christina L.

2009-01-01

Altered dietary choline availability early in life leads to persistent changes in spatial memory and hippocampal plasticity in adulthood. Developmental programming by early choline nutrition may determine the range of adult choline intake that is optimal for the types of neural plasticity involved in cognitive function. To test this, male Sprague-Dawley rats were exposed to a choline chloride deficient (DEF), sufficient (CON), or supplemented (SUP) diet during embryonic days 12-17 and then returned to a control diet (1.1 g choline chloride/kg). At 70 days of age, we found that DEF and SUP rats required fewer choices to locate 8 baited arms of a 12-arm radial maze than CON rats. When switched to a choline-deficient diet (0 g/kg), SUP rats showed impaired performance while CON and DEF rats were unaffected. In contrast, when switched to a choline-supplemented diet (5.0 g/kg), DEF rats' performance was significantly impaired while CON and SUP rats were less affected. These changes in performance were reversible when the rats were switched back to a control diet. In a second experiment, DEF, CON, and SUP rats were either maintained on a control diet, or the choline-supplemented diet. After 12 weeks, DEF rats were significantly impaired by choline supplementation on a matching-to-place water-maze task, which was also accompanied by a decrease in dentate cell proliferation in DEF rats only. IGF-1 levels were elevated by both prenatal and adult choline supplementation. Taken together, these findings suggest that the in utero availability of an essential nutrient, choline, causes differential behavioral and neuroplastic sensitivity to the adult choline supply. PMID:18778697

Spatial memory and hippocampal plasticity are differentially sensitive to the availability of choline in adulthood as a function of choline supply in utero.

PubMed

Wong-Goodrich, Sarah J E; Glenn, Melissa J; Mellott, Tiffany J; Blusztajn, Jan K; Meck, Warren H; Williams, Christina L

2008-10-27

Altered dietary choline availability early in life leads to persistent changes in spatial memory and hippocampal plasticity in adulthood. Developmental programming by early choline nutrition may determine the range of adult choline intake that is optimal for the types of neural plasticity involved in cognitive function. To test this, male Sprague-Dawley rats were exposed to a choline chloride deficient (DEF), sufficient (CON), or supplemented (SUP) diet during embryonic days 12-17 and then returned to a control diet (1.1 g choline chloride/kg). At 70 days of age, we found that DEF and SUP rats required fewer choices to locate 8 baited arms of a 12-arm radial maze than CON rats. When switched to a choline-deficient diet (0 g/kg), SUP rats showed impaired performance while CON and DEF rats were unaffected. In contrast, when switched to a choline-supplemented diet (5.0 g/kg), DEF rats' performance was significantly impaired while CON and SUP rats were less affected. These changes in performance were reversible when the rats were switched back to a control diet. In a second experiment, DEF, CON, and SUP rats were either maintained on a control diet, or the choline-supplemented diet. After 12 weeks, DEF rats were significantly impaired by choline supplementation on a matching-to-place water-maze task, which was also accompanied by a decrease in dentate cell proliferation in DEF rats only. IGF-1 levels were elevated by both prenatal and adult choline supplementation. Taken together, these findings suggest that the in utero availability of an essential nutrient, choline, causes differential behavioral and neuroplastic sensitivity to the adult choline supply.

Glow discharge based device for solving mazes

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

Dubinov, Alexander E., E-mail: dubinov-ae@yandex.ru; Mironenko, Maxim S.; Selemir, Victor D.

2014-09-15

A glow discharge based device for solving mazes has been designed and tested. The device consists of a gas discharge chamber and maze-transformer of radial-azimuth type. It allows changing of the maze pattern in a short period of time (within several minutes). The device has been tested with low pressure air. Once switched on, a glow discharge has been shown to find the shortest way through the maze from the very first attempt, even if there is a section with potential barrier for electrons on the way. It has been found that ionization waves (striations) can be excited in themore » maze along the length of the plasma channel. The dependancy of discharge voltage on the length of the optimal path through the maze has been measured. A reduction in discharge voltage with one or two potential barriers present has been found and explained. The dependency of the magnitude of discharge ignition voltage on the length of the optimal path through the maze has been measured. The reduction of the ignition voltage with the presence of one or two potential barriers has been observed and explained.« less

An elevated plus-maze in mixed reality for studying human anxiety-related behavior.

PubMed

Biedermann, Sarah V; Biedermann, Daniel G; Wenzlaff, Frederike; Kurjak, Tim; Nouri, Sawis; Auer, Matthias K; Wiedemann, Klaus; Briken, Peer; Haaker, Jan; Lonsdorf, Tina B; Fuss, Johannes

2017-12-21

A dearth of laboratory tests to study actual human approach-avoidance behavior has complicated translational research on anxiety. The elevated plus-maze (EPM) is the gold standard to assess approach-avoidance behavior in rodents. Here, we translated the EPM to humans using mixed reality through a combination of virtual and real-world elements. In two validation studies, we observed participants' anxiety on a behavioral, physiological, and subjective level. Participants reported higher anxiety on open arms, avoided open arms, and showed an activation of endogenous stress systems. Participants' with high anxiety exhibited higher avoidance. Moreover, open arm avoidance was moderately predicted by participants' acrophobia and sensation seeking, with opposing influences. In a randomized, double blind, placebo controlled experiment, GABAergic stimulation decreased avoidance of open arms while alpha-2-adrenergic antagonism increased avoidance. These findings demonstrate cross-species validity of open arm avoidance as a translational measure of anxiety. We thus introduce the first ecologically valid assay to track actual human approach-avoidance behavior under laboratory conditions.

Assessment of learning, memory, and attention in developmental neurotoxicity regulatory studies: synthesis, commentary, and recommendations.

PubMed

Vorhees, Charles V; Makris, Susan L

2015-01-01

Cognitive tests of learning and memory (L&M) have been required by U.S. Environmental Protection Agency (EPA) developmental neurotoxicity test (DNT) guidelines for more than two decades. To evaluate the utility of these guidelines, the EPA reviewed 69 pesticide DNT studies. This review found that the DNT provided or could provide the point-of-departure for risk assessment by showing the Lowest Observable Adverse Effect Level (LOAEL) in 28 of these studies in relation to other reported end points. Among the behavioral tests, locomotor activity and auditory/acoustic startle provided the most LOAELs, and tests of cognitive function and the Functional Observational Battery (FOB) the fewest. Two issues arose from the review: (1) what is the relative utility of cognitive tests versus tests of unconditioned behavior, and (2) how might cognitive tests be improved? The EPA sponsored a symposium to address this. Bushnell reviewed studies in which both screening (locomotor activity, FOB, reflex ontogeny, etc.) and complex tests (those requiring training) were used within the same study; he found relatively little evidence that complex tests provided a LOAEL lower than screening tests (with exceptions). Levin reviewed reasons for including cognitive tests in regulatory studies and methods and evidence for the radial arm maze and its place in developmental neurotoxicity assessments. Driscoll and Strupp reviewed the value of serial reaction time operant methods for assessing executive function in developmental neurotoxicity studies. Vorhees and Williams reviewed the value of allocentric (spatial) and egocentric cognitive tests and presented methods for using the Morris water maze for spatial and the Cincinnati water maze for egocentric cognitive assessment. They also reviewed the possible use of water radial mazes. The relatively lower impact of cognitive tests in previous DNT studies in the face of the frequency of human complaints of chemical-induced cognitive dysfunction indicates that animal cognitive tests need improvement. The contributors to this symposium suggest that if the guidelines are updated, they be made more specific by recommending preferred tests and providing greater detail on key characteristics of such tests. Additionally, it is recommended that guidance be developed to address important issues with cognitive tests and to provide the information needed to improve the design, conduct, and interpretation of tests of higher function within a regulatory context. These steps will maximize the value of cognitive tests for use in hazard evaluation and risk assessment. Copyright © 2015 Elsevier Inc. All rights reserved.

Diet-induced effects on neuronal and glial elements in the middle-aged rat hippocampus

PubMed Central

Freeman, Linnea R.; Haley-Zitlin, Vivian; Stevens, Cheryl; Granholm, Ann-Charlotte

2014-01-01

Consumption of a high-fat and/or high-cholesterol diet can have detrimental effects on the brain. In the present study, dietary treatment with saturated fats, trans fats, or cholesterol to middle-aged Fischer 344 rats resulted in alterations to serum triglyceride and cholesterol levels, organ weights, and hippocampal morphology. Previously, we demonstrated that a 10% hydrogenated coconut oil and 2% cholesterol diet resulted in worse performance on the 12-day water radial arm maze, increased cholesterol and triglyceride levels, and decreased dendritic microtubule associated protein 2 (MAP2) staining in the hippocampus. The diets administered herein were used to examine components from the previous diet and further examine their effects on hippocampal morphology. Specifically, neuronal morphology, dendritic integrity, fatty acid metabolism, microgliosis, and blood vessel structure in the hippocampus and/or adjacent structures were explored. Our results indicate alterations to peripheral and neural systems following each of the diets. PMID:21535919

Combined organizational and activational effects of short and long photoperiods on spatial and temporal memory in rats.

PubMed

MacDonald, Christopher J; Cheng, Ruey-Kuang; Williams, Christina L; Meck, Warren H

2007-02-22

The present study examined the effects of photoperiod on spatial and temporal memory in adult Sprague-Dawley rats that were conceived and reared in different day lengths, i.e., short day (SD-8:16 light/dark) and long day (LD-16:8 light/dark). Both male and female LD rats demonstrated increased spatial memory capacity as evidenced by a lower number of choices to criterion in a 12-arm radial maze task relative to the performance of SD rats. SD rats also demonstrated a distortion in the content of temporal memory as evidenced by a proportional rightward shift in the 20 and 60 s temporal criteria trained using the peak-interval procedure that is consistent with reduced cholinergic function. The conclusion is that both spatial and temporal memory are sensitive to photoperiod variation in laboratory rats in a manner similar to that previously observed for reproductive behaviour.

Cerebral morphology and functional sparing after prenatal frontal cortex lesions in rats.

PubMed

Kolb, B; Cioe, J; Muirhead, D

1998-03-01

Rats were given suction lesions of the presumptive frontal cortex on embryonic day 18 (E18) and subsequently tested, as adults, on tests of spatial navigation (Morris water task, radial arm maze), motor tasks (Whishaw reaching task, beam walking), and locomotor activity. Frontal cortical lesions at E18 affected cerebral morphogenesis, producing unusual morphological structures including abnormal patches of neurons in the cortex and white matter as well as neuronal bridges between the hemispheres. A small sample of E18 operates also had hydrocephaly. The animals with E18 lesions without hydrocephalus were behaviorally indistinguishable from littermate controls. The results demonstrate that animals with focal lesions of the presumptive frontal cortex have gross abnormalities in cerebral morphology but the lesions leave the functions normally subserved by the frontal cortex in adult rats unaffected. The results are discussed in the context of a hypothesis regarding the optimal times for functional recovery from cortical injury.

Lithium ameliorates open-field and elevated plus maze behaviors, and brain phospho-glycogen synthase kinase 3-beta expression in fragile X syndrome model mice.

PubMed

Chen, Xi; Sun, Weiwen; Pan, Ying; Yang, Quan; Cao, Kaiyi; Zhang, Jin; Zhang, Yizhi; Chen, Mincong; Chen, Feidi; Huang, Yueling; Dai, Lijun; Chen, Shengqiang

2013-10-01

To investigate whether lithium modifies open-field and elevated plus maze behavior, and brain phospho-glycogen synthase kinase 3 (P-GSK3beta) expression in Fmr1 knockout mice. One hundred and eighty FVB mice, including knockout and wild type, with an age of 30 days were used. An open-field and elevated plus maze was utilized to test behavior, while western blot was used to measure the P-GSK3beta expression. Six groups were formed: control (saline), lithium chloride 30, 60, 90, 120, and 200 mg/kg. The experiments were carried out in the Institute of Neuroscience, Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China between January and June 2012. Lithium significantly decreased total distance, crossing, central area time, and center entry in the open-field test (p<0.05), and significantly reduced open-arm tracking, open-arm entry, and open-arm time in the elevated plus maze (p<0.05) in knockout mice. In wild type mice, significant changes were observed in both behavior tests in some treatment groups. Lithium ameliorated P-GSK3beta expression in the hippocampus of all the treatment groups in knockout mice (p<0.05). However, lithium did not modify either GSK3beta expression in tissues of knockout mice, or P-GSK3beta or GSK3beta expression in tissues of wild type mice. Lithium ameliorated open-field and elevated plus maze behaviors of Fmr1 knockout mice. This effect may be related to its enhancement of P-GSK3beta expression. Our findings suggest that lithium might have a therapeutic effect in fragile X syndrome.

Can rats solve a simple version of the traveling salesman problem?

PubMed

Bures, J; Buresová, O; Nerad, L

1992-12-31

Whereas correct tours through the radial arm maze are almost equally long, free choice mazes with multiple goals scattered in an open field allow the animal to select the shortest one from a multitude of correct tours. Thirteen rats were trained (at 10 trials per day) to visit an array of cylindrical feeders in an open field (40 x 100 cm) with reward available only when visiting the last feeder of the set. In Expt. 1 with eight feeders arranged in five different configurations the rats made after 10 days of training 1 error in the first 8 choices and incidence of errorless trials was about 20%. In Expt. 2. the use of six feeders in a rectangular (A) or double triangle (B) configuration increased the incidence of errorless trials to 60%. Expt. 3 showed that performance in the 6-feeder maze was significantly impaired by 6 mg/kg ketamine or 0.25 mg/kg scopolamine but not by lower dosages of these drugs. Tours generated on errorless trials (each feeder visited only once) during 10 days of Expt. 2 were analyzed. Six places can be visited in 6! = 720 different closed tours the lengths of which (in arbitrary units) range from 6.00 to 10.12 for A and from 6.83 to 10.47 for B. Whereas random generation of correct routes yielded only 5% of the shortest tours, they were clearly preferred by rats (41% in A and 45% in B). The apparent proficiency of rats in this optimization problem is probably not due to cognitive comparison of the possible correct routes but rather to following a simple rule 'Always go to the nearest not yet visited feeder'.

Pathological changes in hippocampal neuronal circuits underlie age-associated neurodegeneration and memory loss: positive clue toward SAD.

PubMed

Moorthi, P; Premkumar, P; Priyanka, R; Jayachandran, K S; Anusuyadevi, M

2015-08-20

Among vertebrates hippocampus forms the major component of the brain in consolidating information from short-term memory to long-term memory. Aging is considered as the major risk factor for memory impairment in sporadic Alzheimer's disease (SAD) like pathology. Present study thus aims at investigating whether age-specific degeneration of neuronal-circuits in hippocampal formation (neural-layout of Subiculum-hippocampus proper-dentate gyrus (DG)-entorhinal cortex (EC)) results in cognitive impairment. Furthermore, the neuroprotective effect of Resveratrol (RSV) was attempted to study in the formation of hippocampal neuronal-circuits. Radial-Arm-Maze was conducted to evaluate hippocampal-dependent spatial and learning memory in control and experimental rats. Nissl staining of frontal cortex (FC), subiculum, hippocampal-proper (CA1→CA2→CA3→CA4), DG, amygdala, cerebellum, thalamus, hypothalamus, layers of temporal and parietal lobe of the neocortex were examined for pathological changes in young and aged wistar rats, with and without RSV. Hippocampal trisynaptic circuit (EC layerII→DG→CA3→CA1) forming new memory and monosynaptic circuit (EC→CA1) that strengthen old memories were found disturbed in aged rats. Loss of Granular neuron observed in DG and polymorphic cells of CA4 can lead to decreased mossy fibers disturbing neural-transmission (CA4→CA3) in perforant pathway. Further, intensity of nissl granules (stratum lacunosum moleculare (SLM)-SR-SO) of CA3 pyramidal neurons was decreased, disturbing the communication in schaffer collaterals (CA3-CA1) during aging. We also noticed disarranged neuronal cell layer in Subiculum (presubiculum (PrS)-parasubiculum (PaS)), interfering output from hippocampus to prefrontal cortex (PFC), EC, hypothalamus, and amygdala that may result in interruption of thought processes. We conclude from our observations that poor memory performance of aged rats as evidenced through radial arm maze (RAM) analysis was due to the defect in neuronal-circuits of hippocampus (DG-CA4-CA1-Sub) that were significantly damaged leading to memory impairment. Interestingly, RSV was observed to culminate pathological events in the hippocampal neuronal circuit during aging, proving them as potent therapeutic drug against age-associated neurodegeneration and memory loss. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Effect of rotation preference on spontaneous alternation behavior on Y maze and introduction of a new analytical method, entropy of spontaneous alternation.

PubMed

Bak, Jia; Pyeon, Hae-In; Seok, Jin-I; Choi, Yun-Sik

2017-03-01

Y maze has been used to test spatial working memory in rodents. To this end, the percentage of spontaneous alternation has been employed. Alternation indicates sequential entries into all three arms; e.g., when an animal visits all three arms clockwise or counterclockwise sequentially, alternation is achieved. Interestingly, animals have a tendency to rotate or turn to a preferred side. Thus, when an animal has a high rotation preference, this may influence their alternation behavior. Here, we have generated a new analytical method, termed entropy of spontaneous alternation, to offset the effect of rotation preference on Y maze. To validate the entropy of spontaneous alternation, we employed a free rotation test using a cylinder and a spatial working memory test on Y maze. We identified that mice showed 65.1% rotation preference on average. Importantly, the percentage of spontaneous alternation in the high preference group (more than 70% rotation to a preferred side) was significantly higher than that in the no preference group (<55%). In addition, there was a clear correlation between rotation preference on cylinder and turning preference on Y maze. On the other hand, this potential leverage effect that arose from rotation preference disappeared when the animal behavior on Y maze was analyzed with the entropy of spontaneous alternation. Further, entropy of spontaneous alternation significantly determined the loss of spatial working memory by scopolamine administration. Combined, these data indicate that the entropy of spontaneous alternation provides higher credibility when spatial working memory is evaluated using Y maze. Copyright © 2016 Elsevier B.V. All rights reserved.

GABA receptors in the region of the dorsomedial hypothalamus of rats regulate anxiety in the elevated plus-maze test. II. Physiological measures.

PubMed

Shekhar, A; Sims, L S; Bowsher, R R

1993-11-05

In the previous report, we had shown that blockade and enhancement of GABAA receptors in the DMH of rats increased or decreased the level of anxiety, respectively, as measured by the elevated plus-maze test. The present study was conducted to assess the effects of enhancing GABAA neurotransmission in the DMH of rats on the physiological concomitants of anxiety such as increases in heart rate (HR), blood pressure (BP) and plasma norepinephrine (NE) levels while the animals were placed on the elevated plus-maze. Male Sprague-Dawley rats were equipped with arterial and venous catheters and stereotaxically implanted with microinjection cannulae in the cardiostimulatory region of the DMH where injection of bicuculline methiodide (BMI) elicited increases in heart rate under anesthesia. After recovery, rats were injected with either saline or the GABAA agonist muscimol and their HR, BP and plasma NE responses were measured when confined in the open or the closed arm of the elevated plus-maze. Injection of muscimol into the DMH reduced the increases seen in HR, BP and plasma NE when the rats were confined to either the closed or the open arms in addition to decreasing 'anxiety' in the plus-maze. Injection of muscimol into the areas of the hypothalamus surrounding the DMH did not significantly affect the changes in HR, BP and plasma NE in the plus-maze. Blocking the changes in HR and BP elicited by microinjecting GABAergic drugs into the DMH of rats, with systemic injections of a combination of atropine and the beta-blocker atenolol, did not block the behavioral effects of the GABAergic drugs in the plus-maze test.

Nootropic and hypophagic effects following long term intake of almonds (Prunus amygdalus) in rats.

PubMed

Haider, S; Batool, Z; Haleem, D J

2012-01-01

Over a period of time researchers have become more interested in finding out the potential of various foods to maintain the general health and to treat diseases. Almonds are a very good source of many nutrients which may help to sharpen the memory and to reduce cardiovascular risk factors. The present study was conducted to evaluate the nootropic effects of almonds. Effect of oral intake of almond was also monitored on food intake and plasma cholesterol levels. Rats were given almond paste orally with the help of feeding tube for 28 days. Memory function in rats was assessed by Elevated Plus Maze (EPM) and Radial Arm Maze (RAM). Brain tryptophan, 5-HT and 5-HIAA were estimated at the end of the treatment by HPLC-EC method. A significant improvement in learning and memory of almond treated rats compared to controls was observed. Almond treated rats also exhibited a significant decrease in food intake and plasma cholesterol levels while the change in growth rate (in terms of percentage) remained comparable between the two groups. Analysis of brain tryptophan (TRP) monoamines exhibited enhanced TRP levels and serotonergic turnover in rat brain following oral intake of almonds. The findings show that almonds possess significant hypophagic and nootropic effects. Results are discussed in context of enhanced 5-HT metabolism following almond administration.

Effects of melatonin on aluminium-induced neurobehavioral and neurochemical changes in aging rats.

PubMed

Allagui, M S; Feriani, A; Saoudi, M; Badraoui, R; Bouoni, Z; Nciri, R; Murat, J C; Elfeki, A

2014-08-01

This study aimed to investigate the potential protective effects of melatonin (Mel) against aluminium-induced neurodegenerative changes in aging Wistar rats (24-28months old). Herein, aluminium chloride (AlCl3) (50mg/kg BW/day) was administered by gavage, and melatonin (Mel) was co-administered to a group of Al-treated rats by an intra-peritoneal injection at a daily dose of 10mg/kg BW for four months. The findings revealed that aluminium administration induced a significant decrease in body weight associated with marked mortality for the old group of rats, which was more pronounced in old Al-treated rats. Behavioural alterations were assessed by 'open fields', 'elevated plus maze' and 'Radial 8-arms maze' tests. The results demonstrated that Mel co-administration alleviated neurobehavioral changes in both old and old Al-treated rats. Melatonin was noted to play a good neuroprotective role, reducing lipid peroxidation (TBARs), and enhancing enzymatic (SOD, CAT and GPx) activities in the brain organs of old control and old Al-treated rats. Mel treatment also reversed the decrease of AChE activity in the brain tissues, which was confirmed by histological sections. Overall, the results showed that Mel administration can induce beneficial effects for the treatment of Al-induced neurobehavioral and neurochemical changes in the central nervous system (CNS). Copyright © 2014 Elsevier Ltd. All rights reserved.

Nicotine versus 6-hydroxy-l-nicotine against chlorisondamine induced memory impairment and oxidative stress in the rat hippocampus.

PubMed

Hritcu, Lucian; Ionita, Radu; Motei, Diana Elena; Babii, Cornelia; Stefan, Marius; Mihasan, Marius

2017-02-01

6-Hydroxy-l-nicotine (6HLN), a nicotine derivative from nicotine degradation by Arthrobacter nicotinovorans pAO1 strain was found to improve behavioral deficits and to reverse oxidative stress in the rat hippocampus. Rats were given CHL (10mg/kg, i.p.) were used as an Alzheimer's disease-like model. The nicotine (0.3mg/kg) and 6HLN (0.3mg/kg) were administered alone or in combination in the CHL-treated rats. Memory-related behaviors were evaluated using Y-maze and radial arm-maze tests. The antioxidant enzymes activity and the levels of the biomarkers of oxidative stress were measured in the hippocampus. Statistical analyses were performed using two-way ANOVA and Tukey's post hoc test. F values for which p<0.05 were regarded as statistically significant. CHL-caused memory deficits and oxidative stress enhancing were observed. Both nicotine and 6HLN administration attenuated the cognitive deficits and recovered the antioxidant capacity in the rat hippocampus of the CHL rat model. Our results suggest that 6HLN versus nicotine confers anti-amnesic properties in the CHL-induced a rat model of memory impairment via reversing cholinergic function and decreasing brain oxidative stress, suggesting the use of this compound as an alternative agent in AD treatment. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Invertebrate neurobiology: visual direction of arm movements in an octopus.

PubMed

Niven, Jeremy E

2011-03-22

An operant task in which octopuses learn to locate food by a visual cue in a three-choice maze shows that they are capable of integrating visual and mechanosensory information to direct their arm movements to a goal. Copyright © 2011 Elsevier Ltd. All rights reserved.

Elevated plus-maze performance of Fischer-344 rats as a function of age and of exposure to 56Fe particles

NASA Astrophysics Data System (ADS)

Rabin, Bernard M.; Carrihill-Knoll, Kirsty L.; Carey, Amanda N.; Shukitt-Hale, Barbara; Joseph, James A.; Foster, Brian C.

The aging process is characterized by a series of changes in neurochemical functioning and in motor and cognitive performance. In addition to changes in cognitive/behavioral performance, aged rats also show an increase in baseline anxiety measured using the elevated plus-maze. Exposure to 56Fe particles, a component of cosmic rays, produces neurochemical and behavioral changes in young animals which are characteristic of aged organisms. The present study was designed to determine the relationships between aging and exposure to 56Fe particles on anxiety. Fischer-344 (F-344), which were 2, 7, 12, and 16 months of age at the time of irradiation, were exposed to 56Fe particles (50 200 cGy). Concordant with previous results, the oldest rats spent less time exploring the open arms of the maze. Exposure to 56Fe particles also produced decreased exploration of the open arms of the plus-maze. The dose needed to produce increased levels of anxiety was a function of age at the time of irradiation. The dose of 56Fe particles needed to produce a decrease in open arm exploration was significantly lower in the rats that were irradiated at 7 and 12 months of age than in the rats irradiated at 2 months of age. These results suggest the possibility that exposing middle-aged astronauts to cosmic rays during exploratory class missions outside the magnetosphere, and the resultant effects on exploration-induced anxiety, may affect their ability to successfully complete mission requirements.

Influence of magnetic field on zebrafish activity and orientation in a plus maze.

PubMed

Osipova, Elena A; Pavlova, Vera V; Nepomnyashchikh, Valentin A; Krylov, Viacheslav V

2016-01-01

We describe an impact of the geomagnetic field (GMF) and its modification on zebrafish's orientation and locomotor activity in a plus maze with four arms oriented to the north, east, south and west. Zebrafish's directional preferences were bimodal in GMF: they visited two arms oriented in opposed directions (east-west) most frequently. This bimodal preference remained stable for same individuals across experiments divided by several days. When the horizontal GMF component was turned 90° clockwise, the preference accordingly shifted by 90° to arms oriented to the north and south. Other modifications of GMF (reversal of both vertical and horizontal GMF components; reversal of vertical component only; and reversal of horizontal component only) did not exert any discernible effect on the orientation of zebrafish. The 90° turn of horizontal component also resulted in a significant increase of fish's locomotor activity in comparison with the natural GMF. This increase became even more pronounced when the horizontal component was repeatedly turned by 90° and back with 1min interval between turns. Our results show that GMF and its variations should be taken into account when interpreting zebrafish's directional preferences and locomotor activity in mazes and other experimental devices. Copyright © 2015. Published by Elsevier B.V.

Concentric tube support assembly

DOEpatents

Rubio, Mark F.; Glessner, John C.

2012-09-04

An assembly (45) includes a plurality of separate pie-shaped segments (72) forming a disk (70) around a central region (48) for retaining a plurality of tubes (46) in a concentrically spaced apart configuration. Each segment includes a support member (94) radially extending along an upstream face (96) of the segment and a plurality of annularly curved support arms (98) transversely attached to the support member and radially spaced apart from one another away from the central region for receiving respective upstream end portions of the tubes in arc-shaped spaces (100) between the arms. Each segment also includes a radial passageway (102) formed in the support member for receiving a fluid segment portion (106) and a plurality of annular passageways (104) formed in the support arms for receiving respective arm portions (108) of the fluid segment portion from the radial passageway and for conducting the respective arm portions into corresponding annular spaces (47) formed between the tubes retained by the disk.

Central and peripheral administration of antisense oligonucleotide targeting amyloid-β protein precursor improves learning and memory and reduces neuroinflammatory cytokines in Tg2576 (AβPPswe) mice.

PubMed

Farr, Susan A; Erickson, Michelle A; Niehoff, Michael L; Banks, William A; Morley, John E

2014-01-01

Alzheimer's disease (AD) is a progressive neurodegenerative disease. Currently, there are no therapies to stop or reverse the symptoms of AD. We have developed an antisense oligonucleotide (OL-1) against the amyloid-β protein precursor (AβPP) that can decrease AβPP expression and amyloid-β protein (Aβ) production. This antisense rapidly crosses the blood-brain barrier, reverses learning and memory impairments, reduces oxidative stress, and restores brain-to-blood efflux of Aβ in SAMP8 mice. Here, we examined the effects of this AβPP antisense in the Tg2576 mouse model of AD. We administered the OL-1 antisense into the lateral ventricle 3 times at 2week intervals. Seventy-two hours after the third injection, we tested learning and memory in T-maze foot shock avoidance. In the second study, we injected the mice with OL-1 antisense 3 times at 2-week intervals via the tail vein. Seventy-two hours later, we tested learning and memory T-maze, novel object recognition, and elevated plus maze. At the end of behavioral testing, brain tissue was collected. OL-1 antisense administered centrally improved acquisition and retention of T-maze foot shock avoidance. OL-1 antisense administered via tail vein improved learning and memory in both T-maze foot shock avoidance and novel object-place recognition. In the elevated plus maze, the mice which received OL-1 antisense spent less time in the open arms and had fewer entries into the open arms indicating reduced disinhibitation. Biochemical analyses reveal significant reduction of AβPP signal and a reduction of measures of neuroinflammation. The current findings support the therapeutic potential of OL-1 AβPP antisense.

Glucocorticoids mediate stress-induced impairment of retrieval of stimulus-response memory.

PubMed

Atsak, Piray; Guenzel, Friederike M; Kantar-Gok, Deniz; Zalachoras, Ioannis; Yargicoglu, Piraye; Meijer, Onno C; Quirarte, Gina L; Wolf, Oliver T; Schwabe, Lars; Roozendaal, Benno

2016-05-01

Acute stress and elevated glucocorticoid hormone levels are well known to impair the retrieval of hippocampus-dependent 'declarative' memory. Recent findings suggest that stress might also impair the retrieval of non-hippocampal memories. In particular, stress shortly before retention testing was shown to impair the retrieval of striatal stimulus-response associations in humans. However, the mechanism underlying this stress-induced retrieval impairment of non-hippocampal stimulus-response memory remains elusive. In the present study, we investigated whether an acute elevation in glucocorticoid levels mediates the impairing effects of stress on retrieval of stimulus-response memory. Male Sprague-Dawley rats were trained on a stimulus-response task in an eight-arm radial maze until they learned to associate a stimulus, i.e., cue, with a food reward in one of the arms. Twenty-four hours after successful acquisition, they received a systemic injection of vehicle, corticosterone (1mg/kg), the corticosterone-synthesis inhibitor metyrapone (35mg/kg) or were left untreated 1h before retention testing. We found that the corticosterone injection impaired the retrieval of stimulus-response memory. We further found that the systemic injection procedure per se was stressful as the vehicle administration also increased plasma corticosterone levels and impaired the retrieval of stimulus-response memory. However, memory retrieval was not impaired when rats were tested 2min after the systemic vehicle injection, before any stress-induced elevation in corticosterone levels had occurred. Moreover, metyrapone treatment blocked the effect of injection stress on both plasma corticosterone levels and memory retrieval impairment, indicating that the endogenous corticosterone response mediates the stress-induced memory retrieval impairment. None of the treatments affected rats' locomotor activity or motivation to search for the food reward within the maze. These findings show that stress may affect memory processes beyond the hippocampus and that these stress effects are due to the action of glucocorticoids. Copyright © 2016 Elsevier Ltd. All rights reserved.

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 parallel pathology and behavior in the same mice. Copyright © 2011. Published by Elsevier Inc.

Investigating virtual reality navigation in amnestic mild cognitive impairment using fMRI.

PubMed

Migo, E M; O'Daly, O; Mitterschiffthaler, M; Antonova, E; Dawson, G R; Dourish, C T; Craig, K J; Simmons, A; Wilcock, G K; McCulloch, E; Jackson, S H D; Kopelman, M D; Williams, S C R; Morris, R G

2016-01-01

Spatial navigation requires a well-established network of brain regions, including the hippocampus, caudate nucleus, and retrosplenial cortex. Amnestic Mild Cognitive Impairment (aMCI) is a condition with predominantly memory impairment, conferring a high predictive risk factor for dementia. aMCI is associated with hippocampal atrophy and subtle deficits in spatial navigation. We present the first use of a functional Magnetic Resonance Imaging (fMRI) navigation task in aMCI, using a virtual reality analog of the Radial Arm Maze. Compared with controls, aMCI patients showed reduced activity in the hippocampus bilaterally, retrosplenial cortex, and left dorsolateral prefrontal cortex. Reduced activation in key areas for successful navigation, as well as additional regions, was found alongside relatively normal task performance. Results also revealed increased activity in the right dorsolateral prefrontal cortex in aMCI patients, which may reflect compensation for reduced activations elsewhere. These data support suggestions that fMRI spatial navigation tasks may be useful for staging of progression in MCI.

Multi-characteristic opsin enabled vision restoration

NASA Astrophysics Data System (ADS)

Wright, Weldon; Pradhan, Sanjay; Bhattacharya, Sulgana; Mahapatra, Vasu; Tripathy, Ashutosh; Gajjeraman, Sivakumar; Mohanty, Samarendra

2017-02-01

Photodegenerative retinal diseases such as retinitis pigmentosa (RP) and dry age related macular degeneration (dry- AMD) lead to loss of vision in millions of individuals. Currently, no surgical or medical treatment is available though optogenetic therapies are in clinical development. Here, we demonstrate vision restoration using Multi- Characteristics Opsin (MCO1) in animal models with photo-degenerated retina. MCO1 is reliably delivered to specific retinal cells via intravitreal injection of Adeno-Associated Virus, leading to significant improvement in visually guided behavior conducted using a radial-arm water maze. The time to reach platform significantly reduced after delivery of MCO1. Notably, the improvement in visually guided behavior was observed even at light intensity levels orders of magnitude lower than that required for Channelrhodopsin-2 opsin. Chronic light exposure study showed that chronic light exposure did not compromise viability of vMCO1-treated retina. Safe virus-mediated MCO1-delivery has potential for effective gene therapy of diverse retinal degenerations in patients.

The lateral septum and anterior hypothalamus act in tandem to regulate burying in the shock-probe test but not open-arm avoidance in the elevated plus-maze.

PubMed

Lamontagne, Steven J; Olmstead, Mary C; Menard, Janet L

2016-11-01

Both the lateral septum (LS) and anterior hypothalamus (AHA) regulate behavioural defense. We tested whether those two interconnected structures act in serial in that regard. Infusions of the GABAA agonist muscimol into one side of the LS and the contralateral (but not ipsilateral) AHA suppressed rats' burying in the shock-probe test whereas none of our muscimol infusion approaches altered their open-arm avoidance in the elevated plus-maze. These results suggest that the LS-AHA circuit serves a specialized role in defensive responses towards discrete, localizable threat stimuli but not towards potential threats. Copyright © 2016 Elsevier B.V. All rights reserved.

Maternal choline supplementation improves spatial learning and adult hippocampal neurogenesis in the Ts65Dn mouse model of Down syndrome.

PubMed

Velazquez, Ramon; Ash, Jessica A; Powers, Brian E; Kelley, Christy M; Strawderman, Myla; Luscher, Zoe I; Ginsberg, Stephen D; Mufson, Elliott J; Strupp, Barbara J

2013-10-01

In addition to intellectual disability, individuals with Down syndrome (DS) exhibit dementia by the third or fourth decade of life, due to the early onset of neuropathological changes typical of Alzheimer's disease (AD). Deficient ontogenetic neurogenesis contributes to the brain hypoplasia and hypocellularity evident in fetuses and children with DS. A murine model of DS and AD (the Ts65Dn mouse) exhibits key features of these disorders, notably deficient ontogenetic neurogenesis, degeneration of basal forebrain cholinergic neurons (BFCNs), and cognitive deficits. Adult hippocampal (HP) neurogenesis is also deficient in Ts65Dn mice and may contribute to the observed cognitive dysfunction. Herein, we demonstrate that supplementing the maternal diet with additional choline (approximately 4.5 times the amount in normal rodent chow) dramatically improved the performance of the adult trisomic offspring in a radial arm water maze task. Ts65Dn offspring of choline-supplemented dams performed significantly better than unsupplemented Ts65Dn mice. Furthermore, adult hippocampal neurogenesis was partially normalized in the maternal choline supplemented (MCS) trisomic offspring relative to their unsupplemented counterparts. A significant correlation was observed between adult hippocampal neurogenesis and performance in the water maze, suggesting that the increased neurogenesis seen in the supplemented trisomic mice contributed functionally to their improved spatial cognition. These findings suggest that supplementing the maternal diet with additional choline has significant translational potential for DS. Copyright © 2013 Elsevier Inc. All rights reserved.

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

Maternal choline supplementation improves spatial learning and adult hippocampal neurogenesis in the Ts65Dn mouse model of Down syndrome

PubMed Central

Velazquez, Ramon; Ash, Jessica A.; Powers, Brian E.; Kelley, Christy M.; Strawderman, Myla; Luscher, Zoe I.; Ginsberg, Stephen D.; Mufson, Elliott J.; Strupp, Barbara J.

2014-01-01

In addition to intellectual disability, individuals with Down syndrome (DS) exhibit dementia by the third or fourth decade of life, due to the early onset of neuropathological changes typical of Alzheimer’s disease (AD). Deficient ontogenetic neurogenesis contributes to the brain hypoplasia and hypocellularity evident in fetuses and children with DS. A murine model of DS and AD (the Ts65Dn mouse) exhibits key features of these disorders, notably deficient ontogenetic neurogenesis, degeneration of basal forebrain cholinergic neurons (BFCNs), and cognitive deficits. Adult hippocampal (HP) neurogenesis is also deficient in Ts65Dn mice and may contribute to the observed cognitive dysfunction. Herein, we demonstrate that supplementing the maternal diet with additional choline (approximately 4.5 times the amount in normal rodent chow) dramatically improved the performance of the adult trisomic offspring in a radial arm water maze task. Ts65Dn offspring of choline-supplemented dams performed significantly better than unsupplemented Ts65Dn mice. Furthermore, adult hippocampal neurogenesis was partially normalized in the maternal choline supplemented (MCS) trisomic offspring relative to their unsupplemented counterparts. A significant correlation was observed between adult hippocampal neurogenesis and performance in the water maze, suggesting that the increased neurogenesis seen in the supplemented trisomic mice contributed functionally to their improved spatial cognition. These findings suggest that supplementing the maternal diet with additional choline has significant translational potential for DS. PMID:23643842

Long-term behavioral consequences of prenatal MDMA exposure.

PubMed

Thompson, Valerie B; Heiman, Justin; Chambers, James B; Benoit, Stephen C; Buesing, William R; Norman, Mantana K; Norman, Andrew B; Lipton, Jack W

2009-03-23

The current study sought to determine whether prenatal 3,4-methylenedioxy-N-methamphetamine (MDMA) exposure from E14-20 in the rat resulted in behavioral sequelae in adult offspring. Prenatal MDMA exposure results in increased dopaminergic fiber density in the prefrontal cortex, striatum and nucleus accumbens of young rats. Since these areas are critical in response to novelty, reward, attention and locomotor activity, we hypothesized that prenatal MDMA exposure would produce significant changes in the performance of tasks that examine such behaviors in adult rats. Adult rats prenatally exposed to MDMA exhibited greater activity and spent more time in the center during a novel open field test as compared to controls. This increased activity was not reflected in normal home cage activity. Prenatal exposure to MDMA did not affect feeding or food reward. It did not alter cocaine self-administration behaviors, nor did it have an effect on the locomotor response to amphetamine challenge. Finally, while prenatal MDMA did not affect performance in the radial arm maze or the Morris water maze (MWM), these animals demonstrated altered performance in a cued MWM paradigm. Prenatal MDMA exposure resulted in perseverative attendance to a hanging cue when the platform in the MWM was removed as compared to controls. Together, these data demonstrate that prenatal exposure to MDMA results in a behavioral phenotype in adult rats characterized by reduced anxiety, a heightened response to novelty, and "hyperattentiveness" to environmental cues during spatial learning.

Effects of the estrous cycle and ovarian hormones on behavioral indices of anxiety in female rats.

PubMed

Mora, S; Dussaubat, N; Díaz-Véliz, G

1996-10-01

The influence of the estrous cycle and the effects of exogenous administration of estradiol and progesterone on level of anxiety were studied in intact and ovariectomized rats. Intact Sprague-Dawley female rats were classified according to the stages of estrous cycle. Another group of rats was ovariectomized bilaterally and, 14 days after surgery, they received estradiol benzoate (10 micrograms/kg, s.c.) and/or progesterone (25 mg/kg, s.c.) or corn oil (1 ml/kg). The behavioral tests began 3 h after estradiol or 6 h after progesterone and consisted of: (1) exploration of an elevated plus-maze; and (2) retention of a passive avoidance response. Open-arm exploration of the plus-maze varied according to light intensity and the stages of the estrous cycle. There was a slight increase in open-arm exploration by rats in metestrus, under high light intensity. Low light intensity increased the exploration of the open arms by rats in proestrus and estrus, compared to the other phases of the cycle. Retention of the passive avoidance response was inhibited during proestrus and estrus. Progesterone increased open-arm exploration of the plus-maze under high light conditions, whereas estradiol antagonized this effect. Retention of passive avoidance was inhibited after estradiol or progesterone injection. These results suggest that the behavioral indices of anxiety can vary across the estrous cycle, that low light intensities have anxiolytic-like effects, and that the sensitivity to this effect is higher during proestrus and estrus. This could be explained through modulatory effects of ovarian hormones upon behavioral indices of anxiety.

Anxiolytic-like effect of Sonchus oleraceus L. in mice.

PubMed

Cardoso Vilela, Fabiana; Soncini, Roseli; Giusti-Paiva, Alexandre

2009-07-15

Sonchus oleraceus L. has been used as a general tonic in Brazilian folk medicine. Nevertheless, available scientific information regarding this species is scarce; there are no reports related to its possible effect on the central nervous system. This study was conducted to establish the anxiolytic effect of extracts from the aerial parts of Sonchus oleraceus. This study evaluated the effect of hydroethanolic and dichloromethane extracts of Sonchus oleraceus in mice submitted to the elevated plus-maze and open-field tests. Clonazepam was used as the standard drug. In the elevated plus-maze test, the Sonchus oleraceus extracts increased the percentage of open arm entries (P<0.05) and time spent in the open-arm portions of the maze (P<0.05). The extracts induce an anti-thigmotactic effect, evidenced by increased locomotor activity into the central part of the open field set-up (P<0.05). The extracts administered at 30-300 mg/kg, p.o. had a similar anxiolytic effect to clonazepam (0.5 mg/kg, p.o.). These data indicate that Sonchus oleraceus extract exerts an anxiolytic-like effect on mice.

Threshold relationship between lesion extent of the cholinergic basal forebrain in the rat and working memory impairment in the radial maze.

PubMed

Wrenn, C C; Lappi, D A; Wiley, R G

1999-11-20

The cholinergic basal forebrain (CBF) degenerates in Alzheimer's Disease (AD), and the degree of this degeneration correlates with the degree of dementia. In the present study we have modeled this degeneration in the rat by injecting various doses of the highly selective immunotoxin 192 IgG-saporin (192-sap) into the ventricular system. The ability of 192-sap-treated rats to perform in a previously learned radial maze working memory task was then tested. We report here that 192-sap created lesions of the CBF and, to a lesser extent, cerebellar Purkinje cells in a dose-dependent fashion. Furthermore, we found that rats harboring lesions of the entire CBF greater than 75% had impaired spatial working memory in the radial maze. Correlational analysis of working memory impairment and lesion extent of the component parts of the CBF revealed that high-grade lesions of the hippocampal-projecting neurons of the CBF were not sufficient to impair working memory. Only rats with high-grade lesions of the hippocampal and cortical projecting neurons of the CBF had impaired working memory. These data are consistent with other 192-sap reports that found behavioral deficits only with high-grade CBF lesions and indicate that the relationship between CBF lesion extent and working memory impairment is a threshold relationship in which a high degree of neuronal loss can be tolerated without detectable consequences. Additionally, the data suggest that the CBF modulates spatial working memory via its connections to both the hippocampus and cortex.

Radial nerve dysfunction (image)

MedlinePlus

The radial nerve travels down the arm and supplies movement to the triceps muscle at the back of the upper arm. ... the wrist and hand. The usual causes of nerve dysfunction are direct trauma, prolonged pressure on the ...

Color Doppler Sonographic and Cadaveric Study of the Arterial Vascularity of the Lateral Upper Arm Flap.

PubMed

Sun, Ruimei; Ding, Yu; Sun, Chuanzheng; Li, Xiaojiang; Wang, Jinde; Li, Lei; Yang, Jie; Ren, Yanxin; Zhong, Zhaoming

2016-04-01

To determine the importance of adequate preoperative assessment with color Doppler sonography to assist in the successful transfer of lateral upper arm flaps by studying the lateral upper arm flap with color Doppler sonography and analyzing the anatomic features of the radial collateral artery. A clinical case-control study was performed. The radial collateral artery was studied with color Doppler sonography in 15 healthy volunteers. The origins, courses, variations, and locations of the perforators of the radial collateral artery were recorded. The results and data from the color Doppler sonographic investigation were compared with an anatomic study that was performed on 22 adult cadaveric upper limb specimens. The volunteer group (14 of 15 volunteers) and the cadaveric group (19 of 22 upper arm specimens) clearly showed that the branch pattern of the arterial supply was as follows: brachial artery → deep brachial artery → radial collateral artery → posterior radial collateral artery → myocutaneous perforator. Variations in the origin of the radial collateral artery were identified in 1 volunteer bilaterally and in 3 upper arm specimens. The diameters of the artery and vein measured at the distal insertion of the deltoid and the origin of the deep brachial artery were not significantly different between the volunteer and cadaver groups (P > .05). Due to the difference in measuring methods, the length of the vascular pedicles was significantly different between the groups (P < .05). Color Doppler sonography can facilitate the preoperative assessment of the origin, course, variations, and locations of the radial collateral artery and therefore may increase the success rate of lateral upper arm flap transfer. © 2016 by the American Institute of Ultrasound in Medicine.

Effect of experience with pine (Pituophis melanoleucus) and king (Lampropeltis getulus) snake odors on Y-maze behavior of pine snake hatchlings.

PubMed

Burger, J; Boarman, W; Kurzava, L; Gochfeld, M

1991-01-01

The abilities of hatchling pine snakes (Pituophis melanoleucus) and king snakes (Lampropeltis getulus) to discriminate the chemical trails of pine and king snakes was investigated inY-maze experiments. Pine snakes were housed for 17 days either with shavings impregnated with pine snake odor, king snake odor, or no odor to test for the effect of experience on choice. Both pine and king snake hatchlings entered the arm with the pine snake odor and did not enter the arm with the king snake odor. The data support the hypothesis that hatchlings of both species can distinguish conspecific odors from other odors and that our manipulation of previous experience was without effect for pine snake hatchlings.

A Chronic Longitudinal Characterization of Neurobehavioral and Neuropathological Cognitive Impairment in a Mouse Model of Gulf War Agent Exposure

PubMed Central

Zakirova, Zuchra; Crynen, Gogce; Hassan, Samira; Abdullah, Laila; Horne, Lauren; Mathura, Venkatarajan; Crawford, Fiona; Ait-Ghezala, Ghania

2016-01-01

Gulf War Illness (GWI) is a chronic multisymptom illness with a central nervous system component that includes memory impairment as well as neurological and musculoskeletal deficits. Previous studies have shown that in the First Persian Gulf War conflict (1990–1991) exposure to Gulf War (GW) agents, such as pyridostigmine bromide (PB) and permethrin (PER), were key contributors to the etiology of GWI. For this study, we used our previously established mouse model of GW agent exposure (10 days PB+PER) and undertook an extensive lifelong neurobehavioral characterization of the mice from 11 days to 22.5 months post exposure in order to address the persistence and chronicity of effects suffered by the current GWI patient population, 24 years post-exposure. Mice were evaluated using a battery of neurobehavioral testing paradigms, including Open Field Test (OFT), Elevated Plus Maze (EPM), Three Chamber Testing, Radial Arm Water Maze (RAWM), and Barnes Maze (BM) Test. We also carried out neuropathological analyses at 22.5 months post exposure to GW agents after the final behavioral testing. Our results demonstrate that PB+PER exposed mice exhibit neurobehavioral deficits beginning at the 13 months post exposure time point and continuing trends through the 22.5 month post exposure time point. Furthermore, neuropathological changes, including an increase in GFAP staining in the cerebral cortices of exposed mice, were noted 22.5 months post exposure. Thus, the persistent neuroinflammation evident in our model presents a platform with which to identify novel biological pathways, correlating with emergent outcomes that may be amenable to therapeutic targeting. Furthermore, in this work we confirmed our previous findings that GW agent exposure causes neuropathological changes, and have presented novel data which demonstrate increased disinhibition, and lack of social preference in PB+PER exposed mice at 13 months after exposure. We also extended upon our previous work to cover the lifespan of the laboratory mouse using a battery of neurobehavioral techniques. PMID:26793076

INTERIOR VIEW WITH CARLTON RADIAL ARM DRILL PRESS (THE CARLTON ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

INTERIOR VIEW WITH CARLTON RADIAL ARM DRILL PRESS (THE CARLTON MACHINE TOOL CO., CINCINNATI, OHIO) WITH MACHINE OPERATOR, EDDIE BURTTRAM. - O'Neal Steel, Incorporated, Fabrication Shop, 744 Forty-first Avenue North, Birmingham, Jefferson County, AL

Preliminary evidence that abscisic acid improves spatial memory in rats.

PubMed

Qi, Cong-Cong; Ge, Jin-Fang; Zhou, Jiang-Ning

2015-02-01

Abscisic acid (ABA) is a crucial phytohormone that exists in a wide range of animals, including humans, and has multiple bioactivities. As direct derivatives of carotenoids, ABA and retinoic acid (RA) share similar molecular structures, and RA has been reported to improve spatial memory in rodents. To explore the potential effects of ABA on spatial learning and memory in rodents, 20mg/kg ABA was administered to young rats for 6weeks, and its effects on behaviour performance were evaluated through a series of behavioural tests. ABA pharmacokinetic analysis revealed that the exogenous ABA was distributed widely in the rat brain, characterised by rapid absorption and slow elimination. The behavioural tests showed that ABA increased both the duration spent in the target quadrant and the frequency it was entered in the probe test of the Morris water maze (MWM) and decreased the latency to locate the target quadrant. Moreover, ABA decreased the latency to enter the novel arm in the Y-maze test, accompanied by increases in the total entries and distance travelled in the three arms. However, there were no significant differences between the ABA-treated and control rats in the open field test and elevated plus-maze test. These results preliminarily indicate that ABA improves spatial memory in MWM and exploratory activity in Y-maze in young rats. Copyright © 2014 Elsevier Inc. All rights reserved.

Memory deficits associated with sublethal cyanide poisoning relative to cyanate toxicity in rodents.

PubMed

Kimani, S; Sinei, K; Bukachi, F; Tshala-Katumbay, D; Maitai, C

2014-03-01

Food (cassava) linamarin is metabolized into neurotoxicants cyanide and cyanate, metabolites of which we sought to elucidate the differential toxicity effects on memory. Young 6-8 weeks old male rats were treated intraperitoneally with either 2.5 mg/kg body weight (bw) cyanide (NaCN), or 50 mg/kg bw cyanate (NaOCN), or 1 μl/g bw saline, daily for 6 weeks. Short-term and long-term memories were assessed using a radial arm maze (RAM) testing paradigm. Toxic exposures had an influence on short-term working memory with fewer correct arm entries (F(2, 19) = 4.57 p < 0.05), higher working memory errors (WME) (F(2, 19) = 5.09, p < 0.05) and longer RAM navigation time (F(2, 19) = 3.91, p < 0.05) for NaOCN relative to NaCN and saline treatments. The long-term working memory was significantly impaired by cyanide with fewer correct arm entries (F(2, 19) = 7.45, p < 0.01) and increased working memory errors (F(2, 19) = 9.35 p < 0.05) in NaCN relative to NaOCN or vehicle treated animals. Reference memory was not affected by either cyanide or cyanate. Our study findings provide an experimental evidence for the biological plausibility that cassava cyanogens may induce cognition deficits. Differential patterns of memory deficits may reflect the differences in toxicity mechanisms of NaOCN relative to NaCN. Cognition deficits associated with cassava cyanogenesis may reflect a dual toxicity effect of cyanide and cyanate.

Memory deficits associated with sublethal cyanide poisoning relative to cyanate toxicity in rodents

PubMed Central

Kimani, S.; Sinei, K.; Bukachi, F.; Tshala-Katumbay, D.; Maitai, C.

2014-01-01

Background Food (cassava) linamarin is metabolized into neurotoxicants cyanide and cyanate, metabolites of which we sought to elucidate the differential toxicity effects on memory. Methods Young 6-8 weeks old male rats were treated intraperitoneally with either 2.5 mg/kg body weight (bw) cyanide (NaCN), or 50 mg/kg bw cyanate (NaOCN), or 1 μl/g bw saline, daily for 6 weeks. Short-term and long-term memories were assessed using a radial arm maze (RAM) testing paradigm. Results Toxic exposures had an influence on short-term working memory with fewer correct arm entries (F 2, 19 = 4.57 p <0.05), higher working memory errors (WME) (F 2, 19 = 5.09, p <0.05) and longer RAM navigation time (F2, 19 = 3.91, p <0.05) for NaOCN relative to NaCN and saline treatments. The long-term working memory was significantly impaired by cyanide with fewer correct arm entries (F 2, 19 = 7.45, p <0.01) and increased working memory errors (F 2, 19 = 9.35 p <0.05) in NaCN relative to NaOCN or vehicle treated animals. Reference memory was not affected by either cyanide or cyanate. Conclusion Our study findings provide an experimental evidence for the biological plausibility that cassava cyanogens may induce cognition deficits. Differential patterns of memory deficits may reflect the differences in toxicity mechanisms of NaOCN relative to NaCN. Cognition deficits associated with cassava cyanogenesis may reflect a dual toxicity effect of cyanide and cyanate. PMID:24293006

Characterization of Peripheral Activity States and Cortical Local Field Potentials of Mice in an Elevated Plus Maze Test.

PubMed

Okonogi, Toya; Nakayama, Ryota; Sasaki, Takuya; Ikegaya, Yuji

2018-01-01

Elevated plus maze (EPM) tests have been used to assess animal anxiety levels. Little information is known regarding how physiological activity patterns of the brain-body system are altered during EPM tests. Herein, we monitored cortical local field potentials (LFPs), electrocardiograms (ECGs), electromyograms (EMGs), and respiratory signals in individual mice that were repeatedly exposed to EPM tests. On average, mouse heart rates were higher in open arms. In closed arms, the mice occasionally showed decreased heart and respiratory rates lasting for several seconds or minutes, characterized as low-peripheral activity states of peripheral signals. The low-activity states were observed only when the animals were in closed arms, and the frequencies of the states increased as the testing days proceeded. During the low-activity states, the delta and theta powers of cortical LFPs were significantly increased and decreased, respectively. These results demonstrate that cortical oscillations crucially depend on whether an animal exhibits low-activity states in peripheral organs rather than the EPM arm in which the animal is located. These results suggest that combining behavioral tests with physiological makers enables a more accurate evaluation of rodent mental states.

Alteration in Memory and Electroencephalogram Waves with Sub-acute Noise Stress in Albino Rats and Safeguarded by Scoparia dulcis.

PubMed

Loganathan, Sundareswaran; Rathinasamy, Sheeladevi

2016-01-01

Noise stress has different effects on memory and novelty and the link between them with an electroencephalogram (EEG) has not yet been reported. To find the effect of sub-acute noise stress on the memory and novelty along with EEG and neurotransmitter changes. Eight-arm maze (EAM) and Y-maze to analyze the memory and novelty by novel object test. Four groups of rats were used: Control, control treated with Scoparia dulcis extract, noise exposed, and noise exposed which received Scoparia extract. The results showed no marked difference observed between control and control treated with Scoparia extract on EAM, Y-maze, novel object test, and EEG in both prefrontal and occipital region, however, noise stress exposed rats showed significant increase in the reference memory and working memory error in EAM and latency delay, triad errors in Y-maze, and prefrontal and occipital EEG frequency rate with the corresponding increase in plasma corticosterone and epinephrine, and significant reduction in the novelty test, and significant reduction in the novelty test, amplitude of prefrontal, occipital EEG, and acetylcholine. These noise stress induced changes in EAM, Y-maze, novel object test, and neurotransmitters were significantly prevented when treated with Scoparia extract and these changes may be due to the normalizing action of Scoparia extract on the brain, which altered due to noise stress. Noise stress exposure causes EEG, behavior, and neurotransmitter alteration in the frontoparietal and occipital regions mainly involved in planning and recognition memoryOnly the noise stress exposed animals showed the significant alteration in the EEG, behavior, and neurotransmittersHowever, these noise stress induced changes in EEG behavior and neurotransmitters were significantly prevented when treated with Scoparia extractThese changes may be due to the normalizing action of Scoparia dulcis (adoptogen) on the brain which altered by noise stress. Abbreviations used: EEG: Electroencephalogram, dB: Decibel, EPI: Epinephrine, ACH: Acetylcholine, EAM: Eight-arm maze.

Alteration in Memory and Electroencephalogram Waves with Sub-acute Noise Stress in Albino Rats and Safeguarded by Scoparia dulcis

PubMed Central

Loganathan, Sundareswaran; Rathinasamy, Sheeladevi

2016-01-01

Background: Noise stress has different effects on memory and novelty and the link between them with an electroencephalogram (EEG) has not yet been reported. Objective: To find the effect of sub-acute noise stress on the memory and novelty along with EEG and neurotransmitter changes. Materials and Methods: Eight-arm maze (EAM) and Y-maze to analyze the memory and novelty by novel object test. Four groups of rats were used: Control, control treated with Scoparia dulcis extract, noise exposed, and noise exposed which received Scoparia extract. Results: The results showed no marked difference observed between control and control treated with Scoparia extract on EAM, Y-maze, novel object test, and EEG in both prefrontal and occipital region, however, noise stress exposed rats showed significant increase in the reference memory and working memory error in EAM and latency delay, triad errors in Y-maze, and prefrontal and occipital EEG frequency rate with the corresponding increase in plasma corticosterone and epinephrine, and significant reduction in the novelty test, and significant reduction in the novelty test, amplitude of prefrontal, occipital EEG, and acetylcholine. Conclusion: These noise stress induced changes in EAM, Y-maze, novel object test, and neurotransmitters were significantly prevented when treated with Scoparia extract and these changes may be due to the normalizing action of Scoparia extract on the brain, which altered due to noise stress. SUMMARY Noise stress exposure causes EEG, behavior, and neurotransmitter alteration in the frontoparietal and occipital regions mainly involved in planning and recognition memoryOnly the noise stress exposed animals showed the significant alteration in the EEG, behavior, and neurotransmittersHowever, these noise stress induced changes in EEG behavior and neurotransmitters were significantly prevented when treated with Scoparia extractThese changes may be due to the normalizing action of Scoparia dulcis (adoptogen) on the brain which altered by noise stress. Abbreviations used: EEG: Electroencephalogram, dB: Decibel, EPI: Epinephrine, ACH: Acetylcholine, EAM: Eight-arm maze PMID:27041862

Effects of acute caffeine on anxiety-related behavior in rats chronically exposed to the drug, with some evidence of possible withdrawal-reversal.

PubMed

Hughes, Robert N; Hancock, Nicola J

2017-03-15

For 20days male and female PVG/c hooded rats were provided with caffeinated (approximately 50mg/kg/day) or unadulterated drinking water, and then their anxiety-related behavior was observed in an open field and elevated plus maze. Their choices of a brightness change were also observed in a Y maze to assess any caffeine effects on spatial memory. 24h later, all rats were tested again following an intraperitoneal injection of 50mg/kg acute caffeine, or vehicle. Earlier chronic caffeine decreased ambulation, walking, rearing, center occupancy and increased immobility in the open field thereby suggesting increased anxiety. However, occupancy of the plus-maze open arms and the Y-maze novel arm were increased by caffeine for male rats, but decreased for females probably because of sex differences in control levels of the response rather than to drug effects on anxiety and memory respectively. Following caffeine withdrawal, acute caffeine had the opposite effect to chronic treatment namely, increased open-field ambulation, walking, center occupancy and decreased immobility and defecation for caffeine-naïve rats that were suggestive of decreased anxiety. Similar but more consistent effects (plus decreased emergence latencies from a darkened start box into the open field) also typified the caffeine-experienced rats which in this case may have been accentuated by caffeine withdrawal-reversal. There was no evidence of either chronic or acute caffeine affecting spatial memory measured in the Y maze. There were also examples of lower overall activity and higher anxiety in male rats, than in females, and some sex-dependent caffeine effects. Copyright © 2016 Elsevier B.V. All rights reserved.

Pro-social ultrasonic communication in rats: insights from playback studies.

PubMed

Seffer, Dominik; Schwarting, Rainer K W; Wöhr, Markus

2014-08-30

Rodent ultrasonic vocalizations (USV) serve as situation-dependent affective signals and convey important communicative functions. In the rat, three major USV types exist: (I) 40-kHz USV, which are emitted by pups during social isolation; (II) 22-kHz USV, which are produced by juvenile and adult rats in aversive situations, including social defeat; and (III) 50-kHz USV, which are uttered by juvenile and adult rats in appetitive situations, including rough-and-tumble play. Here, evidence for a communicative function of 50-kHz USV is reviewed, focusing on findings obtained in the recently developed 50-kHz USV radial maze playback paradigm. Up to now, the following five acoustic stimuli were tested in this paradigm: (A) natural 50-kHz USV, (B) natural 22-kHz USV, (C) artificial 50-kHz sine wave tones, (D) artificial time- and amplitude-matched white noise, and (E) background noise. All studies using the 50-kHz USV radial maze playback paradigm indicate that 50-kHz USV serve a pro-social affiliative function as social contact calls. While playback of the different kinds of acoustic stimuli used so far elicited distinct behavioral response patterns, 50-kHz USV consistently led to social approach behavior in the recipient, indicating that pro-social ultrasonic communication can be studied in a reliable and highly standardized manner by means of the 50-kHz USV radial maze playback paradigm. This appears to be particularly relevant for rodent models of neurodevelopmental disorders, as there is a tremendous need for reliable behavioral assays with face validity to social communication deficits seen in autism and schizophrenia in order to study underlying genetic and neurobiological alterations. Copyright © 2014 Elsevier B.V. All rights reserved.

Behavioral effects of diazepam in the murine plus-maze: flumazenil antagonism of enhanced head dipping but not the disinhibition of open-arm avoidance.

PubMed

Dalvi, A; Rodgers, R J

1999-04-01

Although it is widely believed that benzodiazepines reduce anxiety through positive allosteric modulation of the GABA(A)-chloride channel complex, this is not the only mechanism through which agents of this class can modify CNS function. Furthermore, a significant number of reports of apparent flumazenil blockade of diazepam anxiolysis in animal models have paid limited attention to possible intrinsic behavioral actions of the antagonist per se. In the present study, ethological methods were employed to assess in detail the effects of diazepam, flumazenil, and their combination on the behavior of male DBA/2 mice in the elevated plus-maze paradigm. In two experiments, diazepam (1.5 mg/kg) alone reduced open-arm avoidance and increased head dipping, whereas flumazenil (10-40 mg/kg) alone was without significant behavioral effect. However, with the sole exception of head dipping, prior administration of flumazenil (10 and 40 mg/kg) failed to block the behavioral effects of diazepam under present test conditions. These findings imply that the anxiolytic effects of diazepam in the mouse plus-maze are not mediated through flumazenil-sensitive benzodiazepine receptors and that alternate mechanisms must be considered.

Radial migration in numerical simulations of Milky-Way sized galaxies

NASA Astrophysics Data System (ADS)

Grand, R. J. J.; Kawata, D.

2016-09-01

We show that in ßrm N-body simulations of isolated spiral discs, spiral arms appear to transient, recurring features that co-rotate with the stellar disc stars at all radii. As a consequence, stars around the spiral arm continually feel a tangential force from the spiral and gain/lose angular momentum at all radii where spiral structure exists, without gaining significant amounts of random energy. We demonstrate that the ubiquitous radial migration in these simulations can be seen as outward (inward) systematic streaming motions along the trailing (leading) side of the spiral arms. We characterise these spiral induced peculiar motions and compare with those of the Milky Way obtained from APOGEE red clump data. We find that transient, co-rotating spiral arms are consistent with the data, in contrast with density wave-like spirals which are qualitatively inconsistent. In addition, we show that, in our simulations, radial migration does not change the radial metallicity gradient significantly, and broadens the metallicity distribution function at all radii, similar to some previous studies.

Spatial learning, monoamines and oxidative stress in rats exposed to 900 MHz electromagnetic field in combination with iron overload.

PubMed

Maaroufi, Karima; Had-Aissouni, Laurence; Melon, Christophe; Sakly, Mohsen; Abdelmelek, Hafedh; Poucet, Bruno; Save, Etienne

2014-01-01

The increasing use of mobile phone technology over the last decade raises concerns about the impact of high frequency electromagnetic fields (EMF) on health. More recently, a link between EMF, iron overload in the brain and neurodegenerative disorders including Parkinson's and Alzheimer's diseases has been suggested. Co-exposure to EMF and brain iron overload may have a greater impact on brain tissues and cognitive processes than each treatment by itself. To examine this hypothesis, Long-Evans rats submitted to 900 MHz exposure or combined 900 MHz EMF and iron overload treatments were tested in various spatial learning tasks (navigation task in the Morris water maze, working memory task in the radial-arm maze, and object exploration task involving spatial and non spatial processing). Biogenic monoamines and metabolites (dopamine, serotonin) and oxidative stress were measured. Rats exposed to EMF were impaired in the object exploration task but not in the navigation and working memory tasks. They also showed alterations of monoamine content in several brain areas but mainly in the hippocampus. Rats that received combined treatment did not show greater behavioral and neurochemical deficits than EMF-exposed rats. None of the two treatments produced global oxidative stress. These results show that there is an impact of EMF on the brain and cognitive processes but this impact is revealed only in a task exploiting spontaneous exploratory activity. In contrast, there are no synergistic effects between EMF and a high content of iron in the brain. Copyright © 2013 Elsevier B.V. All rights reserved.

Spatial learning and memory is preserved in rats after early development in a microgravity environment.

PubMed

Temple, Meredith D; Kosik, Kenneth S; Steward, Oswald

2002-09-01

This study evaluated the cognitive mapping abilities of rats that spent part of their early development in a microgravity environment. Litters of male and female Sprague-Dawley rat pups were launched into space aboard the National Aeronautics and Space Administration space shuttle Columbia on postnatal day 8 or 14 and remained in space for 16 days. These animals were designated as FLT groups. Two age-matched control groups remained on Earth: those in standard vivarium housing (VIV) and those in housing identical to that aboard the shuttle (AGC). On return to Earth, animals were tested in three different tasks that measure spatial learning ability, the Morris water maze (MWM), and a modified version of the radial arm maze (RAM). Animals were also tested in an open field apparatus to measure general activity and exploratory activity. Performance and search strategies were evaluated in each of these tasks using an automated tracking system. Despite the dramatic differences in early experience, there were remarkably few differences between the FLT groups and their Earth-bound controls in these tasks. FLT animals learned the MWM and RAM as quickly as did controls. Evaluation of search patterns suggested subtle differences in patterns of exploration and in the strategies used to solve the tasks during the first few days of testing, but these differences normalized rapidly. Together, these data suggest that development in an environment without gravity has minimal long-term impact on spatial learning and memory abilities. Any differences due to development in microgravity are quickly reversed after return to earth normal gravity.

Longitudinal attentional engagement rescues mice from age-related cognitive declines and cognitive inflexibility

PubMed Central

Matzel, Louis D.; Light, Kenneth R.; Wass, Christopher; Colas-Zelin, Danielle; Denman-Brice, Alexander; Waddel, Adam C.; Kolata, Stefan

2011-01-01

Learning, attentional, and perseverative deficits are characteristic of cognitive aging. In this study, genetically diverse CD-1 mice underwent longitudinal training in a task asserted to tax working memory capacity and its dependence on selective attention. Beginning at 3 mo of age, animals were trained for 12 d to perform in a dual radial-arm maze task that required the mice to remember and operate on two sets of overlapping guidance (spatial) cues. As previously reported, this training resulted in an immediate (at 4 mo of age) improvement in the animals' aggregate performance across a battery of five learning tasks. Subsequently, these animals received an additional 3 d of working memory training at 3-wk intervals for 15 mo (totaling 66 training sessions), and at 18 mo of age were assessed on a selective attention task, a second set of learning tasks, and variations of those tasks that required the animals to modify the previously learned response. Both attentional and learning abilities (on passive avoidance, active avoidance, and reinforced alternation tasks) were impaired in aged animals that had not received working memory training. Likewise, these aged animals exhibited consistent deficits when required to modify a previously instantiated learned response (in reinforced alternation, active avoidance, and spatial water maze). In contrast, these attentional, learning, and perseverative deficits were attenuated in aged animals that had undergone lifelong working memory exercise. These results suggest that general impairments of learning, attention, and cognitive flexibility may be mitigated by a cognitive exercise regimen that requires chronic attentional engagement. PMID:21521768

Ketamine-induced behavioural and brain oxidative changes in mice: an assessment of possible beneficial effects of zinc as mono- or adjunct therapy.

PubMed

Onaolapo, Olakunle James; Ademakinwa, Olayemi Quyyom; Olalekan, Temitayo Opeyemi; Onaolapo, Adejoke Yetunde

2017-09-01

We studied the influence of zinc, haloperidol or olanzapine on neurobehaviour (open-field, radial arm maze and elevated plus maze) and brain antioxidant status in vehicle- or ketamine-treated mice, with the aim of ascertaining the potentials of zinc in counteracting ketamine's effects. Experiment 1 assessed the effects of zinc in healthy animals and the relative degrees of modulation of ketamine's effects by zinc, haloperidol or olanzapine, respectively. Experiment 2 assessed the modulation of ketamine's effects following co-administration of zinc with haloperidol or olanzapine. Male mice weighing 18-20 g each were used. Animals were pretreated with ketamine (except vehicle, zinc, haloperidol and olanzapine controls) for 10 days before commencement of 14-day treatment (day 11-24) with vehicle, zinc, haloperidol or olanzapine (alone or in combination). Ketamine injection also continued alongside zinc and/or standard drugs in the ketamine-treated groups. Zinc, haloperidol and olanzapine were administered by gavage. Treatments were given daily and behaviours assessed on days 11 and 24. On day 24, animals were sacrificed and whole brain homogenates used for estimation of glutathione, nitric oxide and malondialdehyde (MDA) levels. Ketamine increased open-field behaviours, nitric oxide and MDA levels, while it decreased working memory, social interaction and glutathione. Administration of zinc alone or in combination with haloperidol or olanzapine was associated with variable degrees of reversal of these effects. Zinc may have the potential of a possible therapeutic agent and/or adjunct in the reversal of schizophrenia-like changes in behaviour and brain oxidative status.

Long-term cognitive, emotional and neurogenic alterations induced by alcohol and methamphetamine exposure in adolescent rats.

PubMed

Loxton, David; Canales, Juan J

2017-03-06

A high proportion of young methamphetamine (MA) users simultaneously consume alcohol. However, the potential neurological and behavioural alterations induced by such a drug combination have not been systematically examined. We studied in adolescent rats the long-term effects of alcohol, MA, and alcohol and MA combined on anxiety-like behaviour, memory, and neurogenesis in the adult hippocampus. Rats received saline, ethanol (ETOH, 1.5g/kg), MA (MA, 2mg/kg), or ethanol and MA combined (ETHOH-MA, 1.5g/kg ethanol plus 2mg/kg MA) via oral gavage, once daily for 5 consecutive days. Open field (OF), elevated plus maze (EPM) and radial arm maze (RAM) tests were conducted following a 15-day withdrawal period. The results showed alterations in exploratory behaviour in the OF in the MA and ETOH-MA groups, and anxiety-like effects in the EPM in all three drug treatment groups. All three drug groups exhibited reference memory deficits in the RAM, but only the combination treatment group displayed alterations in working memory. Both MA and ETOH-MA treatments increased the length of doublecortin (DCX)-void gaps in the dentate gyrus but only ETOH-MA treatment increased the number of such gaps. An increased number and length of DCX-void gaps correlated with decreased exploratory activity in the OF, and impaired working memory in the RAM was associated with an augmented number of gaps. These findings suggest that alterations in adult hippocampal neurogenesis are linked to the persistent cognitive and behavioural deficits produced by alcohol and MA exposure. Copyright © 2016 Elsevier Inc. All rights reserved.

Spatial learning and memory is preserved in rats after early development in a microgravity environment

NASA Technical Reports Server (NTRS)

Temple, Meredith D.; Kosik, Kenneth S.; Steward, Oswald

2002-01-01

This study evaluated the cognitive mapping abilities of rats that spent part of their early development in a microgravity environment. Litters of male and female Sprague-Dawley rat pups were launched into space aboard the National Aeronautics and Space Administration space shuttle Columbia on postnatal day 8 or 14 and remained in space for 16 days. These animals were designated as FLT groups. Two age-matched control groups remained on Earth: those in standard vivarium housing (VIV) and those in housing identical to that aboard the shuttle (AGC). On return to Earth, animals were tested in three different tasks that measure spatial learning ability, the Morris water maze (MWM), and a modified version of the radial arm maze (RAM). Animals were also tested in an open field apparatus to measure general activity and exploratory activity. Performance and search strategies were evaluated in each of these tasks using an automated tracking system. Despite the dramatic differences in early experience, there were remarkably few differences between the FLT groups and their Earth-bound controls in these tasks. FLT animals learned the MWM and RAM as quickly as did controls. Evaluation of search patterns suggested subtle differences in patterns of exploration and in the strategies used to solve the tasks during the first few days of testing, but these differences normalized rapidly. Together, these data suggest that development in an environment without gravity has minimal long-term impact on spatial learning and memory abilities. Any differences due to development in microgravity are quickly reversed after return to earth normal gravity.

Longitudinal attentional engagement rescues mice from age-related cognitive declines and cognitive inflexibility.

PubMed

Matzel, Louis D; Light, Kenneth R; Wass, Christopher; Colas-Zelin, Danielle; Denman-Brice, Alexander; Waddel, Adam C; Kolata, Stefan

2011-01-01

Learning, attentional, and perseverative deficits are characteristic of cognitive aging. In this study, genetically diverse CD-1 mice underwent longitudinal training in a task asserted to tax working memory capacity and its dependence on selective attention. Beginning at 3 mo of age, animals were trained for 12 d to perform in a dual radial-arm maze task that required the mice to remember and operate on two sets of overlapping guidance (spatial) cues. As previously reported, this training resulted in an immediate (at 4 mo of age) improvement in the animals' aggregate performance across a battery of five learning tasks. Subsequently, these animals received an additional 3 d of working memory training at 3-wk intervals for 15 mo (totaling 66 training sessions), and at 18 mo of age were assessed on a selective attention task, a second set of learning tasks, and variations of those tasks that required the animals to modify the previously learned response. Both attentional and learning abilities (on passive avoidance, active avoidance, and reinforced alternation tasks) were impaired in aged animals that had not received working memory training. Likewise, these aged animals exhibited consistent deficits when required to modify a previously instantiated learned response (in reinforced alternation, active avoidance, and spatial water maze). In contrast, these attentional, learning, and perseverative deficits were attenuated in aged animals that had undergone lifelong working memory exercise. These results suggest that general impairments of learning, attention, and cognitive flexibility may be mitigated by a cognitive exercise regimen that requires chronic attentional engagement.

Long-term effects of interference on short-term memory performance in the rat

PubMed Central

Missaire, Mégane; Fraize, Nicolas; Joseph, Mickaël Antoine; Hamieh, Al Mahdy; Parmentier, Régis; Marighetto, Aline; Salin, Paul Antoine; Malleret, Gaël

2017-01-01

A distinction has always been made between long-term and short-term memory (also now called working memory, WM). The obvious difference between these two kinds of memory concerns the duration of information storage: information is supposedly transiently stored in WM while it is considered durably consolidated into long-term memory. It is well acknowledged that the content of WM is erased and reset after a short time, to prevent irrelevant information from proactively interfering with newly stored information. In the present study, we used typical WM radial maze tasks to question the brief lifespan of spatial WM content in rodents. Groups of rats were submitted to one of two different WM tasks in a radial maze: a WM task involving the repetitive presentation of a same pair of arms expected to induce a high level of proactive interference (PI) (HIWM task), or a task using a different pair in each trial expected to induce a low level of PI (LIWM task). Performance was effectively lower in the HIWM group than in LIWM in the final trial of each training session, indicative of a “within-session/short-term” PI effect. However, we also observed a different “between-session/long-term” PI effect between the two groups: while performance of LIWM trained rats remained stable over days, the performance of HIWM rats dropped after 10 days of training, and this impairment was visible from the very first trial of the day, hence not attributable to within-session PI. We also showed that a 24 hour-gap across training sessions known to allow consolidation processes to unfold, was a necessary and sufficient condition for the long-term PI effect to occur. These findings suggest that in the HIWM task, WM content was not entirely reset between training sessions and that, in specific conditions, WM content can outlast its purpose by being stored more permanently, generating a long-term deleterious effect of PI. The alternative explanation is that WM content could be transferred and stored more permanently in an intermediary form or memory between WM and long-term memory. PMID:28288205

Long-term effects of interference on short-term memory performance in the rat.

PubMed

Missaire, Mégane; Fraize, Nicolas; Joseph, Mickaël Antoine; Hamieh, Al Mahdy; Parmentier, Régis; Marighetto, Aline; Salin, Paul Antoine; Malleret, Gaël

2017-01-01

A distinction has always been made between long-term and short-term memory (also now called working memory, WM). The obvious difference between these two kinds of memory concerns the duration of information storage: information is supposedly transiently stored in WM while it is considered durably consolidated into long-term memory. It is well acknowledged that the content of WM is erased and reset after a short time, to prevent irrelevant information from proactively interfering with newly stored information. In the present study, we used typical WM radial maze tasks to question the brief lifespan of spatial WM content in rodents. Groups of rats were submitted to one of two different WM tasks in a radial maze: a WM task involving the repetitive presentation of a same pair of arms expected to induce a high level of proactive interference (PI) (HIWM task), or a task using a different pair in each trial expected to induce a low level of PI (LIWM task). Performance was effectively lower in the HIWM group than in LIWM in the final trial of each training session, indicative of a "within-session/short-term" PI effect. However, we also observed a different "between-session/long-term" PI effect between the two groups: while performance of LIWM trained rats remained stable over days, the performance of HIWM rats dropped after 10 days of training, and this impairment was visible from the very first trial of the day, hence not attributable to within-session PI. We also showed that a 24 hour-gap across training sessions known to allow consolidation processes to unfold, was a necessary and sufficient condition for the long-term PI effect to occur. These findings suggest that in the HIWM task, WM content was not entirely reset between training sessions and that, in specific conditions, WM content can outlast its purpose by being stored more permanently, generating a long-term deleterious effect of PI. The alternative explanation is that WM content could be transferred and stored more permanently in an intermediary form or memory between WM and long-term memory.

Pigeons (Columba livia) plan future moves on computerized maze tasks.

PubMed

Miyata, Hiromitsu; Fujita, Kazuo

2008-07-01

Planning, the internal process of formulating an organized method about one's future behavior, should be advantageous for non-human animals as well as for humans. However, little is known about this process in avian species. We examined planning processes in pigeons (Columba livia) using a computerized maze task. In Experiment 1, we found that the pigeons plan their next one step, and in some cases even correctly adjust their actions after change of goal locations, while performing on a plus-shaped maze. We also showed that the pigeons might even plan two steps on familiar, well-practiced mazes. In Experiment 2, we discovered that the subjects plan the direction they would go first before starting to solve a four-arm shuriken (a Japanese traditional throwing knife)-shaped maze. The birds also corrected their previously planned actions after change of goal locations. Our results from these experiments suggest that planning ahead is within the cognitive capacity of a "bird brain", and that it may be more widespread in the animal kingdom than has been presumed.

Levosimendan enhances memory through antioxidant effect in rat model: behavioral and molecular study.

PubMed

Rababa'h, Abeer M; Alzoubi, Karem H; Atmeh, Ala'a

2018-06-01

Impairment of learning and memory has been associated with accumulation of reactive oxygen species in the body. It has also been found that antioxidants enhance learning and memory. Levosimendan is a cardiac inotropic and vasodilator agent that has pleotropic effects including antioxidant, anti-inflammatory, and smooth muscle vasodilatory actions. In this study, we investigated the effect of levosimendan on learning and memory in rats. Levosimendan (12 µg/kg, intraperitoneally) or vehicle was administered once a week for 8 weeks. The radial arm water maze was used to assess spatial learning and memory. In addition, hippocampus levels of antioxidant biomarkers/enzyme - reduced glutathione (GSH), oxidized glutathione (GSSG), GSH/GSSG ratio, glutathione peroxidase, superoxide dismutase, catalase, and thiobarbituric acid reactive substance - were assessed. Levosimendan significantly enhanced short-term (30 min) and long-term (5 h) memory. Levosimendan also significantly increased levels of glutathione peroxidase and GSH and decreased thiobarbituric acid reactive substance. There were no significant effects on the level of other oxidative stress biomarkers. In conclusion, levosimendan enhanced short-term and long-term memory by potentiating antioxidant defense mechanism in the hippocampus.

Behavioral deficit and decreased GABA receptor functional regulation in the cerebellum of epileptic rats: effect of Bacopa monnieri and bacoside A.

PubMed

Mathew, Jobin; Peeyush Kumar, T; Khan, Reas S; Paulose, C S

2010-04-01

In the present study, the effects of Bacopa monnieri and its active component, bacoside A, on motor deficit and alterations of GABA receptor functional regulation in the cerebellum of epileptic rats were investigated. Scatchard analysis of [(3)H]GABA and [(3)H]bicuculline in the cerebellum of epileptic rats revealed a significant decrease in B(max) compared with control. Real-time polymerase chain reaction amplification of GABA(A) receptor subunits-GABA(Aalpha1), GABA(Aalpha5,) and GABA(Adelta)-was downregulated (P<0.001) in the cerebellum of epileptic rats compared with control rats. Epileptic rats exhibit deficits in radial arm and Y-maze performance. Treatment with B. monnieri and bacoside A reversed these changes to near-control levels. Our results suggest that changes in GABAergic activity, motor learning, and memory deficit are induced by the occurrence of repetitive seizures. Treatment with B. monnieri and bacoside A prevents the occurrence of seizures thereby reducing the impairment of GABAergic activity, motor learning, and memory deficit. Copyright (c) 2010 Elsevier Inc. All rights reserved.

Elements of episodic-like memory in animal models.

PubMed

Crystal, Jonathon D

2009-03-01

Representations of unique events from one's past constitute the content of episodic memories. A number of studies with non-human animals have revealed that animals remember specific episodes from their past (referred to as episodic-like memory). The development of animal models of memory holds enormous potential for gaining insight into the biological bases of human memory. Specifically, given the extensive knowledge of the rodent brain, the development of rodent models of episodic memory would open new opportunities to explore the neuroanatomical, neurochemical, neurophysiological, and molecular mechanisms of memory. Development of such animal models holds enormous potential for studying functional changes in episodic memory in animal models of Alzheimer's disease, amnesia, and other human memory pathologies. This article reviews several approaches that have been used to assess episodic-like memory in animals. The approaches reviewed include the discrimination of what, where, and when in a radial arm maze, dissociation of recollection and familiarity, object recognition, binding, unexpected questions, and anticipation of a reproductive state. The diversity of approaches may promote the development of converging lines of evidence on the difficult problem of assessing episodic-like memory in animals.

Melatonin prevents memory impairment induced by high-fat diet: Role of oxidative stress.

PubMed

Alzoubi, Karem H; Mayyas, Fadia A; Mahafzah, Rania; Khabour, Omar F

2018-01-15

Consumption of high-fat diet (HFD) induces oxidative stress in the hippocampus that leads to memory impairment. Melatonin has antioxidant and neuroprotective effects. In this study, we hypothesized that chronic administration of melatonin can prevent memory impairment induced by consumption of HFD. Melatonin was administered to rats via oral gavage (100mg/kg/day) for 4 weeks. HFD was also instituted for the same duration. Behavioral studies were conducted to test spatial memory using the radial arm water maze. Additionally, oxidative stress biomarkers were assessed in the hippocampus. Results showed that HFD impaired both short- and long- term memory (P<0.05), while melatonin treatment prevented such effects. Furthermore, melatonin prevented HFD-induced reduction in levels of GSH, and ratio of GSH/GSSG, and increase in GSSG in the hippocampus. Melatonin also prevented reduction in the catalase activity in hippocampus of animals on HFD. In conclusion, HFD induced memory impairment and melatonin prevented this impairment probably by preventing alteration of oxidative stress in the hippocampus. Copyright © 2017 Elsevier B.V. All rights reserved.

Improved spatial learning is associated with increased hippocampal but not prefrontal long-term potentiation in mGluR4 knockout mice.

PubMed

Iscru, E; Goddyn, H; Ahmed, T; Callaerts-Vegh, Z; D'Hooge, R; Balschun, D

2013-08-01

Although much information about metabotropic glutamate receptors (mGluRs) and their role in normal and pathologic brain function has been accumulated during the last decades, the role of group III mGluRs is still scarcely documented. Here, we examined mGluR4 knockout mice for types of behavior and synaptic plasticity that depend on either the hippocampus or the prefrontal cortex (PFC). We found improved spatial short- and long-term memory in the radial arm maze, which was accompanied by enhanced long-term potentiation (LTP) in hippocampal CA1 region. In contrast, LTP in the PFC was unchanged when compared with wild-type controls. Changes in paired-pulse facilitation that became overt in the presence of the GABAA antagonist picrotoxin indicated a function of mGluR4 in maintaining the excitation/inhibition balance, which is of crucial importance for information processing in the brain and the deterioration of these processes in neuropsychological disorders such as autism, epilepsy and schizophrenia. © 2013 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

Considerations for SphygmoCor radial artery pulse wave analysis: side selection and peripheral arterial blood pressure calibration.

PubMed

Martin, Jeffrey S; Borges, Alexandra R; Christy, John B; Beck, Darren T

2015-10-01

Methods employed for pulse wave analysis (PWA) and peripheral blood pressure (PBP) calibration vary. The purpose of this study was to evaluate the agreement of SphygmoCor PWA parameters derived from radial artery tonometry when considering (1) timing (before vs. after tonometry) and side selection (ipsilateral vs. contralateral limb) for PBP calibration and (2) side selection for tonometry (left vs. right arm). In 34 subjects (aged 21.9 ± 2.3 years), bilateral radial artery tonometry was performed simultaneously on three instances. PBP assessment via oscillometric sphygmomanometry in the left arm only and both arms simultaneously occurred following the first and second instances of tonometry, respectively. Significant within arm differences in PWA parameters derived before and after PBP measurement were observed in the right arm only (for example, aortic systolic blood pressure, Δ=0.38 ± 0.64 mm Hg). Simultaneously captured bilateral PWA variables demonstrated significant between arm differences in 88% (14/16) and 56% (9/16) of outcome variables when calibrated to within arm and equivalent PBP, respectively. Moreover, the right arm consistently demonstrated lower values for clinical PWA variables (for example, augmentation index, bias=-2.79%). However, 26% (n=9) of participants presented with clinically significant differences (>10 mm Hg) in bilateral PBP and their exclusion from analysis abolished most between arm differences observed. SphygmoCor PWA in the right radial artery results in greater variability independent of the timing of PBP measurement and magnitude of calibration pressures in young subjects. Moreover, bilateral PBP measurement is imperative to identify subjects in whom a significant difference in bilateral PWA outcomes may exist.

Diazepam-stress interactions in the rat: effects on autoanalgesia and a plus-maze model of anxiety.

PubMed

Taukulis, H K; Goggin, C E

1990-03-01

On six occasions spaced at least a week apart, two groups of rats were subjected to a variety of stressful conditions consisting of a restraint/bright light complex, either alone or in combination with a tail pinch, whole-body inversion, or partial immersion in cold water. One of these groups was injected with diazepam (2.0 mg/kg) 30 min prior to the stressors, while the other group experienced the drug in their home cages the following day. A third group also received the diazepam but was not exposed to the stressors. In three test sessions all animals were injected with either diazepam or saline and were then exposed to a novel stressor: a plus-maze used as a screening device for anxiolytic drugs. This was immediately followed by a tail-flick measure of analgesia. The longest tail-flick latencies, indicating stress-induced analgesia ("autoanalgesia"), were observed in the group that had not been exposed to stress prior to testing. The other two groups exhibited substantially shorter latencies but did not differ from one another, thus showing a "stress inoculation" effect that was uninfluenced by diazepam. In the plus-maze, diazepam tends to increase the amount of time rats will spend in the two exposed arms of the maze relative to the two enclosed arms. This effect was significantly attenuated in the group that had previously experienced the variety of stressors after a diazepam injection, suggesting a learned association between drug and stress that resulted in a diminution of the drug's anxiolytic property.

Coriandrum sativum: evaluation of its anxiolytic effect in the elevated plus-maze.

PubMed

Emamghoreishi, Masoumeh; Khasaki, Mohammad; Aazam, Maryam Fath

2005-01-15

The clinical applications of benzodiazepines as anxiolytics are limited by their unwanted side effects. Therefore, the development of new pharmacological agents is well justified. Among medicinal plants, Coriandrum sativum L. has been recommended for relief of anxiety and insomnia in Iranian folk medicine. Nevertheless, no pharmacological studies have thus far evaluated its effects on central nervous system. Therefore, the aim of this study was to examine if the aqueous extract of Coriandrum sativum seed has anxiolytic effect in mice. Additionally, its effect on spontaneous activity and neuromuscular coordination were evaluated. The anxiolytic effect of aqueous extract (10, 25, 50, 100 mg/kg, i.p.) was examined in male albino mice using elevated plus-maze as an animal model of anxiety. The effects of the extract on spontaneous activity and neuromuscular coordination were assessed using Animex Activity Meter and rotarod, respectively. In the elevated plus-maze, aqueous extract at 100 mg/kg showed an anxiolytic effect by increasing the time spent on open arms and the percentage of open arm entries, compared to control group. Aqueous extract at 50, 100 and 500 mg/kg significantly reduced spontaneous activity and neuromuscular coordination, compared to control group. These results suggest that the aqueous extract of Coriandrum sativum seed has anxiolytic effect and may have potential sedative and muscle relaxant effects.

The adenosine A2A antagonist MSX-3 reverses the effects of the dopamine antagonist haloperidol on effort-related decision making in a T-maze cost/benefit procedure

PubMed Central

Mott, Allison M.; Nunes, Eric J.; Collins, Lyndsey E.; Port, Russell G.; Sink, Kelly S.; Hockemeyer, Jörg; Müller, Christa E.

2010-01-01

Rationale Mesolimbic dopamine (DA) is a critical component of the brain circuitry regulating behavioral activation and effort-related processes. Research involving choice tasks has shown that rats with impaired DA transmission reallocate their instrumental behavior away from food-reinforced tasks with high response requirements and instead select less effortful food-seeking behaviors. Objective Previous work showed that adenosine A2A antagonism can reverse the effects of the DA antagonist haloperidol in an operant task that assesses effort-related choice. The present work used a T-maze choice procedure to assess the effects of adenosine A2A and A1 antagonism. Materials and methods With this task, the two arms of the maze have different reinforcement densities (four vs. two food pellets), and a vertical 44 cm barrier is positioned in the arm with the higher density, presenting the animal with an effort-related challenge. Untreated rats strongly prefer the arm with the high density of food reward and climb the barrier in order to obtain the food. Results Haloperidol produced a dose-related (0.05–0.15 mg/kg i.p.) reduction in the number of trials in which the rats chose the high-barrier arm. Co-administration of the adenosine A2A receptor antagonist MSX-3 (0.75, 1.5, and 3.0 mg/kg i.p.), but not the A1 antagonist 8-cyclopentyl-1,3-dipropylxanthine (0.75, 1.5, and 3.0 mg/kg i.p.), reversed the effects of haloperidol on effort-related choice and latency. Conclusions Adenosine A2A and D2 receptors interact to regulate effort-related decision making, which may have implications for the treatment of psychiatric symptoms such as psychomotor slowing or anergia that can be observed in depression, parkinsonism, and other disorders. PMID:19132351

The adenosine A2A antagonist MSX-3 reverses the effects of the dopamine antagonist haloperidol on effort-related decision making in a T-maze cost/benefit procedure.

PubMed

Mott, Allison M; Nunes, Eric J; Collins, Lyndsey E; Port, Russell G; Sink, Kelly S; Hockemeyer, Jörg; Müller, Christa E; Salamone, John D

2009-05-01

Mesolimbic dopamine (DA) is a critical component of the brain circuitry regulating behavioral activation and effort-related processes. Research involving choice tasks has shown that rats with impaired DA transmission reallocate their instrumental behavior away from food-reinforced tasks with high response requirements and instead select less effortful food-seeking behaviors. Previous work showed that adenosine A(2A) antagonism can reverse the effects of the DA antagonist haloperidol in an operant task that assesses effort-related choice. The present work used a T-maze choice procedure to assess the effects of adenosine A(2A) and A(1) antagonism. With this task, the two arms of the maze have different reinforcement densities (four vs. two food pellets), and a vertical 44 cm barrier is positioned in the arm with the higher density, presenting the animal with an effort-related challenge. Untreated rats strongly prefer the arm with the high density of food reward and climb the barrier in order to obtain the food. Haloperidol produced a dose-related (0.05-0.15 mg/kg i.p.) reduction in the number of trials in which the rats chose the high-barrier arm. Co-administration of the adenosine A(2A) receptor antagonist MSX-3 (0.75, 1.5, and 3.0 mg/kg i.p.), but not the A(1) antagonist 8-cyclopentyl-1,3-dipropylxanthine (0.75, 1.5, and 3.0 mg/kg i.p.), reversed the effects of haloperidol on effort-related choice and latency. Adenosine A(2A) and D2 receptors interact to regulate effort-related decision making, which may have implications for the treatment of psychiatric symptoms such as psychomotor slowing or anergia that can be observed in depression, parkinsonism, and other disorders.

Self-administration of morphine into the lateral hypothalamus in the mouse.

PubMed

Cazala, P; Darracq, C; Saint-Marc, M

1987-07-28

BALB/c mice were chronically and unilaterally implanted with a guide cannula, the tip of which was positioned 1 mm above the lateral hypothalamus (LH). On each experimental day, a stainless-steel injection cannula was inserted into the LH, and self-administration of morphine or vehicle in this brain area was studied by using a spatial discrimination test in a Y-maze. In a first experiment, we observed that when mice had access to morphine (0.1 microgram by injection) they rapidly discriminated the reinforced arm from the neutral arm of the maze in order to self administer, with increasing frequency, the drug into the LH. In contrast when only vehicle was present, the two arms were no longer discriminated. In a second experiment we compared the effects of 3 doses of morphine (0.1 microgram, 0.05 microgram and 0.025 microgram by injection); optimal discrimination was obtained with the lowest dose used. In a third experiment we observed that subcutaneous injections of naloxone (4 mg/kg) progressively reduced the number of self-administrations of morphine into the LH, a result which suggests that this response is dependent on an opiate receptor mechanism.

Deletion of Glutamate Delta-1 Receptor in Mouse Leads to Enhanced Working Memory and Deficit in Fear Conditioning

PubMed Central

Yadav, Roopali; Hillman, Brandon G.; Gupta, Subhash C.; Suryavanshi, Pratyush; Bhatt, Jay M.; Pavuluri, Ratnamala; Stairs, Dustin J.; Dravid, Shashank M.

2013-01-01

Glutamate delta-1 (GluD1) receptors are expressed throughout the forebrain during development with high levels in the hippocampus during adulthood. We have recently shown that deletion of GluD1 receptor results in aberrant emotional and social behaviors such as hyperaggression and depression-like behaviors and social interaction deficits. Additionally, abnormal expression of synaptic proteins was observed in amygdala and prefrontal cortex of GluD1 knockout mice (GluD1 KO). However the role of GluD1 in learning and memory paradigms remains unknown. In the present study we evaluated GluD1 KO in learning and memory tests. In the eight-arm radial maze GluD1 KO mice committed fewer working memory errors compared to wildtype mice but had normal reference memory. Enhanced working memory in GluD1 KO was also evident by greater percent alternation in the spontaneous Y-maze test. No difference was observed in object recognition memory in the GluD1 KO mice. In the Morris water maze test GluD1 KO mice showed no difference in acquisition but had longer latency to find the platform in the reversal learning task. GluD1 KO mice showed a deficit in contextual and cue fear conditioning but had normal latent inhibition. The deficit in contextual fear conditioning was reversed by D-Cycloserine (DCS) treatment. GluD1 KO mice were also found to be more sensitive to foot-shock compared to wildtype. We further studied molecular changes in the hippocampus, where we found lower levels of GluA1, GluA2 and GluK2 subunits while a contrasting higher level of GluN2B in GluD1 KO. Additionally, we found higher postsynaptic density protein 95 (PSD95) and lower glutamate decarboxylase 67 (GAD67) expression in GluD1 KO. We propose that GluD1 is crucial for normal functioning of synapses and absence of GluD1 leads to specific abnormalities in learning and memory. These findings provide novel insights into the role of GluD1 receptors in the central nervous system. PMID:23560106

GAUGING APPARATUS

DOEpatents

Ruggles, C.A.

1957-08-27

A swinging arm gage designed to measure radial angles, tapering, sloping, or arcuate concave surfaces is described. The principle of the swinging arm gage is that in any spherical system, radii and radial lines established by them pass through the center of the sphere. Thus if an arm be made to pivot at the sphere center, the path of the swinging end can be guided by a can so set as to establish the proper center angle, and dial indicators on the arm can be zeroed on a master object, angular and dimensional manufacturing errors can be determined on a duplicate object. This device makes possible a considerable saving of time in measuring complex arcuate contours.

The effect of GABA transporter 1 (GAT1) inhibitor, tiagabine, on scopolamine-induced memory impairments in mice.

PubMed

Sałat, Kinga; Podkowa, Adrian; Mogilski, Szczepan; Zaręba, Paula; Kulig, Katarzyna; Sałat, Robert; Malikowska, Natalia; Filipek, Barbara

2015-12-01

GABAergic neurotransmission is involved in long-term potentiation, a neurophysiological basis for learning and memory. On the other hand, GABA-enhancing drugs may impair memory and learning in humans and animals. The present study aims at investigating the effect of GAT1 inhibitor tiagabine on memory and learning. Albino Swiss (CD-1) and C57BL/6J mice were used in the passive avoidance (PA), Morris water maze (MWM) and radial arm water maze (RAWM) tasks. Scopolamine (1mg/kg ip) was applied to induce cognitive deficits. In the retention trial of PA scopolamine reduced step-through latency as compared to vehicle-treated mice, and pretreatment with tiagabine did not have any influence on this effect. In MWM the results obtained for vehicle-treated mice, scopolamine-treated group and combined scopolamine+tiagabine-treated mice revealed variable learning abilities in these groups. Tiagabine did not impair learning in the acquisition trial. In RAWM on day 1 scopolamine-treated group made nearly two-fold more errors than vehicle-treated mice and mice that received combined scopolamine and tiagabine. Learning abilities in the latter group were similar to those of vehicle-treated mice in the corresponding trial block on day 1, except for the last trial block, during which tiagabine+scopolamine-injected mice made more errors than control mice and the scopolamine-treated group. In all groups a complete reversal of memory deficits was observed in the last trial block of day 2. The lack of negative influence of tiagabine on cognitive functions in animals with scopolamine-induced memory impairments may be relevant for patients treated with this drug. Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

A comparison of progestins within three classes: Differential effects on learning and memory in the aging surgically menopausal rat.

PubMed

Braden, B Blair; Andrews, Madeline G; Acosta, Jazmin I; Mennenga, Sarah E; Lavery, Courtney; Bimonte-Nelson, Heather A

2017-03-30

For decades, progestins have been included in hormone therapies (HT) prescribed to women to offset the risk of unopposed estrogen-induced endometrial hyperplasia. However, the potential effects on cognition of subcategories of clinically used progestins have been largely unexplored. In two studies, the present investigation evaluated the cognitive effects of norethindrone acetate (NETA), levonorgestrel (LEVO), and medroxyprogesterone acetate (MPA) on the water radial-arm maze (WRAM) and Morris water maze (MM) in middle-aged ovariectomized rats. In Study 1, six-weeks of a high-dose NETA treatment impaired learning and delayed retention on the WRAM, and impaired reference memory on the MM. Low-dose NETA treatment impaired delayed retention on the WRAM. In Study 2, high-dose NETA treatment was reduced to four-weeks and compared to MPA and LEVO. As previously shown, MPA impaired working memory performance during the lattermost portion of testing, at the highest working memory load, impaired delayed retention on the WRAM, and impaired reference memory on the MM. NETA also impaired performance on these WRAM and MM measures. Interestingly, LEVO did not impair performance, but instead enhanced learning on the WRAM. The current study corroborates previous evidence that the most commonly prescribed FDA-approved progestin for HT, MPA, impairs learning and memory in the ovariectomized middle-aged rat. When progestins from two different additional subcategories were investigated, NETA impaired learning and memory similarly to MPA, but LEVO enhanced learning. Future research is warranted to determine LEVO's potential as an ideal progestin for optimal health in women, including for cognition. Copyright © 2016 Elsevier B.V. All rights reserved.

Disruption of the ErbB signaling in adolescence increases striatal dopamine levels and affects learning and hedonic-like behavior in the adult mouse.

PubMed

Golani, Idit; Tadmor, Hagar; Buonanno, Andres; Kremer, Ilana; Shamir, Alon

2014-11-01

The ErbB signaling pathway has been genetically and functionally implicated in schizophrenia. Numerous findings support the dysregulation of Neuregulin (NRG) and epidermal growth factor (EGF) signaling in schizophrenia. However, it is unclear whether alterations of these pathways in the adult brain or during development are involved in the pathophysiology of schizophrenia. Herein we characterized the behavioral profile and molecular changes resulting from pharmacologically blocking the ErbB signaling pathway during a critical period in the development of decision making, planning, judgments, emotions, social cognition and cognitive skills, namely adolescence. We demonstrate that chronic administration of the pan-ErbB kinase inhibitor JNJ-28871063 (JNJ) to adolescent mice elevated striatal dopamine levels and reduced preference for sucrose without affecting locomotor activity and exploratory behavior. In adulthood, adolescent JNJ-treated mice continue to consume less sucrose and needed significantly more correct-response trials to reach the learning criterion during the discrimination phase of the T-maze reversal learning task than their saline-injected controls. In addition, JNJ mice exhibited deficit in reference memory but not in working memory as measured in the radial arm maze. Inhibition of the pathway during adolescence did not affect exploratory behavior and locomotor activity in the open field, social interaction, social memory, and reversal learning in adult mice. Our data suggest that alteration of ErbB signaling during adolescence resulted in changes in the dopaminergic systems that emerge in pathological learning and hedonic behavior in adulthood, and pinpoints the possible role of the pathway in the development of cognitive skills and motivated behavior. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.

Interleukin-6 (IL-6) receptor/IL-6 fusion protein (Hyper IL-6) effects on the neonatal mouse brain: possible role for IL-6 trans-signaling in brain development and functional neurobehavioral outcomes.

PubMed

Brunssen, Susan H; Moy, Sheryl S; Toews, Arrel D; McPherson, Christopher A; Harry, G Jean

2013-01-01

Adverse neurodevelopmental outcomes are linked to perinatal production of inflammatory mediators, including interleukin 6 (IL-6). While a pivotal role for maternal elevation in IL-6 has been established in determining neurobehavioral outcomes in the offspring and considered the primary target mediating the fetal inflammatory response, questions remain as to the specific actions of IL-6 on the developing brain. CD-1 male mice received a subdural injection of the bioactive fusion protein, hyper IL-6 (HIL-6) on postnatal-day (PND)4 and assessed from preweaning until adulthood. Immunohistochemical evaluation of astrocytes and microglia and mRNA levels for pro-inflammatory cytokines and host response genes indicated no evidence of an acute neuroinflammatory injury response. HIL-6 accelerated motor development and increased reactivity to stimulation and number of entries in a light/dark chamber, decreased ability to learn to withhold a response in passive avoidance, and effected deficits in social novelty behavior. No changes were observed in motor activity, pre-pulse startle inhibition, or learning and memory in the Morris water maze or radial arm maze, as have been reported for models of more severe developmental neuroinflammation. In young animals, mRNA levels for MBP and PLP/DM20 decreased and less complexity of MBP processes in the cortex was evident by immunohistochemistry. The non-hydroxy cerebroside fraction of cerebral lipids was increased. These results provide evidence for selective effects of IL-6 signaling, particularly trans-signaling, in the developing brain in the absence of a general neuroinflammatory response. These data contribute to our further understanding of the multiple aspects of IL-6 signaling in the developing brain. Published by Elsevier Inc.

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.

Reward-based spatial learning in unmedicated adults with obsessive-compulsive disorder.

PubMed

Marsh, Rachel; Tau, Gregory Z; Wang, Zhishun; Huo, Yuankai; Liu, Ge; Hao, Xuejun; Packard, Mark G; Peterson, Bradley S; Simpson, H Blair

2015-04-01

The authors assessed the functioning of mesolimbic and striatal areas involved in reward-based spatial learning in unmedicated adults with obsessive-compulsive disorder (OCD). Functional MRI blood-oxygen-level-dependent response was compared in 33 unmedicated adults with OCD and 33 healthy, age-matched comparison subjects during a reward-based learning task that required learning to use extramaze cues to navigate a virtual eight-arm radial maze to find hidden rewards. The groups were compared 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 pseudorandomly to experimentally prevent learning. Both groups learned to navigate the maze to find hidden rewards, but group differences in neural activity during navigation and reward processing were detected in mesolimbic and striatal areas. During navigation, the OCD group, unlike the healthy comparison group, exhibited activation in the left posterior hippocampus. Unlike healthy subjects, participants in the OCD group did not show activation in the left ventral putamen and amygdala when anticipating rewards or in the left hippocampus, amygdala, and ventral putamen when receiving unexpected rewards (control condition). Signal in these regions decreased relative to baseline during unexpected reward receipt among those in the OCD group, and the degree of activation was inversely associated with doubt/checking symptoms. Participants in the OCD group displayed abnormal recruitment of mesolimbic and ventral striatal circuitry during reward-based spatial learning. Whereas healthy comparison subjects exhibited activation in this circuitry in response to the violation of reward expectations, unmedicated OCD participants did not and instead over-relied on the posterior hippocampus during learning. Thus, dopaminergic innervation of reward circuitry may be altered, and future study of anterior/posterior hippocampal dysfunction in OCD is warranted.

Ellagic acid ameliorates learning and memory deficits in a rat model of Alzheimer's disease: an exploration of underlying mechanisms.

PubMed

Kiasalari, Zahra; Heydarifard, Rana; Khalili, Mohsen; Afshin-Majd, Siamak; Baluchnejadmojarad, Tourandokht; Zahedi, Elham; Sanaierad, Ashkan; Roghani, Mehrdad

2017-06-01

Alzheimer's disease (AD) is a neurodegenerative disorder with irreversible loss of intellectual abilities. Current therapies for AD are still insufficient. In this study, the effect of ellagic acid on learning and memory deficits was evaluated in intrahippocampal amyloid beta (Aβ 25-35 )-microinjected rats and its modes of action were also explored. AD rat model was induced by bilateral intrahippocampal microinjection of Aβ 25-35 and ellagic acid was daily administered (10, 50, and 100 mg/kg), and learning, recognition memory, and spatial memory were evaluated in addition to histochemical assessment, oxidative stress, cholinesterases activity, and level of nuclear factor-kappaB (NF-κB), Toll-like receptor 4 (TLR4), and nuclear factor (erythroid-derived 2)-like 2 (Nrf2). The amyloid beta-microinjected rats showed a lower discrimination ratio in novel object and alternation score in Y maze tasks and exhibited an impairment of retention and recall capability in passive avoidance paradigm and higher working and reference memory errors in radial arm maze (RAM). In addition, amyloid beta group showed a lower number of Nissl-stained neurons in CA1 area in addition to enhanced oxidative stress, higher activity of cholinesterases, greater level of NF-κB and TLR4, and lower level of nuclear/cytoplasmic ratio for Nrf2 and ellagic acid at a dose of 100 mg/kg significantly prevented most of these abnormal alterations. Ellagic acid pretreatment of intrahippocampal amyloid beta-microinjected rats could dose-dependently improve learning and memory deficits via neuronal protection and at molecular level through mitigation of oxidative stress and acetylcholinesterase (AChE) activity and modulation of NF-κB/Nrf2/TLR4 signaling pathway.

Maternal protein-free diet during lactation programs male Wistar rat offspring for increased novelty-seeking, locomotor activity, and visuospatial performance.

PubMed

Lotufo, Bruna M; Tenório, Frank; Barradas, Penha C; Guedes, Paulo L; Lima, Sebastião S; Rocha, Michael L M; Duarte-Pinheiro, Vitor Hugo; Rodrigues, Vanessa S T; Lisboa, Patrícia C; Filgueiras, Cláudio C; Abreu-Villaça, Yael; Manhães, Alex C

2018-04-01

It is well established that chronic undernutrition has detrimental impacts on brain development and maturation. However, protein malnutrition during the period specifically encompassing the brain growth spurt has not been widely studied, particularly regarding its effects on adolescent and adult offspring behavior. Here, we assessed the effects of a protein-free diet during the 1st 10 postnatal days on the macronutrient content of the milk produced by lactating Wistar rats, on their maternal behavior, and on the offspring's behavior. Lactating dams were fed either a protein-free or a normoprotein diet from litter parturition to Postnatal Day 10 (P10). All dams received the normoprotein diet after P10. Offspring were tested in the elevated plus-maze (anxiety-like behavior), hole board arena (novelty-seeking and locomotor activity), and radial arm water maze (memory-learning) at either P40 (adolescents) or P90 (adults). The protein-free diet reduced milk protein content at P10 but not at P20. Carbohydrate and lipid contents were unaffected. Serum corticosterone levels in the offspring (at P10, P40, or P90) and dams (at P21) were not affected by the protein-free diet. Maternal behavior was also unchanged. In the offspring, no differences were observed between groups regarding anxiety-like behaviors at both ages. The protein-free diet increased adolescent locomotor activity as well as adult novelty-seeking behavior and memory performance. Our results indicate that the brain growth spurt period is particularly sensitive to protein malnutrition, showing that even a brief nutritional insult during this period can cause specific age-dependent behavioral effects on the offspring. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Selective GABA(A) α5 positive allosteric modulators improve cognitive function in aged rats with memory impairment.

PubMed

Koh, Ming Teng; Rosenzweig-Lipson, Sharon; Gallagher, Michela

2013-01-01

A condition of excess activity in the hippocampal formation is observed in the aging brain and in conditions that confer additional risk during aging for Alzheimer's disease. Compounds that act as positive allosteric modulators at GABA(A) α5 receptors might be useful in targeting this condition because GABA(A) α5 receptors mediate tonic inhibition of principal neurons in the affected network. While agents to improve cognitive function in the past focused on inverse agonists, which are negative allosteric modulators at GABA(A) α5 receptors, research supporting that approach used only young animals and predated current evidence for excessive hippocampal activity in age-related conditions of cognitive impairment. Here, we used two compounds, Compound 44 [6,6-dimethyl-3-(3-hydroxypropyl)thio-1-(thiazol-2-yl)-6,7-dihydro-2-benzothiophen-4(5H)-one] and Compound 6 [methyl 3,5-diphenylpyridazine-4-carboxylate], with functional activity as potentiators of γ-aminobutyric acid at GABA(A) α5 receptors, to test their ability to improve hippocampal-dependent memory in aged rats with identified cognitive impairment. Improvement was obtained in aged rats across protocols differing in motivational and performance demands and across varying retention intervals. Significant memory improvement occurred after either intracereboventricular infusion with Compound 44 (100 μg) in a water maze task or systemic administration with Compound 6 (3 mg/kg) in a radial arm maze task. Furthermore, systemic administration improved behavioral performance at dosing shown to provide drug exposure in the brain and in vivo receptor occupancy in the hippocampus. These data suggest a novel approach to improve neural network function in clinical conditions of excess hippocampal activity. This article is part of a Special Issue entitled 'Cognitive Enhancers'. Copyright © 2012 Elsevier Ltd. All rights reserved.

An Evaluation of the Media Coverage Concerning the Mission to Secure the Dog Kennel during the Panama Invasion on December 20, 1989

DTIC Science & Technology

1990-12-01

34 Reflections, Winter 1989, 13. Matthews, William. "Commanders Downplay Women In Combat," Army Times, February 26, 1990, 9. Maze, Rick . "Byron: No Women in...Combat," Army Times, March 26, 1990. 18. Maze, Rick . "Women Need To Learn Infantry Skills, Warner Says," Arm7y Times, February 5, 1990, 10. McCarthy...January 4, 1990, 3. Yancey , Matt. "Women-Combat," Associated Press, January 14, 1990. Yarbrough, Jean. "The Feminist Mistake," Policy Review, 1983, 48

Effects of age and exposure to heavy particles on a behavioral measure of anxiety

NASA Astrophysics Data System (ADS)

Rabin, B. M.; Joseph, J. A.; Shukitt-Hale, B.; Carrihill-Knoll, K. L.; Carey, A.; Foster, B. C.

On forthcoming exploratory class missions astronauts will be expected to function in novel and possibly dangerous environments This requirement may produce anticipatory fear or anxiety Previous research has shown that exposure to HZE particles such as those experienced on missions beyond the protection provided by the magnetic shield of the earth can affect the performance of the organism on a variety of tasks In addition research has shown that there is an interaction between age and exposure to heavy particles on a variety of behavioral tasks such that older organisms are more susceptible to the deleterious effects of irradiation Because there are changes in exploration-induced anxiety as a function of age it is possible that exposure to HZE particles will also affect a middle-aged astronaut s ability to respond appropriately in anxiety producing situations The present experiment utilized the elevated plus-maze to evaluate the effects of age and exposure to HZE particle radiation on anxiety Fischer-344 rats 2 7 12 and 16 months of age at the time of irradiation were exposed to 56 Fe particles 1 GeV n 0 25-2 00 Gy in the NASA Space Radiation Laboratory at Brookhaven National Laboratory Control rats at each age were not irradiated At the time of testing the rats were 3- 11- 13- and 20-months old respectively Anxiety was studied using an elevated plus-maze The maze is composed of four arms in the shape of a sign placed 90 cm above the floor Two of the arms are enclosed and two of the arms are open The amount of

THE ROLE OF AMYGDALAR MU OPIOID RECEPTORS IN ANXIETY-RELATED RESPONSES IN TWO RAT MODELS

PubMed Central

Wilson, Marlene A.; Junor, Lorain

2009-01-01

Amygdala opioids such as enkephalin appear to play some role in the control of anxiety and the anxiolytic effects of benzodiazepines, although the opioid receptor subtypes mediating such effects are unclear. This study compared the influences of mu opioid receptor (MOR) activation in the central nucleus of the amygdala (CEA) on unconditioned fear or anxiety-like responses in two models, the elevated plus maze and the defensive burying test. The role of MOR in the anxiolytic actions of the benzodiazepine agonist diazepam was also examined using both models. Either the MOR agonist [D-Ala2, NMe-Phe4, Gly-ol5]-enkephalin (DAMGO) or the MOR antagonists Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP) or β-funaltrexamine (FNA) were bilaterally infused into the CEA of rats prior to testing. The results show that microinjection of DAMGO in the CEA decreased open arm time in the plus maze, while CTAP increased open arm behaviors. In contrast, DAMGO injections in the CEA reduced burying behaviors and increased rearing following exposure to a predator odor, suggesting a shift in the behavioral response in this context. Amygdala injections of the MOR agonist DAMGO or the MOR antagonist CTAP failed to change the anxiolytic effects of diazepam in either test. Our results demonstrate that MOR activation in the central amygdala exerts distinctive effects in two different models of unconditioned fear or anxiety-like responses, and suggest that opioids may exert context-specific regulation of amygdala output circuits and behavioral responses during exposure to potential threats (open arms of the maze) versus discrete threats (predator odor). PMID:18216773

Spontaneous alternation: A potential gateway to spatial working memory in Drosophila.

PubMed

Lewis, Sara A; Negelspach, David C; Kaladchibachi, Sevag; Cowen, Stephen L; Fernandez, Fabian

2017-07-01

Despite their ubiquity in biomedical research, Drosophila have yet to be widely employed as model organisms in psychology. Many complex human-like behaviors are observed in Drosophila, which exhibit elaborate displays of inter-male aggression and female courtship, self-medication with alcohol in response to stress, and even cultural transmission of social information. Here, we asked whether Drosophila can demonstrate behavioral indices of spatial working memory in a Y-maze, a classic test of memory function and novelty-seeking in rodents. Our data show that Drosophila, like rodents, alternate their visits among the three arms of a Y-maze and spontaneously favor entry into arms they have explored less recently versus ones they have just seen. These findings suggest that Drosophila possess some of the information-seeking and working memory facilities mammals depend on to navigate through space and might be relevant models for understanding human psychological phenomena such as curiosity. Copyright © 2017 Elsevier Inc. All rights reserved.

Sex-dependent modification by chronic caffeine of acute methamphetamine effects on anxiety-related behavior in rats.

PubMed

Hughes, Robert N; Hamilton, Jennifer J

2018-06-01

For fourteen days, male and female PVG/c hooded rats were provided continuously with either pure drinking water, or water containing caffeine in a quantity approximating a daily dose of 31.1 mg/kg. Then at intervals of 3 days, they were administered 1, 2 mg/kg methamphetamine (MA) or saline before being tested for anxiety-related behavior in a zero maze or a light/dark box, or their short-term spatial memory was assessed in a Y maze following introduction of a novel brightness change in one of the arms. Each rat experienced each type of apparatus with the same acute MA or saline treatment while still exposed to chronic caffeine or pure drinking water. While chronic caffeine on its own did not affect any behavioral measure, acute MA was anxiolytic for male rats suggested by increased entries and occupancy of zero-maze enclosed areas, and decreased emergence latencies and increased entries into the light/dark-box light compartment. Females were less affected than males by MA in both types of apparatus unless they also consumed caffeine. For male rats, choices of the Y-maze novel arm were affected by neither caffeine nor MA, but for females provided with unadulterated water, such choices were reduced by 1 mg/kg MA but increased for those exposed to caffeine, thereby suggesting either impaired or improved memory respectively. However, changes in anxiety could also explain these results. Overall, results generated in the three types of apparatus supported potentiation by caffeine of any effects of MA on anxiety for females only. Copyright © 2018 Elsevier B.V. All rights reserved.

Behavioural characterization of vitamin D receptor knockout mice.

PubMed

Burne, Thomas H J; McGrath, John J; Eyles, Darryl W; Mackay-Sim, Alan

2005-02-28

Vitamin D (calcitriol) is a nuclear transcription regulator acting via a nuclear hormone receptor (VDR). In addition to its role in the regulation of calcium and phosphate homeostasis and in bone formation, Vitamin D is also thought to be involved in brain function. The aim of this study was to behaviourally phenotype VDR knockout mice. We characterized the behaviour of VDR null mutant mice and wildtype littermate controls by subjecting them to a range of tests including a primary behavioural screen (using the SHIRPA protocol), rotarod, gait analysis, Y-maze, marble burying test, bedding test, holeboard test, elevated plus maze, open field test and prepulse inhibition of the acoustic startle response. There were no effects of genotype on most of the scores from the SHIRPA protocol except that VDR -/- mice had alopecia, were shorter and weighed less than VDR +/+ mice. VDR -/- mice had a shorter gait as well as impairments on the rotarod, in the bedding test and impaired habituation in both the open field and on the acoustic startle response. The VDR -/- mice had normal acoustic startle responses but had impaired PPI at long (256 ms) but not short (64 ms) prepulse to pulse intervals. The VDR -/- mice were less active in the open field and buried fewer marbles in the marble burying test. However, there were no differences in the time spent on the open arms of the elevated plus maze or in working memory as assessed by repeat arm entries on the Y-maze. Therefore, it appears that VDR -/- mice have muscular and motor impairments that significantly affects locomotor behaviour but seemingly no impairments in cognition as indicated by exploration, working memory or anxiety.

MDMA in adolescent male rats: decreased serotonin in the amygdala and behavioral effects in the elevated plus-maze test.

PubMed

Faria, Raquel; Magalhães, Ana; Monteiro, Pedro R R; Gomes-Da-Silva, Joana; Amélia Tavares, Maria; Summavielle, Teresa

2006-08-01

Long-term behavioral consequences of the neurotoxicity produced by 3,4-methylenedioxymethamphetamine (MDMA) in the adolescent rat are still mostly unknown. Here, adolescent male rats (postnatal day 45 PND [45]) were exposed to 10 mg/kg of MDMA, intraperitoneally, every 2 h for 6 h. Controls were given 0.9% saline in the same protocol. Ten days after exposure, the behavioral effects of MDMA were assessed in the elevated plus-maze (n = 6 per group). After behavioral testing, animals were sacrificed and the amygdalae were dissected and processed for HPLC determination of dopamine (DA), serotonin (5-HT), and metabolites. Results showed a significant decrease in the 5-HT content (P < 0.05), but no significant alterations in DA or its metabolites. Behavioral observation in the elevated plus-maze showed a decreased number of entries in the unprotected arms (P < 0.05), which were correlated to the number of entries and time spent in the central platform. Rearing was also decreased (P < 0.05). No differences were observed in head dips, grooming, or number of entries in the protected arms of the apparatus. Therefore, we conclude that, as in the adult rat, exposure to MDMA in the adolescent rat is associated to long-term depletion of the 5-HT content and increased anxiety-like behavior.

Acute and subchronic effects of MDMA ("ecstasy") on anxiety in male mice tested in the elevated plus-maze.

PubMed

Navarro, José Francisco; Maldonado, Enrique

2002-10-01

3,4-Methylenedioxymethamphetamine (MDMA) is a compound structurally similar to methamphetamine, which has become one of the most widely used illicit substances. Animal studies investigating acute effects of MDMA on anxiety are unclear since, although an anxiogenic-like action of MDMA in different animal models of anxiety has been mainly described, there is also evidence supporting an anxiolytic-like effect for this drug. An attempt was made to clarify the possible anxiogenic-like profile of MDMA (1, 8 and 15 mg/kg i.p.) by analyzing its effect on behavior of male mice in the elevated plus-maze test. Moreover, the possible development of tolerance to the effects of MDMA on anxiety after its subchronic administration for 5 consecutive days was examined. The parameters evaluated included: (1) total time in open arms, (2) total time in closed arms, (3) total time in central area, (4) number of open arm entries, (5) number of closed arm entries and (6) number of central area entries. Acute treatment with MDMA (8 mg/kg) significantly reduced the time spent in the open arms, as well as markedly increasing the number of entries in the closed arms and in the central area, as compared with the control group, suggesting that MDMA, at this dose, has an anxiogenic-like activity. Mice subchronically treated with the drug (1 and 8 mg/kg) displayed a notable reduction in the time spent in the open arms, accompanied by an increase in the time spent in the closed arms and in the central platform. These results indicate that the anxiogenic-like effect found after acute treatment is not only maintained but also more marked after subchronic treatment. In contrast, mice treated subchronically with the highest dose of MDMA (15 mg/kg) exhibited a significant increase in the time spent in the open arms as well as a marked reduction in the time spent in the closed arms, supporting an anxiolytic-like activity of the drug. A possible dual pharmacological property of MDMA on anxiety is suggested.

Dynamics of memory-guided choice behavior in Drosophila

PubMed Central

ICHINOSE, Toshiharu; TANIMOTO, Hiromu

2016-01-01

Memory retrieval requires both accuracy and speed. Olfactory learning of the fruit fly Drosophila melanogaster serves as a powerful model system to identify molecular and neuronal substrates of memory and memory-guided behavior. The behavioral expression of olfactory memory has traditionally been tested as a conditioned odor response in a simple T-maze, which measures the result, but not the speed, of odor choice. Here, we developed multiplexed T-mazes that allow video recording of the choice behavior. Automatic fly counting in each arm of the maze visualizes choice dynamics. Using this setup, we show that the transient blockade of serotonergic neurons slows down the choice, while leaving the eventual choice intact. In contrast, activation of the same neurons impairs the eventual performance leaving the choice speed unchanged. Our new apparatus contributes to elucidating how the speed and the accuracy of memory retrieval are implemented in the fly brain. PMID:27725473

Decreased GABA receptor in the cerebral cortex of epileptic rats: effect of Bacopa monnieri and Bacoside-A.

PubMed

Mathew, Jobin; Balakrishnan, Savitha; Antony, Sherin; Abraham, Pretty Mary; Paulose, C S

2012-02-24

Gamma amino butyric acid (GABA), the principal inhibitory neurotransmitter in the cerebral cortex, maintains the inhibitory tones that counter balances neuronal excitation. When this balance is perturbed, seizures may ensue. In the present study, alterations of the general GABA, GABAA and GABAB receptors in the cerebral cortex of the epileptic rat and the therapeutic application of Bacopa monnieri were investigated. Scatchard analysis of [3H]GABA, [3H]bicuculline and [3H]baclofen in the cerebral cortex of the epileptic rat showed significant decrease in Bmax (P < 0.001) compared to control. Real Time PCR amplification of GABA receptor subunits such as GABAAά1, GABAAγ, GABAAδ, GABAB and GAD where down regulated (P < 0.001) in epileptic rats. GABAAά5 subunit and Cyclic AMP responsible element binding protein were up regulated. Confocal imaging study confirmed the decreased GABA receptors in epileptic rats. Epileptic rats have deficit in radial arm and Y maze performance. Bacopa monnieri and Bacoside-A treatment reverses epilepsy associated changes to near control suggesting that decreased GABA receptors in the cerebral cortex have an important role in epileptic occurrence; Bacopa monnieri and Bacoside-A have therapeutic application in epilepsy management.

Persistent increased PKMζ in long-term and remote spatial memory.

PubMed

Hsieh, Changchi; Tsokas, Panayiotis; Serrano, Peter; Hernández, A Iván; Tian, Dezhi; Cottrell, James E; Shouval, Harel Z; Fenton, André Antonio; Sacktor, Todd Charlton

2017-02-01

PKMζ is an autonomously active PKC isoform that is thought to maintain both LTP and long-term memory. Whereas persistent increases in PKMζ protein sustain the kinase's action in LTP, the molecular mechanism for the persistent action of PKMζ during long-term memory has not been characterized. PKMζ inhibitors disrupt spatial memory when introduced into the dorsal hippocampus from 1day to 1month after training. Therefore, if the mechanisms of PKMζ's persistent action in LTP maintenance and long-term memory were similar, persistent increases in PKMζ would last for the duration of the memory, far longer than most other learning-induced gene products. Here we find that spatial conditioning by aversive active place avoidance or appetitive radial arm maze induces PKMζ increases in dorsal hippocampus that persist from 1day to 1month, coinciding with the strength and duration of memory retention. Suppressing the increase by intrahippocampal injections of PKMζ-antisense oligodeoxynucleotides prevents the formation of long-term memory. Thus, similar to LTP maintenance, the persistent increase in the amount of autonomously active PKMζ sustains the kinase's action during long-term and remote spatial memory maintenance. Copyright © 2016. Published by Elsevier Inc.

AAV serotype 2/1-mediated gene delivery of anti-inflammatory interleukin-10 enhances neurogenesis and cognitive function in APP+PS1 mice.

PubMed

Kiyota, T; Ingraham, K L; Swan, R J; Jacobsen, M T; Andrews, S J; Ikezu, T

2012-07-01

Brain inflammation is a double-edged sword. It is required for brain repair in acute damage, whereas chronic inflammation and autoimmune disorders are neuropathogenic. Certain proinflammatory cytokines and chemokines are closely related to cognitive dysfunction and neurodegeneration. Representative anti-inflammatory cytokines, such as interleukin (IL)-10, can suppress neuroinflammation and have significant therapeutic potentials in ameliorating neurodegenerative disorders such as Alzheimer's disease (AD). Here, we show that adeno-associated virus (AAV) serotype 2/1 hybrid-mediated neuronal expression of the mouse IL-10 gene ameliorates cognitive dysfunction in amyloid precursor protein+ presenilin-1 bigenic mice. AAV2/1 infection of hippocampal neurons resulted in sustained expression of IL-10 without its leakage into the blood, reduced astro/microgliosis, enhanced plasma amyloid-β peptide (Aβ) levels and enhanced neurogenesis. Moreover, increased levels of IL-10 improved spatial learning, as determined by the radial arm water maze. Finally, IL-10-stimulated microglia enhanced proliferation but not differentiation of primary neural stem cells in the co-culture system, whereas IL-10 itself had no effect. Our data suggest that IL-10 gene delivery has a therapeutic potential for a non-Aβ-targeted treatment of AD.

Mutation of Dcdc2 in mice leads to impairments in auditory processing and memory ability.

PubMed

Truong, D T; Che, A; Rendall, A R; Szalkowski, C E; LoTurco, J J; Galaburda, A M; Holly Fitch, R

2014-11-01

Dyslexia is a complex neurodevelopmental disorder characterized by impaired reading ability despite normal intellect, and is associated with specific difficulties in phonological and rapid auditory processing (RAP), visual attention and working memory. Genetic variants in Doublecortin domain-containing protein 2 (DCDC2) have been associated with dyslexia, impairments in phonological processing and in short-term/working memory. The purpose of this study was to determine whether sensory and behavioral impairments can result directly from mutation of the Dcdc2 gene in mice. Several behavioral tasks, including a modified pre-pulse inhibition paradigm (to examine auditory processing), a 4/8 radial arm maze (to assess/dissociate working vs. reference memory) and rotarod (to examine sensorimotor ability and motor learning), were used to assess the effects of Dcdc2 mutation. Behavioral results revealed deficits in RAP, working memory and reference memory in Dcdc2(del2/del2) mice when compared with matched wild types. Current findings parallel clinical research linking genetic variants of DCDC2 with specific impairments of phonological processing and memory ability. © 2014 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

Conjunctivally administered NGF antibody reduces pain sensitivity and anxiety-like behavioral responses in aged female mice.

PubMed

Berry, Alessandra; Aloe, Luigi; Rossi, Simona; Bonsignore, Luca T; Capone, Francesca; Alleva, Enrico; Cirulli, Francesca

2010-07-11

This study reports that peripheral administration of Nerve Growth Factor antibodies (ANA) affects behavior in aged female CD-1 mice. ANA increased the propensity of mice to stay and perform behaviors in the anxiogenic open arms of the maze, lowered pain sensitivity and reduced behavioral flexibility in a Morris water maze task, also reducing ChAT immunoreactivity in the basal forebrain. These findings support the hypothesis that topical eye application can represent an alternative route for delivering biologically active compounds into the brain allowing studying the role of NGF on brain cell function. Copyright 2010 Elsevier B.V. All rights reserved.

Principles of Jet Engine Operation

DTIC Science & Technology

1978-05-01

and discharged from the rotor radially (perpendicular-to the axis .,f rotation). In-contrast, the axial flow compressor both admits and dis- charges... TurbofanS for most contemporary turbojet powered aircraft applications, the axial flow compressor is utilized. The remainder of the discussion will...usually installed on several radial arms which are evenly spaced around the compressor face. The spacing of the probes on the arms is such that they are

Influence of age on cognition and scopolamine induced memory impairment in rats measured in the radial maze paradigm.

PubMed

Appenroth, Dorothea; Fleck, Christian

2010-01-01

The influence of age on (1) cognition and (2) scopolamine (CAS 51-34-3) induced memory impairment in female rats was measured in the radial maze paradigm (RAM). (1) First training trials were done with 3 and 12 months old rats. Rats were trained to find all eight food baits in the RAM without errors and within 1 min. Both 3- and 12-month old rats need about 15 trials for the first-time learning of the RAM task. After intervals of 3 6 months, respectively, initially young rats were re-trained with an age of 6 and 12 months. Surprisingly, re-trained rats successfully completed the maze runs already after one re-training trial. Thus the phenomenon of preserved spatial memory was approved for female rats. (2) Memory impairment by scopolamine in the RAM was tested for the time in rats with an age of 3 months. first rats with thesame After a control run,the rats received an i.p. injection of either scopolamine hydrochloride (0.05 mg/100 g b. wt.) or saline vehicle. The effect of scopolamine on working memory was measured 20 min after administration. Training procedure and scopolamine administration were repeated at an age of 6, 12, 18, and 24 months in the same manner. The cognition impairment after scopolamine (number of errors: control: <1; scopolamine: 5-6) remains constant between 3 and 24 months of age. The only significant difference was the increase in run time in rats older than 18 months caused by degenerative changes developing with age.

Assessment of attention and inhibitory control in rodent developmental neurotoxicity studies.

PubMed

Driscoll, Lori L; Strupp, Barbara J

2015-01-01

In designing screens to assess potential neurotoxicants, the paramount goal is that the selected assessment tools detect dysfunction if it exists. This goal is particularly challenging in the case of cognitive assessments. Cognition is not a unitary phenomenon, and indeed there is growing evidence that different aspects of cognitive functioning are subserved by distinct neural systems. As a result, if a particular neurotoxicant selectively damages certain neural systems but not others, it can impair some cognitive, sensory, or affective functions, but leave many others intact. Accordingly, studies with human subjects use batteries of cognitive tests, cognizant of the fact that no one test is capable of detecting all forms of cognitive dysfunction. In contrast, assessment of cognitive functioning in non-human animal developmental neurotoxicity (DNT) studies typically consists of a single, presumably representative, "learning and memory" task that is expected to detect all potential effects on cognitive functioning. Streamlining the cognitive assessment in these studies saves time and money, but these shortcuts can have serious consequences if the aspect of cognitive functioning that is impaired is not tapped by the single selected task. In particular, executive functioning - a constellation of cognitive functions which enables the organism to focus on multiple streams of information simultaneously, and revise plans as necessary - is poorly assessed in most animal DNT studies. The failure to adequately assess these functions - which include attention, working memory, inhibitory control, and planning - is particularly worrisome in light of evidence that the neural systems that subserve these functions may be uniquely vulnerable to early developmental insults. We illustrate the importance of tapping these areas of functioning in DNT studies by describing the pattern of effects produced by early developmental Pb exposure. Rats exposed to lead (Pb) early in development were tested on a series of automated attention tasks, as well as on a radial arm maze task. The lead-exposed rats were not impaired in this demanding radial arm maze task, despite conditions which tapped the limits of both working and long-term memory. In contrast, the automated tests designed to assess rodent executive functioning revealed selective and functionally important deficits in attention and regulation of emotion or negative affect (produced by committing an error or not receiving an expected reward). This example underscores the importance of including tasks to specifically tap executive functioning in DNT batteries. Such tasks are not only sensitive but can also shed light on the specific nature of the dysfunction, and they can implicate dysfunction of specific neural systems, information which can be used to design therapeutic interventions. Although the use of such tasks increases the time and effort needed to complete the battery, the benefits outweigh the cost, in light of the greater sensitivity of the battery and the more complete characterization of effects. Copyright © 2014 Elsevier Inc. All rights reserved.

Pigeons may not use dual coding in the radial maze analog task.

PubMed

DiGian, Kelly A; Zentall, Thomas R

2007-07-01

Using a radial maze analog task, T. R. Zentall, J. N. Steirn, and P. Jackson-Smith (1990) found evidence that when a delay was interpolated early in a trial, pigeons coded locations retrospectively, but when the delay was interpolated late in the trial, they coded locations prospectively (support for a dual coding hypothesis). In Experiment 1 of the present study, the authors replicated the original finding of dual coding. In Experiments 2 and 3, they used a 2-alternative test procedure that does not require the assumption that pigeons' choice criterion, which changes over the course of the trial, is the same on delay and control trials. Under these conditions, the pigeons no longer showed evidence for dual coding. Instead, there was some evidence that they showed prospective coding, but a more parsimonious account of the results may be that the delay produced a relatively constant decrement in performance at all points of delay interpolation. The original finding of dual coding by Zentall et al. might have been biased by more impulsive choices early in control trials but not in delay trials and by a more stringent choice criterion late in delay trials. ((c) 2007 APA, all rights reserved).

Sex-specific effects of Cacna1c haploinsufficiency on object recognition, spatial memory, and reversal learning capabilities in rats.

PubMed

Braun, Moria D; Kisko, Theresa M; Vecchia, Débora Dalla; Andreatini, Roberto; Schwarting, Rainer K W; Wöhr, Markus

2018-05-23

The CACNA1C gene is strongly implicated in the etiology of multiple major neuropsychiatric disorders, such as bipolar disorder, major depression, and schizophrenia, with cognitive deficits being a common feature. It is unclear, however, by which mechanisms CACNA1C variants advance the risk of developing neuropsychiatric disorders. This study set out to investigate cognitive functioning in a newly developed genetic Cacna1c rat model. Specifically, spatial and reversal learning, as well as object recognition memory were assessed in heterozygous Cacna1c +/- rats and compared to wildtype Cacna1c +/+ littermate controls in both sexes. Our results show that both Cacna1c +/+ and Cacna1c +/- animals were able to learn the rewarded arm configuration of a radial maze over the course of seven days. Both groups also showed reversal learning patterns indicative of intact abilities. In females, genotype differences were evident in the initial spatial learning phase, with Cacna1c +/- females showing hypo-activity and fewer mixed errors. In males, a difference was found during probe trials for both learning phases, with Cacna1c +/- rats displaying better distinction between previously baited and non-baited arms; and regarding cognitive flexibility in favor of the Cacna1c +/+ animals. All experimental groups proved to be sensitive to reward magnitude and fully able to distinguish between novel and familiar objects in the novel object recognition task. Taken together, these results indicate that Cacna1c haploinsufficiency has a minor, but positive impact on (spatial) memory functions in rats. Copyright © 2018 Elsevier Inc. All rights reserved.

Revealing past memories: proactive interference and ketamine-induced memory deficits.

PubMed

Chrobak, James J; Hinman, James R; Sabolek, Helen R

2008-04-23

Memories of events that occur often are sensitive to interference from memories of similar events. Proactive interference plays an important and often unexamined role in memory testing for spatially and temporally unique events ("episodes"). Ketamine (NMDA receptor antagonist) treatment in humans and other mammals induces a constellation of cognitive deficits, including impairments in working and episodic memory. We examined the effects of the ketamine (2.5-100 mg/kg) on the acquisition, retrieval, and retention of memory in a delayed-match-to-place radial water maze task that can be used to assess proactive interference. Ketamine (2.5-25 mg/kg, i.p.) given 20 min before the sample trial, impaired encoding. The first errors made during the test trial were predominantly to arms located spatially adjacent to the goal arm, suggesting an established albeit weakened representation. Ketamine (25-100 mg/kg) given immediately after the sample trial had no effect on retention. Ketamine given before the test trial impaired retrieval. First errors under the influence of ketamine were predominantly to the goal location of the previous session. Thus, ketamine treatment promoted proactive interference. These memory deficits were not state dependent, because ketamine treatment at both encoding and retrieval only increased the number of errors during the test session. These data demonstrate the competing influence of distinct memory representations during the performance of a memory task in the rat. Furthermore, they demonstrate the subtle disruptive effects of the NMDA antagonist ketamine on both encoding and retrieval. Specifically, ketamine treatment disrupted retrieval by promoting proactive interference from previous episodic representations.

Stellar metallicity variations across spiral arms in disk galaxies with multiple populations

NASA Astrophysics Data System (ADS)

Khoperskov, S.; Di Matteo, P.; Haywood, M.; Combes, F.

2018-03-01

This Letter studies the formation of azimuthal metallicity variations in the disks of spiral galaxies in the absence of initial radial metallicity gradients. Using high-resolution N-body simulations, we model composite stellar discs, made of kinematically cold and hot stellar populations, and study their response to spiral arm perturbations. We find that, as expected, disk populations with different kinematics respond differently to a spiral perturbation, with the tendency for dynamically cooler populations to show a larger fractional contribution to spiral arms than dynamically hotter populations. By assuming a relation between kinematics and metallicity, namely the hotter the population, the more metal-poor it is, this differential response to the spiral arm perturbations naturally leads to azimuthal variations in the mean metallicity of stars in the simulated disk. Thus, azimuthal variations in the mean metallicity of stars across a spiral galaxy are not necessarily a consequence of the reshaping, by radial migration, of an initial radial metallicity gradient. They indeed arise naturally also in stellar disks which have initially only a negative vertical metallicity gradient.

The young star cluster population of M51 with LEGUS - II. Testing environmental dependences

NASA Astrophysics Data System (ADS)

Messa, Matteo; Adamo, A.; Calzetti, D.; Reina-Campos, M.; Colombo, D.; Schinnerer, E.; Chandar, R.; Dale, D. A.; Gouliermis, D. A.; Grasha, K.; Grebel, E. K.; Elmegreen, B. G.; Fumagalli, M.; Johnson, K. E.; Kruijssen, J. M. D.; Östlin, G.; Shabani, F.; Smith, L. J.; Whitmore, B. C.

2018-06-01

It has recently been established that the properties of young star clusters (YSCs) can vary as a function of the galactic environment in which they are found. We use the cluster catalogue produced by the Legacy Extragalactic UV Survey (LEGUS) collaboration to investigate cluster properties in the spiral galaxy M51. We analyse the cluster population as a function of galactocentric distance and in arm and inter-arm regions. The cluster mass function exhibits a similar shape at all radial bins, described by a power law with a slope close to -2 and an exponential truncation around 105 M⊙. While the mass functions of the YSCs in the spiral arm and inter-arm regions have similar truncation masses, the inter-arm region mass function has a significantly steeper slope than the one in the arm region, a trend that is also observed in the giant molecular cloud mass function and predicted by simulations. The age distribution of clusters is dependent on the region considered, and is consistent with rapid disruption only in dense regions, while little disruption is observed at large galactocentric distances and in the inter-arm region. The fraction of stars forming in clusters does not show radial variations, despite the drop in the H2 surface density measured as a function of galactocentric distance. We suggest that the higher disruption rate observed in the inner part of the galaxy is likely at the origin of the observed flat cluster formation efficiency radial profile.

A robust animal model of state anxiety: fear-potentiated behaviour in the elevated plus-maze.

PubMed

Korte, S Mechiel; De Boer, Sietse F

2003-02-28

Fear (i.e., decreased percentage time spent on open-arm exploration) in the elevated plus-maze can be potentiated by prior inescapable stressor exposure, but not by escapable stress. The use of fear-potentiated plus-maze behaviour has several advantages as compared to more traditional animal models of anxiety. (a) In contrast to the traditional (spontaneous) elevated plus-maze, which measures innate fear of open spaces, fear-potentiated plus-maze behaviour reflects an enhanced anxiety state (allostatic state). This "state anxiety" can be defined as an unpleasant emotional arousal in face of threatening demands or dangers. A cognitive appraisal of threat is a prerequisite for the experience of this type of emotion. (b) Depending on the stressor used (e.g., fear of shock, predator odour, swim stress, restraint, social defeat, predator stress (cat)), this enhanced anxiety state can last from 90 min to 3 weeks. Stress effects are more severe when rats are isolated in comparison to group housing. (c) Drugs can be administered in the absence of the original stressor and after stressor exposure. As a consequence, retrieval mechanisms are not affected by drug treatment. (d) Fear-potentiated plus-maze behaviour is sensitive to proven/putative anxiolytics and anxiogenics which act via mechanisms related to the benzodiazepine-gamma-aminobutyric acid receptor, but it is also sensitive to corticotropin-releasing receptor antagonists and glucocorticoid receptor antagonists and serotonin receptor agonists/antagonists complex (high predictive validity). (e) Fear-potentiated plus-maze behaviour is very robust, and experiments can easily be replicated in other labs. (f) Fear-potentiated plus-maze behaviour can be measured both in males and females. (g) Neural mechanisms involved in contextual fear conditioning, fear potentiation and state anxiety can be studied.Thus, fear-potentiated plus-maze behaviour may be a valuable measure in the understanding of neural mechanisms involved in the development of anxiety disorders and in the search for novel anxiolytics. Finally, the involvement of corticotropin-releasing factor and corticosteroid-corticotropin-releasing factor interactions in the production of fear-potentiated plus-maze behaviour are discussed.

Akt2 deficiency is associated with anxiety and depressive behavior in mice.

PubMed

Leibrock, Christina; Ackermann, Teresa F; Hierlmeier, Michael; Lang, Florian; Borgwardt, Stefan; Lang, Undine E

2013-01-01

The economic burden associated with major depressive disorder and anxiety disorders render both disorders the most common and debilitating psychiatric illnesses. To date, the exact cellular and molecular mechanisms underlying the pathophysiology, successful treatment and prevention of these highly associated disorders have not been identified. Akt2 is a key protein in the phosphatidylinositide-3 (PI3K) / glycogen synthase 3 kinase (GSK3) signaling pathway, which in turn is involved in brain-derived neurotrophic factor (BDNF) effects on fear memory, mood stabilisation and action of several antidepressant drugs. The present study thus explored the impact of Akt2 on behaviour of mice. Behavioural studies (Open-Field, Light-Dark box, O-Maze, Forced Swimming Test, Emergence Test, Object Exploration Test, Morris Water Maze, Radial Maze) have been performed with Akt2 knockout mice (akt(-/-)) and corresponding wild type mice (akt(+/+)). Anxiety and depressive behavior was significantly higher in akt(-/-) than in akt(+/+) mice. The akt(-/-) mice were cognitively unimpaired but displayed increased anxiety in several behavioral tests (O-Maze test, Light-Dark box, Open Field test). Moreover, akt(-/-) mice spent more time floating in the Forced Swimming test, which is a classical feature of experimental depression. Akt2 might be a key factor in the pathophysiology of depression and anxiety. © 2013 S. Karger AG, Basel.

Following of conspecific and avoidance of predator chemical cues by pine snakes (Pituophis melanoleucus).

PubMed

Burger, J

1989-03-01

The ability of hatchling pine snakes (Pituophis melanoleucus) to follow or avoid the chemical trails of conspecifics and a king snake (Lampropeltis getulus) on paper substrates was investigated inY-maze experiments. Hatchlings entered the arm with the adult conspecific trail and avoided the arm containing the king snake trail at a frequency much greater than that due to chance. The data support the hypotheses that pine snakes follow the chemical trails of adult conspecifics and avoid the chemical trails of a predator.

Methylene Blue Facilitates Memory Retention in Zebrafish in a Dose-Dependent Manner.

PubMed

Echevarria, David J; Caramillo, Erika M; Gonzalez-Lima, Francisco

2016-12-01

Methylene blue (MB) is an FDA-grandfathered drug with memory-enhancing effects at low doses, but opposite effects at high doses. We investigated the effects of four MB doses (0.1, 0.5, 5.0, or 10.0 μM) on zebrafish memory retention in the T-maze task. After training fish to swim into a certain arm of the T-maze, the fish were placed into a tank containing one of the four MB doses or a control tank containing blue food dye. Subsequently, fish were placed into the T-maze for memory retention testing. Results indicated that MB produced hormetic dose-response effects on memory. Fish that received the 0.5 μM dose performed significantly better at the T-maze than those that received higher doses. Fish who received 5.0 μM did not exhibit a significant difference in performance from control fish, and the fish that received the 10.0 μM dose performed significantly worse than lower doses. These findings support the utility of zebrafish in comparative research and their potential value for testing of MB and other neuropsychopharmacological treatments in animal models of memory disorders.

Pharmacological evidence for the role of nitric oxide in the modulation of stress-induced anxiety by morphine in rats.

PubMed

Anand, Rashmi; Gulati, Kavita; Ray, Arunabha

2012-02-15

The present study evaluated the effects of the opioid agonist, morphine on stress induced anxiogenesis and the possible involvement of nitric oxide (NO) in such effects in rats. Acute restraint stress consistently induced an anxiety-like response in the elevated plus maze test, i.e. reduced number of open arm entries and time spent in the open arms as compared to controls. Pretreatment with morphine (1 and 5mg/kg), attenuated the restraint stress induced anxiogenic response in a dose related manner. Restraint stress induced neurobehavioral suppression was associated with reductions in brain NO oxidation products (NOx) levels, which were also reversed with morphine. Interaction studies showed that sub-effective doses of morphine and l-arginine (a NO precursor) had synergistic effects on stress induced elevated plus maze activity and brain NOx, whereas, l-NAME (a NO synthase inhibitor) neutralized these effects of morphine. Repeated restraint stress (×5) induced adaptative changes as evidenced by normalization of behavioral suppression and elevations in brain NOx, as compared to acute stress. Pretreatment with morphine in combination with repeated stress (×5) showed potentiating effects in the induction of behavioral adaptation in the elevated plus maze and elevations in brain NOx, as compared to repeated stress alone. Further, l-NAME, when administered prior to morphine, blocked this effect of morphine on stress adaptation. These results suggest differential morphine-NO interactions during acute and repeated restraint stress. Copyright © 2011 Elsevier B.V. All rights reserved.

Band-notched spiral antenna

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

Jeon, Jae; Chang, John

A band-notched spiral antenna having one or more spiral arms extending from a radially inner end to a radially outer end for transmitting or receiving electromagnetic radiation over a frequency range, and one or more resonance structures positioned adjacent one or more segments of the spiral arm associated with a notch frequency band or bands of the frequency range so as to resonate and suppress the transmission or reception of electromagnetic radiation over said notch frequency band or bands.

Sodium benzoate, a food preservative, induces anxiety and motor impairment in rats.

PubMed

Noorafshan, Ali; Erfanizadeh, Mahboobeh; Karbalay-Doust, Saied

2014-01-01

To investigate the behavioral characteristics, including anxiety and motor impairment, in sodium benzoate (NaB) treated rats. The study was carried out between July and September 2012 in the Laboratory Animal Center of Shiraz University of Medical Sciences, Shiraz, Iran. The rats were divided into 2 groups receiving distilled water and NaB (200mg/kg/day). All the animals received daily gavages for 4 weeks. At the end of the fourth week, anxiety, and motor function were assessed in elevated plus maze and rotarod test. According to the results, NaB-treated rats spent less time in the open arm and had fewer entrances to the open arms in comparison with the control group (p<0.04). Also, the performance of the NaB-treated rats in fixed and accelerating speed rotarods was impaired, and the riding time (endurance) was lower than the control group (p<0.01). The performance of the NaB-treated rats was impaired in the elevated plus maze, an indicator of anxiety. Their riding time in fixed and accelerating speed rotarods was decreased, indicating motor impairment.

Relations between open-field, elevated plus-maze, and emergence tests in C57BL/6JIco and BALB/cAnN@Ico mice injected with ethanol.

PubMed

Lalonde, R; Strazielle, C

2012-04-01

The effects of ethanol were examined on three tests of exploratory activity in two mouse strains. Although ethanol reduced open-field rearing in both strains, it increased ambulation only in the less active BALB/cAnN@Ico strain, not in the C57BL/6JIco strain. Likewise, ethanol increased open and enclosed arm entries in the elevated plus-maze only in the more anxious BALB/cAnN@Ico strain. However, both strains injected with ethanol emerged faster than placebo from a small chamber at doses not affecting behaviors in the other two tests. Significant correlations were found between emergence latencies on one hand and either slow stereotyped movements or open and enclosed arm entries on the other. The strain-specific effects may be attributable to differences in GABA(A) -related receptor binding or catalase activity. © 2011 The Authors Fundamental and Clinical Pharmacology © 2011 Société Française de Pharmacologie et de Thérapeutique.

Spatial and kinematic structure of Monoceros star-forming region

NASA Astrophysics Data System (ADS)

Costado, M. T.; Alfaro, E. J.

2018-05-01

The principal aim of this work is to study the velocity field in the Monoceros star-forming region using the radial velocity data available in the literature, as well as astrometric data from the Gaia first release. This region is a large star-forming complex formed by two associations named Monoceros OB1 and OB2. We have collected radial velocity data for more than 400 stars in the area of 8 × 12 deg2 and distance for more than 200 objects. We apply a clustering analysis in the subspace of the phase space formed by angular coordinates and radial velocity or distance data using the Spectrum of Kinematic Grouping methodology. We found four and three spatial groupings in radial velocity and distance variables, respectively, corresponding to the Local arm, the central clusters forming the associations and the Perseus arm, respectively.

Kv4 Potassium Channels Modulate Hippocampal EPSP-Spike Potentiation and Spatial Memory in Rats

ERIC Educational Resources Information Center

Truchet, Bruno; Manrique, Christine; Sreng, Leam; Chaillan, Franck A.; Roman, Francois S.; Mourre, Christiane

2012-01-01

Kv4 channels regulate the backpropagation of action potentials (b-AP) and have been implicated in the modulation of long-term potentiation (LTP). Here we showed that blockade of Kv4 channels by the scorpion toxin AmmTX3 impaired reference memory in a radial maze task. In vivo, AmmTX3 intracerebroventricular (i.c.v.) infusion increased and…

Learning and memory effects of neonatal methamphetamine exposure in rats: Role of reactive oxygen species and age at assessment.

PubMed

Jablonski, Sarah A; Williams, Michael T; Vorhees, Charles V

2017-11-01

In utero methamphetamine (MA) exposure leads to a range of adverse effects, such as decreased attention, reduced working-memory capability, behavioral dysregulation, and spatial memory impairments in exposed children. In the current experiment, preweaning Sprague-Dawley rats-as a model of third trimester human exposure-were administered the spin trapping agent, N-tert-butyl-α-phenylnitrone (PBN), daily prior to MA. Rats were given 0 (SAL) or 40 mg/kg PBN prior to each MA dose (10 mg/kg, 4× per day) from postnatal day (P) 6-15. Littermates underwent Cincinnati water maze, Morris water maze, and radial water maze assessment beginning on P30 (males) or P60 (females). Males were also tested for conditioned contextual and cued freezing, while females were trained in passive avoidance. Findings show that, regardless of age/sex, neonatal MA induced deficits in all tests, except passive avoidance. PBN did not ameliorate these effects, but had a few minor effects. Taken together, MA induced learning deficits emerge early and persist, but the mechanism remains unknown. © 2017 Wiley Periodicals, Inc.

Activity in prelimbic cortex is required for adjusting the anxiety response level during the elevated plus-maze retest.

PubMed

Stern, C A J; Do Monte, F H M; Gazarini, L; Carobrez, A P; Bertoglio, L J

2010-09-29

The prelimbic (PL) subregion of medial prefrontal cortex has been implicated in anxiety regulation. It is unknown, however, whether PL cortex also serves to fine-tuning the level of anxiety-related behavior exhibited on the next exposure to the same potentially threatening situation. To address this, we infused cobalt (1.0 mM) to temporarily inactivate the PL cortex during testing, post-testing or retesting in the elevated plus-maze (EPM). This protocol was chosen because it allowed us to concurrently investigate anxiety and the process of aversive learning and memory. PL cortex inactivation during the EPM testing increased the exploration of open-arms, substantiating its role in anxiety. PL cortex inactivation during the EPM retesting counteracted the further avoidance to open-arms exhibited by rats. Interestingly, as evidenced by min-by-min analysis, the cobalt-treated group behaved on EPM retesting as did the vehicle-treated group on EPM testing. This result may imply that activity in PL cortex is necessary for retrieving previously learned information that adjusts the anxiety response level on EPM retesting. Alternatively, a simple reduction in anxiety could explain the cobalt-induced increase in retest open-arms exploration. Neither test nor post-test PL cortex inactivation affected the further avoidance to open-arms observed on EPM retesting. To extend the investigation of PL cortex role in the regulation of open-arms avoidance, we infused other drugs prior to testing or retesting in the EPM. Antagonism of PL cortex adrenergic beta-1 receptors with atenolol (10 nmol), cholinergic muscarinic receptors with scopolamine (20 nmol) or glutamatergic N-methyl-d-aspartic acid (NMDA) receptors with AP5 (6.0 nmol) interfered with the level of open-arms exploration on testing, but not on retesting. Copyright 2010 IBRO. Published by Elsevier Ltd. All rights reserved.

Handling of Adolescent Rats Improves Learning and Memory and Decreases Anxiety

PubMed Central

Costa, Rafaela; Tamascia, Mariana L; Nogueira, Marie D; Casarini, Dulce E; Marcondes, Fernanda K

2012-01-01

Some environmental interventions can result in physiologic and behavioral changes in laboratory animals. In this context, the handling of adolescent or adult rodents has been reported to influence exploratory behavior and emotionality. Here we examined the effects of handling on memory and anxiety levels of adolescent rats. Male Sprague–Dawley rats (age, 60 d) were divided into a control group and a handled group, which were handled for 5 min daily, 5 d per week, for 6 wk. During handling bouts, the rat was removed from its cage, placed in the experimenter's lap or on the top of a table, and had its neck and back gently stroked by the experimenter's fingers. During week 6, each rat's anxiety level was evaluated in the elevated plus-maze (EPM) test. Learning and memory were evaluated 48 h later, by measuring escape latency in the elevated plus-maze test. Plasma corticosterone and catecholamine levels were measured also. Norepinephrine levels were lower in the handled rats compared with control animals, with no differences in epinephrine and corticosterone. As compared with the control rats, the handled rats showed increases in the percentage of time spent in the open arms of the test apparatus, percentage of entries into open arms, and number of visits to the end of the open arms and decreases in the latency of the first open arm entry. Escape latency was lower in the handled rats compared with control rats in both the first and second trials. The data obtained suggest that handling decreases anxiety levels and improves learning skills and memory in rats. PMID:23312082

The role of dopamine in the dorsomedial striatum in place and response learning.

PubMed

Lex, B; Sommer, S; Hauber, W

2011-01-13

The posterior subregion of the dorsomedial striatum (pDMS) has been implicated in spatial learning. Here we investigated the role of dopamine (DA) signals in the pDMS in place and response learning using a T-maze task. Rats subjected to a DA depletion of the pDMS and sham controls were trained for 7 days to retrieve food from the west arm of the maze starting from the south, that is to make a left turn at the choice point. On day 8, a probe test was given in which the starting arm was inserted as the north arm. On days 9-16 animals received further training, and on day 17, a second probe test was performed. We examined whether animals responded on probe tests according to a response strategy (left turn at choice point) or to a place strategy (right turn at choice point). Our results revealed that, unlike sham controls, rats with a pDMS DA depletion preferentially used a response rather than a place strategy already on the first probe test. These findings provide further support for a role of the pDMS in spatially guided behavior and indicate that DA signals in the pDMS are critical for the use of a place strategy. Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

Topographical anatomy of the radial nerve and its muscular branches related to surface landmarks.

PubMed

Cho, Hyejin; Lee, Hye-Yeon; Gil, Young-Chun; Choi, Yun-Rak; Yang, Hee-Jun

2013-10-01

Understanding of the anatomy of the radial nerve and its branches is vital to the treatment of humeral fracture or the restoration of upper extremity function. In this study, we dissected 40 upper extremities from adult cadavers to locate the course of the radial nerve and the origins and insertions of the branches of the radial nerve using surface landmarks. The radial nerve reached and left the radial groove and pierced the lateral intermuscular septum, at the levels of 46.7, 60.5, and 66.8% from the acromion to the transepicondylar line, respectively. Branches to the long head of the triceps brachii originated in the axilla, and branches to the medial and lateral heads originated in the axilla or in the arm. The muscular attachments to the long, medial, and lateral heads were on average 34.0 mm proximal, 16.4 mm distal, and 19.3 mm proximal to the level of inferior end of the deltoid muscle, respectively. The radial nerve innervated 65.0% of the brachialis muscles. Branches to the brachioradialis and those to the extensor carpi radialis longus arose from the radial nerve above the transepicondylar line. Branches to the extensor carpi radialis brevis usually arose from the deep branch of radial nerve (67.5%); however, in some cases, branches to the extensor carpi radialis brevis arose from either the radial nerve (20.0%) or the superficial branch of the radial nerve (12.5%). Using these data, the course of the radial nerve can be estimated by observing the surface of the arm. Copyright © 2012 Wiley Periodicals, Inc.

Epigenetic regulation of neuronal immediate early genes is associated with decline in their expression and memory consolidation in scopolamine-induced amnesic mice.

PubMed

Srivas, Sweta; Thakur, Mahendra K

2017-09-01

Recently, we reported a correlation of scopolamine mediated decline in memory consolidation with increase in the expression of DNA methyltransferase 1 (DNMT1) and histone deacetylase 2 (HDAC2) in the mouse hippocampus. Memory consolidation is a protein synthesis-dependent process which involves the expression of synaptic plasticity genes, particularly neuronal immediate early genes (IEGs). However, the mechanism of regulation of these genes during decline in memory is poorly understood. Therefore, we have studied the epigenetic regulation of expression of neuronal IEGs in scopolamine-induced amnesic mice. Scopolamine significantly impaired memory consolidation as tested by radial arm maze, and the expression of neuronal IEGs was downregulated in the hippocampus as revealed by qRT-PCR and Western blotting. Further, methylated DNA immunoprecipitation (MeDIP) analysis showed increase in DNA methylation, while chromatin immunoprecipitation (ChIP) revealed decrease in H3K9/14 acetylation at the promoter of neuronal IEGs. Taken together, the present study shows that increased DNA methylation and decreased histone acetylation at the promoter of neuronal IEGs are associated with decline in their expression and memory consolidation during scopolamine-induced amnesia. These findings suggest that the epigenetic regulation through altered DNA methylation and histone acetylation might be explored further to develop potential therapeutic interventions for amnesia.

Decreased GABA receptor in the cerebral cortex of epileptic rats: effect of Bacopa monnieri and Bacoside-A

PubMed Central

2012-01-01

Abstact Background Gamma amino butyric acid (GABA), the principal inhibitory neurotransmitter in the cerebral cortex, maintains the inhibitory tones that counter balances neuronal excitation. When this balance is perturbed, seizures may ensue. Methods In the present study, alterations of the general GABA, GABAA and GABAB receptors in the cerebral cortex of the epileptic rat and the therapeutic application of Bacopa monnieri were investigated. Results Scatchard analysis of [3H]GABA, [3H]bicuculline and [3H]baclofen in the cerebral cortex of the epileptic rat showed significant decrease in Bmax (P < 0.001) compared to control. Real Time PCR amplification of GABA receptor subunits such as GABAAά1, GABAAγ, GABAAδ, GABAB and GAD where down regulated (P < 0.001) in epileptic rats. GABAAά5 subunit and Cyclic AMP responsible element binding protein were up regulated. Confocal imaging study confirmed the decreased GABA receptors in epileptic rats. Epileptic rats have deficit in radial arm and Y maze performance. Conclusions Bacopa monnieri and Bacoside-A treatment reverses epilepsy associated changes to near control suggesting that decreased GABA receptors in the cerebral cortex have an important role in epileptic occurrence; Bacopa monnieri and Bacoside-A have therapeutic application in epilepsy management. PMID:22364254

Behavioral deficit and decreased GABA receptor functional regulation in the hippocampus of epileptic rats: effect of Bacopa monnieri.

PubMed

Mathew, Jobin; Gangadharan, Gireesh; Kuruvilla, Korah P; Paulose, C S

2011-01-01

In the present study, alterations of the General GABA and GABA(A) receptors in the hippocampus of pilocarpine-induced temporal lobe epileptic rats and the therapeutic application of Bacopa monnieri and its active component Bacoside-A were investigated. Bacopa monnieri (Linn.) is a herbaceous plant belonging to the family Scrophulariaceae. Hippocampus is the major region of the brain belonging to the limbic system and plays an important role in epileptogenesis, memory and learning. Scatchard analysis of [³H]GABA and [³H]bicuculline in the hippocampus of the epileptic rat showed significant decrease in B(max) (P < 0.001) compared to control. Real Time PCR amplification of GABA(A) receptor sub-units such as GABA(Aά₁), GABA(Aά₅) GABA(Aδ), and GAD were down regulated (P < 0.001) in the hippocampus of the epileptic rats compared to control. GABA(Aγ) subunit was up regulated. Epileptic rats have deficit in the radial arm and Y maze performance. Bacopa monnieri and Bacoside-A treatment reverses all these changes near to control. Our results suggest that decreased GABA receptors in the hippocampus have an important role in epilepsy associated behavioral deficit, Bacopa monnieri and Bacoside-A have clinical significance in the management of epilepsy.

Pioglitazone and exenatide enhance cognition and downregulate hippocampal beta amyloid oligomer and microglia expression in insulin-resistant rats.

PubMed

Gad, Enas S; Zaitone, Sawsan A; Moustafa, Yasser M

2016-08-01

Insulin resistance is known to be a risk factor for cognitive impairment, most likely linked to insulin signaling, microglia overactivation, and beta amyloid (Aβ) deposition in the brain. Exenatide, a long lasting glucagon-like peptide-1 (GLP-1) analogue, enhances insulin signaling and shows neuroprotective properties. Pioglitazone, a peroxisome proliferated-activated receptor-γ (PPAR-γ) agonist, was previously reported to enhance cognition through its effect on Aβ accumulation and clearance. In the present study, insulin resistance was induced in male rats by drinking fructose for 12 weeks. The effect of monotherapy with pioglitazone (10 mg·kg(-1)) and exenatide or their combination on memory dysfunction was determined and some of the probable underlying mechanisms were studied. The current results confirmed that (1) feeding male rats with fructose syrup for 12 weeks resulted in a decline of learning and memory registered in eight-arm radial maze test; (2) treatment with pioglitazone or exenatide enhanced cognition, reduced hippocampal neurodegeneration, and reduced hippocampal microglia expression and beta amyloid oligomer deposition in a manner that is equal to monotherapies. These results may give promise for the use of pioglitazone or exenatide for ameliorating the learning and memory deficits associated with insulin resistance in clinical setting.

Midline thalamic reuniens lesions improve executive behaviors.

PubMed

Prasad, J A; Abela, A R; Chudasama, Y

2017-03-14

The role of the thalamus in complex cognitive behavior is a topic of increasing interest. Here we demonstrate that lesions of the nucleus reuniens (NRe), a midline thalamic nucleus interconnected with both hippocampal and prefrontal circuitry, lead to enhancement of executive behaviors typically associated with the prefrontal cortex. Rats were tested on four behavioral tasks: (1) the combined attention-memory (CAM) task, which simultaneously assessed attention to a visual target and memory for that target over a variable delay; (2) spatial memory using a radial arm maze, (3) discrimination and reversal learning using a touchscreen operant platform, and (4) decision-making with delayed outcomes. Following NRe lesions, the animals became more efficient in their performance, responding with shorter reaction times but also less impulsively than controls. This change, combined with a decrease in perseverative responses, led to focused attention in the CAM task and accelerated learning in the visual discrimination task. There were no observed changes in tasks involving either spatial memory or value-based decision making. These data complement ongoing efforts to understand the role of midline thalamic structures in human cognition, including the development of thalamic stimulation as a therapeutic strategy for acquired cognitive disabilities (Schiff, 2008; Mair et al., 2011), and point to the NRe as a potential target for clinical intervention. Published by Elsevier Ltd.

Eicosanoyl-5-hydroxytryptamide (EHT) prevents Alzheimer's disease-related cognitive and electrophysiological impairments in mice exposed to elevated concentrations of oligomeric beta-amyloid.

PubMed

Asam, Kesava; Staniszewski, Agnieszka; Zhang, Hong; Melideo, Scott L; Mazzeo, Adolfo; Voronkov, Michael; Huber, Kristen L; Pérez, Eduardo; Stock, Maxwell; Stock, Jeffry B; Arancio, Ottavio; Nicholls, Russell E

2017-01-01

Soluble forms of oligomeric beta-amyloid (Aβ) are thought to play a central role in Alzheimer's disease (AD). Transgenic manipulation of methylation of the serine/threonine protein phosphatase, PP2A, was recently shown to alter the sensitivity of mice to AD-related impairments resulting from acute exposure to elevated levels of Aβ. In addition, eicosanoyl-5-hydroxytryptamide (EHT), a naturally occurring component from coffee beans that modulates PP2A methylation, was shown to confer therapeutic benefits in rodent models of AD and Parkinson's disease. Here, we tested the hypothesis that EHT protects animals from the pathological effects of exposure to elevated levels of soluble oligomeric Aβ. We treated mice with EHT-containing food at two different doses and assessed the sensitivity of these animals to Aβ-induced behavioral and electrophysiological impairments. We found that EHT administration protected animals from Aβ-induced cognitive impairments in both a radial-arm water maze and contextual fear conditioning task. We also found that both chronic and acute EHT administration prevented Aβ-induced impairments in long-term potentiation. These data add to the accumulating evidence suggesting that interventions with pharmacological agents, such as EHT, that target PP2A activity may be therapeutically beneficial for AD and other neurological conditions.

Effects of a Saturated Fat and High Cholesterol Diet on Memory and Hippocampal Morphology in the Middle-Aged Rat

PubMed Central

Granholm, Ann-Charlotte; Bimonte-Nelson, Heather A.; Moore, Alfred B.; Nelson, Matthew E.; Freeman, Linnea R.; Sambamurti, Kumar

2009-01-01

Diets rich in cholesterol and/or saturated fats have been shown to be detrimental to cognitive performance. Therefore, we fed a cholesterol (2%) and saturated fat (hydrogenated coconut oil, Sat Fat 10%) diet to 16-month old rats for 8 weeks to explore the effects on the working memory performance of middle-aged rats. Lipid profiles revealed elevated plasma triglycerides, total cholesterol, HDL, and LDL for the Sat-Fat group as compared to an iso-caloric control diet (12% soybean oil). Weight gain and food consumption were similar in both groups. Sat-Fat treated rats committed more working memory errors in the water radial arm maze, especially at higher memory loads. Cholesterol, amyloid-β peptide of 40 (Aβ40) or 42 (Aβ42) residues, and nerve growth factor in cortical regions was unaffected, but hippocampal Map-2 staining was reduced in rats fed a Sat-Fat diet, indicating a loss of dendritic integrity. Map-2 reduction correlated with memory errors. Microglial activation, indicating inflammation and/or gliosis, was also observed in the hippocampus of Sat-Fat fed rats. These data suggest that saturated fat, hydrogenated fat and cholesterol can profoundly impair memory and hippocampal morphology. PMID:18560126

Neuroprotective effects of sildenafil against oxidative stress and memory dysfunction in mice exposed to noise stress.

PubMed

Sikandaner, Hu Erxidan; Park, So Young; Kim, Min Jung; Park, Shi Nae; Yang, Dong Won

2017-02-15

Noise exposure has been well characterized as an environmental stressor, and is known to have auditory and non-auditory effects. Phosphodiesterase 5 (PDE5) inhibitors affect memory and hippocampus plasticity through various signaling cascades which are regulated by cGMP. In this study, we investigated the effects of sildenafil on memory deficiency, neuroprotection and oxidative stress in mice caused by chronic noise exposure. Mice were exposed to noise for 4h every day up to 14days at 110dB SPL of noise level. Sildenafil (15mg/kg) was orally administered 30min before noise exposure for 14days. Behavioral assessments were performed using novel object recognition (NOR) test and radial arm maze (RAM) test. Higher levels of memory dysfunction and oxidative stress were observed in noise alone-induced mice compared to control group. Interestingly, sildenafil administration increased memory performance, decreased oxidative stress, and increased neuroprotection in the hippocampus region of noise alone-induced mice likely through affecting memory related pathways such as cGMP/PKG/CREB and p25/CDK5, and induction of free radical scavengers such as SOD1, SOD2, SOD3, Prdx5, and catalase in the brain of stressed mice. Copyright © 2016. Published by Elsevier B.V.

Flexible arms provide constant force for pressure switch calibration

NASA Technical Reports Server (NTRS)

Cain, D. E.; Kunz, R. W.

1966-01-01

In-place calibration of a pressure switch is provided by a system of radially oriented flexing arms which, when rotated at a known velocity, convert the centrifugal force of the arms to a linear force along the shaft. The linear force, when applied to a pressure switch diaphragm, can then be calculated.

[Behavior of mice from different strains: modifications produced by noopept].

PubMed

Bel'nik, A P; Ostrovskaia, R U; Poletaeva, I I

2007-01-01

Genotype-dependent behavioral effects were demonstrated in BALB/c, C57BL/6J [Russian character: see text] DBA/2J mice after injections of nootropic drug Noopept. In an elevated plus maze, drug administration induced an increase in the number of enterings into bright arms in BALB/c mice, whereas the opposite effect was observed in C57BL/6J. After the Noopept administration, animals from all the three strains increased the number of active avoidance reactions in stress-inducing slip-funnel test. A significant intensification of exploration behavior was observed in a closed plus-maze in BALB/c and C57BL/6J. The Noopept affected weakly or had no effect on the behavior of DBA/2J mice.

Comprehensive behavioral analysis of pituitary adenylate cyclase-activating polypeptide (PACAP) knockout mice

PubMed Central

Hattori, Satoko; Takao, Keizo; Tanda, Koichi; Toyama, Keiko; Shintani, Norihito; Baba, Akemichi; Hashimoto, Hitoshi; Miyakawa, Tsuyoshi

2012-01-01

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide acting as a neurotransmitter, neuromodulator, or neurotrophic factor. PACAP is widely expressed throughout the brain and exerts its functions through the PACAP-specific receptor (PAC1). Recent studies reveal that genetic variants of the PACAP and PAC1 genes are associated with mental disorders, and several behavioral abnormalities of PACAP knockout (KO) mice are reported. However, an insufficient number of backcrosses was made using PACAP KO mice on the C57BL/6J background due to their postnatal mortality. To elucidate the effects of PACAP on neuropsychiatric function, the PACAP gene was knocked out in F1 hybrid mice (C57BL/6J × 129SvEv) for appropriate control of the genetic background. The PACAP KO mice were then subjected to a behavioral test battery. PACAP deficiency had no significant effects on neurological screen. As shown previously, the mice exhibited significantly increased locomotor activity in a novel environment and abnormal anxiety-like behavior, while no obvious differences between genotypes were shown in home cage (HC) activity. In contrast to previous reports, the PACAP KO mice showed normal prepulse inhibition (PPI) and slightly decreased depression-like behavior. Previous study demonstrates that the social interaction (SI) in a resident-intruder test was decreased in PACAP KO mice. On the other hand, we showed that PACAP KO mice exhibited increased SI in Crawley's three-chamber social approach test, although PACAP KO had no significant impact on SI in a HC. PACAP KO mice also exhibited mild performance deficit in working memory in an eight-arm radial maze (RM) and the T-maze (TM), while they did not show any significant abnormalities in the left-right discrimination task in the TM. These results suggest that PACAP has an important role in the regulation of locomotor activity, social behavior, anxiety-like behavior and, potentially, working memory. PMID:23060763

Recovery after chronic stress within spatial reference and working memory domains: correspondence with hippocampal morphology.

PubMed

Hoffman, A N; Krigbaum, A; Ortiz, J B; Mika, A; Hutchinson, K M; Bimonte-Nelson, H A; Conrad, C D

2011-09-01

Chronic stress results in reversible spatial learning impairments in the Morris water maze that correspond with hippocampal CA3 dendritic retraction in male rats. Whether chronic stress impacts different types of memory domains, and whether these can similarly recover, is unknown. This study assessed the effects of chronic stress with and without a post-stress delay to evaluate learning and memory deficits within two memory domains, reference and working memory, in the radial arm water maze (RAWM). Three groups of 5-month-old male Sprague-Dawley rats were either not stressed [control (CON)], or restrained (6 h/day for 21 days) and then tested on the RAWM either on the next day [stress immediate (STR-IMM)] or following a 21-day delay [stress delay (STR-DEL)]. Although the groups learned the RAWM task similarly, groups differed in their 24-h retention trial assessment. Specifically, the STR-IMM group made more errors within both the spatial reference and working memory domains, and these deficits corresponded with a reduction in apical branch points and length of hippocampal CA3 dendrites. In contrast, the STR-DEL group showed significantly fewer errors in both the reference and working memory domains than the STR-IMM group. Moreover, the STR-DEL group showed better RAWM performance in the reference memory domain than did the CON group, and this corresponded with restored CA3 dendritic complexity, revealing long-term enhancing actions of chronic stress. These results indicate that chronic stress-induced spatial working and reference memory impairments, and CA3 dendritic retraction, are reversible, with chronic stress having lasting effects that can benefit spatial reference memory, but with these lasting beneficial effects being independent of CA3 dendritic complexity. © 2011 The Authors. European Journal of Neuroscience © 2011 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

Memantine can improve chronic ethanol exposure-induced spatial memory impairment in male C57BL/6 mice by reducing hippocampal apoptosis.

PubMed

Wang, Xiaolong; Yu, Hao; You, Jiabin; Wang, Changliang; Feng, Chunmei; Liu, Zhaodi; Li, Ya; Wei, Rucheng; Xu, Siqi; Zhao, Rui; Wu, Xu; Zhang, Guohua

2018-05-22

Chronic ethanol intake can induce neuronal apoptosis, leading to dementia. We investigated the protective effects of memantine on spatial memory impairment induced by chronic ethanol exposure in mice. Male C57BL/6 mice were administered 10% (m/V) or 20% (m/V) ethanol as the only choice of drinking water. Mice were treated for 60 d, 90 d, or 180 d. Mice were treated with memantine for the same duration (daily 10 mg/kg oral). The Morris water maze and radial arm maze test were used to measure spatial memory. Mice were sacrificed after the behavioral tests. Brains were removed to prepare for paraffin sections, and hippocampi were isolated for protein and RNA extraction. 4',6-diamidino-2-phenylindole (DAPI) staining and immunohistochemical staining of cleaved caspase-3 were performed. Western blot analysis was used to detect the expression of cleaved caspase-3 and calcium-related proteins, including N-methyl-d-aspartic acid receptor 1 (NR1), 1,4,5-trisphosphate receptor 1 (IP3R1), and sarco/endoplasmic reticulum calcium adenosine triphosphatase 1 (SERCA1). The changes of NR1, IP3R1 and SERCA1 mRNA were detected using quantitative polymerase chain reaction (qPCR). The results revealed that chronic ethanol exposure induced spatial memory impairment in mice, as well as increasing the expression of NR1, IP3R1 and SERCA1, the activation of caspase-3 and apoptosis in hippocampus. The effect was particularly prominent in the 20% ethanol group after 180 d exposure. Memantine decreased ethanol-induced spatial memory impairment, caspase-3 activation and apoptosis in the mouse hippocampus. These results suggest that disruption of intracellular calcium balance by ethanol can induce caspase-3 activation and apoptosis, which underlies subsequent spatial memory impairment in mice. Copyright © 2018 Elsevier B.V. All rights reserved.

Spatial and Working Memory Is Linked to Spine Density and Mushroom Spines

PubMed Central

Aher, Yogesh D.; Sase, Ajinkya; Gröger, Marion; Mokhtar, Maher; Höger, Harald; Lubec, Gert

2015-01-01

Background Changes in synaptic structure and efficacy including dendritic spine number and morphology have been shown to underlie neuronal activity and size. Moreover, the shapes of individual dendritic spines were proposed to correlate with their capacity for structural change. Spine numbers and morphology were reported to parallel memory formation in the rat using a water maze but, so far, there is no information on spine counts or shape in the radial arm maze (RAM), a frequently used paradigm for the evaluation of complex memory formation in the rodent. Methods 24 male Sprague-Dawley rats were divided into three groups, 8 were trained, 8 remained untrained in the RAM and 8 rats served as cage controls. Dendritic spine numbers and individual spine forms were counted in CA1, CA3 areas and dentate gyrus of hippocampus using a DIL dye method with subsequent quantification by the Neuronstudio software and the image J program. Results Working memory errors (WME) and latency in the RAM were decreased along the training period indicating that animals performed the task. Total spine density was significantly increased following training in the RAM as compared to untrained rats and cage controls. The number of mushroom spines was significantly increased in the trained as compared to untrained and cage controls. Negative significant correlations between spine density and WME were observed in CA1 basal dendrites and in CA3 apical and basal dendrites. In addition, there was a significant negative correlation between spine density and latency in CA3 basal dendrites. Conclusion The study shows that spine numbers are significantly increased in the trained group, an observation that may suggest the use of this method representing a morphological parameter for memory formation studies in the RAM. Herein, correlations between WME and latency in the RAM and spine density revealed a link between spine numbers and performance in the RAM. PMID:26469788

Behavioural pharmacology of the α5-GABAA receptor antagonist S44819: Enhancement and remediation of cognitive performance in preclinical models.

PubMed

Gacsályi, István; Móricz, Krisztina; Gigler, Gábor; Wellmann, János; Nagy, Katalin; Ling, István; Barkóczy, József; Haller, József; Lambert, Jeremy J; Szénási, Gábor; Spedding, Michael; Antoni, Ferenc A

2017-10-01

Previous work has shown that S44819 is a novel GABAA receptor (GABA A R) antagonist, which is selective for extrasynaptic GABA A Rs incorporating the α5 subunit (α5-GABA A Rs). The present study reports on the preclinical neuropsychopharmacological profile of S44819. Significantly, no sedative or pro-convulsive side effects of S44819 were found at doses up to 30 mg/kg i.p. Object recognition (OR) memory in intact mice was enhanced by S44819 (0.3 mg/kg p.o.) given before the acquisition trial. Mice treated with phencyclidine for two weeks and tested six days after the cessation of treatment failed to show OR memory. This deficit was corrected by a single administration of S44819 (0.1, 0.3 or 1 mg/kg p.o.) prior to the acquisition trial. The amnestic effect of ketamine in rats tested in the eight-arm radial maze (reference and working memory versions) was blocked by S44819 (3 mg/kg p.o.). Extinction of cued fear was preserved during treatment with S44819 (3 mg/kg/diem i.p.). Administration of S44819 had no significant effect in the Vogel-conflict test, the elevated plus maze, the forced swim, the marble-burying and the tail-suspension tests. In contrast, anxiolytic/antidepressant-like effects of the compound were found in paradigms that have mnemonic components, such as social interaction, fear-potentiated startle and social avoidance induced by negative life experience. In summary, S44819 enhanced intact recognition memory and ameliorated memory deficits induced by inhibition of NMDA receptors. Anxiolytic/antidepressant efficacy was limited to paradigms involving cognitive function. In conclusion, S44819 is a novel psychoactive pro-cognitive compound with potential as a therapeutic agent in dementia. Copyright © 2017 Elsevier Ltd. All rights reserved.

Diphenyl diselenide diet intake improves spatial learning and memory deficits in hypothyroid female rats.

PubMed

Dias, Glaecir Roseni Mundstock; Vieira, Francielli Araújo; Dobrachinski, Fernando; Bridi, Jéssika Cristina; Balk, Rodrigo de Souza; Soares, Félix Antunes; Nogueira, Cristina Wayne; Barbosa, Nilda Berenice de Vargas

2012-04-01

Cognitive deficits have been observed in different animal models of adult-onset hypothyroidism. Thus, this study was delineated to evaluate whether diphenyl diselenide, an organoselenium compound with neuroprotective and antioxidant properties, could afford protection against the detrimental effects of hypothyroidism on behavioral parameters. Hypothyroidism condition was induced in female rats by continuous exposure to methimazole (MTZ) at 20 mg/100 ml in the drinking water, during 3 months. MTZ-induced hypothyroid rats were fed with either standard or a diet containing 5 ppm of diphenyl diselenide for 3 months. Behavioral assessments were performed monthly, in the following order: elevated plus maze, open field and Morris water maze. The levels of thyroid hormones in the animals exposed to MTZ were lower than control until the end of experimental period. The rats exposed to MTZ had a significant weight loss from the first month, which was not modified by diphenyl diselenide supplementation. In elevated plus maze test, MTZ exposure caused a reduction on the number of entries of animals in closed arms, which was avoided by diphenyl diselenide supplementation. In Morris water maze, the parameters latency to reach the platform and distance performed to find the escape platform in the test session were significantly greater in MTZ group when compared to control. These cognitive deficits observed in MTZ-induced hypothyroid rats were restored by dietary diphenyl diselenide. The group fed with diphenyl diselenide alone exhibited a better spatial learning and memory capability in some parameters of Morris water maze when compared to the control group. In summary, our data provide evidence of the effectiveness of dietary diphenyl diselenide in improving the performance of control and hypothyroid rats in the water maze test. Copyright © 2012 ISDN. Published by Elsevier Ltd. All rights reserved.

Multivariate temporal pattern analysis applied to the study of rat behavior in the elevated plus maze: methodological and conceptual highlights.

PubMed

Casarrubea, M; Magnusson, M S; Roy, V; Arabo, A; Sorbera, F; Santangelo, A; Faulisi, F; Crescimanno, G

2014-08-30

Aim of this article is to illustrate the application of a multivariate approach known as t-pattern analysis in the study of rat behavior in elevated plus maze. By means of this multivariate approach, significant relationships among behavioral events in the course of time can be described. Both quantitative and t-pattern analyses were utilized to analyze data obtained from fifteen male Wistar rats following a trial 1-trial 2 protocol. In trial 2, in comparison with the initial exposure, mean occurrences of behavioral elements performed in protected zones of the maze showed a significant increase counterbalanced by a significant decrease of mean occurrences of behavioral elements in unprotected zones. Multivariate t-pattern analysis, in trial 1, revealed the presence of 134 t-patterns of different composition. In trial 2, the temporal structure of behavior become more simple, being present only 32 different t-patterns. Behavioral strings and stripes (i.e. graphical representation of each t-pattern onset) of all t-patterns were presented both for trial 1 and trial 2 as well. Finally, percent distributions in the three zones of the maze show a clear-cut increase of t-patterns in closed arm and a significant reduction in the remaining zones. Results show that previous experience deeply modifies the temporal structure of rat behavior in the elevated plus maze. In addition, this article, by highlighting several conceptual, methodological and illustrative aspects on the utilization of t-pattern analysis, could represent a useful background to employ such a refined approach in the study of rat behavior in elevated plus maze. Copyright © 2014 Elsevier B.V. All rights reserved.

Working memory span capacity improved by a D2 but not D1 receptor family agonist.

PubMed

Tarantino, Isadore S; Sharp, Richard F; Geyer, Mark A; Meves, Jessica M; Young, Jared W

2011-06-01

Patients with schizophrenia exhibit poor working memory (WM). Although several subcomponents of WM can be measured, evidence suggests the primary subcomponent affected in schizophrenia is span capacity (WMC). Indeed, the NIMH-funded MATRICS initiative recommended assaying the WMC when assessing the efficacy of a putative therapeutic for FDA approval. Although dopamine D1 receptor agonists improve delay-dependent memory in animals, evidence for improvements in WMC due to dopamine D1 receptor activation is limited. In contrast, the dopamine D2-family agonist bromocriptine improves WMC in humans. The radial arm maze (RAM) can be used to assess WMC, although complications due to ceiling effects or strategy confounds have limited its use. We describe a 12-arm RAM protocol designed to assess whether the dopamine D1-family agonist SKF 38393 (0, 1, 3, and 10 mg/kg) or bromocriptine (0, 1, 3, and 10 mg/kg) could improve WMC in C57BL/6N mice (n=12) in cross-over designs. WMC increased and strategy usage decreased with training. The dopamine D1 agonist SKF 38393 had no effect on WMC or long-term memory. Bromocriptine decreased WMC errors, without affecting long-term memory, consistent with human studies. These data confirm that WMC can be measured in mice and reveal drug effects that are consistent with reported effects in humans. Future research is warranted to identify the subtype of the D2-family of receptors responsible for the observed improvement in WMC. Finally, this RAM procedure may prove useful in developing animal models of deficient WMC to further assess putative treatments for the cognitive deficits in schizophrenia. Copyright © 2011 Elsevier B.V. All rights reserved.

Sex and strategy use matters for pattern separation, adult neurogenesis, and immediate early gene expression in the hippocampus.

PubMed

Yagi, Shunya; Chow, Carmen; Lieblich, Stephanie E; Galea, Liisa A M

2016-01-01

Adult neurogenesis in the dentate gyrus (DG) plays a crucial role for pattern separation, and there are sex differences in the regulation of neurogenesis. Although sex differences, favoring males, in spatial navigation have been reported, it is not known whether there are sex differences in pattern separation. The current study was designed to determine whether there are sex differences in the ability for separating similar or distinct patterns, learning strategy choice, adult neurogenesis, and immediate early gene (IEG) expression in the DG in response to pattern separation training. Male and female Sprague-Dawley rats received a single injection of the DNA synthesis marker, bromodeoxyuridine (BrdU), and were tested for the ability of separating spatial patterns in a spatial pattern separation version of delayed nonmatching to place task using the eight-arm radial arm maze. Twenty-seven days following BrdU injection, rats received a probe trial to determine whether they were idiothetic or spatial strategy users. We found that male spatial strategy users outperformed female spatial strategy users only when separating similar, but not distinct, patterns. Furthermore, male spatial strategy users had greater neurogenesis in response to pattern separation training than all other groups. Interestingly, neurogenesis was positively correlated with performance on similar pattern trials during pattern separation in female spatial strategy users but negatively correlated with performance in male idiothetic strategy users. These results suggest that the survival of new neurons may play an important positive role for pattern separation of similar patterns in females. Furthermore, we found sex and strategy differences in IEG expression in the CA1 and CA3 regions in response to pattern separation. These findings emphasize the importance of studying biological sex on hippocampal function and neural plasticity. © 2015 Wiley Periodicals, Inc.

Sex-dependent effects of letrozole on anxiety in middle-aged rats.

PubMed

Borbélyová, Veronika; Domonkos, Emese; Csongová, Melinda; Kačmárová, Mária; Ostatníková, Daniela; Celec, Peter; Hodosy, Július

2017-12-01

Aromatase catalyzes the conversion of testosterone to estradiol and is involved in the physiological effects of sex hormones on brain function. Animal experiments have shown that the aromatase inhibitor, letrozole, can induce anxiety in young ovariectomized females that are used as a model of aging. Whether or not these effects would be similar in intact middle-aged animals is unknown. The aim of our study was to analyze the effects of letrozole on anxiety in middle-aged rats of both sexes. Fifteen month old male and female rats were treated daily with either letrozole or vehicle for 2 weeks. The elevated plus maze was used to test anxiety-like behaviour. Sex differences were found not only in plasma concentrations of testosterone but also in the effects of letrozole treatment on plasma testosterone (P<.05). The interaction between sex and treatment was also proven in locomotor activity (P<.05) and time spent in the open arms of the elevated plus maze (P<.05). Letrozole-treated male rats spent 95% less time in the open arms of the elevated plus maze than the control rats did (P<.05) suggesting an anxiogenic effect of aromatase inhibition. This difference was not found between letrozole-treated and vehicle-treated females. In contrast to previous experiments on young animals, letrozole seems to induce anxiety in male but not in female middle-aged rats. This sex-specific effect might be related to sex differences of oestrogen and androgen signalling in aging brains. These results should be taken into account in clinical applications of letrozole, especially in men. © 2017 John Wiley & Sons Australia, Ltd.

Anti-HIV drugs nevirapine and efavirenz affect anxiety-related behavior and cognitive performance in mice.

PubMed

Romão, Pedro R T; Lemos, Joelson C; Moreira, Jeverson; de Chaves, Gisele; Moretti, Morgana; Castro, Adalberto A; Andrade, Vanessa M; Boeck, Carina R; Quevedo, João; Gavioli, Elaine C

2011-01-01

Nevirapine (NVP) and efavirenz (EFV) belong to the class of anti-HIV drugs called non-nucleoside reverse transcriptase inhibitors (NNRTIs), commonly used as part of highly active antiretroviral therapy (HAART). Although the HAART is able to bring down viral load to undetectable levels and restore immune function, their prolonged use causes several adverse effects. It has been demonstrated that both NVP and EFV are able to cross the blood-brain barrier, causing important central nervous system-related side effects. Thus, this study investigated the effects of chronic administration of EFV (10 mg/kg) and NVP (3.3 mg/kg) in mice submitted to two distinct series of experiments, which aimed to evaluate: (1) the emotional behavior (elevated plus-maze, forced swimming, and open-field test) and (2) the cognitive performance (object recognition and inhibitory avoidance test) of mice. Our results demonstrated that EFV, but not NVP, reduced the exploration to open arms in the elevated plus-maze test. Neither NVP nor EFV altered mouse behavior in the forced swimming and open-field tests. Both drugs reduced the recognition index in the object recognition test, but only EFV significantly impaired the aversive memory assessed in the inhibitory avoidance test 24 h after training. In conclusion, our findings point to a genuine anxiogenic-like effect to EFV, since it reduced exploration to open arms of elevated plus-maze test without affecting spontaneous locomotion. Additionally, both drugs impaired recognition memory, while only the treatment with EFV impaired significantly aversive memory.

Anxiogenic effects of chronic exposure to nandrolone decanoate (ND) at supraphysiological dose in rats: a brief report.

PubMed

Rosic, Gvozden; Joksimovic, Jovana; Selakovic, Dragica; Milovanovic, Dragan; Jakovljevic, Vladimir

2014-01-01

Nandrolone decanoate (ND) is frequently used anabolic androgenic steroid (AAS) among the athletes. Despite the health risks, there is significant increase in prevalence of AAS abuse. The aim of this study was to investigate the effects of chronic exposure to ND at supraphysiological dose (to mimic the doses for human AAS abusers) on anxiety levels in adult rats. We performed several behavioral tests (open field test, elevated plus maze test, beam-walking test, evoked beam-walking test and tail suspension test) for estimation of anxiety in rats. Adult rats received 20 mg/kg intraperitoneal injection of ND weekly for four weeks. Behavioral test were performed on the seventh day after the last dose of ND. Anxiogenic-like pattern of behavior was clearly observed in several behavioral tests, such as open field test (decrease of total distance moved and cumulative duration of moving, decrease of an average velocity of the animals, decrease of frequency and total time in centre zone); elevated plus maze (decreased total time spent in open arms and the number of entries in open arms of the elevated plus maze); evoked beam-walking test (decreased time to cross the beam) and tail suspension test (increased latency to first immobility and decreased total duration of immobility). Results of this study show that four-week treatment with the supraphysiological dose of ND produced anxiogenic effects in sedentary male rats. Our results show that rats after chronic treatment with a supraphysiological dose of ND exhibited anxiety-like behavior.

The effects of long-term honey, sucrose or sugar-free diets on memory and anxiety in rats.

PubMed

Chepulis, Lynne M; Starkey, Nicola J; Waas, Joseph R; Molan, Peter C

2009-06-22

Sucrose is considered by many to be detrimental to health, giving rise to deterioration of the body associated with ageing. This study was undertaken to determine whether replacing sucrose in the diet long-term with honey that has a high antioxidant content could decrease deterioration in brain function during ageing. Forty-five 2-month old Sprague Dawley rats were fed ad libitum for 52 weeks on a powdered diet that was either sugar-free or contained 7.9% sucrose or 10% honey (which is the equivalent amount of sugar). Anxiety levels were assessed using an Elevated Plus Maze, whilst a Y maze and an Object Recognition task were used to assess memory. Locomotor activity was also measured using an Open Field task to ensure that differences in activity levels did not bias results in the other tasks. Anxiety generally decreased overall from 3 to 12 months, but the honey-fed rats showed significantly less anxiety at all stages of ageing compared with those fed sucrose. Honey-fed animals also displayed better spatial memory throughout the 12-month period: at 9 and 12 months a significantly greater proportion of honey-fed rats recognised the novel arm as the unvisited arm of the maze compared to rats on a sugar-free or sucrose-based diet. No significant differences among groups were observed in the Object Recognition task, and there appeared to be no differences in locomotor activity among groups at either 6 or 12 months. In conclusion, it appears that consumption of honey may reduce anxiety and improve spatial memory in middle age.

Early olfactory environment influences social behaviour in adult Octodon degus.

PubMed

Márquez, Natalia; Martínez-Harms, Jaime; Vásquez, Rodrigo A; Mpodozis, Jorge

2015-01-01

We evaluated the extent to which manipulation of early olfactory environment can influence social behaviours in the South American Hystricognath rodent Octodon degus. The early olfactory environment of newborn degus was manipulated by scenting all litter members with eucalyptol during the first month of life. The social behaviour of sexually mature animals (5-7 months old) towards conspecifics was then assessed using a y-maze to compare the response of control (naïve) and treated animals to two different olfactory configurations (experiment 1): (i) a non-familiarized conspecific impregnated with eucalyptol (eucalyptol arm) presented against (ii) a non-familiarized unscented conspecific (control arm). In addition, in dyadic encounters, we assessed the behaviour of control and eucalyptol treated animals towards a non-familiarized conspecific scented with eucalyptol (experiment 2). We found that control subjects explored and spent significantly less time in the eucalyptol arm, indicating neophobic behaviours towards the artificially scented conspecific. Treated subjects explored and spent similar time in both arms of the maze, showing the same interest for both olfactory stimuli presented. During dyadic encounters in experiment 2, an interaction effect between early experience and sex was observed. Control males escaped and avoided their scented partner more frequently than eucalyptol treated male subjects and than females. Both groups did not differ in the exploration of their scented partners, suggesting that avoidance within agonistic context does not relate to neophobic behaviours. Our results suggest that the exposure to eucalyptol during early ontogeny decreases evasive behaviours within an agonistic context as a result of olfactory learning. Altogether, these results indicate that olfactory cues learned in early ontogeny can influence olfactory-guided behaviours in adult degus.

Spontaneous laterality in mouse Crl:CD1.

PubMed

Maciejewska, Maria; Zięba, Katarzyna; Szymańska, Justyna; Warońska, Magdalena

2016-01-01

Lateralization developed very early in evolution and it is a characteristic of a wide range of representatives from the animal kingdom. The aim of the present study was to examine the spontaneous laterality in mice (Mus musculus) with the T-maze test. We wanted to check if this kind of functional asymmetry occurs at a population level, and also if there are gender differences in this regard. The study involved 40 mice Crl:CD1. The research procedure was simple: mice had to choose one arm of the T-shaped apparatus to find the exit. The animals performed the 10 trails one after another. We took into account only the animals' fist reactions while preparing results. Most of the animals (68%) chose the right arm of the maze. The lateralization was stronger among females--75% of them had preferences for the right side. The majority of animals, which preferred the right side, were from the food deprivation group. However, the results did not unequivocally resolve whether mice evince the functional asymmetry at the population level, or whether there are gender differences in this area. Further research with a larger group and multiple observations for each animal are required to answer these questions.

Acute high dose of chlorpyrifos alters performance of rats in the elevated plus-maze and the elevated T-maze.

PubMed

López-Crespo, G A; Flores, P; Sánchez-Santed, F; Sánchez-Amate, M C

2009-11-01

Chlorpyrifos (CPF) is a broad spectrum organophosphate (OP) pesticide widely used in agriculture, industry and household. Several animal studies indicate emotional disturbances after CPF exposure, although the results are sometimes puzzling. Thus, both anxiolytic and anxiogenic effects of CPF have been reported in different animal models of anxiety [Sánchez-Amate MC, Flores P, Sánchez-Santed F. Effects of chlorpyrifos in the plus-maze model of anxiety. Behav Pharmacol 2001;12:285-92; Sánchez-Amate MC, Dávila E, Cañadas F, Flores P, Sánchez-Santed F. Chlorpyrifos shares stimulus properties with pentilenetetrazol as evaluated by and operant drug discrimination task. Neurotoxicology 2002;23:795-803; López-Crespo G, Carvajal F, Flores P, Sánchez-Santed F, Sánchez-Amate MC. Time-course of biochemical and behavioural effects of a single high dose of chlorpyrifos. Neurotoxicology 2007;28:541-7]. On the other hand, other behavioural effects of CPF are time-dependent [López-Crespo G, Carvajal F, Flores P, Sánchez-Santed F, Sánchez-Amate MC. Time-course of biochemical and behavioural effects of a single high dose of chlorpyrifos. Neurotoxicology 2007;28:541-7], raising the question that the effects of CPF could be task and post-administration time dependent. To test this hypothesis, three groups of rats were treated with a single high dose of CPF (250 mg/kg); one of the groups was tested on day 5 on the elevated plus-maze, to complete our previous study on day 2 [Sánchez-Amate MC, Flores P, Sánchez-Santed F. Effects of chlorpyrifos in the plus-maze model of anxiety. Behav Pharmacol 2001;12:285-92]. The remaining groups were tested on the elevated T-maze on days 2 and 5. CPF produced an increased open arm activity on the elevated plus-maze on day 5, an increased escape latency on the elevated T-maze on day 2 and an impaired inhibitory avoidance on day 5. Data are discussed taking together all studies carried out in our laboratory, confirming that CPF effects on emotional behaviour are dependent on both task contingencies and post-administration time.

Exploration of a novel object in late adolescence predicts novelty-seeking behavior in adulthood: Associations among behavioral responses in four novelty-seeking tests.

PubMed

Cuenya, Lucas; Sabariego, Marta; Donaire, Rocío; Callejas-Aguilera, José Enrique; Torres, Carmen; Fernández-Teruel, Alberto

2016-04-01

The sensation/novelty seeking behavioral trait refers to the exploration/preference for a novel environment. Novelty seeking increases during late adolescence and it has been associated with several neurobehavioral disorders. In this experiment, we asked whether inbred Roman high- and low-avoidance (RHA-I, RLA-I) rats (1) differ in novelty seeking in late adolescence and (2) whether late adolescent novelty seeking predicts this trait in adulthood. Thirty six male RHA-I and 36 RLA-I rats were exposed to a novel object exploration (NOE) test during late adolescence (pnd: 52-59; contact latency, contact time, contact frequency). Head-dipping (hole-board, HB), time and visits to a novel-arm (Y-maze), and latency-in and emergence latency (emergence test) were registered in adulthood (pnd: 83-105). The results showed strain differences in all these tests (RHA-I>RLA-I). Factor analysis (RHA-I+RLA-I) revealed two clusters. The first one grouped HB and emergence test measures. The second one grouped NOE and Y-maze variables. Time exploring a novel object (NOE) was a significant predictor of novel arm time (RHA-I+RLA, RHA-I); contact latency was a significant predictor of novel arm frequency (RLA-I). Present results show consistent behavioral associations across four novelty-seeking tests and suggest that late adolescent novelty seeking predicts this genetically-influenced temperamental trait in adult Roman rats. Copyright © 2016 Elsevier B.V. All rights reserved.

Behavioral responses of Pacific lamprey to alarm cues

USGS Publications Warehouse

Porter, Laurie L.; Hayes, Michael C.; Jackson, Aaron D.; Burke, Brian J.; Moser, Mary L.; Wagner, R. Steven

2017-01-01

Pacific lamprey (Entosphenus tridentatus), an anadromous ectoparasite, faces several challenges during adult migration to spawning grounds. Developing methods to address these challenges is critical to the success of ongoing conservation efforts. The challenges are diverse, and include anthropogenic alterations to the ecosystem resulting in loss of habitat, impassable barriers such as dams, climate change impacts, and altered predator fields. We conducted a behavioral study to understand how adult migrating Pacific lamprey respond to potential alarm cues: White Sturgeon (Acipenser transmontanus), human saliva, decayed Pacific lamprey, and river otter (Lontra canadensis). Research has shown that some species of lamprey can be guided to a location using odors and similar cues may be useful as a management tool for Pacific lamprey. Experiments were conducted over 2 nights and measured the number of entries (count) and duration of time spent (occupancy) by adult lamprey in each arm of a two-choice maze. During the first night, no odor was added to test for selection bias between arms. During the second night odor was added to one arm of the maze. Contrary to expectations, lamprey were significantly attracted to the river otter odor in both count and occupancy. No significant differences were found in the response of lamprey to the other three odors. Results from this study indicate that Pacific lamprey do respond to some odors; however, additional tests are necessary to better identify the types of odors and concentrations that elicit a repeatable response.

[Effect of delta-sleep inducing peptide preparation Deltaran on longevity, physiological functions, and carcinogenesis in mice].

PubMed

Voĭtenkov, V B; Popovich, I G; Zabezhinskiĭ, M A; Iurova, M A; Piskunova, T A; Mikhaleva, I I

2009-01-01

Female SHR mice received 5-days long monthly courses of delta-sleep inducing peptide (DSIP) preparation "Deltaran" subcutaneously in dose 5 mkg/kg during all their lives. It was demonstrated, that last 10% (most aged) of mice which received Deltaran lived for 16% longer than the controls. They had significantly higher amount of vertical activity in the "open field" test, than the controls, starting from time when they were 6 months old and until their natural death. Mice of Deltaran group spent 73% more time in the open arms of elevated plus maze, and 9 times more often explored the extremities of this maze, than controls. Also Deltaran slowed the spontaneous carcinogenesis parameters. It's assumed that DSIP preparation "Deltaran" have geroprotective, anxiolytic and antitumor activity.

Radial spoke proteins of Chlamydomonas flagella

PubMed Central

Yang, Pinfen; Diener, Dennis R.; Yang, Chun; Kohno, Takahiro; Pazour, Gregory J.; Dienes, Jennifer M.; Agrin, Nathan S.; King, Stephen M.; Sale, Winfield S.; Kamiya, Ritsu; Rosenbaum, Joel L.; Witman, George B.

2007-01-01

Summary The radial spoke is a ubiquitous component of ‘9+2’ cilia and flagella, and plays an essential role in the control of dynein arm activity by relaying signals from the central pair of microtubules to the arms. The Chlamydomonas reinhardtii radial spoke contains at least 23 proteins, only 8 of which have been characterized at the molecular level. Here, we use mass spectrometry to identify 10 additional radial spoke proteins. Many of the newly identified proteins in the spoke stalk are predicted to contain domains associated with signal transduction, including Ca2+-, AKAP- and nucleotide-binding domains. This suggests that the spoke stalk is both a scaffold for signaling molecules and itself a transducer of signals. Moreover, in addition to the recently described HSP40 family member, a second spoke stalk protein is predicted to be a molecular chaperone, implying that there is a sophisticated mechanism for the assembly of this large complex. Among the 18 spoke proteins identified to date, at least 12 have apparent homologs in humans, indicating that the radial spoke has been conserved throughout evolution. The human genes encoding these proteins are candidates for causing primary ciliary dyskinesia, a severe inherited disease involving missing or defective axonemal structures, including the radial spokes. PMID:16507594

Prosocial Choice in Rats Depends on Food-Seeking Behavior Displayed by Recipients.

PubMed

Márquez, Cristina; Rennie, Scott M; Costa, Diana F; Moita, Marta A

2015-06-29

Animals often are prosocial, displaying behaviors that result in a benefit to one another [1-15] even in the absence of self-benefit [16-21] (but see [22-25]). Several factors have been proposed to modulate these behaviors, namely familiarity [6, 13, 18, 20] or display of seeking behavior [16, 21]. Rats have been recently shown to be prosocial under distress [17, 18] (but see [26-29]); however, what drives prosociality in these animals remains unclear. To address this issue, we developed a two-choice task in which prosocial behavior did not yield a benefit or a cost to the focal rat. We used a double T-maze in which only the focal rat controlled access to the food-baited arms of its own and the recipient rat's maze. In this task, the focal rat could choose between one side of the maze, which yielded food only to itself (selfish choice), and the opposite side, which yielded food to itself and the recipient rat (prosocial choice). Rats showed a high proportion of prosocial choices. By manipulating reward delivery to the recipient and its ability to display a preference for the baited arm, we found that the display of food-seeking behavior leading to reward was necessary to drive prosocial choices. In addition, we found that there was more social investigation between rats in selfish trials than in prosocial trials, which may have influenced the focals' choices. This study shows that rats provide access to food to others in the absence of added direct self-benefit, bringing new insights into the factors that drive prosociality. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effects of arm elevation on radial artery pressure: a new method to distinguish hypovolemic shock and septic shock from hypotension.

PubMed

Xie, Zhiyi; Zhang, Zhenyu; Xu, Yuan; Zhou, Hua; Wu, Sheng; Wang, Zhong

2018-06-01

In this prospective observational study, we investigated the variability in radial artery invasive blood pressure associated with arm elevation in patients with different hemodynamic types. We carried out a prospective observational study using data from 73 general anesthesia hepatobiliary postoperative adult patients admitted to an ICU over a 1-year period. A standard procedure was used for the arm elevation test. The value of invasive radial arterial pressure was recorded at baseline, and 30 and 60 s after the arm had been raised from 0° to 90°. We compared the blood pressure before versus after arm elevation, and between hemodynamically stable, hypovolemic shock, and septic shock patient groups. In all 73 patients, systolic arterial pressure (SAP) decreased, diastolic arterial pressure (DAP) increased, and pulse pressure (PP) decreased at 30 and 60 s after arm elevation (P<0.01), but the mean arterial pressure (MAP) was unchanged (P>0.05). On comparing 30 and 60 s, there was no significant difference in SAP, DAP, PP, or MAP (P>0.05). In 40 hemodynamically stable patients, SAP and PP decreased, and DAP and MAP increased significantly at 30 and 60 s after arm elevation compared with baseline (P<0.01). In 16 hypovolemic patients, SAP, DAP, and MAP increased significantly compared with baseline at 30 and 60 s (P<0.01), but PP was unchanged (P>0.05). In 17 patients with septic shock, SAP, PP, and MAP decreased significantly versus baseline at 30 and 60 s (P<0.01), but DAP was unchanged (P>0.05). Comparison of the absolute value of pressure change of septic shock patients at 30 s after raising the arm showed that SAP, DAP, and MAP changes were significantly lower compared with those in hypovolemic shock and hemodynamically stable patients (P<0.01). The areas under the receiver operator characteristic curve for predicting septic shock was 0.930 [95% confidence interval (CI): 0.867-0.992, P< 0.001] for change value at 30 s after arm elevation of SAP. The best cut-off point for the SAP change value was -5 mmHg or less, with a sensitivity of 94.12%, a specificity of 80.36%, a positive likelihood ratio of 4.79 (95% CI: 2.8-8.2), and a negative likelihood ratio of 0.073 (95% CI: 0.01-0.5). Our study shows that hypovolemic shock and septic shock patients have significantly different radial artery invasive blood pressure changes in an arm elevation test, which could be applied as a new method to distinguish hypovolemic shock and septic shock from hypotension.

Ion velocity analysis of rotating structures in a magnetic linear plasma device

NASA Astrophysics Data System (ADS)

Claire, N.; Escarguel, A.; Rebont, C.; Doveil, F.

2018-06-01

The MISTRAL device is designed to produce a linear magnetized plasma column. It has been used a few years ago to study a nonlinear low frequency instability exhibiting an azimuthal number m = 2. By changing the experimental configuration of MISTRAL, this work shows experimental results on an m = 1 rotating instability with strongly different behavior. The spatio-temporal evolution of the ion velocity distribution function given by a laser-induced fluorescence diagnostic is measured to infer the radial and azimuthal velocities, ion fluxes, and electric fields. The naive image of a plasma exhibiting a global rotation is again invalidated in this m = 1 mode but in a different way. Contrary to the m = 2 mode, the rotation frequency of the instability is lower than the ion cyclotron frequency and ions exhibit a complex behavior with a radial outward flux inside the unstable arm and azimuthal ion fluxes always directed toward the unstable arm. The azimuthal ion velocity is close to zero inside the ionization region, whereas the radial ion velocity grows linearly with radius. The radial electric field is oriented inward inside the unstable arm and outward outside. An axial velocity perturbation is also present, indicating that contrary to the m = 2 mode, the m = 1 mode is not a flute mode. These results cannot be easily interpreted with existing theories.

Intraseptal infusion of oxotremorine impairs memory in a delayed-non-match-to-sample radial maze task.

PubMed

Bunce, J G; Sabolek, H R; Chrobak, J J

2003-01-01

The medial septal nucleus is part of the forebrain circuitry that supports memory. This nucleus is rich in cholinergic receptors and is a putative target for the development of cholinomimetic cognitive-enhancing drugs. Septal neurons, primarily cholinergic and GABAergic, innervate the entire hippocampal formation and regulate hippocampal formation physiology and emergent function. Direct intraseptal drug infusions can produce amnestic or promnestic effects depending upon the type of drug administered. However, intraseptal infusion of the cholinomimetic oxotremorine has been reported to produce both promnestic and amnestic effects when administered prior to task performance. The present study examined whether post-acquisition intraseptal infusion of oxotremorine would be promnestic or amnestic in a delayed-non-match-to-sample radial maze task. In this task rats must remember information about spatial locations visited during a daily sample session and maintain that information over extended retention intervals (hours) in order to perform accurately on the daily test session. Treatments may then be administered during the retention interval. Alterations in maze performance during the test session an hour or more after treatment evidences effects on memory. In the present study, intraseptal infusion of oxotremorine (1.0-10.0 microg) produced a linear dose-related impairment of memory performance. Importantly, we also observed disrupted performance on the day after treatment. This persistent deficit was related only to memory over the retention interval and did not affect indices of short-term memory (ability to avoid repetitive or proactive errors during both the pre- and post-delay sessions). The persistent deficit contrasts with the acute amnestic effects of other intraseptally administered drugs including the cholinomimetics carbachol and tacrine. Thus, intraseptal oxotremorine produced a preferential disruption of memory consolidation as well as a persistent alteration of medial septal circuits. These findings are discussed with regards to multi-stage models of hippocampal-dependent memory formation and the further development of therapeutic strategies in the treatment of mild cognitive impairment as well as age-related decline and Alzheimer's dementia.

Strychnine and taurine modulation of amygdala-associated anxiety-like behavior is 'state' dependent.

PubMed

McCool, Brian A; Chappell, Ann

2007-03-12

Strychnine-sensitive glycine receptors are expressed in many adult forebrain regions, yet the biological function of these receptors outside the spinal cord/brainstem is poorly understood. We have recently shown that rat lateral/basolateral amygdala neurons express strychnine-sensitive glycine-gated currents whose pharmacological and molecular characteristics are consistent with those established for classic ligand-gated chloride channels. The current studies were undertaken to establish the behavioral role, if any, of these strychnine-sensitive glycine receptors. Adult Long-Evans male rats were implanted with guide cannulae targeted at the lateral amygdala and were microinjected with standard artificial cerebrospinal fluid with or without various doses of strychnine or taurine. Anxiety-like behaviors were assessed with the elevated plus maze or the light/dark box. In the elevated plus maze, strychnine decreased closed-arm time and increased open-arm time, suggestive of an anxiolytic effect. Similarly, strychnine produced a modest anxiolytic effect in the light/dark box. Post hoc analysis of 'open-arm' time and 'light-side' time indicated that aCSF-treated animals were distributed into two apparent groups that displayed either high or low amounts of anxiety-like behavior in a given apparatus. Surprisingly, the pharmacological effects of both strychnine and taurine in these assays were dependent upon a given animal's behavioral phenotype. Together, these findings are significant because they suggest that the basal 'emotional state' of the animal could influence the behavioral outcome associated with drug application directly into the lateral/basolateral amygdala. Furthermore, our findings also suggest that compounds acting at amygdala strychnine-sensitive glycine receptors may actively modulate this basal anxiety-like state.

Anxiolytic property of hydro-alcohol extract of Lactuca sativa and its effect on behavioral activities of mice.

PubMed

Harsha, Singapura Nagesh; Anilakumar, Kandangath Raghavan

2013-01-01

Lactuca sativa, belonging to the Asteraceae family, is a leafy vegetable known for its medicinal properties. This study aimed to understand the mechanism of Lactuca sativa extract with respect to pharmacological action.We investigated the anxiolytic effects of hydro-alcoholic extract of leaves of Lactuca sativa on mice. The behavioral tests performed on mice models to assess anti-anxiety properties were: open field test (OFT), elevated plus maze test (EPM), elevated T maze test, and marble burying test. Increased locomotor activity and time spent in the "open-arm" were observed in extract fed group. Malondialdehyde (MDA) and nitrite levels were decreased, catalase and glutathione levels were increased in Lactuca sativa treated mice. The data obtained in the present study suggests that the extract of Lactuca sativa can afford significant protection against anxiolytic activity.

Effects of concomitant methylphenidate and ethanol administration on working and reference memory in rats.

PubMed

Sloan, Anthony R; McGovern, Robin; Buffalari, Deanne M

Recent studies have suggested that college students are heavily engaged in non-medical use of stimulant drugs prescribed to treat attention deficit hyperactivity disorder. This age group is also at high risk for alcohol use. Despite their potential co-abuse, little work has examined how these drugs interact to affect cognitive abilities. In fact, these drugs have opposing effects on working memory, which brings into question how they may interact to affect this particular behavior. The purpose of this research was to examine the concomitant effects of methylphenidate (MPH) and ethanol (EtOH) on working and reference memory. Rats were first trained on the radial arm maze task to establish a baseline performance rate measured as average number of reference and working memory errors. Performance was then assessed after injections of saline, MPH alone, EtOH alone, and MPH+EtOH combined. While both doses of MPH caused nonsignificant improvements in working memory, when combined with EtOH, there was an overall impairment in working and reference memory compared to other conditions. EtOH alone also decreased memory. These data indicate increased impairment of memory function with combined MPH and EtOH use. By understanding how the combination of methylphenidate and alcohol affects memory, we can better assess the risks of taking both substances simultaneously. Copyright © 2016 Elsevier Inc. All rights reserved.

Eicosanoyl-5-hydroxytryptamide (EHT) prevents Alzheimer’s disease-related cognitive and electrophysiological impairments in mice exposed to elevated concentrations of oligomeric beta-amyloid

PubMed Central

Asam, Kesava; Staniszewski, Agnieszka; Zhang, Hong; Melideo, Scott L.; Mazzeo, Adolfo; Voronkov, Michael; Huber, Kristen L.; Pérez, Eduardo; Stock, Maxwell; Stock, Jeffry B.; Arancio, Ottavio

2017-01-01

Soluble forms of oligomeric beta-amyloid (Aβ) are thought to play a central role in Alzheimer’s disease (AD). Transgenic manipulation of methylation of the serine/threonine protein phosphatase, PP2A, was recently shown to alter the sensitivity of mice to AD-related impairments resulting from acute exposure to elevated levels of Aβ. In addition, eicosanoyl-5-hydroxytryptamide (EHT), a naturally occurring component from coffee beans that modulates PP2A methylation, was shown to confer therapeutic benefits in rodent models of AD and Parkinson’s disease. Here, we tested the hypothesis that EHT protects animals from the pathological effects of exposure to elevated levels of soluble oligomeric Aβ. We treated mice with EHT-containing food at two different doses and assessed the sensitivity of these animals to Aβ-induced behavioral and electrophysiological impairments. We found that EHT administration protected animals from Aβ-induced cognitive impairments in both a radial-arm water maze and contextual fear conditioning task. We also found that both chronic and acute EHT administration prevented Aβ-induced impairments in long-term potentiation. These data add to the accumulating evidence suggesting that interventions with pharmacological agents, such as EHT, that target PP2A activity may be therapeutically beneficial for AD and other neurological conditions. PMID:29253878

Lithium Treatment Prevents Apoptosis in Neonatal Rat Hippocampus Resulting from Sevoflurane Exposure.

PubMed

Zhou, Xue; da Li, Wen-; Yuan, Bao-Long; Niu, Li-Jun; Yang, Xiao-Yu; Zhou, Zhi-Bin; Chen, Xiao-Hui; Feng, Xia

2016-08-01

We aimed to observe the therapeutic effects of lithium on inhalational anesthetic sevoflurane-induced apoptosis in immature brain hippocampus. From postnatal day 5 (P5) to P28, male Sprague-Dawley pups were intraperitoneally injected with lithium chloride or 0.9 % sodium chloride. On P7 after the injection, pups were exposed to 2.3 % sevoflurane or air for 6 h. Brain tissues were harvested 12 h and 3 weeks after exposure. Cleaved caspase-3, nNOS protein, GSK-3β,p-GSK-3β were assessed by Western blot, and histopathological changes were assessed using Nissl stain and TUNEL stain. From P28, we used the eight-arm radial maze test and step-through test to evaluate the influence of sevoflurane exposure on the learning and memory of juvenile rats. The results showed that neonatal sevoflurane exposure induced caspase-3 activation and histopathological changes in hippocampus can be attenuated by lithium chloride. Sevoflurane increased GSK-3β activity while pretreatment of lithium decreased GSK-3β activity. Moreover, sevoflurane showed possibly slight but temporal influence on the spatial learning and the memory of juvenile rats, and chronic use of lithium chloride might have the therapeutic effect. Our current study suggests that lithium attenuates sevoflurane induced neonatal hippocampual damage by GSK-3β pathway and might improve learning and memory deficits in rats after neonatal exposure.

Astaxanthin ameliorates aluminum chloride-induced spatial memory impairment and neuronal oxidative stress in mice.

PubMed

Al-Amin, Md Mamun; Reza, Hasan Mahmud; Saadi, Hasan Mahmud; Mahmud, Waich; Ibrahim, Abdirahman Adam; Alam, Musrura Mefta; Kabir, Nadia; Saifullah, A R M; Tropa, Sarjana Tarannum; Quddus, A H M Ruhul

2016-04-15

Aluminum chloride induces neurodegenerative disease in animal model. Evidence suggests that aluminum intake results in the activation of glial cells and generation of reactive oxygen species. By contrast, astaxanthin is an antioxidant having potential neuroprotective activity. In this study, we investigate the effect of astaxanthin on aluminum chloride-exposed behavioral brain function and neuronal oxidative stress (OS). Male Swiss albino mice (4 months old) were divided into 4 groups: (i) control (distilled water), (ii) aluminum chloride, (iii) astaxanthin+aluminum chloride, and (iv) astaxanthin. Two behavioral tests; radial arm maze and open field test were conducted, and OS markers were assayed from the brain and liver tissues following 42 days of treatment. Aluminum exposed group showed a significant reduction in spatial memory performance and anxiety-like behavior. Moreover, aluminum group exhibited a marked deterioration of oxidative markers; lipid peroxidation (MDA), nitric oxide (NO), glutathione (GSH) and advanced oxidation of protein products (AOPP) in the brain. To the contrary, co-administration of astaxanthin and aluminum has shown improved spatial memory, locomotor activity, and OS. These results indicate that astaxanthin improves aluminum-induced impaired memory performances presumably by the reduction of OS in the distinct brain regions. We suggest a future study to determine the underlying mechanism of astaxanthin in improving aluminum-exposed behavioral deficits. Copyright © 2016 Elsevier B.V. All rights reserved.

Caffeine prevents cognitive impairment induced by chronic psychosocial stress and/or high fat-high carbohydrate diet.

PubMed

Alzoubi, K H; Abdul-Razzak, K K; Khabour, O F; Al-Tuweiq, G M; Alzubi, M A; Alkadhi, K A

2013-01-15

Caffeine alleviates cognitive impairment associated with a variety of health conditions. In this study, we examined the effect of caffeine treatment on chronic stress- and/or high fat-high carbohydrate Western diet (WD)-induced impairment of learning and memory in rats. Chronic psychosocial stress, WD and caffeine (0.3 g/L in drinking water) were simultaneously administered for 3 months to adult male Wistar rats. At the conclusion of the 3 months, and while the previous treatments continued, rats were tested in the radial arm water maze (RAWM) for learning, short-term and long-term memory. This procedure was applied on a daily basis to all animals for 5 consecutive days or until the animal reaches days to criterion (DTC) in the 12th learning trial and memory tests. DTC is the number of days that the animal takes to make zero error in two consecutive days. Chronic stress and/or WD groups caused impaired learning, which was prevented by chronic caffeine administration. In the memory tests, chronic caffeine administration also prevented memory impairment during chronic stress conditions and/or WD. Furthermore, DTC value for caffeine treated stress, WD, and stress/WD groups indicated that caffeine normalizes memory impairment in these groups. These results showed that chronic caffeine administration prevented stress and/or WD-induced impairment of spatial learning and memory. Copyright © 2012 Elsevier B.V. All rights reserved.

Combination therapy in a transgenic model of Alzheimer’s disease

PubMed Central

Aytan, Nurgul; Choi, Ji-Kyung; Carreras, Isabel; Kowall, Neil W.

2013-01-01

The pathological accumulation of the β-amyloid protein (Aβ) has been closely associated with synaptic loss and neurotoxicity contributing to cognitive dysfunction in Alzheimer’s disease (AD). Oligomers of Aβ42 appear to be the most neurotoxic form. Two of the most promising attempts to reduce Aβ accumulation have been with scyllo-inositol, an inositol steroisomer, that stabilizes Aβ42 peptide and prevents it from progressing to oligomers and fibrils and R-flurbiprofen, a purified enantiomer of the classical racemic non-steroidal anti-inflammatory drugs (NSAID), flurbiprofen, that retains the ability to specifically lower Aβ42. In the present study we evaluated the effects of scyllo-inositol and the combination treatment of scyllo-inositol + R-flurbiprofen on amyloid pathology and hippocampal-dependent memory function in 5XFAD mice, a model of Aβ pathology characterized by an enormous production of Aβ42. Our expectations were that the combination treatment of scylloinositol + R-flurbiprofen would have an additive effect in preventing Aβ accumulation and that cognition would be improved. Mice treated with scyllo-inositol exhibit 41 and 35% reduction in the deposition of the amyloid plaques stained by antibody against Aβ42 and Aβ40 respectively. Scyllo-inositol was not more effective when combined with R-flurbiprofen for the measures tested. Scyllo-inositol treated mice performed significantly better at the radial arm water maze (RAWM) task than untreated and scyllo-inositol + R-flurbiprofen treated mice. PMID:24120437

Separate effects of sex hormones and sex chromosomes on brain structure and function revealed by high-resolution magnetic resonance imaging and spatial navigation assessment of the Four Core Genotype mouse model.

PubMed

Corre, Christina; Friedel, Miriam; Vousden, Dulcie A; Metcalf, Ariane; Spring, Shoshana; Qiu, Lily R; Lerch, Jason P; Palmert, Mark R

2016-03-01

Males and females exhibit several differences in brain structure and function. To examine the basis for these sex differences, we investigated the influences of sex hormones and sex chromosomes on brain structure and function in mice. We used the Four Core Genotype (4CG) mice, which can generate both male and female mice with XX or XY sex chromosome complement, allowing the decoupling of sex chromosomes from hormonal milieu. To examine whole brain structure, high-resolution ex vivo MRI was performed, and to assess differences in cognitive function, mice were trained on a radial arm maze. Voxel-wise and volumetric analyses of MRI data uncovered a striking independence of hormonal versus chromosomal influences in 30 sexually dimorphic brain regions. For example, the bed nucleus of the stria terminalis and the parieto-temporal lobe of the cerebral cortex displayed steroid-dependence while the cerebellar cortex, corpus callosum, and olfactory bulbs were influenced by sex chromosomes. Spatial learning and memory demonstrated strict hormone-dependency with no apparent influence of sex chromosomes. Understanding the influences of chromosomes and hormones on brain structure and function is important for understanding sex differences in brain structure and function, an endeavor that has eventual implications for understanding sex biases observed in the prevalence of psychiatric disorders.

L-carnitine prevents memory impairment induced by chronic REM-sleep deprivation.

PubMed

Alzoubi, Karem H; Rababa'h, Abeer M; Owaisi, Amani; Khabour, Omar F

2017-05-01

Sleep deprivation (SD) negatively impacts memory, which was related to oxidative stress induced damage. L-carnitine is a naturally occurring compound, synthesized endogenously in mammalian species and known to possess antioxidant properties. In this study, the effect of L-carnitine on learning and memory impairment induced by rapid eye movement sleep (REM-sleep) deprivation was investigated. REM-sleep deprivation was induced using modified multiple platform model (8h/day, for 6 weeks). Simultaneously, L-carnitine was administered (300mg/kg/day) intraperitoneally for 6 weeks. Thereafter, the radial arm water maze (RAWM) was used to assess spatial learning and memory. Additionally, the hippocampus levels of antioxidant biomarkers/enzymes: reduced glutathione (GSH), oxidized glutathione (GSSG), GSH/GSSG ratio, glutathione peroxidase (GPx), catalase, and superoxide dismutase (SOD) and thiobarbituric acid reactive substance (TBARS) were assessed. The results showed that chronic REM-sleep deprivation impaired both short- and long-term memory (P<0.05), whereas L-carnitine treatment protected against this effect. Furthermore, L-carnitine normalized chronic REM-sleep deprivation induced reduction in the hippocampus ratio of GSH/GSSG, activity of catalase, GPx, and SOD. No change was observed in TBARS among tested groups (P>0.05). In conclusion, chronic REM-sleep deprivation induced memory impairment, and treatment with L-carnitine prevented this impairment through normalizing antioxidant mechanisms in the hippocampus. Copyright © 2017 Elsevier Inc. All rights reserved.

Army and Air Force Unmanned Air Reconnaissance: Warrior and Hydra Navigating a Maze of Strategic Hedges

DTIC Science & Technology

2009-06-01

Chambliss; Colonel Michael Stickney; Colonel Eric Mathewson; Lieutenant Colonel Robert Kiebler; Lieutenant Colonel Kenneth Kilmurray; Lieutenant...16 Peter Layton , Group Captain, Royal Air Force, “Hedging Strategies, UCAVs, budgets, and improbable threats,” Armed Forces Journal...10 Colonel Eric Mathewson, US Air Force HAF/A2 DCS ISR, “Air Force ISR in a Changed World: ISR Transformation, the Importance

The Floating Upper Limb: Multiple Injuries Involving Ipsilateral, Proximal, Humeral, Supracondylar, and Distal Radial Limb

PubMed Central

Manaan, Qazi; Bashir, Adil; Zahoor, Adnan; Mokhdomi, Taseem A.

2016-01-01

Floating arm injury represents a common yet complicated injury of the childhood severely associated with limb deformation and even morbidity, if not precisely addressed and credibly operated. Here, we report a rare floating upper limb case of a 9-year-old boy with multiple injuries of ipsilateral proximal humeral, supracondylar and distal radial limb. This is the first report to document such a combined floating elbow and floating arm injury in the same limb. In this report, we discuss the surgical procedures used and recovery of the patient monitored to ascertain the effectiveness of the method in limb reorganisation. PMID:27583121

The Floating Upper Limb: Multiple Injuries Involving Ipsilateral, Proximal, Humeral, Supracondylar, and Distal Radial Limb.

PubMed

Manaan, Qazi; Bashir, Adil; Zahoor, Adnan; Mokhdomi, Taseem A; Danish, Qazi

2016-09-01

Floating arm injury represents a common yet complicated injury of the childhood severely associated with limb deformation and even morbidity, if not precisely addressed and credibly operated. Here, we report a rare floating upper limb case of a 9-year-old boy with multiple injuries of ipsilateral proximal humeral, supracondylar and distal radial limb. This is the first report to document such a combined floating elbow and floating arm injury in the same limb. In this report, we discuss the surgical procedures used and recovery of the patient monitored to ascertain the effectiveness of the method in limb reorganisation.

Dose-response effects of systemic anandamide administration in mice sequentially submitted to the open field and elevated plus-maze tests.

PubMed

Ribeiro, A; Ferraz-de-Paula, V; Pinheiro, M L; Palermo-Neto, J

2009-06-01

The endocannabinoid system is involved in the control of many physiological functions, including the control of emotional states. In rodents, previous exposure to an open field increases the anxiety-like behavior in the elevated plus-maze. Anxiolytic-like effects of pharmacological compounds that increase endocannabinoid levels have been well documented. However, these effects are more evident in animals with high anxiety levels. Several studies have described characteristic inverted U-shaped dose-response effects of drugs that modulate the endocannabinoid levels. However, there are no studies showing the effects of different doses of exogenous anandamide, an endocannabinoid, in animal models of anxiety. Thus, in the present study, we determined the dose-response effects of exogenous anandamide at doses of 0.01, 0.1, and 1.0 mg/kg in C57BL/6 mice (N = 10/group) sequentially submitted to the open field and elevated plus-maze. Anandamide was diluted in 0.9% saline, ethyl alcohol, Emulphor (18:1:1) and administered ip (0.1 mL/10 g body weight); control animals received the same volume of anandamide vehicle. Anandamide at the dose of 0.1 mg/kg (but not of 0.01 or 1 mg/kg) increased (P < 0.05) the time spent and the distance covered in the central zone of the open field, as well as the exploration of the open arms of the elevated plus-maze. Thus, exogenous anandamide, like pharmacological compounds that increase endocannabinoid levels, promoted a characteristic inverted U-shaped dose-response effect in animal models of anxiety. Furthermore, anandamide (0.1 mg/kg) induced an anxiolytic-like effect in the elevated plus-maze (P < 0.05) after exposing the animals to the open field test.

Octopus vulgaris uses visual information to determine the location of its arm.

PubMed

Gutnick, Tamar; Byrne, Ruth A; Hochner, Binyamin; Kuba, Michael

2011-03-22

Octopuses are intelligent, soft-bodied animals with keen senses that perform reliably in a variety of visual and tactile learning tasks. However, researchers have found them disappointing in that they consistently fail in operant tasks that require them to combine central nervous system reward information with visual and peripheral knowledge of the location of their arms. Wells claimed that in order to filter and integrate an abundance of multisensory inputs that might inform the animal of the position of a single arm, octopuses would need an exceptional computing mechanism, and "There is no evidence that such a system exists in Octopus, or in any other soft bodied animal." Recent electrophysiological experiments, which found no clear somatotopic organization in the higher motor centers, support this claim. We developed a three-choice maze that required an octopus to use a single arm to reach a visually marked goal compartment. Using this operant task, we show for the first time that Octopus vulgaris is capable of guiding a single arm in a complex movement to a location. Thus, we claim that octopuses can combine peripheral arm location information with visual input to control goal-directed complex movements. Copyright © 2011 Elsevier Ltd. All rights reserved.

How do octopuses use their arms?

PubMed

Mather, J A

1998-09-01

A taxonomy of the movement patterns of the 8 flexible arms of octopuses is constructed. Components consist of movements of the arm itself, the ventral suckers and their stalks, as well as the relative position of arms and the skin web between them. Within 1 arm, combinations of components result in a variety of behaviors. At the level of all arms, 1 group of behaviors is described as postures, on the basis of the spread of all arms and the web to make a 2-dimensional surface whose position differs in the 3rd dimension. Another group of arm behaviors is actions, more or less coordinated and involving several to all arms. Arm control appears to be based on radial symmetry, relative equipotentiality of all arms, relative independence of each arm, and separability of components within the arm. The types and coordination of arm behaviors are discussed with relationship to biomechanical limits, muscle structures, and neuronal programming.

Piezoelectric micromotor using a metal-ceramic composite structure.

PubMed

Koc, B; Bouchilloux, P; Uchino, K

2000-01-01

This paper presents a new piezoelectric micromotor design, in which a uniformly electroded piezoelectric ring bonded to a metal ring is used as the stator. Four inward arms at the inner circumference of the metal ring transfer radial displacements into tangential displacements. The rotor ends in a truncated cone shape and touches the tips of the arms. A rotation takes place by exciting coupled modes of the stator element, such as a radial mode and a second bending mode of the arms. The behavior of the free stator was analyzed using the ATILA finite element software. Torque vs. speed relationship was measured from the transient speed change with a motor load. A starting torque of 17 microNm was obtained at 20 Vrms. The main features of this motor are low cost and easy assembly because of a simple structure and small number of components.

Effects of the aqueous extract of Pimpinella anisum L. seeds on exploratory activity and emotional behavior in rats using the open field and elevated plus maze tests.

PubMed

Gamberini, Maria Thereza; Rodrigues, Domingos Sávio; Rodrigues, Daniela; Pontes, Victoria Bottino

2015-06-20

Pimpinella anisum L. is considered one of the first plants used for medicinal purposes. Pharmacological actions of the plant on the central nervous system have been proven but previous analyses have focused on anticonvulsant and neuroprotective actions. In traditional medicine worldwide, the use of Pimpinella is commonly recommended as a tranquilizer, although no scientific information supporting this use is available. Therefore, it was decided to investigate the central actions of the plant to observe behavioral responses, with an emphasis on the emotional component. To investigate the effects of the aqueous extract of Pimpinella seeds on exploratory activity and emotional behavior in rats using the open field and elevated plus maze tests. Seeds of Pimpinella were extracted with distilled water, concentrated and freeze-dried yielding the aqueous extract(AE). Rats were divided into four groups: control(water 5 mL/kg, p.o.) and AE 0.5, 1.0 and 2.0 g/kg, p.o. Individual observations were performed in an open field and the parameters locomotor activity, rearing, grooming and defecation were recorded. In elevated plus maze test, rats were divided into four groups: control(water 5 mL/kg, p.o.) and AE 0.5, 1.0 and 2.0 g/kg, p.o. The parameters arm entries, total time spent in open and closed arms; and total number of arrivals at the end of an open or closed arm were recorded for each rat. Among the parameters assessed with the open field test, only rearing was reduced in the AE 0.5 g/kg group. When AE 1.0 g/kg was administered, only the initiation of exploratory activity was delayed, without impairing the animals' general activity. The highest dose of AE (2.0 g/kg) induced a reduction in the animals' habituation during the open field test within the same session, as evidenced by the maintenance of high levels of peripheral locomotion and rearing throughout the test. On the elevated plus maze test, no alterations were observed in the responses of the animals relative to controls for all doses tested. These results failed to support anxiety-related central action of the aqueous extract of Pimpinella seeds, invalidating popular beliefs regarding a tranquilizing effect. However, a habituation-related central action of the extract was demonstrated, suggesting action of bioactive compounds on central learning-related areas. The characterization of effects that may interfere with cognitive processes reinforces caution regarding indiscriminate consumption of the plant, especially in individuals with deficits, such as Alzheimer's Disease patients. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

The effects of MDMA pretreatment on the behavioural effects of other drugs of abuse in the rat elevated plus-maze test.

PubMed

Sumnall, H R; O'Shea, E; Marsden, C A; Cole, J C

2004-04-01

Few preclinical studies have found long-term behavioural consequences of the serotonergic neurotoxicity produced by 3,4-methylenedioxymethamphetamine (MDMA). This study investigated whether pretreatment with MDMA altered the behavioural effects of other drugs of abuse. Adult male Lister hooded rats (n=10/group) were pretreated with 10 mg/kg MDMA or 1 ml/kg saline vehicle intraperitoneally every 2 h for 6 h. Fourteen days later, the behavioural effects of d-amphetamine (2 mg/kg), cocaine (10 mg/kg), ethanol (2.0 g/kg), heroin (0.5 mg/kg), or MDMA (10 mg/kg) were assessed in the elevated plus-maze test. MDMA pretreatment produced approximately 20-25% decrease in hippocampal 5-HT and 5-HIAA concentrations, and [(3)H]paroxetine binding when analysed 2 weeks later. Despite inducing neurotoxicity, this regimen had no effect upon the plus-maze behaviour induced by ethanol, heroin, and MDMA. Acutely, and independent of neurotoxic pretreatment, MDMA produced a clear anxiogenic-like behavioural profile with a reduction of open arm entries and suppression of explorative behaviours. Despite being acutely anxiogenic, pretreatment with a neurotoxic regimen of MDMA has little effect on the anxiety-related effects of other drugs of abuse. It is possible that extended time points would produce significant changes, although the available evidence suggests that the plus-maze may not be a suitable model for detection of behavioural dysfunction after neurotoxic MDMA.

Contrasting effects of acute and chronic treatment with imipramine and fluoxetine on inhibitory avoidance and escape responses in mice exposed to the elevated T-maze.

PubMed

Gomes, Karina Santos; de Carvalho-Netto, Eduardo Ferreira; Monte, Kátia Cristina Da Silva; Acco, Bruno; Nogueira, Paulo José de Campos; Nunes-de-Souza, Ricardo Luiz

2009-03-30

The elevated T-maze (ETM) is an animal model of anxiety-like behavior that assesses two different defensive behavioral tasks in the same animal-acquisition of inhibitory avoidance and latency to escape from an open and elevated arm. In rats, cute and chronic treatments with anxiolytic-like drugs impair avoidance acquisition while only chronic administration of panicolytic-like drugs impairs open arm withdrawal. To date, only the acute effects of anxiolytic/anxiogenic or panicolytic/panicogenic drugs have been tested in the mouse ETM and the results have partially corroborated those found in the rat ETM. This study investigated the effects of acute (a single intraperitoneal injection 30 min before testing) and chronic (daily i.p. injections for 15 consecutive days) treatment with imipramine or fluoxetine, non-selective and selective serotonin reuptake inhibitors, respectively, on inhibitory avoidance and escape tasks in the mouse ETM. Neither acute nor chronic treatment with imipramine (0, 1, 5 or 10 mg/kg, i.p.) significantly changed the behavioral profile of mice in the two ETM tasks. Interestingly, while acute fluoxetine (0, 5, 10, 20 or 40 mg/kg, i.p.) facilitated inhibitory avoidance and impaired escape latency, chronic treatment (0, 5, 20 or 40 mg/kg, i.p.) with this selective serotonin reuptake inhibitor (SSRI) produced an opposite effect, i.e., it impaired inhibitory avoidance acquisition and facilitated open arm withdrawal. Importantly, acute or chronic treatment with imipramine (except at the highest dose that increased locomotion when given acutely) or fluoxetine failed to alter general locomotor activity in mice as assessed in an ETM in which all arms were enclosed by lateral walls (eETM). These results suggest that inhibitory avoidance acquisition is a useful task for the evaluation of acute and chronic effects of SSRI treatment on anxiety in mice. However, as open arm latency was actually increased and reduced by acute and chronic fluoxetine, respectively, this does not seem to be a useful measure of escape from a proximal threat in this species.

Effect of ketamine on exploratory behaviour in BALB/C and C57BL/6 mice.

PubMed

Akillioglu, Kubra; Melik, Emine Babar; Melik, Enver; Boga, Ayper

2012-01-01

In this study, we evaluated the effect of ketamine on exploratory locomotion behaviours in the Balb/c and C57BL/6 strains of mice, which differ in their locomotion behaviours. Intraperitoneal administration of ketamine at three different doses (1, 5 or 10 mg/kg, 0.1 ml/10 gr body weight) was performed on adult male Balb/c and C57BL/6 mice. The same volume of saline was applied to the control group. The open-field and elevated plus maze apparatus were used to evaluate exploratory locomotion. In the open-field test, Balb/c mice less spend time in the centre of the field and was decreased locomotor activity compared to C57BL/6 mice (p<0.01). Ketamine treatment of Balb/c mice at 10 mg/kg dose caused an increase in locomotor activity and an increase in the amount of time spent in the centre in the open-field test, compared to the control group (p<0.05). In C57BL/6 mice, ketamine treatment (1 and 10 mg/kg) decreased locomotor activity (p<0.05). In C57BL/6 mice, the three different doses of ketamine application each caused a decrease in the frequency of centre crossing (p<0.001) and the spent time in the centre (p<0.05). In the elevated plus maze, the number of open-arm entries, the percentage of open-arm time and total arm entries were decreased in Balb/c mice compared to C57BL/6 mice (p<0.001). Ketamine treatment of Balb/c mice at 10 mg/kg dose caused an increase in the open-arm activity (p<0.001). Ketamine application (10 mg/kg) decreased the open-arm activity in C57BL/6 mice (p<0.05). A subanaesthetic dose of ketamine increased exploratory locomotion in Balb/c mice. In contrast, a subanaesthetic dose of ketamine decreased exploratory locomotion in C57BL/6 mice. In conclusion, hereditary factors may play an important role in ketamine-induced responses. Copyright © 2011 Elsevier Inc. All rights reserved.

Ophioderma peruana, a new species of brittlestar (Echinodermata, Ophiuroidea, Ophiodermatidae) from the Peruvian coast

PubMed Central

Pineda-Enríquez, Tania; Solís-Marín, Francisco A.; Hooker, Yuri; Alfredo Laguarda-Figueras

2013-01-01

Abstract Ophioderma peruana sp. n. is a new species of Ophiodermatidae, extending the distribution of the genus Ophioderma to Lobos de Afuera Island, Peru, easily distinguishable from its congeners by its peculiarly fragmented dorsal arm plates. Dense granules, rounded or polygonal cover the disc, the radial shields may be naked or completely covered by granules. A good character for recognizing this species in the field is the dorsal side of the disc which is brown with disc granules lighter cream and brown, the arms are mottled with whitish spots and the ventral part of the disc on the interradial part is brown and the radial part bright yellow. PMID:24363579

Companions for ``Nessie'' in the Milky Way's Skeleton

NASA Astrophysics Data System (ADS)

Kohler, Susanna

2015-12-01

The recent discovery of a purported bone of the Milky Way, a dark cloud nicknamed Nessie, has provided us with new clues for mapping out the spiral structure of our galaxy. It turns out that Nessie may not be alone: a follow-up study has identified more bones, potentially making up a skeleton of the Milky Way that traces out the densest parts of its spiral arms.Inconvenient Vantage PointHow many spiral arms does the Milky Way have? Where are they located? What does the structure look like between the arms? It may seem surprising that these fundamental questions dont yet have clear answers. But because were stuck in the galaxys disk, were forced to piece together our understanding of the Milky Ways structure based primarily on measurements of position and radial velocity of structures within the galactic plane.The discovery of Nessie presents an intriguing new tool to identify the layout of the galaxy. Nessie is a very long, thin, infrared-dark filament that runs along the modeled position of the Scutum-Centaurus arm and is believed therefore to trace the structure of the arm. In a new study led by Catherine Zucker (University of Virginia, Harvard-Smithsonian Center for Astrophysics), the authors have searched for additional bones like Nessie, hoping to use them to map out the skeleton of the Milky Way.New Bones DiscoveredIn this map of radial velocity vs. galactic longitude, the bone candidates are indicated by the numbered points. The colored lines indicate the positions of two of the galactic spiral arms, according to various models. Click for a closer look! [Zucker et al. 2015]Zucker and collaborators began by using World Wide Telescope, a tool that facilitates visualization of multiple layers of data at a variety of scales, to search through Spitzer infrared data for additional structures like Nessie. Searching specifically along the predicted positions of galactic arms, they found 15 initial bone candidates.Next, the team obtained radial-velocity data for the candidates from five separate radio surveys. Five of the candidates did not have radial velocities consistent with the galactic rotation curve at the predicted positions of the nearby arms.Hope for a SkeletonThe authors used the remaining ten candidates to construct rough criteria for an object to be a Milky Way bone:Largely continuous mid-infrared extinction featureParallel to the galactic plane, to within 30Position within 20 pc of the galactic mid-planeRadial velocity within 10 km/s of the predicted velocity of a Milky Way armNo abrupt shifts in velocity within the extinction featureProjected aspect ratio of 50:1Of the ten candidates, six meet all the criteria and are thought to mark the location of significant spiral features in the galaxy. The authors believe that this method may be used to identify hundreds of Milky Way bones in the future. Combining this skeleton with other tracers of galactic structure will ultimately help us to piece together a more accurate map of our galaxy.BonusCheck out this video, produced by the authors using World Wide Telescope, that shows the locations of the newly discovered bone candidates within Spitzer images of the Milky Way galactic plane. [Credit: Zucker et al. 2015]Click here to view the video on YouTube.CitationCatherine Zucker et al 2015 ApJ 815 23. doi:10.1088/0004-637X/815/1/23

ONO-8590580, a Novel GABAAα5 Negative Allosteric Modulator Enhances Long-Term Potentiation and Improves Cognitive Deficits in Preclinical Models.

PubMed

Kawaharada, Soichi; Nakanishi, Miki; Nakanishi, Nobuto; Hazama, Keisuke; Higashino, Masato; Yasuhiro, Tetsuya; Lewis, Arwel; Clark, Gary S; Chambers, Mark S; Maidment, Scott A; Katsumata, Seishi; Kaneko, Shuji

2018-07-01

GABA A receptors containing α 5 subunits (GABA A α 5) are highly expressed in the hippocampus and negatively involved in memory processing, as shown by the fact that GABA A α 5-deficient mice show higher hippocampus-dependent performance than wild-type mice. Accordingly, small-molecule GABA A α 5 negative allosteric modulators (NAMs) are known to enhance spatial learning and memory in rodents. Here we introduce a new, orally available GABA A α 5 NAM that improves hippocampal functions. ONO-8590580 [1-(cyclopropylmethyl)-5-fluoro-4-methyl- N -[5-(1-methyl-1H-imidazol-4-yl)-2-pyridinyl]-1H-benzimidazol-6-amine] binds to the benzodiazepine binding sites on recombinant human α 5-containing GABA A receptors with a K i of 7.9 nM, and showed functionally selective GABA A α 5 NAM activity for GABA-induced Cl - channel activity with a maximum 44.4% inhibition and an EC 50 of 1.1 nM. In rat hippocampal slices, tetanus-induced long-term potentiation of CA1 synapse response was significantly augmented in the presence of 300 nM ONO-8590580. Orally administered ONO-8590580 (1-20 mg/kg) dose-dependently occupied hippocampal GABA A α 5 in a range of 40%-90% at 1 hour after intake. In the rat passive avoidance test, ONO-8590580 (3-20 mg/kg, by mouth) significantly prevented (+)-MK-801 hydrogen maleate (MK-801)-induced memory deficit. In addition, ONO-8590580 (20 mg/kg, p.o.) was also effective in improving the cognitive deficit induced by scopolamine and MK-801 in the rat eight-arm radial maze test with equal or greater activity than 0.5 mg/kg donepezil. No anxiogenic-like or proconvulsant effect was associated with ONO-8590580 at 20 mg/kg p.o. in the elevated plus maze test or pentylenetetrazole-induced seizure test, respectively. In sum, ONO-8590580 is a novel GABA A α 5 NAM that enhances hippocampal memory function without an anxiogenic or proconvulsant risk. Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics.

Neural Development Under Conditions of Spaceflight

NASA Technical Reports Server (NTRS)

Kosik, Kenneth S.; Steward, Oswald; Temple, Meredith D.; Denslow, Maria J.

2003-01-01

One of the key tasks the developing brain must learn is how to navigate within the environment. This skill depends on the brain's ability to establish memories of places and things in the environment so that it can form cognitive maps. Earth's gravity defines the plane of orientation of the spatial environment in which animals navigate, and cognitive maps are based on this plane of orientation. Given that experience during early development plays a key role in the development of other aspects of brain function, experience in a gravitational environment is likely to be essential for the proper organization of brain regions mediating learning and memory of spatial information. Since the hippocampus is the brain region responsible for cognitive mapping abilities, this study evaluated the development of hippocampal structure and function in rats that spent part of their early development in microgravity. Litters of male and female Sprague-Dawley rats were launched into space aboard the Space Shuttle Columbia on either postnatal day eight (P8) or 14 (P14) and remained in space for 16 days. Upon return to Earth, the rats were tested for their ability to remember spatial information and navigate using a variety of tests (the Morris water maze, a modified radial arm maze, and an open field apparatus). These rats were then tested physiologically to determine whether they exhibited normal synaptic plasticity in the hippocampus. In a separate group of rats (flight and controls), the hippocampus was analyzed using anatomical, molecular biological, and biochemical techniques immediately postlanding. There were remarkably few differences between the flight groups and their Earth-bound controls in either the navigation and spatial memory tasks or activity-induced synaptic plasticity. Microscopic and immunocytochemical analyses of the brain also did not reveal differences between flight animals and ground-based controls. These data suggest that, within the developmental window studied, microgravity has minimal long-term impact on cognitive mapping function and cellular substrates important for this function. Any differences due to development in microgravity were transient and returned to normal soon after return to Earth.

Orthotic arm joint. [for use in mechanical arms

NASA Technical Reports Server (NTRS)

Dane, D. H. (Inventor)

1974-01-01

An improved orthopedic (orthotic) arm joint that can be used in various joint of mechanical arms is described. The arm joints includes a worm, which is coupled to an electric motor for rotating a worm gear carried within a rotatable housing. The worm gear is supported on a thrust bearing and the rotatable housing is supported on a radial thrust bearing. A bolt extends through the housing, bearings, and worm gear for securing the device together. A potentiometer extends through the bolt, and is coupled to the rotatable housing for rotating therewith, so as to produce an electrical signal indicating the angular position of the rotatable housing.

Scented guide ropes as a method to enhance brown treesnake (Boiga irregularis) trap capture success on Guam

USGS Publications Warehouse

Mason, L.C.; Savidge, J.A.; Rodda, G.H.; Yackel Adams, A.A.

2011-01-01

Current methods for controlling the invasive Brown Treesnake (Boiga irregularis) on Guam include a modified minnow trap with a live mouse lure. We investigated the effects on capture success of augmenting these traps with scented guide ropes leading to trap entrances. Initial screening of scent preferences was based on time spent in scented and unscented arms of a Y-maze. Preferences of large and small snakes were scored for six different prey scents (live and carrion gecko, skink, and mouse). Large snakes spent more time in the maze arm scented with live gecko and carrion gecko, whereas small snakes spent more time in the arm scented with carrion mouse and carrion gecko. After the laboratory study, a pilot trapping session was conducted in the field using three treatments (live mouse-scented ropes, carrion gecko-scented ropes, and carrion mouse-scented ropes) and two controls (traps with unscented guide ropes and those with no ropes attached). Contrary to laboratory results, live mouse-scented ropes were most effective. We conducted a second trapping session using live mouse-scented ropes as well as the two controls used in the pilot study. For snakes of below-average to average condition, the number of captures for traps with live mouse-scented ropes was higher than for traps with no ropes. However, for snakes of above-average condition, there were no differences in capture rates between trap treatments. Overall, treatment effects were weaker than latent individual heterogeneity and the influence of snake body size, with large snakes trapped more readily. ?? 2011 Society for the Study of Amphibians and Reptiles.

Noradrenergic modulation of vicarious trial-and-error behavior during a spatial decision-making task in rats.

PubMed

Amemiya, S; Noji, T; Kubota, N; Nishijima, T; Kita, I

2014-04-18

Deliberation between possible options before making a decision is crucial to responding with an optimal choice. However, the neural mechanisms regulating this deliberative decision-making process are still unclear. Recent studies have proposed that the locus coeruleus-noradrenaline (LC-NA) system plays a role in attention, behavioral flexibility, and exploration, which contribute to the search for an optimal choice under uncertain situations. In the present study, we examined whether the LC-NA system relates to the deliberative process in a T-maze spatial decision-making task in rats. To quantify deliberation in rats, we recorded vicarious trial-and-error behavior (VTE), which is considered to reflect a deliberative process exploring optimal choices. In experiment 1, we manipulated the difficulty of choice by varying the amount of reward pellets between the two maze arms (0 vs. 4, 1 vs. 3, 2 vs. 2). A difficulty-dependent increase in VTE was accompanied by a reduction of choice bias toward the high reward arm and an increase in time required to select one of the two arms in the more difficult manipulation. In addition, the increase of c-Fos-positive NA neurons in the LC depended on the task difficulty and the amount of c-Fos expression in LC-NA neurons positively correlated with the occurrence of VTE. In experiment 2, we inhibited LC-NA activity by injection of clonidine, an agonist of the alpha2 autoreceptor, during a decision-making task (1 vs. 3). The clonidine injection suppressed occurrence of VTE in the early phase of the task and subsequently impaired a valuable choice later in the task. These results suggest that the LC-NA system regulates the deliberative process during decision-making. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

New velocimetry and revised cartography of the spiral arms in the Milky Way—a consistent symbiosis

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

Vallée, Jacques P., E-mail: jacques.vallee@cnrc.gc.ca

Recent advances in the determinations of the positions (pitch angle, shape, numbers, interarm separation) and velocities (rotation curve) of the spiral arms are evaluated and compared to previous determinations. Based on these results, an average cartographic model is developed that fits the means of basic input data and provides predictions for the locations of the arms in the Milky Way, for each galactic quadrant. For each spiral arm segment in each galactic quadrant, the LSR radial velocities are calculated for the radial distance as well as for its galactic longitude. From our velocimetric model, arm intercepts (between line of sightsmore » and spiral arms) are indicated in velocity space and may be used to find the distance and velocity to any arm, in a given longitude range. Velocity comparisons between model predictions and published CO velocity distribution are done for each galactic quadrant, with good results. Our velocimetric model is not hydromagnetic in character, nor is it a particle-simulation scheme, yet it is simple to use for comparisons with the observations and it is in symbiosis and consistent with our cartographic model (itself simple to use for comparisons with observations). A blending in velocity of the Perseus and Cygnus arms is further demonstrated, as well as an apparent longitude-velocity blending of the starting points of the four spiral arms near 4 kpc (not a physical ring). An integrated (distance, velocity) model for the mass in the disk is employed, to yield the total mass of 3.0 × 10{sup 11} M{sub ☉} within a galactic radius of 28 kpc.« less

Effect of Cage-Induced Stereotypies on Measures of Affective State and Recurrent Perseveration in CD-1 and C57BL/6 Mice

PubMed Central

Novak, Janja; Bailoo, Jeremy D.; Melotti, Luca; Würbel, Hanno

2016-01-01

Stereotypies are abnormal repetitive behaviour patterns that are highly prevalent in laboratory mice and are thought to reflect impaired welfare. Thus, they are associated with impaired behavioural inhibition and may also reflect negative affective states. However, in mice the relationship between stereotypies and behavioural inhibition is inconclusive, and reliable measures of affective valence are lacking. Here we used an exploration based task to assess cognitive bias as a measure of affective valence and a two-choice guessing task to assess recurrent perseveration as a measure of impaired behavioural inhibition to test mice with different forms and expression levels of stereotypic behaviour. We trained 44 CD-1 and 40 C57BL/6 female mice to discriminate between positively and negatively cued arms in a radial maze and tested their responses to previously inaccessible ambiguous arms. In CD-1 mice (i) mice with higher stereotypy levels displayed a negative cognitive bias and this was influenced by the form of stereotypy performed, (ii) negative cognitive bias was evident in back-flipping mice, and (iii) no such effect was found in mice displaying bar-mouthing or cage-top twirling. In C57BL/6 mice neither route-tracing nor bar-mouthing was associated with cognitive bias, indicating that in this strain these stereotypies may not reflect negative affective states. Conversely, while we found no relation of stereotypy to recurrent perseveration in CD-1 mice, C57BL/6 mice with higher levels of route-tracing, but not bar-mouthing, made more repetitive responses in the guessing task. Our findings confirm previous research indicating that the implications of stereotypies for animal welfare may strongly depend on the species and strain of animal as well as on the form and expression level of the stereotypy. Furthermore, they indicate that variation in stereotypic behaviour may represent an important source of variation in many animal experiments. PMID:27145080

Loofah-like gel network formed by the self-assembly of a 3D radially symmetrical organic-inorganic hybrid gelator.

PubMed

Tang, Guodong; Chen, Si; Ye, Feng; Xu, Xiaopeng; Fang, Jing; Wang, Xu

2014-07-11

We report a unique loofah-like gel network that is supported by the sectional type hexagonal columnar assembly of flexuous furcate fibers, which are constructed by plane-to-plane stacking of a novel 3D radially symmetrical gelator with POSS as the core and L-lysine as the arm.

Attenuation of ethanol abstinence-induced anxiety- and depressive-like behavior by the phosphodiesterase-4 inhibitor rolipram in rodents.

PubMed

Gong, Mei-Fang; Wen, Rui-Ting; Xu, Ying; Pan, Jian-Chun; Fei, Ning; Zhou, Yan-Meng; Xu, Jiang-Ping; Liang, Jian-Hui; Zhang, Han-Ting

2017-10-01

Withdrawal symptoms stand as a core feature of alcohol dependence. Our previous results have shown that inhibition of phosphodiesterase-4 (PDE4) decreased ethanol seeking and drinking in alcohol-preferring rodents. However, little is known about whether PDE4 is involved in ethanol abstinence-related behavior. The objective of this study was to characterize the role of PDE4 in the development of anxiety- and depressive-like behavior induced by abstinence from ethanol exposure in different animal models. Using three rodent models of ethanol abstinence, we examined the effects of rolipram, a prototypical, selective PDE4 inhibitor, on (1) anxiety-like behavior induced by repeated ethanol abstinence in the elevated plus maze test in fawn-hooded (FH/Wjd) rats, (2) anxiety-like behavior in the open-field test and light-dark transition test following acute ethanol abstinence in C57BL/6J mice, and (3) anxiety- and depressive-like behavior induced by protracted ethanol abstinence in the elevated plus maze, forced-swim, and tail-suspension tests in C57BL/6J mice. Pretreatment with rolipram (0.1 or 0.2 mg/kg) significantly increased entries and time spent in the open arms of the elevated plus maze test in rats with repeated ethanol abstinence. Similarly, in mice with acute ethanol abstinence, administration of rolipram (0.25 or 0.5 mg/kg) dose-dependently increased the crossings in the central zone of the open-field test and duration and transitions on the light side of the light-dark transition test, suggesting anxiolytic-like effects of rolipram. Consistent with these, chronic treatment with rolipram (0.1, 0.3, or 1.0 mg/kg) increased entries in the open arms of the elevated plus maze test; it also reduced the increased duration of immobility in both the forced-swim and tail-suspension tests in mice after protracted ethanol abstinence, suggesting antidepressant-like effects of rolipram. These results provide the first demonstration for that PDE4 plays a role in modulating the development of negative emotional reactions associated with ethanol abstinence, including anxiety and depression. PDE4 inhibitors may be a novel class of drugs for treatment of alcoholism.

Evaluation of anxiolytic and sedative effects of 80% ethanolic Carica papaya L. (Caricaceae) pulp extract in mice.

PubMed

Kebebew, Zerihun; Shibeshi, Workineh

2013-11-25

Carica papaya has been used in the Ethiopian traditional medicine to relieve stress and other disease conditions. The present study was undertaken to evaluate the anxiolytic and sedative effects of 80% ethanolic Carica papaya (Caricaceae) pulp extract in mice. Carica papaya pulp extract was screened for anxiolytic effect by using elevated plus maze, staircase and open field tests, and ketamine-induced sleeping time test for sedation at doses of 50, 100, 200, 400 mg/kg. Distilled water and Diazepam were employed as negative and positive control groups, respectively. Carica papaya pulp extract 100 mg/kg significantly increased the percentage of open arm time and entry, and reduced the percentage of entry and time spent in closed arm in elevated plus maze test; reduced the number of rearing in the staircase test; and increased the time spent and entries in the central squares while the total number of entries into the open field were not significantly affected, suggesting anxiolytic activity without altering locomotor and sedative effects. A synergistic reduction in the number of rearing and an inverted U-shaped dose response curves were obtained with important parameters of anxiety The results of this study established a support for the traditional usage of Carica papaya as anxiolytic medicinal plant. © 2013 Elsevier Ireland Ltd. All rights reserved.

Associative memory or algorithmic search: a comparative study on learning strategies of bats and shrews.

PubMed

Page, Rachel A; von Merten, Sophie; Siemers, Björn M

2012-07-01

Two common strategies for successful foraging are learning to associate specific sensory cues with patches of prey ("associative learning") and using set decision-making rules to systematically scan for prey ("algorithmic search"). We investigated whether an animal's life history affects which of these two foraging strategies it is likely to use. Natterer's bats (Myotis nattereri) have slow life-history traits and we predicted they would be more likely to use associative learning. Common shrews (Sorex araneus) have fast life-history traits and we predicted that they would rely more heavily on routine-based search. Apart from their marked differences in life-history traits, these two mammals are similar in body size, brain weight, habitat, and diet. We assessed foraging strategy, associative learning ability, and retention time with a four-arm maze; one arm contained a food reward and was marked with four sensory stimuli. Bats and shrews differed significantly in their foraging strategies. Most bats learned to associate the sensory stimuli with the reward and remembered this association over time. Most shrews searched the maze using consistent decision-making rules, but did not learn or remember the association. We discuss these results in terms of life-history traits and other key differences between these species. Our results suggest a link between an animal's life-history strategy and its use of associative learning.

The anxiolytic activity of n-3 PUFAs enriched egg yolk phospholipids in rat behavioral studies.

PubMed

Rutkowska, M; Słupski, W; Trocha, M; Szandruk, M; Rymaszewska, J

2016-11-02

Phospholipids play an important role in the biochemical and physiological processes of cells. An association between disturbed phospholipids metabolism in neuronal tissue and anxiety it was shown. The aim of this study was to examine the anxiolytic properties of phospholipids obtained from a new generation of eggs enriched in n-3 PUFA and its effect on locomotor activity in rat behavioral studies N-3 PUFA-enriched egg yolk phospholipids ("super lecithin") were added to the standard feed. Rats were fed by chow without (control group) or with (experimental group) addition of phospholipids. After six weeks of supplementation, the effect of phospholipids on locomotor activity in the open field test and anxiolytic properties in elevated plus maze and Vogel conflict test were examined. In the open field test the total distance traveled in the experimental group was similar to the control group. In the elevated plus maze test a six weeks phospholipids' administration significantly prolonged the time spent on the open arms by rats from experimental group compared to control group. The number of entries into the open arms was also increased but the difference was not statistically significant. The number of punished drinking water in the Vogel conflict test increased significantly in experimental versus control group. The obtained results suggest that the phospholipids isolated from n-3 PUFA enriched egg yolk have a specific anxiolytic effect, without general sedative influence.

Spatial Cognition and Range Use in Free-Range Laying Hens

PubMed Central

Campbell, Dana L. M.; Loh, Ziyang A.; Dyall, Tim R.; Lee, Caroline

2018-01-01

Simple Summary Individual free-range laying hens vary in their use of the outdoor range. The outdoor environment is typically more complex and variable than indoor housing and thus range use may be related to differences in spatial abilities. Individual adult hens that never went outside were slower to learn a T-maze task—which requires birds to repeatedly find a food reward in one arm of the maze, compared to outdoor-preferring hens. Pullets that were faster to learn the maze also showed more visits to the range in their first month of range access but only in one of two tested groups. Early enrichment improved learning of the maze but only when the birds were tested before onset of lay. Fear may play a role in inhibiting bird’s spatial learning and their range use. More studies of different enriched rearing treatments and their impacts on fear and learning would be needed to confirm these findings. Overall, these results contribute to our understanding of why some birds choose to never access the outdoor range area. Abstract Radio-frequency identification tracking shows individual free-range laying hens vary in range use, with some never going outdoors. The range is typically more environmentally complex, requiring navigation to return to the indoor resources. Outdoor-preferring hens may have improved spatial abilities compared to indoor-preferring hens. Experiment 1 tested 32 adult ISA Brown hens in a T-maze learning task that showed exclusively-indoor birds were slowest to reach the learning success criterion (p < 0.05). Experiment 2 tested 117 pullets from enriched or non-enriched early rearing treatments (1 pen replicate per treatment) in the same maze at 15–16 or 17–18 weeks. Enriched birds reached learning success criterion faster at 15–16 weeks (p < 0.05) but not at 17–18 weeks (p > 0.05), the age that coincided with the onset of lay. Enriched birds that were faster to learn the maze task showed more range visits in the first 4 weeks of range access. Enriched and non-enriched birds showed no differences in telencephalon or hippocampal volume (p > 0.05). Fear may reduce spatial abilities but further testing with more pen replicates per early rearing treatments would improve our understanding of the relationship between spatial cognitive abilities and range use. PMID:29419742

Leptin/LepRb in the Ventral Tegmental Area Mediates Anxiety-Related Behaviors

PubMed Central

Liu, Jing; Guo, Ming

2016-01-01

Background: Leptin, an adipose-derived hormone, has been implicated in emotional regulation. We have previously shown that systemic administration of leptin produces anxiolytic-like effects and deletion of the leptin receptor, LepRb, in midbrain dopamine neurons leads to an anxiogenic phenotype. This study investigated whether activation or deletion of LepRb in the ventral tegmental area of adult mice is capable of inducing anxiolytic and anxiogenic effects, respectively. Methods: Mice were cannulated in the ventral tegmental area and received bilateral intra-ventral tegmental area infusions of leptin or the JAK2/STAT3 inhibitor AG490. Anxiety-like behaviors were assessed using the elevated plus-maze, light-dark box, and novelty suppressed feeding tests. Deletion of LepRb in the ventral tegmental area was achieved by bilateral injection of AAV-Cre into the ventral tegmental area of adult Leprflox/flox mice. Anxiety-related behaviors were evaluated 3 weeks after viral injection. Results: Intra-ventral tegmental area infusions of leptin reduced anxiety-like behaviors, as indicated by increased percent open-arm time and open-arm entries in the elevated plus-maze test, increased time spent in the light side and decreased latency to enter the light side of the light-dark box, and decreased latency to feed in the novelty suppressed feeding test. Blockade of JAK2/STAT3 signaling in the ventral tegmental area by AG490 attenuated the anxiolytic effect produced by systemic administration of leptin. Leprflox/flox mice injected with AAV-Cre into the ventral tegmental area showed decreased leptin-induced STAT3 phosphorylation and enhanced anxiety-like behaviors in the elevated plus-maze test and the novelty suppressed feeding test. Conclusions: These findings suggest that leptin-LepRb signaling in the ventral tegmental area plays an important role in the regulation of anxiety-related behaviors. PMID:26438799

Marsh frogs, Pelophylax ridibundus, determine migratory direction by magnetic field.

PubMed

Shakhparonov, Vladimir V; Ogurtsov, Sergei V

2017-01-01

Orientation by magnetic cues appears to be adaptive during animal migrations. Whereas the magnetic orientation in birds, mammals, and urodele amphibians is being investigated intensively, the data about anurans are still scarce. This study tests whether marsh frogs could determine migratory direction between the breeding pond and the wintering site by magnetic cues in the laboratory. Adult frogs (N = 32) were individually tested in the T-maze 127 cm long inside the three-axis Helmholtz coil system (diameter 3 m). The arms of the maze were positioned parallel to the natural migratory route of this population when measured in accordance with magnetic field. The frogs were tested under two-motivational conditions mediated by temperature/light regime: the breeding migratory state and the wintering state. The frogs' choice in a T-maze was evident only when analyzed in accordance with the direction of the magnetic field: they moved along the migratory route to the breeding pond and followed the reversion of the horizontal component of the magnetic field. This preference has been detected in both sexes only in the breeding migratory state. This suggests that adult ranid frogs can obtain directional information from the Earth's magnetic field as was shown earlier in urodeles and anuran larvae.

The Neuron-Specific Protein TMEM59L Mediates Oxidative Stress-Induced Cell Death.

PubMed

Zheng, Qiuyang; Zheng, Xiaoyuan; Zhang, Lishan; Luo, Hong; Qian, Lingzhi; Fu, Xing; Liu, Yiqian; Gao, Yuehong; Niu, Mengxi; Meng, Jian; Zhang, Muxian; Bu, Guojun; Xu, Huaxi; Zhang, Yun-Wu

2017-08-01

TMEM59L is a newly identified brain-specific membrane-anchored protein with unknown functions. Herein we found that both TMEM59L and its homolog, TMEM59, are localized in Golgi and endosomes. However, in contrast to a ubiquitous and relatively stable temporal expression of TMEM59, TMEM59L expression was limited in neurons and increased during development. We also found that both TMEM59L and TMEM59 interacted with ATG5 and ATG16L1, and that overexpression of them triggered cell autophagy. However, overexpression of TMEM59L induced intrinsic caspase-dependent apoptosis more dramatically than TMEM59. In addition, downregulation of TMEM59L prevented neuronal cell death and caspase-3 activation caused by hydrogen peroxide insults and reduced the lipidation of LC3B. Finally, we found that AAV-mediated knockdown of TMEM59L in mice significantly ameliorated caspase-3 activation, increased mouse duration in the open arm during elevated plus maze test, reduced mouse immobility time during forced swim test, and enhanced mouse memory during Y-maze and Morris water maze tests. Together, our study indicates that TMEM59L is a pro-apoptotic neuronal protein involved in animal behaviors such as anxiety, depression, and memory, and that TMEM59L downregulation protects neurons against oxidative stress.

Vertical T-maze Choice Assay for Arthropod Response to Odorants

PubMed Central

Stelinski, Lukasz; Tiwari, Siddharth

2013-01-01

Given the economic importance of insects and arachnids as pests of agricultural crops, urban environments or as vectors of plant and human diseases, various technologies are being developed as control tools. A subset of these tools focuses on modifying the behavior of arthropods by attraction or repulsion. Therefore, arthropods are often the focus of behavioral investigations. Various tools have been developed to measure arthropod behavior, including wind tunnels, flight mills, servospheres, and various types of olfactometers. The purpose of these tools is to measure insect or arachnid response to visual or more often olfactory cues. The vertical T-maze oflactometer described here measures choices performed by insects in response to attractants or repellents. It is a high throughput assay device that takes advantage of the positive phototaxis (attraction to light) and negative geotaxis (tendency to walk or fly upward) exhibited by many arthropods. The olfactometer consists of a 30 cm glass tube that is divided in half with a Teflon strip forming a T-maze. Each half serves as an arm of the olfactometer enabling the test subjects to make a choice between two potential odor fields in assays involving attractants. In assays involving repellents, lack of normal response to known attractants can also be measured as a third variable. PMID:23439130

Membrane stabilizer

DOEpatents

Mingenbach, W.A.

1988-02-09

A device is provided for stabilizing a flexible membrane secured within a frame, wherein a plurality of elongated arms are disposed radially from a central hub which penetrates the membrane, said arms imposing alternately against opposite sides of the membrane, thus warping and tensioning the membrane into a condition of improved stability. The membrane may be an opaque or translucent sheet or other material. 10 figs.

Eye tracking, strategies, and sex differences in virtual navigation.

PubMed

Andersen, Nicolas E; Dahmani, Louisa; Konishi, Kyoko; Bohbot, Véronique D

2012-01-01

Reports of sex differences in wayfinding have typically used paradigms sensitive to the female advantage (navigation by landmarks) or sensitive to the male advantage (navigation by cardinal directions, Euclidian coordinates, environmental geometry, and absolute distances). The current virtual navigation paradigm allowed both men and women an equal advantage. We studied sex differences by systematically varying the number of landmarks. Eye tracking was used to quantify sex differences in landmark utilisation as participants solved an eight-arm radial maze task within different virtual environments. To solve the task, participants were required to remember the locations of target objects within environments containing 0, 2, 4, 6, or 8 landmarks. We found that, as the number of landmarks available in the environment increases, the proportion of time men and women spend looking at landmarks and the number of landmarks they use to find their way increases. Eye tracking confirmed that women rely more on landmarks to navigate, although landmark fixations were also associated with an increase in task completion time. Sex differences in navigational behaviour occurred only in environments devoid of landmarks and disappeared in environments containing multiple landmarks. Moreover, women showed sustained landmark-oriented gaze, while men's decreased over time. Finally, we found that men and women use spatial and response strategies to the same extent. Together, these results shed new light on the discrepancy in landmark utilisation between men and women and help explain the differences in navigational behaviour previously reported. Copyright © 2011 Elsevier Inc. All rights reserved.

Phenylethanoid glycosides of Pedicularis muscicola Maxim ameliorate high altitude-induced memory impairment.

PubMed

Zhou, Baozhu; Li, Maoxing; Cao, Xinyuan; Zhang, Quanlong; Liu, Yantong; Ma, Qiang; Qiu, Yan; Luan, Fei; Wang, Xianmin

2016-04-01

Exposure to hypobaric hypoxia causes oxidative stress, neuronal degeneration and apoptosis that leads to memory impairment. Though oxidative stress contributes to neuronal degeneration and apoptosis in hypobaric hypoxia, the ability for phenylethanoid glycosides of Pedicularis muscicola Maxim (PhGs) to reverse high altitude memory impairment has not been studied. Rats were supplemented with PhGs orally for a week. After the fourth day of drug administration, rats were exposed to a 7500 m altitude simulation in a specially designed animal decompression chamber for 3 days. Spatial memory was assessed by the 8-arm radial maze test before and after exposure to hypobaric hypoxia. Histological assessment of neuronal degeneration was performed by hematoxylin-eosin (HE) staining. Changes in oxidative stress markers and changes in the expression of the apoptotic marker, caspase-3, were assessed in the hippocampus. Our results demonstrated that after exposure to hypobaric hypoxia, PhGs ameliorated high altitude memory impairment, as shown by the decreased values obtained for reference memory error (RME), working memory error (WME), and total error (TE). Meanwhile, administration of PhGs decreased hippocampal reactive oxygen species levels and consequent lipid peroxidation by elevating reduced glutathione levels and enhancing the free radical scavenging enzyme system. There was also a decrease in the number of pyknotic neurons and a reduction in caspase-3 expression in the hippocampus. These findings suggest that PhGs may be used therapeutically to ameliorate high altitude memory impairment. Copyright © 2016 Elsevier Inc. All rights reserved.

Beneficial effect of etazolate on depression-like behavior and, learning, and memory impairment in a model of Parkinson's disease.

PubMed

Alzoubi, Karem H; Mokhemer, Enas; Abuirmeileh, Amjad N

2018-09-17

The aim of this study was to evaluate etazolate against depression-like behavior and, learning and memory impairment induced by 6- hydroxydopamine (6-OHDA) rat model of Parkinson's disease (PD). This aim was achieved through comparing 6-OHDA lesioned rats in the presence and absence of etazolate. The 6-OHDA was used to induce lesion as a model of PD. Etazolate was administered at a dose of 1 mg/kg/day for 14 days, starting 7 days after lesion induction. Apomorphine-induced rotation test was used to evaluate 6-OHDA-induced motor deficits, tail suspension test was used to assess depression-like symptoms, and the radial arms water maze (RAWM) was used to evaluate special learning and memory functions. Antioxidant biomarkers and BDNF protein levels were assessed in the hippocampus. Results revealed that etazolate administration significantly improved 6-OHDA-induced PD related symptoms including motor deficits, depression-like behavior and impairment of both short- and long- term memory. Moreover, etazolate significantly prevented 6-OHDA-induced reduction in oxidative stress biomarkers (GSH/GSSG ratio, GPx) and BDNF levels. In conclusion, motor dysfunction, depressive- like behavior, and learning and memory deficits in the 6-OHDA rat model of PD can be significantly prevented by etazolate. This prevention could be attributed to etazolate's ability to prevent reduction in antioxidative stress biomarkers and BDNF levels. Copyright © 2018 Elsevier B.V. All rights reserved.

Pentoxifylline prevents post-traumatic stress disorder induced memory impairment.

PubMed

Alzoubi, Karem H; Khabour, Omar F; Ahmed, Mohammed

2018-05-01

Posttraumatic stress disorder (PTSD) is a disabling prevalent and difficult-to-treat psychiatric disorder, which can develop after the exposure to severe traumatic events such as those occurring during wars and natural disasters. Pentoxifylline (PTX) is a potent antioxidant, which has an important role in prevention of cognitive dysfunctions. In the present study, the effect of PTX on memory impairment induced by PTSD was investigated using the rat animal model. PTSD-like behavior was induced in animals using a single-prolonged stress (SPS) rat model of PTSD (2 h restrain, 20 min forced swimming, 15 min rest, 1-2 min diethyl ether exposure). PTX was administered intraperitoneally at a dose of 100 mg/kg/day. Spatial learning and memory were assessed using the radial arm water maze (RAWM). Changes in oxidative stress biomarkers, brain derived neuroptrophic factor (BDNF), and epigenetics (histones) in the hippocampus following treatments were measured using enzymatic assays. The result revealed that SPS impaired both short- and long- term memory (P < 0.05). Use of PTX prevented memory impairment induced by SPS. Furthermore, PTX normalized SPS induced changes in the hippocampus GSH/GSSG ratio, activity of catalase, and glutathione peroxidase (GPx), BDNF, and certain histones levels. In conclusion, the SPS model of PTSD-like behavior induced memory impairment, whereas PTX prevented this impairment possibly through normalizing antioxidant mechanisms, BDNF and epigenetic changes in the hippocampus. Copyright © 2018 Elsevier Inc. All rights reserved.

Vitamin C prevents memory impairment induced by waterpipe smoke: role of oxidative stress.

PubMed

Alqudah, Mohammad A Y; Alzoubi, Karem H; Ma'abrih, Ghida'a M; Khabour, Omar F

2018-05-22

Waterpipe tobacco smoking (WTS) was previously shown to be associated with memory deficits, which were related to oxidative stress. Vitamin C (VitC) has established antioxidant properties against memory deficits associated with several diseases and conditions. In this study, the potential protective effect of VitC on memory impairment induced by WTS exposure was evaluated in a rat model. VitC was administered to animals via oral gavage (100 mg/kg/day, 6 days a week for 4 weeks). At the same period, animals were exposed to WTS for one hour/day, 6 days a week for 4 weeks. Using radial arm water maze (RAWM), behavioral tests were conducted to evaluate the spatial learning and memory. In addition, hippocampal levels of oxidative stress biomarkers were analyzed. WTS exposure impaired both short- and long-term memory (p < .05). On the other hand, VitC protected memory impairment induced by WTS (p < .05). Moreover, VitC prevented the reduction in hippocampus ratio of GSH/GSSG (p < .05) induced by WTS. Furthermore, WTS reduced hippocampus activity of glutathione peroxidase (GPx) and catalase, which were also normalized by VitC treatment. However, thiobarbituric acid reactive substance (TBARS) levels were not changed by WTS and/or by VitC (p > .05). In conclusion, WTS resulted in inducing memory impairment, which was prevented by VitC administration. This could be related to preserving hippocampus antioxidant mechanisms by VitC during WTS exposure.

Cotinine reduces depressive-like behavior, working memory deficits, and synaptic loss associated with chronic stress in mice.

PubMed

Grizzell, J Alex; Iarkov, Alexandre; Holmes, Rosalee; Mori, Takahashi; Echeverria, Valentina

2014-07-15

Chronic stress underlies and/or exacerbates many psychiatric conditions and often results in memory impairment as well as depressive symptoms. Such afflicted individuals use tobacco more than the general population and this has been suggested as a form of self-medication. Cotinine, the predominant metabolite of nicotine, may underlie such behavior as it has been shown to ameliorate anxiety and memory loss in animal models. In this study, we sought to investigate the effects of cotinine on working memory and depressive-like behavior in mice subjected to prolonged restraint. Cotinine-treated mice displayed better performance than vehicle-treated cohorts on the working memory task, the radial arm water maze test. In addition, with or without chronic stress exposure, cotinine-treated mice engaged in fewer depressive-like behaviors as assessed using the tail suspension and Porsolt's forced swim tests. These antidepressant and nootropic effects of cotinine were associated with an increase in the synaptophysin expression, a commonly used marker of synaptic density, in the hippocampus as well as the prefrontal and entorhinal cortices of restrained mice. The beneficial effects of cotinine in preventing various consequences of chronic stress were underscored by the inhibition of the glycogen synthase kinase 3 β in the hippocampus and prefrontal cortex. Taken together, our results show for the first time that cotinine reduces the negative effects of stress on mood, memory, and the synapse. Published by Elsevier B.V.

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.

Radial ooids from Great Salt Lake (Utah) as paleoenvironmental archives: Insights from radiocarbon chronology and stable isotopes

NASA Astrophysics Data System (ADS)

Paradis, O. P.; Corsetti, F. A.; Bardsley, A.; Hammond, D. E.; Xu, X.; Walker, J. C.

2017-12-01

Ooids (laminated, carbonate coated grains) are ubiquitous in the geologic record in marine and lacustrine settings, and thus remain a common target for geochemical analysis to understand modern and ancient aqueous environments. However, the processes governing ooid formation remain unclear. Recently, radiocarbon dating has revealed that modern marine ooids grow slowly (Beaupre et al. 2015), and laboratory experiments have highlighted the importance of sediment transport and abrasion on net growth rates and ooid size (Trower et al. 2017). Ooid cortex structure includes micritic, tangential and/or radially oriented fabrics. Most modern marine ooids have tangential or micritic cortices, whereas many ancient ooids have radial cortices—thus, there is a need to understand how radial ooids in ancient rocks might inform us about their depositional environment. The Great Salt Lake (GSL), Utah, provides a unique environment to assess the growth rate of primary radial aragonitic ooids. Ooids collected near Antelope Island in the south arm of GSL were sieved, the 355-500 µm fraction was sequentially leached, and 14C of the evolved gas was analyzed to provide a time series of growth. The oldest inorganic carbon of this size fraction has an apparent 14C age of 6600 yr BP, with subsequent growth spanning over 6,000 years. Closed-basin lakes are particularly susceptible to a "reservoir effect" which results in anomalously old apparent radiocarbon ages. The 14C age of the modern dissolved inorganic carbon (DIC) of the south arm was measured to be 295 yr BP, a reservoir age comparable to estimates from lacustrine cave carbonates (McGee et al. 2012). Net growth rate of south arm ooids ranges between 0.01-0.025 µm per year. The δ13C of the outermost cortex suggests that the ooids resemble the modern DIC in the south arm water, suggesting ooids precipitate in equilibrium with lake water. Finer-scale structure in the δ13C of the ooid cortex through time suggests lake level changed in a relative sense, with evidence for a higher lake altitude around 2700 yr BP. We conclude that 1) 14C-dating using sequential leaching methods indicates ooids began forming in Great Salt Lake over 6,000 yr BP and have continued to the present; and 2) lacustrine ooids are robust high-resolution paleoenvironmental archives when paired with radiochronology.

Effects of Acupuncture Stimulation on the Radial artery’s Pressure Pulse Wave in Healthy Young Participants: Protocol for a prospective, single-Arm, Exploratory, Clinical Study

PubMed Central

Shin, Jae-Young; Lee, Jun-Hwan; Ku, Boncho; Bae, Jang Han; un, Min-Ho; Kim, Jaeuk U.; Kim, Tae-Hun

2016-01-01

Introduction: This study aims to investigate the effects of acupuncture stimulation on the radial artery’s pressure pulse wave, along with various hemodynamic parameters, and to explore the possible underlying mechanism of pulse diagnosis in healthy participants in their twenties. Methods and analysis: This study is a prospective, single-arm, exploratory clinical study. A total of 25 healthy participants, without regard to gender, in their twenties will be recruited by physicians. Written informed consent will be obtained from all participants. The participants will receive acupuncture once at ST36 on both sides. The radial arterial pulse waves will be measured on the left arm of the subjects by using an applicable pulse tonometric device (KIOM-PAS). On the right arm (appearing twice), electrocardiogram (ECG), photoplethysmogram (PPG), respiration and cardiac output (CO) signals, will be measured using a physiological data acquisition system (Biopac module), while the velocity of blood flow, and the diameter and the depth of the blood vessel will be measured using an ultrasonogram machine on the right arm (appearing twice). All measurements will be conducted before, during, and after acupuncture. The primary outcome will be the spectral energy at high frequencies above 10 Hz (SE10-30Hz) calculated from the KIOM-PAS device signal. Secondary outcomes will be various variables obtained from the KIOM-PAS device, ECG, PPG, impedance cardiography modules, and an ultrasonogram machine. Discussion: The results of this trial will provide information regarding the physiological and the hemodynamic mechanisms underlying acupuncture stimulation and clinical evidence for the influence of acupuncture on the pressure pulse wave in the radial artery. Ethics and dissemination: This study was approved by the Institutional Review Board (IRB) of Kyung Hee University’s Oriental Medical Center, Seoul, Korea (KOMCIRB-150818-HR-030). The study findings will be published in peer-reviewed journals and presented at national and international conferences. Trial registration number: This trial was registered with the Clinical Research Information Service (CRIS) at the Korea National Institute of Health (NIH), Republic of Korea (KCT0001663), which is a registry in the World Health Organization’s (WHO’s) Registry Network. PMID:27695628

Robotic Two-Wheeled Vehicle

NASA Technical Reports Server (NTRS)

Edlund, Jeffrey E. (Inventor); Burdick, Joel (Inventor); Abad-Manterola, Pablo (Inventor); Matthews, Jaret B. (Inventor); Nesnas, Issa A. D. (Inventor)

2014-01-01

A robotic two-wheeled vehicle comprising a connection body interposed between the two wheels are described. A drum can be coaxially located in a central region of the connection body and can support a hollow arm projecting radially from the drum. A tether can be inserted in the arm and connected to a second drum. Instruments and sensors can be accommodated in a case housed inside each wheel.

Robotic Two-Wheeled Vehicle

NASA Technical Reports Server (NTRS)

Nesnas, Issa A. D. (Inventor); Matthews, Jaret B. (Inventor); Edlund, Jeffrey E. (Inventor); Burdick, Joel (Inventor); Abad-Manterola, Pablo (Inventor)

2013-01-01

A robotic two-wheeled vehicle comprising a connection body interposed between the two wheels are described. A drum can be coaxially located in a central region of the connection body and can support a hollow arm projecting radially from the drum. A tether can be inserted in the arm and connected to a second drum. Instruments and sensors can be accommodated in a case housed inside each wheel.

On the Relationship Between Generalization Error, Hypothesis Complexity, and Sample Complexity for Radial Basis Functions

DTIC Science & Technology

1994-01-01

torque general nature. We then provide in section 3 a precise at a particular joint of a robot arm , and x the set of an- statement of a specific...sampling Y according to first need to introduce some terminology and to define P(ylx). In the robot arm example described above, it a number of...mathematical objects. A summary of the would mean that one could move the robot arm into most common notations and definitions used in this pa- ’Note that

Beat-to-beat agreement of noninvasive tonometric and intra-radial arterial blood pressure during microgravity and hypergravity generated by parabolic flights.

PubMed

Normand, Hervé; Lemarchand, Erick; Arbeille, Philippe; Quarck, Gaëlle; Vaïda, Pierre; Duretete, Arnaud; Denise, Pierre

2007-12-01

Accurate measurement of beat-to-beat arterial blood pressure is essential for understanding the cardiovascular adaptation to weightlessness; however, the intra-arterial standard of beat-to-beat blood pressure measurement has never been used during space flight because of its invasive nature. The aim of the present study was to compare noninvasive radial artery tonometry blood pressure measurement with intra-radial pressure measurement during microgravity and hypergravity generated by parabolic flights. Two study participants, equipped with an intra-radial pressure line on the left arm and a Colin CBM-7000 (Colin Corp., Komaki City, Japan) beat-to-beat pressure measurement apparatus on the right arm, were studied in a supine position, during parabolic flights on board of the Airbus A300 OG of the Centre National d'Etudes Spatiales. The mean and standard deviations of the beat-to-beat difference between tonometric and intra-radial blood pressure were calculated for systolic and diastolic arterial pressure in the three gravity conditions (1g, 0 g and 1.8 g) experienced during parabolic flight. The Colin CBM-7000 met the specifications required by the Association for the Advancement of Medical Instrumentation in the 0 g environment. Gravity, however, significantly affected the difference between tonometric and intra-arterial blood pressure, possibly owing to the effect of gravity on the apparent weight of the device and the corresponding calibration factor. We conclude that the Colin CBM-7000 can be used with confidence during space flight.

Molecular docking and panicolytic effect of 8-prenylnaringenin in the elevated T-maze.

PubMed

Bagatin, Mariane Cristovão; Tozatti, Camila Santos Suniga; Abiko, Layara Akemi; Yamazaki, Diego Alberto dos Santos; Silva, Priscila Rebeca Alves; Perego, Leonardo Martins; Audi, Elisabeth Aparecida; Seixas, Flavio Augusto Vicente; Basso, Ernani Abicht; Gauze, Gisele de Freitas

2014-01-01

The purpose of this study was to investigate the effects of the chronic administration of a racemic mixture of 8-prenylnaringenin (8-PN) on rats submitted to the elevated T-maze (ETM) model of generalized anxiety and panic disorders. The selective serotonin (SERT) reuptake inhibitor fluoxetine was used as a positive control. Rat locomotion was assessed in a circular arena following each drug treatment. The administration of racemic 8-PN for 21 d in rats increased one-way escape latencies from the ETM open arm, indicating a panicolytic effect. To evaluate the interactions of 8-PN with monoamine transporters, a docking study was performed for both the R and S configurations of 8-PN towards SERT, norepinephrine (NET) and dopamine transporters (DAT). The application of the docking protocol showed that (R)-8-PN provides greater affinity to all transporters than does the S enantiomer. This result suggests that enantiomer (R)-8-PN is the active form in the in vivo test of the racemic mixture.

Distance and direction, but not light cues, support response reversal learning.

PubMed

Wright, S L; Martin, G M; Thorpe, C M; Haley, K; Skinner, D M

2018-03-05

Across three experiments, we examined the cuing properties of metric (distance and direction) and nonmetric (lighting) cues in different tasks. In Experiment 1, rats were trained on a response problem in a T-maze, followed by four reversals. Rats that experienced a change in maze orientation (Direction group) or a change in the length of the start arm (Distance group) across reversals showed facilitation of reversal learning relative to a group that experienced changes in room lighting across reversals. In Experiment 2, rats learned a discrimination task more readily when distance or direction cues were used than when light cues were used as the discriminative stimuli. In Experiment 3, performance on a go/no-go task was equivalent using both direction and lighting cues. The successful use of both metric and nonmetric cues in the go/no-go task indicates that rats are sensitive to both types of cues and that the usefulness of different cues is dependent on the nature of the task.

Orexin-A (hypocretin-1) is possibly involved in generation of anxiety-like behavior.

PubMed

Suzuki, Michiyuki; Beuckmann, Carsten T; Shikata, Kohdoh; Ogura, Hiroo; Sawai, Toru

2005-05-17

Orexins (hypocretins) are neuropeptides expressed specifically in neurons in the lateral hypothalamic area and are known to be involved in the regulation of vigilance and feeding behavior. However, the relationship between orexin and emotional behaviors like anxiety is still poorly understood. Therefore, in this report we evaluated the effect of intracerebroventricular injection of orexin-A in two major anxiety tests, the light-dark exploration test (mouse) and the elevated plus-maze test (mouse, rat). Orexin increased time spent in the dark compartment in the light-dark test and time spent on the closed arms in the elevated plus-maze test. These results were not caused by a hypothetical sedative or activity-inducing effect of orexin-A because spontaneous locomotor activity did not alter upon orexin-A application under novel conditions. We therefore suggest an anxiogenic effect of orexin-A. To our knowledge, this is the first report about a relationship between orexin-A and anxiety.

A new neural net approach to robot 3D perception and visuo-motor coordination

NASA Technical Reports Server (NTRS)

Lee, Sukhan

1992-01-01

A novel neural network approach to robot hand-eye coordination is presented. The approach provides a true sense of visual error servoing, redundant arm configuration control for collision avoidance, and invariant visuo-motor learning under gazing control. A 3-D perception network is introduced to represent the robot internal 3-D metric space in which visual error servoing and arm configuration control are performed. The arm kinematic network performs the bidirectional association between 3-D space arm configurations and joint angles, and enforces the legitimate arm configurations. The arm kinematic net is structured by a radial-based competitive and cooperative network with hierarchical self-organizing learning. The main goal of the present work is to demonstrate that the neural net representation of the robot 3-D perception net serves as an important intermediate functional block connecting robot eyes and arms.

[Change of hippocampal NMDA receptor and emotional behavior and spatial learning and memory in status epilepticus rat model].

PubMed

Wang, Wei-Ping; Lou, Yan; Li, Zhen-Zhong; Li, Pan; Duan, Rui-Sheng

2007-02-01

SD rats were utilized for the purpose of the exploration of effects of status epilepticus (SE) on their emotional behavior, spatial learning and memory, and explorating its molecular mechanism. Forty maturity male SD rats, weighing (200 +/- 20) g were divided randomly and equally into SE group (SG) and normal control group (NG). The SG rats were induced by Pentylenetetrazole (PTZ) and the control animals received a saline (0.9%) solution. The change of emotional behavior in two groups were tested in elevated plus maze. Furthermore, Morris water maze was applied to evaluate the effects by SE on spatial learning and memory in rats. At the same time, N-methyl-D-aspartate (NMDA) receptor NR1 subunit mRNA in the hippocampus was determined by reverse transcription polymerase chain reaction (RT-PCR). In elevated plus test, SE rats increased the times of visits as well as the time spent on the open arms of the elevated plus maze (P < 0.01). In Morris water maze, the mean escape latency for the SE rats looking for hidden platform in the place navigation test prolonged (P < 0.01). The efficiency of their search strategy was poor (P < 0.05). The swimming time in platform region and the percentage of their swimming time decreased (P < 0.01). The number of times they crossed the platform area decreased (P < 0.01). Meanwhile the expression of NR1 subunit mRNA in hippocampus was lower (P < 0.01). The experimental results showed that SE could result in the change of emotional behavior and damage of spatial learning and memory in rats. NR1 might be involved in the patho- and physiological process in causing these behavioral changes.

Early effects of 16O radiation on neuronal morphology and cognition in a murine model

NASA Astrophysics Data System (ADS)

Carr, Hannah; Alexander, Tyler C.; Groves, Thomas; Kiffer, Frederico; Wang, Jing; Price, Elvin; Boerma, Marjan; Allen, Antiño R.

2018-05-01

Astronauts exposed to high linear energy transfer radiation may experience cognitive injury. The pathogenesis of this injury is unknown but may involve glutamate receptors or modifications to dendritic structure and/or dendritic spine density and morphology. Glutamate is the major excitatory neurotransmitter in the central nervous system, where it acts on ionotropic and metabotropic glutamate receptors located at the presynaptic terminal and in the postsynaptic membrane at synapses in the hippocampus. Dendritic spines are sites of excitatory synaptic transmission, and changes in spine structure and dendrite morphology are thought to be morphological correlates of altered brain function associated with hippocampal-dependent learning and memory. The aim of the current study is to assess whether behavior, glutamate receptor gene expression, and dendritic structure in the hippocampus are altered in mice after early exposure to 16O radiation in mice. Two weeks post-irradiation, animals were tested for hippocampus-dependent cognitive performance in the Y-maze. During Y-maze testing, mice exposed to 0.1 Gy and 0.25 Gy radiation failed to distinguish the novel arm, spending approximately the same amount of time in all 3 arms during the retention trial. Exposure to 16O significantly reduced the expression of Nr1 and GluR1 in the hippocampus and modulated spine morphology in the dentate gyrus and cornu Ammon 1 within the hippocampus. The present data provide evidence that 16O radiation has early deleterious effects on mature neurons that are associated with hippocampal learning and memory.

Taurine induces anti-anxiety by activating strychnine-sensitive glycine receptor in vivo.

PubMed

Zhang, Cheng Gao; Kim, Sung-Jin

2007-01-01

Taurine has a variety of actions in the body such as cardiotonic, host-defensive, radioprotective and glucose-regulatory effects. However, its action in the central nervous system remains to be characterized. In the present study, we tested to see whether taurine exerts anti-anxiety effects and to explore its mechanism of anti-anxiety activity in vivo. The staircase test and elevated plus maze test were performed to test the anti-anxiety action of taurine. Convulsions induced by strychnine, picrotoxin, yohimbine and isoniazid were tested to explore the mechanism of anti-anxiety activity of taurine. The Rotarod test was performed to test muscle relaxant activity and the passive avoidance test was carried out to test memory activity in response to taurine. Taurine (200 mg/kg, p.o.) significantly reduced rearing numbers in the staircase test while it increased the time spent in the open arms as well as the number of entries to the open arms in the elevated plus maze test, suggesting that it has a significant anti-anxiety activity. Taurine's action could be due to its binding to and activating of strychnine-sensitive glycine receptor in vivo as it inhibited convulsion caused by strychnine; however, it has little effect on picrotoxin-induced convulsion, suggesting its anti-anxiety activity may not be linked to GABA receptor. It did not alter memory function and muscle activity. Taken together, these results suggest that taurine could be beneficial for the control of anxiety in the clinical situations. Copyright (c) 2007 S. Karger AG, Basel.

Effects of NMDA receptor blockade during the early development period on the retest performance of adult Wistar rats in the elevated plus maze.

PubMed

Kocahan, Sayad; Akillioglu, Kubra

2013-07-01

The elevated plus maze (EPM) is an animal model of anxiety used to test the effects of anxioselective drugs. The loss of the anxiolytic effect of drugs during the second exposure to the EPM is called the "one trial tolerance" (OTT) phenomenon. The present study was designed to investigate the relationship between the OTT phenomenon and N-methyl-D-aspartate (NMDA) receptor blockade in the early developmental period of rats. NMDA receptor blockade was accomplished using MK-801 treatment given between postnatal days 20-30. Beginning on postnatal day 20, the rats were subcutaneously injected with MK-801 twice a day at the nape of the neck for a period of 10 days (0.25 mg/kg). Increased open arm exploration was observed in MK-801-treated rats during trial 1 (p = 0.001) and trial 2 (p = 0.003). The rats spent less time in the closed arms as compared to the saline animals in trial 1 (p = 0.006), and this time decreased further in trial 2 (p = 0.02). The fecal boli of the MK-801 group was decreased in trial 1 as compared to the saline group (p = 0.01), but was not significantly different in trial 2 (p = 0.08). In conclusion, NMDA receptor blockade using MK-801 produced an anxiolytic-like effect in trials 1 and 2. Furthermore, OTT was not affected by NMDA receptor blockade.

Increased anxiety-related behavior in male and female adult rats following early and late adolescent exposure to 3,4-methylenedioxymethamphetamine (MDMA).

PubMed

Kolyaduke, Olga V; Hughes, Robert N

2013-02-01

Subsequent behavioral effects in adulthood of daily exposure to MDMA during early or late adolescence were assessed in both male and female rats. From either postnatal day (PND) 35 (early adolescence) or PND45 (late adolescence), PVG/c rats of each sex were exposed via intraperitoneal injections to saline or 10mg/kg MDMA for 10 consecutive days. They were regularly weighed during treatment and again on PND90. At this age, their anxiety-related behavior was determined from frequencies of ambulation, rearing, grooming, defecation and occupancy of the center and corners of an open field, as well as entries into and time spent in the light compartment of a light-dark box. Spatial and working memories were assessed by preferences for a novel Y-maze arm, and by recognition of a novel object. MDMA-exposed rats gained less weight during treatment than saline controls but were heavier on PND90 depending on their sex or age when treated. As shown by decreased open-field ambulation (for males only) and increased defecation plus fewer entries into the light compartment of the light-dark box and entries into both arms of a Y maze, MDMA exposure increased adult anxiety-related behavior particularly for rats treated during late adolescence. There was no evidence of any effects on either spatial or working memory. Copyright © 2012 Elsevier Inc. All rights reserved.

Modulation of elevated plus maze behavior after chronic exposure to the anabolic steroid 17alpha-methyltestosterone in adult mice.

PubMed

Rojas-Ortiz, Yoel Antonio; Rundle-González, Valerie; Rivera-Ramos, Isamar; Jorge, Juan Carlos

2006-01-01

Exposure to supraphysiological doses of androgens may disrupt affective components of behavior. In this study, behavior of adult C57Bl/6 male mice was studied after exposure to the anabolic androgenic steroid (AAS) 17alpha-methyltestosterone (17alpha-meT; 7.5 mg/kg) via a subcutaneous osmotic pump for 17 days. Controls received vehicle implants (0.9% NaCl + 30% cyclodextrine). On day 15, experimental animals were challenged with an ethanol (EtOH) injection (i.p.; 1 g/kg) while controls received saline injections. Five minutes after the injection, animals were tested in an automated elevated plus maze (EPM) or in automated activity chambers. In addition, injection-free animals were tested for ethanol consumption on day 16 after an overnight water deprivation period. Whereas chronic exposure to 17alpha-meT did not modulate open arm behavior, EtOH-exposed animals made more entries into the open arms than controls (P < 0.05). A significant reduction of risk assessment behaviors (rearing, flat approach behavior, and stretch attended posture) over the EPM was noted for EtOH-exposed animals whereas a reduction in stretch attended postures was observed among 17alpha-meT-exposed animals. Locomotor activity, and light-dark transitions in activity chambers remained unaltered. Exposure to AAS did not modulate EtOH consumption. Our data suggest that exposure to a supraphysiological dose of 17alpha-meT has minimal effects on exploratory-based anxiety.

Behavioral phenotyping of mice in pharmacological and toxicological research.

PubMed

Karl, Tim; Pabst, Reinhard; von Hörsten, Stephan

2003-07-01

The evaluation of behavioral effects is an important component for the in vivo screening of drugs or potentially toxic compounds in mice. Ideally, such screening should be composed of monitoring general health, sensory functions, and motor abilities, right before specific behavioral domains are tested. A rational strategy in the design and procedure of testing as well as an effective composition of different well-established and reproducible behavioral tests can minimize the risk of false positive and false negative results in drug screening. In the present review we describe such basic considerations in planning experiments, selecting strains of mice, and propose groups of behavioral tasks suitable for a reliable detection of differences in specific behavioral domains in mice. Screening of general health and neurophysiologic functions (reflexes, sensory abilities) and motor function (pole test, wire hang test, beam walking, rotarod, accelerod, and footprint) as well as specific hypothesis-guided testing in the behavioral domains of learning and memory (water maze, radial maze, conditioned fear, and avoidance tasks), emotionality (open field, hole board, elevated plus maze, and object exploration), nociception (tail flick, hot plate), psychiatric-like conditions (porsolt swim test, acoustic startle response, and prepulse inhibition), and aggression (isolation-induced aggression, spontaneous aggression, and territorial aggression) are described in further detail. This review is designed to describe a general approach, which increases reliability of behavioral screening. Furthermore, it provides an overview on a selection of specific procedures suitable for but not limited to behavioral screening in pharmacology and toxicology.

Effects of spiral arms on star formation in nuclear rings of barred-spiral galaxies

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

Seo, Woo-Young; Kim, Woong-Tae, E-mail: seowy@astro.snu.ac.kr, E-mail: wkim@astro.snu.ac.kr

2014-09-01

We use hydrodynamic simulations to study the effect of spiral arms on the star formation rate (SFR) in nuclear rings of barred-spiral galaxies. We find that spiral arms can be an efficient means of gas transport from the outskirts to the central parts, provided that the arms are rotating slower than the bar. While the ring star formation in models with no arms or corotating arms is active only during around the bar growth phase, arm-driven gas accretion both significantly enhances and prolongs the ring star formation in models with slow-rotating arms. The arm-enhanced SFR is larger by a factormore » of ∼3-20 than in the no-arm model, with larger values corresponding to stronger and slower arms. Arm-induced mass inflows also make dust lanes stronger. Nuclear rings in slow-arm models are ∼45% larger than in the no-arm counterparts. Star clusters that form in a nuclear ring exhibit an age gradient in the azimuthal direction only when the SFR is small, whereas no notable age gradient is found in the radial direction for models with arm-induced star formation.« less

Effects of some dopamine antagonists on spatial memory performance in rats--experimental research.

PubMed

Rusu, Gabriela; Popa, Gratiela; Ochiuz, Lacramioara; Nechifor, M; Tartau, Liliana

2014-01-01

Dopamine is a neurotransmitter with an important role in forming long-lasting memories for some time, especially in episodic memory. Literature data show that dopamine receptor stimulation may be detrimental to spatial working memory functions in lab animals. (R)-(+)-7-Chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride derivative--SCH-23390 is a synthetic compound that acts as a selective, high-affinity antagonist of D1 receptors. Experimental studies suggest that SCH 23390 may prevent the spatial working memory disturbances induced by the active substances of marijuana. Melperone is an atypic antipsychotic drug presenting also dopaminergic D2 and 5-HT2A receptor antagonistic activity. This neuroleptic agent is used in the treatment of some types of schizophrenia. Experimental research on the effects of two dopamine receptor antagonists on spatial memory performance in rats. The experiment was carried out in white Wistar rats (200-250g), divided into 3 groups of 7 animals each, treated intraperitoneally with the same volume of solution for 14 days, as follows: Group I (Control): saline solution 0.1 ml/10g kbw; Group II (coded SCH): SCH-23390 0.3 mg/kbw; Group III (coded MLP): melperone 2 mg/kbw. The dopaminergic agent spatial memory performance was assessed by recording spontaneous alternation behavior in a single session in Y-maze. Each animal was placed at the end of one arm and allowed to move freely through the maze during an 8 min session. Alternation was defined as a consecutive entry in three different arms. The alternation percentage was computed with the following formula: number of alternations divided by total number of arm visits minus 2. Data were presented as +/- standard deviation and significance was tested by SPSS Statistics for Windows version 13.0 and ANOVA method. P-values less than 0.05 were considered statistically significant compared to those in the control group. Experimental researches were carried out in compliance with the regulations of our University Committee for Research and Ethical Issues. SCH-23390 (0.3 mg/kbw) and melperone (2 mg/kbw) intraperitoneal injection for 14 days determined a statistically significant (p < 0.05 and p < 0.01, respectively) increase in spontaneous alternation rate (compared to controls in Y-maze test). Our research revealed that the 14 consecutive days administration of these two dopamine receptor antagonists was associated with the improvement of short-term memory in rats, more intense for SCH-23390 compound.

Constant lift rotor for a heavier than air craft

NASA Technical Reports Server (NTRS)

Stroub, R. H. (Inventor)

1979-01-01

A rotor blade extended radially from a hub, characterized by an elongated spar and a plurality of axially aligned shells pivotally mounted on the spar is presented. Each has an aerodynamic center located in trailing relation with the spar and supported thereby for simultaneous axial and angular displacement as centrifugal forces are applied, a pitch controller plus a plurality of pivotal pitch limiting arms transversely related to the spar. A push-pull link interconnecting the arms is used for imparting simultaneous pivotal motion, whereby the angular relationship of the arms to the spar is varied for varying the motion of the trucks along the arms for thus limiting the pitch of the segments about the spar.

Acute and long-term consequences of single MDMA administration in relation to individual anxiety levels in the rat.

PubMed

Ho, Ying-Jui; Pawlak, Cornelius R; Guo, Lianghao; Schwarting, Rainer K W

2004-03-02

Our previous work has shown that normal male Wistar rats can differ systematically in their behavioral response to the elevated plus-maze (EPM), where animals with high (HA) or low anxiety (LA) levels can be identified based on the percentage of time spent in the open arms. These animals also differ in other behavioral tests (e.g. active avoidance), and in their serotonin levels in the ventral striatum. Here, we tested whether such HA and LA rats might respond differently to the amphetamine analogue 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy"). This drug can affect psychomotor activation and anxiety; effects which are probably due to its pronounced serotonergic and dopaminergic impacts in the rat brain. Based on a routine screening procedure in the plus-maze, male Wistar rats were divided into HA and LA sub-groups, in which rectal temperature was measured. Thirty minutes after the i.p. injection of MDMA (7.5 or 15 mg/kg) or vehicle, they were again tested in the plus-maze. During the next 3 weeks, the animals underwent further behavioral tests (plus-maze, open field, active avoidance, forced swimming) to test for possible long-term consequences of MDMA. Rectal temperature was found to be higher in LA than HA rats and was especially increased with the higher dose of MDMA (15 mg/kg). In the acute plus-maze test, the lower dose of MDMA led to an anxiogenic-like profile, whereas the higher dose led to an anxiolytic-like profile, both in HA and LA rats. Possible long-term consequences of MDMA were only tested with 7.5 mg/kg MDMA, since the 15 mg/kg dose led to a high level of lethality. The analysis of open field, plus-maze (performed after 9-12 days), and forced swimming behavior (performed after 20-21 days) did not provide indications for lasting effects of MDMA. In contrast, active avoidance learning was impaired in LA- but not HA-rats treated with MDMA. A single injection of MDMA does not only have acute effects on anxiety and psychomotor activation, but can also have some prolonged or delayed task-dependent behavioral consequences. The detection of such sequels can require that individual differences are taken into account and here, determining anxiety levels in the EPM seems to serve as a useful approach.

Interaction between Antagonist of Cannabinoid Receptor and Antagonist of Adrenergic Receptor on Anxiety in Male Rat.

PubMed

Komaki, Alireza; Abdollahzadeh, Fatemeh; Sarihi, Abdolrahman; Shahidi, Siamak; Salehi, Iraj

2014-01-01

Anxiety is among the most common and treatable mental disorders. Adrenergic and cannabinoid systems have an important role in the neurobiology of anxiety. The elevated plus-maze (EPM) has broadly been used to investigate anxiolytic and anxiogenic compounds. The present study investigated the effects of intraperitoneal (IP) injection of cannabinoid CB1 receptor antagonist (AM251) in the presence of alpha-1 adrenergic antagonist (Prazosin) on rat behavior in the EPM. In this study, the data were obtained from male Wistar rat, which weighing 200- 250 g. Animal behavior in EPM were videotaped and saved in computer for 10 min after IP injection of saline, AM251 (0.3 mg/kg), Prazosin (0.3 mg/kg) and AM251 + Prazosin, subsequently scored for conventional indices of anxiety. During the test period, the number of open and closed arms entries, the percentage of entries into the open arms of the EPM, and the spent time in open and closed arms were recorded. Diazepam was considered as a positive control drug with anxiolytic effect (0.3, 0.6, 1.2 mg/kg). Diazepam increased the number of open arm entries and the percentage of spent time on the open arms. IP injection of AM251 before EPM trial decreased open arms exploration and open arm entry. Whereas, Prazosin increased open arms exploration and open arm entry. This study showed that both substances in simultaneous injection have conflicting effects on the responses of each of these two compounds in a single injection. Injection of CB1 receptor antagonist may have an anxiogenic profile in rat, whereas adrenergic antagonist has an anxiolytic effect. Further investigations are essential for better understanding of anxiolytic and anxiogenic properties and neurobiological mechanisms of action and probable interactions of the two systems.

Middle-aged, but not young, rats develop cognitive impairment and cortical neurodegeneration following the four-vessel occlusion/internal carotid artery model of chronic cerebral hypoperfusion.

PubMed

Ferreira, Emilene D Fiuza; Romanini, Cássia V; Mori, Marco A; de Oliveira, Rúbia M Weffort; Milani, Humberto

2011-10-01

Permanent, stepwise occlusion of the vertebral arteries (VAs) and internal carotid arteries (ICAs) following the sequence VA→ICA→ICA, with an interstage interval (ISI, →) of 7 days, has been investigated as a four-vessel occlusion (4-VO)/ICA model of chronic cerebral hypoperfusion. This model has the advantage of not causing retinal damage. In young rats, however, 4-VO/ICA with an ISI of 7 days fails to cause behavioral sequelae. We hypothesized that such a long ISI would allow the brain to efficiently compensate for cerebral hypoperfusion, preventing the occurrence of cognitive impairment and neurodegeneration. The present study evaluated whether brain neurodegeneration and learning/memory deficits can be expressed by reducing the length of the ISI and whether aging influences the outcome. Young, male Wistar rats were subjected to 4-VO/ICA with different ISIs (5, 4, 3 or 2 days). An ISI of 4 days was used in middle-aged rats. Ninety days after 4-VO/ICA, the rats were tested for learning/memory impairment in a modified radial maze and then examined for neurodegeneration of the hippocampus and cerebral cortex. Regardless of the ISI, young rats were not cognitively impaired, although hippocampal damage was evident. Learning/memory deficits and hippocampal and cortical neurodegeneration occurred in middle-aged rats. The data indicate that 4-VO/ICA has no impact on the capacity of young rats to learn the radial maze task, despite 51% hippocampal cell death. Such resistance is lost in middle-aged animals, for which the most extensive neurodegeneration observed in both the hippocampus and cerebral cortex may be responsible. © 2011 The Authors. European Journal of Neuroscience © 2011 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

An avulsed radial artery with a high take-off.

PubMed

Rojas-Marte, Geurys; Chen, On; Verma, Shivani; Rao, Atul; Shani, Jacob; Ayzenberg, Sergey

2015-04-01

A 63-year-old female was diagnosed with severe aortic stenosis, who underwent a diagnostic coronary angiography via transradial approach prior an aortic-valve replacement. After imaging the left coronary system, entrapment of the diagnostic catheter was encountered as a result of spasm of the radial artery. An arteriogram of the arm revealed an anatomical variation in the radial artery (high take-off). Several attempts to remove the entrapped catheter resulted in avulsion of the artery, which was managed successfully with coil embolization. To our knowledge, no such complication has been reported. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Radial Distribution of Stellar Motions in Gaia DR2

NASA Astrophysics Data System (ADS)

Kawata, Daisuke; Baba, Junichi; Ciucǎ, Ioana; Cropper, Mark; Grand, Robert J. J.; Hunt, Jason A. S.; Seabroke, George

2018-06-01

By taking advantage of the superb measurements of position and velocity for an unprecedented large number of stars provided in Gaia DR2, we have generated the first maps of the rotation velocity, Vrot, and vertical velocity, Vz, distributions as a function of the Galactocentric radius, Rgal, across a radial range of 5 < Rgal < 12 kpc. In the R - Vrot map, we have identified many diagonal ridge features, which are compared with the location of the spiral arms and the expected outer Lindblad resonance of the Galactic bar. We have detected also radial wave-like oscillations of the peak of the vertical velocity distribution.

Alzheimer disease in a mouse model: MR imaging-guided focused ultrasound targeted to the hippocampus opens the blood-brain barrier and improves pathologic abnormalities and behavior.

PubMed

Burgess, Alison; Dubey, Sonam; Yeung, Sharon; Hough, Olivia; Eterman, Naomi; Aubert, Isabelle; Hynynen, Kullervo

2014-12-01

To validate whether repeated magnetic resonance (MR) imaging-guided focused ultrasound treatments targeted to the hippocampus, a brain structure relevant for Alzheimer disease ( AD Alzheimer disease ), could modulate pathologic abnormalities, plasticity, and behavior in a mouse model. All animal procedures were approved by the Animal Care Committee and are in accordance with the Canadian Council on Animal Care. Seven-month-old transgenic (TgCRND8) (Tg) mice and their nontransgenic (non-Tg) littermates were entered in the study. Mice were treated weekly with MR imaging-guided focused ultrasound in the bilateral hippocampus (1.68 MHz, 10-msec bursts, 1-Hz burst repetition frequency, 120-second total duration). After 1 month, spatial memory was tested in the Y maze with the novel arm prior to sacrifice and immunohistochemical analysis. The data were compared by using unpaired t tests and analysis of variance with Tukey post hoc analysis. Untreated Tg mice spent 61% less time than untreated non-Tg mice exploring the novel arm of the Y maze because of spatial memory impairments (P < .05). Following MR imaging-guided focused ultrasound, Tg mice spent 99% more time exploring the novel arm, performing as well as their non-Tg littermates. Changes in behavior were correlated with a reduction of the number and size of amyloid plaques in the MR imaging-guided focused ultrasound-treated animals (P < .01). Further, after MR imaging-guided focused ultrasound treatment, there was a 250% increase in the number of newborn neurons in the hippocampus (P < .01). The newborn neurons had longer dendrites and more arborization after MR imaging-guided focused ultrasound, as well (P < .01). Repeated MR imaging-guided focused ultrasound treatments led to spatial memory improvement in a Tg mouse model of AD Alzheimer disease . The behavior changes may be mediated by decreased amyloid pathologic abnormalities and increased neuronal plasticity. © RSNA, 2014.

Electro-dynamic machine, system and method

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

Ouyang, Wen; Ramanan, Varagur

One embodiment is a unique Vernier machine comprising a rotor and a stator. The rotor comprises a back portion and a plurality of permanent magnets. The stator comprises a plurality of ferromagnetic arm structures, a plurality of ferromagnetic pole structures extending from each of the ferromagnetic arm structures in a direction toward the permanent magnets, and a plurality of conductive windings disposed about respective ones of the plurality of ferromagnetic arm structures. The ferromagnetic pole structures are structured to collect magnetic flux from the permanent magnets. The ferromagnetic pole structures of each of said ferromagnetic arm structures are spaced apartmore » from one another according to a non-uniform pattern such that the ferromagnetic pole structures of a given ferromagnetic arm structure have substantially the same angular position relative to the permanent magnets radially opposite from the ferromagnetic pole structures of the given ferromagnetic arm structure.« less

7-Nitroindazole, a neuronal nitric oxide synthase inhibitor, impairs passive-avoidance and elevated plus-maze memory performance in rats.

PubMed

Yildiz Akar, Furuzan; Ulak, Guner; Tanyeri, Pelin; Erden, Faruk; Utkan, Tijen; Gacar, Nejat

2007-10-01

The role of nitric oxide (NO) on cognitive performance in a modified elevated plus-maze (mEPM) and passive-avoidance (PA) task was investigated by using the NO synthase (NOS) inhibitor 7-nitroindazole (7-NI) and an NO precursor l-arginine. The interaction between the activation of N-methyl-d-aspartate (NMDA) receptors and NO synthesis on memory retention was also studied. 7-NI, l-arginine or MK-801, a non-competitive NMDA receptor antagonist were injected intraperitoneally (i.p) to male Wistar rats 30 min before the first training session of the PA test or 30 min before on the first day testing (acquisition session) of mEPM task. Transfer latency, the time rat took to move from the open arm to the enclosed arm, was used as an index of learning and memory in a mEPM test. The retention session was performed 24 h after the acquisition one. In the PA task, the retention test was carried out 24 h after training and reduction of retention latency was used to evaluate the acquisition of learning and memory. Blood glucose level and locomotor activity of the rats was also evaluated. 7-NI (10, 20, 25, 50 mg/kg) and MK-801 (0.15 mg/kg) significantly prolonged the transfer latency on retention session in a mEPM test and shortened step-through latency in PA test. 7-NI-induced impairment in memory and learning was partly reversed by l-arginine (200 mg/kg), a competitive substrate for NOS. However subeffective doses of 7-NI (5 mg/kg) and MK-801 (0.075 mg/kg) given in combination significantly impaired plus-maze and PA performances in rats. Thus NMDA receptor mediated NO pathways may be implicated in the PA and mEPM behaviours in rats. Since 7-NI does not affect blood pressure and did not alter blood glucose level and locomotor activity in conscious rats, 7-NI-induced impairment of memory is not due to either hypertension, changes in blood glucose level or effects on locomotor activity.

Chronic Stress Impairs Prefrontal Cortex-Dependent Response Inhibition and Spatial Working Memory

PubMed Central

Mika, Agnieszka; Mazur, Gabriel J.; Hoffman, Ann N.; Talboom, Joshua S.; Bimonte-Nelson, Heather A.; Sanabria, Federico; Conrad, Cheryl D.

2012-01-01

Chronic stress leads to neurochemical and structural alterations in the prefrontal cortex (PFC) that correspond to deficits in PFC-mediated behaviors. The present study examined the effects of chronic restraint stress on response inhibition (using a response-withholding task, fixed-minimum interval schedule of reinforcement, or FMI), and working memory (using a radial arm water maze, RAWM). Adult male Sprague Dawley rats were first trained on the RAWM and subsequently trained on FMI. Following acquisition of FMI, rats were assigned to a restraint stress (6h/d/28d in wire mesh restrainers) or control condition. Immediately after chronic stress, rats were tested on FMI and subsequently on RAWM. FMI results suggest that chronic stress reduces response inhibition capacity and motivation to initiate the task on selective conditions when food reward was not obtained on the preceding trial. RAWM results suggest that chronic stress produces transient deficits in working memory without altering previously consolidated reference memory. Behavioral measures from FMI failed to correlate with metrics from RAWM except for one in which changes in FMI timing precision negatively correlated with changes in RAWM working memory errors for the controls, a finding that was not observed following chronic stress. Fisher’s r to z transformation revealed no significant differences between control and stress with correlation coefficients. These findings are the first to show that chronic stress impairs both response inhibition and working memory, two behaviors that have never been direct compared within the same animals following chronic stress, using FMI, an appetitive task, and RAWM, a non-appetitive task. PMID:22905921

Maternal choline supplementation improves spatial mapping and increases basal forebrain cholinergic neuron number and size in aged Ts65Dn mice.

PubMed

Ash, Jessica A; Velazquez, Ramon; Kelley, Christy M; Powers, Brian E; Ginsberg, Stephen D; Mufson, Elliott J; Strupp, Barbara J

2014-10-01

Down syndrome (DS) is marked by intellectual disability (ID) and early-onset of Alzheimer's disease (AD) neuropathology, including basal forebrain cholinergic neuron (BFCN) degeneration. The present study tested the hypothesis that maternal choline supplementation (MCS) improves spatial mapping and protects against BFCN degeneration in the Ts65Dn mouse model of DS and AD. During pregnancy and lactation, dams were assigned to either a choline sufficient (1.1g/kg choline chloride) or choline supplemented (5.0g/kg choline chloride) diet. Between 13 and 17months of age, offspring were tested in the radial arm water maze (RAWM) to examine spatial mapping followed by unbiased quantitative morphometry of BFCNs. Spatial mapping was significantly impaired in unsupplemented Ts65Dn mice relative to normal disomic (2N) littermates. Additionally, a significantly lower number and density of medial septum (MS) hippocampal projection BFCNs was also found in unsupplemented Ts65Dn mice. Notably, MCS significantly improved spatial mapping and increased number, density, and size of MS BFCNs in Ts65Dn offspring. Moreover, the density and number of MS BFCNs correlated significantly with spatial memory proficiency, providing support for a functional relationship between these behavioral and morphometric effects of MCS for trisomic offspring. Thus, increasing maternal choline intake during pregnancy may represent a safe and effective treatment approach for expectant mothers carrying a DS fetus, as well as a possible means of BFCN neuroprotection during aging for the population at large. Copyright © 2014 Elsevier Inc. All rights reserved.

Chronic traumatic stress impairs memory in mice: Potential roles of acetylcholine, neuroinflammation and corticotropin releasing factor expression in the hippocampus.

PubMed

Bhakta, Ami; Gavini, Kartheek; Yang, Euitaek; Lyman-Henley, Lani; Parameshwaran, Kodeeswaran

2017-09-29

Chronic stress in humans can result in multiple adverse psychiatric and neurobiological outcomes, including memory deficits. These adverse outcomes can be more severe if each episode of stress is very traumatic. When compared to acute or short term stress relatively little is known about the effects of chronic traumatic stress on memory and molecular changes in hippocampus, a brain area involved in memory processing. Here we studied the effects of chronic traumatic stress in mice by exposing them to adult Long Evan rats for 28 consecutive days and subsequently analyzing behavioral outcomes and the changes in the hippocampus. Results show that stressed mice developed memory deficits when assayed with radial arm maze tasks. However, chronic traumatic stress did not induce anxiety, locomotor hyperactivity or anhedonia. In the hippocampus of stressed mice interleukin-1β protein expression was increased along with decreased corticotropin releasing hormone (CRH) gene expression. Furthermore, there was a reduction in acetylcholine levels in the hippocampus of stressed mice. There were no changes in brain derived neurotrophic factor (BDNF) or nerve growth factor (NGF) levels in the hippocampus of stressed mice. Gene expression of immediate early genes (Zif268, Arc, C-Fos) as well as glucocorticoid and mineralocorticoid receptors were also not affected by chronic stress. These data demonstrate that chronic traumatic stress followed by a recovery period might lead to development of resilience resulting in the development of selected, most vulnerable behavioral alterations and molecular changes in the hippocampus. Copyright © 2017 Elsevier B.V. All rights reserved.

R-flurbiprofen improves tau, but not Aß pathology in a triple transgenic model of Alzheimer's disease

PubMed Central

Carreras, Isabel; McKee, Ann C.; Choi, Ji-Kyung; Aytan, Nurgul; Kowall, Neil W.

2013-01-01

We have previously reported that chronic ibuprofen treatment improves cognition and decreases intracellular Aß and phosphorylated-tau levels in 3xTg-AD mice. Ibuprofen is a non-steroidal anti-inflammatory drug (NSAID) that independently of its anti-inflammatory effects has anti-amyloidogenic activity as a gamma-secretase modulator (GSM) and both activities have the potential to decrease Aß pathology. To further understand the effects of NSAIDs in 3xTg-AD mice, we treated 3xTg-AD mice with R-flurbiprofen, an enantiomer of the NSAID flurbiprofen that maintains the GSM activity but has greatly reduced anti-inflammatory activity, and analyzed its effect on cognition, Aß, tau, and the neurochemical profile of the hippocampus. Treatment with R-flurbiprofen from 5 to 7 months of age resulted in improved cognition on the radial arm water maze (RAWM) test and decreased the level of hyperphosphorylated tau immunostained with AT8 and PHF-1 antibodies. No significant changes in the level of Aß (using 6E10 and NU-1 antibodies) were detected. Using magnetic resonance spectroscopy (MRS) we found that R-flurbiprofen treatment decreased the elevated level of glutamine in 3xTg-AD mice down to the level detected in non-transgenic mice. Glutamine levels correlated with PHF-1 immunostained hyperphosphorylated tau. We also found an inverse correlation between the concentration of glutamate and learning across all the mice in the study. Glutamine and glutamate, neurochemicals that shuttles between neurons and astrocytes to maintain glutamate homeostasis in the synapses, deserve further attention as MR markers of cognitive function. PMID:24161403

Intranasal deferoxamine engages multiple pathways to decrease memory loss in the APP/PS1 model of amyloid accumulation.

PubMed

Fine, Jared M; Renner, Daniel B; Forsberg, Anna C; Cameron, Rachel A; Galick, Benjamin T; Le, Clint; Conway, Patrick M; Stroebel, Benjamin M; Frey, William H; Hanson, Leah R

2015-01-01

In addition to the hallmark accumulation of amyloid and hyper-phosphorylation of tau, brain changes in Alzheimer's disease are multifactorial including inflammation, oxidative stress, and metal dysregulation. Metal chelators have been explored as a less well known approach to treatment. One chelator currently being developed is deferoxamine (DFO), administered via the intranasal (IN) route. In the current study, APP/PS1 amyloid mice were treated with a chronic, low dose of IN DFO, subjected to a rigorous battery of behavior tests, and the mechanism of action was examined. Mice were treated 3x/week with 0.24 C IN DFO for 18 weeks from 36 to 54 weeks of age, 4 weeks of behavior tests were performed that included both working and reference memory, anxiolytic and motor behaviors, and finally brain tissues were analyzed for amyloid, protein oxidation, and other proteins affected by DFO. We found that IN DFO treatment significantly decreased loss of both reference and working memory in the Morris and radial arm water mazes (p < 0.05), and also decreased soluble Aβ40 and Aβ42 in cortex and hippocampus (p < 0.05). Further, IN DFO decreased activity of GSK3β, and led to decreases in oxidative stress (p < 0.05). These data demonstrate that low doses of IN DFO can modify several targets along the multiple pathways implicated in the neuropathology of Alzheimer's, making it an attractive candidate for the treatment of this heterogeneous disease. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

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.

The ventral hippocampus, but not the dorsal hippocampus is critical for learned approach-avoidance decision making.

PubMed

Schumacher, Anett; Vlassov, Ekaterina; Ito, Rutsuko

2016-04-01

The resolution of an approach-avoidance conflict induced by ambivalent information involves the appraisal of the incentive value of the outcomes and associated stimuli to orchestrate an appropriate behavioral response. Much research has been directed at delineating the neural circuitry underlying approach motivation and avoidance motivation separately. Very little research, however, has examined the neural substrates engaged at the point of decision making when opposing incentive motivations are experienced simultaneously. We hereby examine the role of the dorsal and ventral hippocampus (HPC) in a novel approach-avoidance decision making paradigm, revisiting a once popular theory of HPC function, which posited the HPC to be the driving force of a behavioral inhibition system that is activated in situations of imminent threat. Rats received pre-training excitotoxic lesions of the dorsal or ventral HPC, and were trained to associate different non-spatial cues with appetitive, aversive and neutral outcomes in three separate arms of the radial maze. On the final day of testing, a state of approach-avoidance conflict was induced by simultaneously presenting two cues of opposite valences, and comparing the time the rats spent interacting with the superimposed 'conflict' cue, and the neutral cue. The ventral HPC-lesioned group showed significant preference for the conflict cue over the neutral cue, compared to the dorsal HPC-lesioned, and control groups. Thus, we provide evidence that the ventral, but not dorsal HPC, is a crucial component of the neural circuitry concerned with exerting inhibitory control over approach tendencies under circumstances in which motivational conflict is experienced. © 2015 Wiley Periodicals, Inc.

Low-dose pterostilbene, but not resveratrol, is a potent neuromodulator in aging and Alzheimer's disease.

PubMed

Chang, Jaewon; Rimando, Agnes; Pallas, Merce; Camins, Antoni; Porquet, David; Reeves, Jennifer; Shukitt-Hale, Barbara; Smith, Mark A; Joseph, James A; Casadesus, Gemma

2012-09-01

Recent studies have implicated resveratrol and pterostilbene, a resveratrol derivative, in the protection against age-related diseases including Alzheimer's disease (AD). However, the mechanism for the favorable effects of resveratrol in the brain remains unclear and information about direct cross-comparisons between these analogs is rare. As such, the purpose of this study was to compare the effectiveness of diet-achievable supplementation of resveratrol to that of pterostilbene at improving functional deficits and AD pathology in the SAMP8 mouse, a model of accelerated aging that is increasingly being validated as a model of sporadic and age-related AD. Furthermore we sought to determine the mechanism of action responsible for functional improvements observed by studying cellular stress, inflammation, and pathology markers known to be altered in AD. Two months of pterostilbene diet but not resveratrol significantly improved radial arm water maze function in SAMP8 compared with control-fed animals. Neither resveratrol nor pterostilbene increased sirtuin 1 (SIRT1) expression or downstream markers of sirtuin 1 activation. Importantly, markers of cellular stress, inflammation, and AD pathology were positively modulated by pterostilbene but not resveratrol and were associated with upregulation of peroxisome proliferator-activated receptor (PPAR) alpha expression. Taken together our findings indicate that at equivalent and diet-achievable doses pterostilbene is a more potent modulator of cognition and cellular stress than resveratrol, likely driven by increased peroxisome proliferator-activated receptor alpha expression and increased lipophilicity due to substitution of hydroxy with methoxy group in pterostilbene. Copyright © 2012 Elsevier Inc. All rights reserved.

Facilitation of the Cognitive Enhancing Effects of Working Memory Training Through Conjoint Voluntary Aerobic Exercise

PubMed Central

Smith, Andrew M.; Spiegler, Kevin M.; Sauce, Bruno; Wass, Christopher D.; Sturzoiu, Tudor; Matzel, Louis D.

2013-01-01

Increases in performance on tests of attention and learning are often observed shortly after a period of aerobic exercise, and evidence suggests that humans who engage in regular exercise are partially protected from age-related cognitive decline. However, the cognitive benefits of exercise are typically short-lived, limiting the practical application of these observations. We explored whether physical exercise would induce lasting changes in general cognitive ability if that exercise was combined with working memory training, which is purported to broadly impact on cognitive performance. Mice received either exercise (six weeks of voluntary running wheel access), working memory training, both treatments, or various control treatments. Near the completion of this period of exercise, working memory training (in a dual radial-arm maze) was initiated (alternating with days of exercise), and was continued for several weeks. Upon completion of these treatments, animals were assessed (2–4 weeks later) for performance on four diverse learning tasks, and the aggregate performance of individual animals across all four learning tasks was estimated. Working memory training alone promoted small increases in general cognitive performance, although any beneficial effects of exercise alone had dissipated by the time of learning assessments. However, the two treatments in combination more than doubled the improvement in general cognitive performance supported by working memory training alone. Unlike the transient effects that acute aerobic exercise can have on isolated learning tasks, these results indicate that an acute period of exercise combined with working memory training can have synergistic and lasting impact on general cognitive performance. PMID:24036169

Maternal choline supplementation improves spatial mapping and increases basal forebrain cholinergic neuron number and size in aged Ts65Dn mice

PubMed Central

Ash, Jessica A.; Velazquez, Ramon; Kelley, Christy M.; Powers, Brian E.; Ginsberg, Stephen D.; Mufson, Elliott J.; Strupp, Barbara J.

2014-01-01

Down syndrome (DS) is marked by intellectual disability (ID) and early-onset of Alzheimer’s disease (AD) neuropathology, including basal forebrain cholinergic neuron (BFCN) degeneration. The present study tested the hypothesis that maternal choline supplementation (MCS) lessens hippocampal dysfunction and protects against BFCN degeneration in the Ts65Dn mouse model of DS and AD. During pregnancy and lactation, dams were assigned to either a choline sufficient (1.1 g/kg choline chloride) or choline supplemented (5.0 g/kg choline chloride) diet. Between 13 and 17 months of age, offspring were tested in the radial arm water maze (RAWM) to examine spatial learning and memory followed by unbiased quantitative morphometry of BFCNs. Spatial mapping was significantly impaired in unsupplemented Ts65Dn mice relative to normal disomic (2N) littermates. Additionally, a significantly lower number and density of medial septum (MS) hippocampal projection BFCNs was also found in unsupplemented Ts65Dn mice. Notably, MCS significantly improved spatial mapping and increased number, density, and size of MS BFCNs in Ts65Dn offspring. Moreover, the density and number of MS BFCNs correlated significantly with spatial memory proficiency, providing powerful support for a functional relationship between these behavioral and morphometric effects of MCS for the trisomic offspring. Thus, increasing maternal choline intake during pregnancy may represent a safe and effective treatment approach for expectant mothers carrying a DS fetus, as well as a possible means of BFCN neuroprotection during aging for the population at large. PMID:24932939

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

Errors made by animals in memory paradigms are not always due to failure of memory.

PubMed

Wilkie, D M; Willson, R J; Carr, J A

1999-01-01

It is commonly assumed that errors in animal memory paradigms such as delayed matching to sample, radial mazes, and food-cache recovery are due to failures in memory for information necessary to perform the task successfully. A body of research, reviewed here, suggests that this is not always the case: animals sometimes make errors despite apparently being able to remember the appropriate information. In this paper a case study of this phenomenon is described, along with a demonstration of a simple procedural modification that successfully reduced these non-memory errors, thereby producing a better measure of memory.

Changes in the bilateral pulse transit time difference with a moving arm.

PubMed

Jiang, Xinge; Wei, Shoushui; Zheng, Dingchang; Huang, Peng; Liu, Chengyu

2018-04-20

Changes of pulse transit time (PTT) induced by arm position were studied for unilateral arm. However, consistency of the PTT changes was not validated for both arm sides. We aimed to quantify the PTT changes between horizontal and non-horizontal positions from right arm and left arm in order to explore the consistency of both arms. Twenty-four normal subjects aged between 21 and 50 (14 male and 10 female) years were enrolled. Left and right radial artery pulses were synchronously recorded from 24 healthy subjects with one arm (left or right) at five angles (90∘, 45∘, 0∘, -45∘ and -90∘) and the other arm at the horizontal level (0∘) for reference. The overall mean PTT changes at the five angles (from 90∘ to -90∘) in the left arm (right as reference) were 16.1, 12.3, -0.5, -2.5 and -2.6 ms, respectively, and in the right arm (left as reference) were 18.0, 12.6, 1.6, -1.6 and -2.0 ms, respectively. Obvious differences were not found in the PTT changes between the two arms (left arm moving or right arm moving) under each of the five different positions (all P> 0.05).

A solid-state control system for dynein-based ciliary/flagellar motility

PubMed Central

2013-01-01

Ciliary and flagellar beating requires the coordinated action of multiple dyneins with different enzymatic and motor properties. In this issue, Yamamoto et al. (2013. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201211048) identify the MIA (modifier of inner arms) complex within the Chlamydomonas reinhardtii axoneme that physically links to a known regulatory structure and provides a signaling conduit from the radial spokes to an inner arm dynein essential for waveform determination. PMID:23569213

Protective effect of exercise and sildenafil on acute stress and cognitive function.

PubMed

Ozbeyli, Dilek; Gokalp, Ayse Gizem; Koral, Tolga; Ocal, Onur Yuksel; Dogan, Berkay; Akakin, Dilek; Yuksel, Meral; Kasimay, Ozgur

2015-11-01

There are contradictory results about the effects of exercise and sildenafil on cognitive functions. To investigate the effects of sildenafil pretreatment and chronic exercise on anxiety and cognitive functions. Wistar rats (n=42) were divided as sedentary and exercise groups. A moderate-intensity swimming exercise was performed for 6 weeks, 5 days/week, 1h/day. Some of the rats were administered orogastrically with sildenafil (25mg/kg/day) either acutely or chronically. Exposure to cat odor was used for induction of stress. The level of anxiety was evaluated by elevated plus maze test, while object recognition test was used to determine cognitive functions. Brain tissues were removed for the measurement of myeloperoxidase (MPO), malondialdehyde (MDA), nitric oxide levels, lucigenin-enhanced chemiluminescence, and for histological analysis. Increased MPO and MDA levels in sedentary-stressed rats were decreased with sildenafil applications. Chronic exercise inhibited the increase in MPO levels. Increased nitric oxide and lucigenin chemiluminescence levels in sedentary-stressed rats, were diminished with chronic sildenafil pretreatment. The time spent in the open arms of the plus maze was declined in sedentary-stressed rats, while chronic sildenafil pretreatment increased the time back to that in non-stressed rats. Acute sildenafil application to exercised rats prolonged the time spent in open arms as compared to non-treated exercise group. The time spent with the novel object, which was decreased in sedentary-stressed rats, was increased with sildenafil pretreatment. Our results suggest that sildenafil pretreatment or exercise exerts a protective effect against acute stress and improves cognitive functions by decreasing oxidative damage. Copyright © 2015 Elsevier Inc. All rights reserved.

Anxiolytic-like effect of hydrogen sulfide (H2S) in rats exposed and re-exposed to the elevated plus-maze and open field tests.

PubMed

Donatti, Alberto Ferreira; Soriano, Renato Nery; Leite-Panissi, Christie Ramos Andrade; Branco, Luiz G S; de Souza, Albert Schiaveto

2017-03-06

Hydrogen sulfide (H 2 S), an endogenous gaseous mediator, modulates many physiological functions in mammals but evidence of its involvement in emotional and behavioral aspects is currently scarce. We hypothesized that this gas plays a modulatory role in behavioral parameters in rats submitted to tests (for 5min) in the open field (OF) and elevated plus-maze (EPM - test and retest). Male Wistar rats (200-250g) were intraperitoneally injected with saline or Na 2 S (a H 2 S donor; 4, 8 and 12mg/kg) either once or for 8days, and submitted to the OF test or to the EPM test and retest. A third group (naïve) was not injected but exposed to the same experimental protocols. In the OF test, Na 2 S injected for 8days caused a decrease in self-cleaning (4, 8 and 12mg/kg) and freezing behaviors (8 and 12mg/kg), and a rise in the rate of line crossings in the central part of the arena (12mg/kg). In the EPM test and retest, Na 2 S at 12mg/kg for 8days caused an increase in the number of open arm entries and in the percentage of time spent on open arms. Our data are consistent with the notion that H 2 S exerts anxiolytic-like effects in rats submitted to the EPM and OF tests. Moreover, this gaseous modulator reduces aversive learning in the EPM retest. Copyright © 2017 Elsevier B.V. All rights reserved.

Anxiolytic effects of orcinol glucoside and orcinol monohydrate in mice.

PubMed

Wang, Xiaohong; Li, Guiyun; Li, Peng; Huang, Linyuan; Huang, Jianmei; Zhai, Haifeng

2015-06-01

Anxiety is a common psychological disorder, often occurring in combination with depression, but therapeutic drugs with high efficacy and safety are lacking. Orcinol glucoside (OG) was recently found to have an antidepressive action. To study the therapeutic potential of OG and orcinol monohydrate (OM) as anxiolytic agents. Anxiolytic effects in mice were measured using the elevated plus-maze, hole-board, and open-field tests. Eight groups of mice were included in each test. Thirty minutes before each test, mice in each group received one oral administration of OG (5, 10, or 20 mg/kg), OM (2.5, 5, or 10 mg/kg), the positive control diazepam (1 or 5 mg/kg), or control vehicle. Each mouse underwent only one test. Uptake of orcinol (5 mg/kg) in the brain was qualitatively detected using the HPLC-MS method. OG (5, 10, and 20 mg/kg) and OM (2.5 and 5 mg/kg) increased the time spent in open arms and the number of entries into open arms in the elevated plus-maze test. OG (5 and 10 mg/kg) and OM (2.5 and 5 mg/kg) increased the number of head-dips in the hole-board test. At all tested doses, OG and OM did not significantly affect the locomotion of mice in the open-field test. Orcinol could be detected in the mouse brain homogenates 30 min after oral OM administration, having confirmed that OM is centrally active. The results demonstrated that OG and OM are anxiolytic agents without sedative effects, indicating their therapeutic potential for anxiety.

Memory modulates journey-dependent coding in the rat hippocampus

PubMed Central

Ferbinteanu, J.; Shirvalkar, P.; Shapiro, M. L.

2011-01-01

Neurons in the rat hippocampus signal current location by firing in restricted areas called place fields. During goal-directed tasks in mazes, place fields can also encode past and future positions through journey-dependent activity, which could guide hippocampus-dependent behavior and underlie other temporally extended memories, such as autobiographical recollections. The relevance of journey-dependent activity for hippocampal-dependent memory, however, is not well understood. To further investigate the relationship between hippocampal journey-dependent activity and memory we compared neural firing in rats performing two mnemonically distinct but behaviorally identical tasks in the plus maze: a hippocampus-dependent spatial navigation task, and a hippocampus-independent cue response task. While place, prospective, and retrospective coding reflected temporally extended behavioral episodes in both tasks, memory strategy altered coding differently before and after the choice point. Before the choice point, when discriminative selection of memory strategy was critical, a switch between the tasks elicited a change in a field’s coding category, so that a field that signaled current location in one task coded pending journeys in the other task. After the choice point, however, when memory strategy became irrelevant, the fields preserved coding categories across tasks, so that the same field consistently signaled either current location or the recent journeys. Additionally, on the start arm firing rates were affected at comparable levels by task and journey, while on the goal arm firing rates predominantly encoded journey. The data demonstrate a direct link between journey-dependent coding and memory, and suggest that episodes are encoded by both population and firing rate coding. PMID:21697365

Valeriana officinalis does not alter the orofacial dyskinesia induced by haloperidol in rats: role of dopamine transporter.

PubMed

Fachinetto, Roselei; Villarinho, Jardel G; Wagner, Caroline; Pereira, Romaiana P; Avila, Daiana Silva; Burger, Marilise E; Calixto, João Batista; Rocha, João B T; Ferreira, Juliano

2007-10-01

Chronic treatment with classical neuroleptics in humans can produce a serious side effect, known as tardive dyskinesia (TD). Here, we examined the effects of V. officinalis, a medicinal herb widely used as calming and sleep-promoting, in an animal model of orofacial dyskinesia (OD) induced by long-term treatment with haloperidol. Adult male rats were treated during 12 weeks with haloperidol decanoate (38 mg/kg, i.m., each 28 days) and with V. officinalis (in the drinking water). Vacuous chewing movements (VCMs), locomotor activity and plus maze performance were evaluated. Haloperidol treatment produced VCM in 40% of the treated rats and the concomitant treatment with V. officinalis did not alter either prevalence or intensity of VCMs. The treatment with V. officinalis increased the percentage of the time spent on open arm and the number of entries into open arm in the plus maze test. Furthermore, the treatment with haloperidol and/or V. officinalis decreased the locomotor activity in the open field test. We did not find any difference among the groups when oxidative stress parameters were evaluated. Haloperidol treatment significantly decreased [(3)H]-dopamine uptake in striatal slices and V. officinalis was not able to prevent this effect. Taken together, our data suggest a mechanism involving the reduction of dopamine transport in the maintenance of chronic VCMs in rats. Furthermore, chronic treatment with V. officinalis seems not produce any oxidative damage to central nervous system (CNS), but it also seems to be devoid of action to prevent VCM, at least in the dose used in this study.

Memory deficit and reduced anxiety in young adult rats given repeated intermittent MDMA treatment during the periadolescent period.

PubMed

Piper, Brian J; Meyer, Jerrold S

2004-12-01

3,4-Methylenedioxymethamphetamine (MDMA, or "Ecstasy") is a popular recreational drug among adolescents that is often taken primarily on weekends. The goals of this study were to develop a model of the typical intermittent pattern of human MDMA use in periadolescent rats and to determine the behavioral consequences of MDMA exposure in this model. Male Sprague-Dawley rats received s.c. injections of 10 mg/kg of MDMA or saline twice daily with an interdose interval of 4 h. Treatments were given every fifth day from postnatal day (PD) 35 to PD 60. Beginning at PD 65, the animals were tested for open-field activity, object recognition memory, and anxiety-related behaviors in the elevated plus-maze. Brain tissues were collected at PD 70 for determination of radiolabeled paroxetine binding to the serotonin transporter (SERT) in the neocortex and hippocampus. Repeated MDMA administration led to a reduced rate of weight gain that was evident by PD 50. There was no treatment effect on ambulatory behavior in the open-field. However, the MDMA group displayed an impairment of object recognition memory and reduced anxiety as indicated by a twofold increase in open-arm duration in the elevated plus-maze. Only modest decreases in SERT binding were observed, although there was a significant negative correlation between hippocampal SERT levels and open-arm duration within the MDMA group. These findings demonstrate that intermittent MDMA exposure during the adolescent period of development can influence subsequent cognitive and affective functioning in the absence of severe serotonergic damage.

Differential behavioral outcomes of 3,4-methylenedioxymethamphetamine (MDMA-ecstasy) in anxiety-like responses in mice.

PubMed

Ferraz-de-Paula, V; Stankevicius, D; Ribeiro, A; Pinheiro, M L; Rodrigues-Costa, E C; Florio, J C; Lapachinske, S F; Moreau, R L M; Palermo-Neto, J

2011-05-01

Anxiolytic and anxiogenic-like behavioral outcomes have been reported for methylenedioxymethamphetamine (MDMA or ecstasy) in rodents. In the present experiment, we attempted to identify behavioral, hormonal and neurochemical outcomes of MDMA treatment to clarify its effects on anxiety-related responses in 2-month-old Balb/c male mice (25-35 g; N = 7-10 mice/group). The behavioral tests used were open field, elevated plus maze, hole board, and defensive behavior against predator odor. Moreover, we also determined striatal dopamine and dopamine turnover, and serum corticosterone levels. MDMA was injected ip at 0.2, 1.0, 5.0, 8.0, 10, or 20 mg/kg. MDMA at 10 mg/kg induced the following significant (P < 0.05) effects: a) a dose-dependent increase in the distance traveled and in the time spent moving in the open field; b) decreased exploratory activity in the hole board as measured by number of head dips and time spent in head dipping; c) increased number of open arm entries and increased time spent in open arm exploration in the elevated plus maze; d) increased time spent away from an aversive stimulus and decreased number of risk assessments in an aversive odor chamber; e) increased serum corticosterone levels, and f) increased striatal dopamine level and turnover. Taken together, these data suggest an anxiogenic-like effect of acute MDMA treatment, despite the fact that behavioral anxiety expression was impaired in some of the behavioral tests used as a consequence of the motor stimulating effects of MDMA.

Modulation of stress-induced neurobehavioral changes and brain oxidative injury by nitric oxide (NO) mimetics in rats.

PubMed

Gulati, Kavita; Chakraborti, Ayanabha; Ray, Arunabha

2007-11-02

The present study evaluated the effects of NO mimetics on stress-induced neurobehavioral changes and the possible involvement of ROS-RNS interactions in rats. Restraint stress (RS) suppressed both percent open arm entries and time spent in the open arms in the elevated plus maze (EPM) test. These RS-induced changes in EPM activity were attenuated by the NO mimetics, l-arginine, isosorbide dinitrate and molsidomine, in a differential manner. RS-exposed rats showed (a) increased lipid peroxidation (MDA) and (b) lowered reduced glutathione (GSH) and NO metabolites (NOx), in brain homogenates of these animals. Pretreatment with the NO mimetics also differentially influenced RS-induced changes in brain oxidative stress markers. The results suggest that NO may protect against stress-induced anxiogenic behavior and oxidative injury in the brain and highlight the significance of ROS-RNS interactions.

The humeral origin of the brachioradialis muscle: an unusual site of high radial nerve compression.

PubMed

Cherchel, A; Zirak, C; De Mey, A

2013-11-01

Radial nerve compression is seldom encountered in the upper arm, and most commonly described compression syndromes have their anatomical cause in the forearm. The teres major, the triceps muscle, the intermuscular septum region and the space between the brachialis and brachioradialis muscles have all been identified as radial nerve compression sites above the elbow. We describe the case of a 38-year-old male patient who presented with dorso-lateral forearm pain and paraesthesias without neurological deficit. Surgical exploration revealed radial nerve compression at the humeral origin of the brachioradialis muscle. Liberation of the nerve at this site was successful at relieving the symptoms. To our knowledge, this compression site has not been described in the literature. Copyright © 2013 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Acute closed radial nerve injury

PubMed Central

Tuncel, Umut; Turan, Aydin; Kostakoglu, Naci

2011-01-01

We present a 45-year-old patient who had acute radial nerve palsy following a blunt trauma without any fracture or dislocation. He was injured by strucking in a combat three months ago. The patient has been followed by application of a long-arm plaster cast before referred to our clinic. Preoperative electromyoneurography and magnetic resonance imaging (MRI) indicated that there was a radial nerve injury on humeral groove. The British Medical Research Council (MRC) grade was 2/5 on his wrist preoperatively. The patient underwent an operation under general anesthesia. It was seen to be a second-degree nerve injury. The patient has subsequently regained full movement on his wrist and finger extension in six months. We suggest that a detailed clinical and electrodiagnostical evaluation is necessary in patients who have radial nerve injury when deciding the treatment, conservative or surgical. PMID:22347334

Interlimb Reflexes Induced by Electrical Stimulation of Cutaneous Nerves after Spinal Cord Injury

PubMed Central

Butler, Jane E.; Godfrey, Sharlene; Thomas, Christine K.

2016-01-01

Whether interlimb reflexes emerge only after a severe insult to the human spinal cord is controversial. Here the aim was to examine interlimb reflexes at rest in participants with chronic (>1 year) spinal cord injury (SCI, n = 17) and able-bodied control participants (n = 5). Cutaneous reflexes were evoked by delivering up to 30 trains of stimuli to either the superficial peroneal nerve on the dorsum of the foot or the radial nerve at the wrist (5 pulses, 300 Hz, approximately every 30 s). Participants were instructed to relax the test muscles prior to the delivery of the stimuli. Electromyographic activity was recorded bilaterally in proximal and distal arm and leg muscles. Superficial peroneal nerve stimulation evoked interlimb reflexes in ipsilateral and contralateral arm and contralateral leg muscles of SCI and control participants. Radial nerve stimulation evoked interlimb reflexes in the ipsilateral leg and contralateral arm muscles of control and SCI participants but only contralateral leg muscles of control participants. Interlimb reflexes evoked by superficial peroneal nerve stimulation were longer in latency and duration, and larger in magnitude in SCI participants. Interlimb reflex properties were similar for both SCI and control groups for radial nerve stimulation. Ascending interlimb reflexes tended to occur with a higher incidence in participants with SCI, while descending interlimb reflexes occurred with a higher incidence in able-bodied participants. However, the overall incidence of interlimb reflexes in SCI and neurologically intact participants was similar which suggests that the neural circuitry underlying these reflexes does not necessarily develop after central nervous system injury. PMID:27049521

Conservative treatment of an acute traumatic extensor carpi ulnaris tendon subluxation in a collegiate basketball player: a case report.

PubMed

Patterson, Steve M; Picconatto, William J; Alexander, Julie A; Johnson, Rachel L

2011-01-01

To present the case of an acute traumatic extensor carpi ulnaris (ECU) subluxation in a National Collegiate Athletic Association Division II female basketball player. The ECU tendon is stabilized in the ulnar groove by a subsheath located inferior to the extensor retinaculum. The subsheath can be injured with forced supination, ulnar deviation, and wrist flexion, resulting in the ECU tendon subluxing in the palmar and ulnar directions during wrist circumduction. Several methods of intervention exist, but controversy remains on how to best treat this condition. Distal ulnar fracture, ulnar collateral ligament sprain, triangular fibrocartilage complex lesion, lunotriquetral instability, distal radioulnar joint injury, pisotriquetral joint injury, ECU tendinopathy or subluxation. The wrist was placed in a short-arm cast in slight extension and radial deviation for 4 weeks. At that time, the patient was still able to actively sublux the ECU tendon, so a long-arm cast was applied with the wrist in slight extension, radial deviation, and pronation for an additional 4 weeks. The ECU tendon was then found to be stable. She wore a rigid wrist brace for 3 more weeks while she pursued rehabilitation. At the final follow-up appointment, the ECU tendon remained stable, and the wrist was asymptomatic. Subluxations of the ECU are rare. If the patient does not improve with conservative measures, surgical intervention is warranted to repair the sixth dorsal compartment. A long-arm cast with the elbow flexed to 90° and the wrist in approximately 30° of extension, radial deviation, and pronation was appropriate treatment for this type of injury.

Effects of Electromagnetic Radiation from Smartphones on Learning Ability and Hippocampal Progenitor Cell Proliferation in Mice.

PubMed

Choi, Yu-Jin; Choi, Yun-Sik

2016-02-01

Nonionizing radiation is emitted from electronic devices, such as smartphones. In this study, we intended to elucidate the effect of electromagnetic radiation from smartphones on spatial working memory and progenitor cell proliferation in the hippocampus. Both male and female mice were randomly separated into two groups (radiated and control) and the radiated group was exposed to electromagnetic radiation for 9 weeks and 11 weeks for male and female mice, respectively. Spatial working memory was examined with a Y maze, and proliferation of hippocampal progenitor cells were examined by 5-bromo-2'-deoxyuridine administration and immunohistochemical detection. When spatial working memory on a Y maze was examined in the 9(th) week, there was no significant difference in the spontaneous alternation score on the Y maze between the two groups. In addition, there was no significant difference in hippocampal progenitor cell proliferation. However, immunoreactivity to glial fibrillary acidic protein was increased in exposed animals. Next, to test the effect of recovery following chronic radiation exposure, the remaining female mice were further exposed to electromagnetic radiation for 2 more weeks (total 11 weeks), and spontaneous alternation was tested 4 weeks later. In this experiment, although there was no significant difference in the spontaneous alternation scores, the number of arm entry was significantly increased. These data indicate that although chronic electromagnetic radiation does not affect spatial working memory and hippocampal progenitor cell proliferation it can mediate astrocyte activation in the hippocampus and delayed hyperactivity-like behavior.

1-Oleoyl Lysophosphatidic Acid: A New Mediator of Emotional Behavior in Rats

PubMed Central

Castilla-Ortega, Estela; Escuredo, Leticia; Bilbao, Ainhoa; Pedraza, Carmen; Orio, Laura; Estivill-Torrús, Guillermo; Santín, Luis J.; de Fonseca, Fernando Rodríguez; Pavón, Francisco Javier

2014-01-01

The role of lysophosphatidic acid (LPA) in the control of emotional behavior remains to be determined. We analyzed the effects of the central administration of 1-oleoyl-LPA (LPA 18∶1) in rats tested for food consumption and anxiety-like and depression-like behaviors. For this purpose, the elevated plus-maze, open field, Y maze, forced swimming and food intake tests were performed. In addition, c-Fos expression in the dorsal periaqueductal gray matter (DPAG) was also determined. The results revealed that the administration of LPA 18∶1 reduced the time in the open arms of the elevated plus-maze and induced hypolocomotion in the open field, suggesting an anxiogenic-like phenotype. Interestingly, these effects were present following LPA 18∶1 infusion under conditions of novelty but not under habituation conditions. In the forced swimming test, the administration of LPA 18∶1 dose-dependently increased depression-like behavior, as evaluated according to immobility time. LPA treatment induced no effects on feeding. However, the immunohistochemical analysis revealed that LPA 18∶1 increased c-Fos expression in the DPAG. The abundant expression of the LPA1 receptor, one of the main targets for LPA 18∶1, was detected in this brain area, which participates in the control of emotional behavior, using immunocytochemistry. These findings indicate that LPA is a relevant transmitter potentially involved in normal and pathological emotional responses, including anxiety and depression. PMID:24409327

NMDA/glutamate mechanism of magnesium-induced anxiolytic-like behavior in mice.

PubMed

Poleszak, Ewa; Wlaź, Piotr; Wróbel, Andrzej; Fidecka, Sylwia; Nowak, Gabriel

2008-01-01

The anxiolytic-like activity of magnesium in mice during the elevated plus maze (EPM) has been demonstrated previously. In the present study, we examined the involvement of NMDA/glutamate receptor ligands on the magnesium effect on the EPM. We demonstrated that low, ineffective doses of NMDA antagonists (the competitive NMDA antagonist CGP 37849, 0.3 mg/kg; an antagonist of the glycineB sites, L-701,324, 1 mg/kg; a partial agonist of the glycineB sites, D-cycloserine, 2.5 mg/kg; and the non-competitive NMDA antagonist MK-801, 0.05 mg/kg) administered together with an ineffective dose of magnesium (10 mg/kg) evoked a significant increase in the percentage of time spent in the open arm of the maze (an index of anxiety). Moreover, magnesium-induced anxiolytic-like activity (20 mg/kg) was antagonized by D-serine (100 nmol/mouse), an agonist of glycineB site of the NMDA receptor complex. The present study demonstrates the involvement of the NMDA/glutamate pathway in the magnesium anxiolytic-like activity in the EPM in mice, and that this activity particularly involves the glycineB sites.

Surgical anatomy of the radial nerve at the elbow.

PubMed

Artico, M; Telera, S; Tiengo, C; Stecco, C; Macchi, V; Porzionato, A; Vigato, E; Parenti, A; De Caro, R

2009-02-01

An anatomical study of the brachial portion of the radial nerve with surgical implications is proposed. Thirty specimens of arm from 20 fresh cadavers (11 male, 9 female) were used to examine the topographical relations of the radial nerve with reference to the following anatomical landmarks: acromion angle, medial and lateral epicondyles, point of division between the lateral and long heads of the triceps brachii, lateral intermuscular septum, site of division of the radial nerve into its superficial and posterior interosseous branches and entry and exit point of the posterior interosseous branch into the supinator muscle. The mean distances between the acromion angle and the medial and lateral levels of crossing the posterior aspect of the humerus were 109 (+/-11) and 157 (+/-11) mm, respectively. The mean length and calibre of the nerve in the groove were 59 (+/-4) and 6 (+/-1) mm, respectively. The division of the lateral and long heads of the triceps was found at a mean distance of 126 (+/-13) mm from the acromion angle. The mean distances between the lateral point of crossing the posterior aspect of the humerus and the medial and lateral epicondyles were 125 (+/-13) and 121 (+/-13) mm, respectively. The mean distance between the lateral point of crossing the posterior aspect of the humerus and the entry point in the lateral intermuscular septum (LIS) was 29 (+/-6) mm. The mean distances between the entry point of the nerve in the LIS and the medial and lateral epicondyles were 133 (+/-14) and 110 (+/-23) mm, respectively. Our study provides reliable and objective data of surgical anatomy of the radial nerve which should be always kept in mind by surgeons approaching to the surgery of the arm, in order to avoid iatrogenic injuries.

The complex simplicity of the brittle star nervous system.

PubMed

Zueva, Olga; Khoury, Maleana; Heinzeller, Thomas; Mashanova, Daria; Mashanov, Vladimir

2018-01-01

Brittle stars (Ophiuroidea, Echinodermata) have been increasingly used in studies of animal behavior, locomotion, regeneration, physiology, and bioluminescence. The success of these studies directly depends on good working knowledge of the ophiuroid nervous system. Here, we describe the arm nervous system at different levels of organization, including the microanatomy of the radial nerve cord and peripheral nerves, ultrastructure of the neural tissue, and localization of different cell types using specific antibody markers. We standardize the nomenclature of nerves and ganglia, and provide an anatomically accurate digital 3D model of the arm nervous system as a reference for future studies. Our results helped identify several general features characteristic to the adult echinoderm nervous system, including the extensive anatomical interconnections between the ectoneural and hyponeural components, neuroepithelial organization of the central nervous system, and the supporting scaffold of the neuroepithelium formed by radial glial cells. In addition, we provide further support to the notion that the echinoderm radial glia is a complex and diverse cell population. We also tested the suitability of a range of specific cell-type markers for studies of the brittle star nervous system and established that the radial glial cells are reliably labeled with the ERG1 antibodies, whereas the best neuronal markers are acetylated tubulin, ELAV, and synaptotagmin B. The transcription factor Brn1/2/4 - a marker of neuronal progenitors - is expressed not only in neurons, but also in a subpopulation of radial glia. For the first time, we describe putative ophiuroid proprioceptors associated with the hyponeural part of the central nervous system. Together, our data help establish both the general principles of neural architecture common to the phylum Echinodermata and the specific ophiuroid features.

Bioinspired locomotion and grasping in water: the soft eight-arm OCTOPUS robot.

PubMed

Cianchetti, M; Calisti, M; Margheri, L; Kuba, M; Laschi, C

2015-05-13

The octopus is an interesting model for the development of soft robotics, due to its high deformability, dexterity and rich behavioural repertoire. To investigate the principles of octopus dexterity, we designed an eight-arm soft robot and evaluated its performance with focused experiments. The OCTOPUS robot presented here is a completely soft robot, which integrates eight arms extending in radial direction and a central body which contains the main processing units. The front arms are mainly used for elongation and grasping, while the others are mainly used for locomotion. The robotic octopus works in water and its buoyancy is close to neutral. The experimental results show that the octopus-inspired robot can walk in water using the same strategy as the animal model, with good performance over different surfaces, including walking through physical constraints. It can grasp objects of different sizes and shapes, thanks to its soft arm materials and conical shape.

Early postnatal effects of noopept and piracetam on declarative and procedural memory of adult male and female rats.

PubMed

Trofimov, S S; Voronina, T A; Guzevatykh, L S

2005-06-01

We studied the effect of a new nootropic dipeptide Noopept and reference nootropic preparation piracetam injected subcutaneously on days 8-20 of life on learning of alternative feeding response in a 6-arm-maze in male and female rats. Early postnatal administration of Noopept disturbed the dynamics of learning by parameters of declarative and procedural memory. Piracetam impaired learning by parameters of procedural, but not declarative memory (only in males). Both preparations decreased the ratio of successfully learned males (but not females). The observed effects were not associated with changes in locomotor activity.

Harmane induces anxiolysis and antidepressant-like effects in rats.

PubMed

Aricioglu, Feyza; Altunbas, Hale

2003-12-01

A forced swim test (FST) and an elevated plus maze (EPM) were used to determine antidepressant and anxiolytic effects of harmane in rats in comparison with a known antidepressant, imipramine (30 mg/kg i.p.). Harmane (2.5, 5.0, or 10 mg/kg, i.p.), saline, or imipramine were given 30 minutes before the tests. Administration of harmane decreased the time of immobility in the FST dose-dependently and increased the time spent in open arms in the EPM, as compared with the saline group. As an endogenous substance, harmane therefore has anti-anxiety and antidepressant effects.

Gut microbiota composition is correlated to grid floor induced stress and behavior in the BALB/c mouse.

PubMed

Bangsgaard Bendtsen, Katja Maria; Krych, Lukasz; Sørensen, Dorte Bratbo; Pang, Wanyong; Nielsen, Dennis Sandris; Josefsen, Knud; Hansen, Lars H; Sørensen, Søren J; Hansen, Axel Kornerup

2012-01-01

Stress has profound influence on the gastro-intestinal tract, the immune system and the behavior of the animal. In this study, the correlation between gut microbiota composition determined by Denaturing Grade Gel Electrophoresis (DGGE) and tag-encoded 16S rRNA gene amplicon pyrosequencing (454/FLX) and behavior in the Tripletest (Elevated Plus Maze, Light/Dark Box, and Open Field combined), the Tail Suspension Test, and Burrowing in 28 female BALB/c mice exposed to two weeks of grid floor induced stress was investigated. Cytokine and glucose levels were measured at baseline, during and after exposure to grid floor. Stressing the mice clearly changed the cecal microbiota as determined by both DGGE and pyrosequencing. Odoribacter, Alistipes and an unclassified genus from the Coriobacteriaceae family increased significantly in the grid floor housed mice. Compared to baseline, the mice exposed to grid floor housing changed the amount of time spent in the Elevated Plus Maze, in the Light/Dark Box, and burrowing behavior. The grid floor housed mice had significantly longer immobility duration in the Tail Suspension Test and increased their number of immobility episodes from baseline. Significant correlations were found between GM composition and IL-1α, IFN-γ, closed arm entries of Elevated Plus Maze, total time in Elevated Plus Maze, time spent in Light/Dark Box, and time spent in the inner zone of the Open Field as well as total time in the Open Field. Significant correlations were found to the levels of Firmicutes, e.g. various species of Ruminococccaceae and Lachnospiraceae. No significant difference was found for the evaluated cytokines, except an overall decrease in levels from baseline to end. A significant lower level of blood glucose was found in the grid floor housed mice, whereas the HbA1c level was significantly higher. It is concluded that grid floor housing changes the GM composition, which seems to influence certain anxiety-related parameters.

Analysis of emotionality and locomotion in radio-frequency electromagnetic radiation exposed rats.

PubMed

Narayanan, Sareesh Naduvil; Kumar, Raju Suresh; Paval, Jaijesh; Kedage, Vivekananda; Bhat, M Shankaranarayana; Nayak, Satheesha; Bhat, P Gopalakrishna

2013-07-01

In the current study the modulatory role of mobile phone radio-frequency electromagnetic radiation (RF-EMR) on emotionality and locomotion was evaluated in adolescent rats. Male albino Wistar rats (6-8 weeks old) were randomly assigned into the following groups having 12 animals in each group. Group I (Control): they remained in the home cage throughout the experimental period. Group II (Sham exposed): they were exposed to mobile phone in switch-off mode for 28 days, and Group III (RF-EMR exposed): they were exposed to RF-EMR (900 MHz) from an active GSM (Global system for mobile communications) mobile phone with a peak power density of 146.60 μW/cm(2) for 28 days. On 29th day, the animals were tested for emotionality and locomotion. Elevated plus maze (EPM) test revealed that, percentage of entries into the open arm, percentage of time spent on the open arm and distance travelled on the open arm were significantly reduced in the RF-EMR exposed rats. Rearing frequency and grooming frequency were also decreased in the RF-EMR exposed rats. Defecation boli count during the EPM test was more with the RF-EMR group. No statistically significant difference was found in total distance travelled, total arm entries, percentage of closed arm entries and parallelism index in the RF-EMR exposed rats compared to controls. Results indicate that mobile phone radiation could affect the emotionality of rats without affecting the general locomotion.

[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.

Analysis of Multi-Arm Caliper Data for the U.S. Strategic Petroleum Reserve

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

Roberts, Barry L.

The U.S. Strategic Petroleum Reserve (SPR) has an increasing reliance on mul t i - arm caliper surveys to assess the integrity of casing for cavern access wells and to determine priorities for casing remediation. Multi - arm caliper (MAC) surveys provide a view of well casing deformation by reporting radial measurements of the inner cas ing wall as the tool is drawn through the casing. Over the last several years the SPR has collected a large number of modern MAC surveys. In total, these surveys account for over 100 million individual measurements. The surveys were collected using diff eringmore » survey vendors and survey hardware. This has resulted in a collection of disparate data sets which confound attempts to make well - to - well or time - dependent evaluations. In addition, the vendor supplied MAC interpretations often involve variables wh ich are not well defined or which may not be applicable to casings for cavern access wells. These factors reduce the usability of these detailed data sets. In order to address this issue and provide an independent analysis of multi - arm caliper survey data, Sandia National Labs has developed processing techniques and analysis variables which allow for the comparison of MAC survey data regardless of the source of the survey data. These techniques use the raw radial arm information and newly developed analysis variables to assess the casing status and provide a means for well - to - well and time - dependent analyses. Well - to - well and t ime - dependent investigation of the MAC survey data provide s information to prioritize well remediation activities and identify wells with integrity issues. This paper presents the challenges in using disparate MAC survey data, techniques developed to address these challenges and some o f the insights gained from these new techniques.« less

Dust-trapping Vortices and a Potentially Planet-triggered Spiral Wake in the Pre-transitional Disk of V1247 Orionis

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

Kraus, Stefan; Kreplin, Alexander; Young, Alison K.

The radial drift problem constitutes one of the most fundamental problems in planet formation theory, as it predicts particles to drift into the star before they are able to grow to planetesimal size. Dust-trapping vortices have been proposed as a possible solution to this problem, as they might be able to trap particles over millions of years, allowing them to grow beyond the radial drift barrier. Here, we present ALMA 0.″04 resolution imaging of the pre-transitional disk of V1247 Orionis that reveals an asymmetric ring as well as a sharply confined crescent structure, resembling morphologies seen in theoretical models ofmore » vortex formation. The asymmetric ring (at 0.″17 = 54 au separation from the star) and the crescent (at 0.″38 = 120 au) seem smoothly connected through a one-armed spiral-arm structure that has been found previously in scattered light. We propose a physical scenario with a planet orbiting at ∼0.″3 ≈ 100 au, where the one-armed spiral arm detected in polarized light traces the accretion stream feeding the protoplanet. The dynamical influence of the planet clears the gap between the ring and the crescent and triggers two vortices that trap millimeter-sized particles, namely, the crescent and the bright asymmetry seen in the ring. We conducted dedicated hydrodynamics simulations of a disk with an embedded planet, which results in similar spiral-arm morphologies as seen in our scattered-light images. At the position of the spiral wake and the crescent we also observe {sup 12}CO(3-2) and H{sup 12}CO{sup +} (4-3) excess line emission, likely tracing the increased scale-height in these disk regions.« less

Dust-trapping Vortices and a Potentially Planet-triggered Spiral Wake in the Pre-transitional Disk of V1247 Orionis

NASA Astrophysics Data System (ADS)

Kraus, Stefan; Kreplin, Alexander; Fukugawa, Misato; Muto, Takayuki; Sitko, Michael L.; Young, Alison K.; Bate, Matthew R.; Grady, Carol; Harries, Tim T.; Monnier, John D.; Willson, Matthew; Wisniewski, John

2017-10-01

The radial drift problem constitutes one of the most fundamental problems in planet formation theory, as it predicts particles to drift into the star before they are able to grow to planetesimal size. Dust-trapping vortices have been proposed as a possible solution to this problem, as they might be able to trap particles over millions of years, allowing them to grow beyond the radial drift barrier. Here, we present ALMA 0.″04 resolution imaging of the pre-transitional disk of V1247 Orionis that reveals an asymmetric ring as well as a sharply confined crescent structure, resembling morphologies seen in theoretical models of vortex formation. The asymmetric ring (at 0.″17 = 54 au separation from the star) and the crescent (at 0.″38 = 120 au) seem smoothly connected through a one-armed spiral-arm structure that has been found previously in scattered light. We propose a physical scenario with a planet orbiting at ˜0.″3 ≈ 100 au, where the one-armed spiral arm detected in polarized light traces the accretion stream feeding the protoplanet. The dynamical influence of the planet clears the gap between the ring and the crescent and triggers two vortices that trap millimeter-sized particles, namely, the crescent and the bright asymmetry seen in the ring. We conducted dedicated hydrodynamics simulations of a disk with an embedded planet, which results in similar spiral-arm morphologies as seen in our scattered-light images. At the position of the spiral wake and the crescent we also observe 12CO(3-2) and H12CO+ (4-3) excess line emission, likely tracing the increased scale-height in these disk regions.

In vivo administration of extracellular cGMP normalizes TNF-α and membrane expression of AMPA receptors in hippocampus and spatial reference memory but not IL-1β, NMDA receptors in membrane and working memory in hyperammonemic rats.

PubMed

Cabrera-Pastor, Andrea; Hernandez-Rabaza, Vicente; Taoro-Gonzalez, Lucas; Balzano, Tiziano; Llansola, Marta; Felipo, Vicente

2016-10-01

Patients with hepatic encephalopathy (HE) show working memory and visuo-spatial orientation deficits. Hyperammonemia is a main contributor to cognitive impairment in HE. Hyperammonemic rats show impaired spatial learning and learning ability in the Y maze. Intracerebral administration of extracellular cGMP restores learning in the Y-maze. The underlying mechanisms remain unknown. It also remains unknown whether extracellular cGMP improves neuroinflammation or restores spatial learning in hyperammonemic rats and if it affects differently reference and working memory. The aims of this work were: Spatial working and reference memory were assessed using the radial and Morris water mazes and neuroinflammation by immunohistochemistry and Western blot. Membrane expression of NMDA and AMPA receptor subunits was analyzed using the BS3 crosslinker. Extracellular cGMP was administered intracerebrally using osmotic minipumps. Chronic hyperammonemia induces neuroinflammation in hippocampus, with astrocytes activation and increased IL-1β, which are associated with increased NMDA receptors membrane expression and impaired working memory. This process is not affected by extracellular cGMP. Hyperammonemia also activates microglia and increases TNF-α, alters membrane expression of AMPA receptor subunits (increased GluA1 and reduced GluA2) and impairs reference memory. All these changes are reversed by extracellular cGMP. These results show that extracellular cGMP modulates spatial reference memory but not working memory. This would be mediated by modulation of TNF-α levels and of membrane expression of GluA1 and GluA2 subunits of AMPA receptors. Copyright © 2016 Elsevier Inc. All rights reserved.

The Effects of Inflammatory Tooth Pain on Anxiety in Adult Male Rats

PubMed Central

Raoof, Maryam; Ebrahimnejad, Hamed; Abbasnejad, Mehdi; Amirkhosravi, Ladan; Raoof, Ramin; Esmaeili Mahani, Saeed; Ramazani, Mohsen; Shokouhinejad, Noushin; Khoshkhounejad, Mehrfam

2016-01-01

Introduction: This study aimed to examine the effects of induced inflammatory tooth pain on anxiety level in adult male rats. Methods: The mandibular incisors of 56 adult male rats were cut off and prefabricated crowns were fixed on the teeth. Formalin and capsaicin were injected intradentally to induce inflammatory tooth pain. Diazepam treated group received diazepam 30 minutes before intradental injection. The anxiety-related behavior was evaluated with elevated plus maze test. Results: Intradental application of chemical noxious stimuli, capsaicin and formalin, significantly affected nociceptive behaviors (P<0.001). Capsaicin (P<0.001) and formalin (P<0.01) significantly increased the anxiety levels in rats by decrease in the duration of time spent in open arm and increase in the duration of time spent in closed arm. Rats that received capsaicin made fewer open arm entries compared to the control animals (P<0.05). Capsaicin (P<0.001) and formalin (P<0.01) treated rats showed more stretch attend postures compared to the control and sham operated animals. In diazepampretreated rats, capsaicin induced algesic effect was prevented (P<0.001). Conclusion: Inflammatory pulpal pain has anxiogenic effect on rats, whereas diazepam premedication showed both anxiolytic and pain reducing effects. PMID:27563419

The relationship of prenatal ethanol exposure and anxiety-related behaviors and central androgen receptor and vasopressin expression in adult male mandarin voles.

PubMed

He, F

2014-04-25

Prenatal exposure to ethanol has been shown to increase the risk of anxiety in offspring. Here, we tested the effect of prenatal ethanol exposure on adult male mandarin voles (Microtus mandarinus). We examined anxiety-like behavior in the open field and elevated plus-maze tests in males exposed to ethanol prenatally. One control group was not exposed to ethanol or saline, while another control group was exposed to saline. At the age of 90days, males were tested and levels of serum testosterone, androgen receptor immunoreactive neurons (AR-IRs) and arginine vasopressin immunoreactive neurons (AVP-IRs) were measured. Animals exposed to ethanol spent less time in the center of the chamber, covered less distance and conducted fewer crossings in the open-field test. These animals also spent less time and conducted fewer crossings in the open arms. However, they spent more time and made more entries in the closed arms, and traveled less total distance during the elevated plus-maze test, compared to the control voles. Serum T was lower in the ethanol group, and the AR-IR number in the bed nucleus of the stria terminalis (BNST), medial preoptic area (mPOA) and medial amygdaloid nucleus (MeA) was significantly lower. The number of AVP-IRs in the paraventricular nucleus (PVN) and supraoptic nucleus (SON) of the ethanol group was higher than that of the control groups. Our findings suggest that prenatal ethanol exposure may lead to reduced serum T levels, decreased AR and increased AVP in the CNS and result in the development of anxiety-like behaviors. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

Strychnine and Taurine Modulation of Amygdala-associated Anxiety-like Behavior is ‘State’ Dependent

PubMed Central

McCool, Brian A.; Chappell, Ann

2007-01-01

Strychnine-sensitive glycine receptors are expressed in many adult forebrain regions, yet the biological function of these receptors outside the spinal cord/brainstem is poorly understood. We have recently shown that rat lateral/basolateral amygdala neurons express strychnine-sensitive glycine-gated currents whose pharmacological and molecular characteristics are consistent with those established for classic ligand-gated chloride channels. The current studies were undertaken to establish the behavioral role, if any, of these strychnine-sensitive glycine receptors. Adult Long-Evans male rats were implanted with guide cannulae targeted at the lateral amygdala and were micro-injected with standard artificial cerebrospinal fluid with or without various doses of strychnine or taurine. Anxiety-like behaviors were assessed with the elevated plus-maze or the light/dark box. In the elevated plus maze, strychnine decreased closed-arm time and increased open-arm time, suggestive of an anxiolytic effect. Similarly, strychnine produced a modest anxiolytic effect in the light/dark box. Post-hoc analysis of ‘open-arm’ time and ‘light-side’ time indicated that aCSF-treated animals were distributed into two apparent groups that displayed either high or low amounts of anxiety-like behavior in a given apparatus. Surprisingly, the pharmacological effects of both strychnine and taurine in these assays were dependent upon a given animal’s behavioral phenotype. Together, these findings are significant because they suggest that the basal ‘emotional state’ of the animal could influence the behavioral outcome associated with drug application directly into the lateral/basolateral amygdala. Furthermore, our findings also suggest that compounds acting at amygdala strychnine-sensitive glycine receptors may actively modulate this basal anxiety-like state. PMID:17207866

The Effects of 4-Methylethcathinone on Conditioned Place Preference, Locomotor Sensitization, and Anxiety-Like Behavior: A Comparison with Methamphetamine.

PubMed

Xu, Peng; Qiu, Yi; Zhang, Yizhi; Βai, Yanping; Xu, Pengfei; Liu, Yuan; Kim, Jee Hyun; Shen, Hao-wei

2016-04-01

4-Methylethcathinone is a drug that belongs to the second generation of synthetic cathinones, and recently it has been ranked among the most popular "legal highs". Although it has similar in vitro neurochemical actions to other drugs such as cocaine, the behavioral effects of 4-methylethcathinone remain to be determined. The addictive potential and locomotor potentiation by 4-methylethcathinone were investigated in rats using the conditioned place preference and sensitization paradigm. Methamphetamine was used as a positive control. Because synthetic cathinones can have psychological effects, we also examined anxiety-like behavior using the elevated plus maze. A conditioning dose of 10 mg/kg 4-methylethcathinone was able to induce conditioned place preference and reinstatement (following 2 weeks of withdrawal). Acute or repeated injections of 4-methylethcathinone at 3 or 10mg/kg failed to alter locomotor activity. At 30 mg/kg, however, acute 4-methylethcathinone increased locomotor activity compared with saline, while chronic 4-methylethcathinone induced a delayed and attenuated sensitization compared with methamphetamine. Additionally, repeated daily injections of 4-methylethcathinone (30 mg/kg) reduced, whereas methamphetamine increased time spent by rats in the open arm of an elevated plus maze compared with saline injections. Interestingly, a 2-week withdrawal period following chronic injections of 4-methylethcathinone or methamphetamine increased time spent in the open arm in all rats. The rewarding properties of 4-methylethcathinone were found to be dissociated from its effects on locomotor activity. Additionally, chronic 4-methylethcathinone use may trigger abnormal anxious behaviors. These behavioral effects caused by 4-methylethcathinone appear to last even after a withdrawal period. © The Author 2015. Published by Oxford University Press on behalf of CINP.

Activation of G-protein-coupled receptor 30 is sufficient to enhance spatial recognition memory in ovariectomized rats.

PubMed

Hawley, Wayne R; Grissom, Elin M; Moody, Nicole M; Dohanich, Gary P; Vasudevan, Nandini

2014-04-01

In ovariectomized rats, administration of estradiol, or selective estrogen receptor agonists that activate either the α or β isoforms, have been shown to enhance spatial cognition on a variety of learning and memory tasks, including those that capitalize on the preference of rats to seek out novelty. Although the effects of the putative estrogen G-protein-coupled receptor 30 (GPR30) on hippocampus-based tasks have been reported using food-motivated tasks, the effects of activation of GPR30 receptors on tasks that depend on the preference of rats to seek out spatial novelty remain to be determined. Therefore, the aim of the current study was to determine if short-term treatment of ovariectomized rats with G-1, an agonist for GPR30, would mimic the effects on spatial recognition memory observed following short-term estradiol treatment. In Experiment 1, ovariectomized rats treated with a low dose (1 μg) of estradiol 48 h and 24 h prior to the information trial of a Y-maze task exhibited a preference for the arm associated with the novel environment on the retention trial conducted 48 h later. In Experiment 2, treatment of ovariectomized rats with G-1 (25 μg) 48 h and 24 h prior to the information trial of a Y-maze task resulted in a greater preference for the arm associated with the novel environment on the retention trial. Collectively, the results indicated that short-term treatment of ovariectomized rats with a GPR30 agonist was sufficient to enhance spatial recognition memory, an effect that also occurred following short-term treatment with a low dose of estradiol. Copyright © 2014 Elsevier B.V. All rights reserved.

Highly Palatable Food during Adolescence Improves Anxiety-Like Behaviors and Hypothalamic-Pituitary-Adrenal Axis Dysfunction in Rats that Experienced Neonatal Maternal Separation

PubMed Central

Lee, Jong-Ho; Kim, Jin Young

2014-01-01

Background This study was conducted to examine the effects of ad libitum consumption of highly palatable food (HPF) during adolescence on the adverse behavioral outcome of neonatal maternal separation. Methods Male Sprague-Dawley pups were separated from dam for 3 hours daily during the first 2 weeks of birth (maternal separation, MS) or left undisturbed (nonhandled, NH). Half of MS pups received free access to chocolate cookies in addition to ad libitum chow from postnatal day 28 (MS+HPF). Pups were subjected to behavioral tests during young adulthood. The plasma corticosterone response to stress challenge was analyzed by radioimmunoassay. Results Daily caloric intake and body weight gain did not differ among the experimental groups. Ambulatory activities were decreased defecation activity and rostral grooming were increased in MS controls (fed with chow only) compared with NH rats. MS controls spent less time in open arms, and more time in closed arms during the elevated plus maze test, than NH rats. Immobility duration during the forced swim test was increased in MS controls compared with NH rats. Cookie access normalized the behavioral scores of ambulatory and defecation activities and grooming, but not the scores during the elevated plus maze and swim tests in MS rats. Stress-induced corticosterone increase was blunted in MS rats fed with chow only, and cookie access normalized it. Conclusion Prolonged access to HPF during adolescence and youth partly improves anxiety-related, but not depressive, symptoms in rats that experienced neonatal maternal separation, possibly in relation with improved function of the hypothalamic-pituitary-adrenal (HPA) axis. PMID:25031890

Deficits in novelty exploration after controlled cortical impact.

PubMed

Wagner, Amy K; Postal, Brett A; Darrah, Shaun D; Chen, Xiangbai; Khan, Amina S

2007-08-01

Experimental models of traumatic brain injury (TBI) have been utilized to characterize the behavioral derangements associated with brain trauma. Several studies exist characterizing motor function in the controlled cortical impact (CCI) injury model of TBI, but less research has focused on how CCI affects exploratory behavior. The goal of this study was to characterize deficits in three novelty exploration tasks after the CCI. Under anesthesia, 37 adult male Sprague Dawley rats received CCI (2.7 mm and 2.9 mm; 4 m/sec) over the right parietal cortex or sham surgery. For days 1-6 post-surgery, the beam balance and beam walking tasks were used to assess motor deficits. The Open Field, Y-Maze, and Free Choice Novelty (FCN) tasks were used to measure exploratory deficits from days 7-14 post-surgery. Injured rats displayed a significant, but transient, deficit on each motor task (p < 0.0001). Open Field results showed that injured rats had lower activity levels than shams (p < 0.0001), displayed less habituation to the task, and had more anxiety related behaviors (thigmotaxis) across days (p < 0.0001). Y-maze results suggest that injured rats spent less time in the novel arm versus the familiar arms when compared to shams (p < 0.0001). For FCN, injured rats were less active (p < 0.05) and spent less time and had fewer interactions with objects in the novel environment compared to shams (p < 0.05). These results suggest that several ethological factors contribute to exploratory deficits after CCI and can be effectively characterized with the behavioral tasks described. Future work will utilize these tasks to evaluate the neural substrates underlying exploratory deficits after TBI.

Sex matters: females in proestrus show greater diazepam anxiolysis and brain-derived neurotrophin factor- and parvalbumin-positive neurons than males.

PubMed

Ravenelle, Rebecca; Berman, Ariel K; La, Jeffrey; Mason, Briana; Asumadu, Evans; Yelleswarapu, Chandra; Donaldson, S Tiffany

2018-04-01

In humans and animal models, sex differences are reported for anxiety-like behavior and response to anxiogenic stimuli. In the current work, we studied anxiety-like behavior and response to the prototypical anti-anxiety drug, diazepam. We used 6th generation outbred lines of adult Long Evans rats with high and low anxiety-like behavior phenotypes to investigate the impact of proestrus on the baseline and diazepam-induced behavior. At three doses of diazepam (0, 0.1, and 1.0 mg/kg, i.p.), we measured anxiogenic responses on the elevated plus maze of adult male and female rats. We assessed parvalbumin and brain-derived neurotrophin protein levels in forebrain and limbic structures implicated in anxiety/stress using immunohistochemistry. At baseline, we saw significant differences between anxiety lines, with high anxiety lines displaying less time on the open arms of the elevated plus maze, and less open arm entries, regardless of sex. During proestrus, high anxiety females showed less anxiety-like behavior at 0.1 mg/kg, while low anxiety females displayed less anxiety-like behavior at 0.1 and 1.0 doses, relative to males. Brain-derived neurotrophin protein was elevated in females in the medial prefrontal cortex and central amygdala, while parvalbumin-immunoreactive cells were greater in males in the medial prefrontal cortex. Parvalbumin-positive cells in high anxiety females were higher in CA2 and dentate gyrus relative to males from the same line. In sum, when tested in proestrus, females showed greater anxiolytic effects of diazepam relative to males, and this correlated with increases in neurotrophin and parvalbumin neuron density in corticolimbic structures. © 2018 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Interaction between morphine and noradrenergic system of basolateral amygdala on anxiety and memory in the elevated plus-maze test based on a test-retest paradigm.

PubMed

Valizadegan, Farhad; Oryan, Shahrbanoo; Nasehi, Mohammad; Zarrindast, Mohammad Reza

2013-05-01

The amygdala is the key brain structure for anxiety and emotional memory storage. We examined the involvement of β-adrenoreceptors in the basolateral amygdala (BLA) and their interaction with morphine in modulating these behaviors. The elevated plus-maze has been employed for investigating anxiety and memory. Male Wistar rats were used for this test. We injected morphine (4, 5, and 6 mg/kg) intraperitoneally, while salbutamol (albuterol) (1, 2, and 4 μg/rat) and propranolol (1, 2, and 4 μg/rat) were injected into the BLA. Open- arms time percentage (%OAT), open- arms entry percentage (%OAE), and locomotor activity were determined by this behavioral test. Retention was tested 24 hours later. Intraperitoneal injection of morphine (6 mg/kg) had an anxiolytic-like effect and improvement of memory. The highest dose of salbutamol decreased the anxiety parameters in test session and improved the memory in retest session. Coadministration of salbutamol and ineffective dose of morphine presenting anxiolytic response. In this case, the memory was improved. Intra-BLA administration of propranolol (4 μg/rat) decreased %OAT in the test session, while had no effect on memory formation. Coadministration of propranolol and morphine (6 mg/kg) showed an increase in %OAT. There was not any significant change in the above- mentioned parameter in the retest session. Coadministration of morphine and propranolol with the effective dose of salbutamol showed that propranolol could reverse anxiolytic-like effect. We found that opioidergic and β-adrenergic systems have the same effects on anxiety and memory in the BLA; but these effects are independent of each other.

Effects of 1H + 16O Charged Particle Irradiation on Short-Term Memory and Hippocampal Physiology in a Murine Model.

PubMed

Kiffer, Frederico; Carr, Hannah; Groves, Thomas; Anderson, Julie E; Alexander, Tyler; Wang, Jing; Seawright, John W; Sridharan, Vijayalakshmi; Carter, Gwendolyn; Boerma, Marjan; Allen, Antiño R

2018-01-01

Radiation from galactic cosmic rays (GCR) poses a significant health risk for deep-space flight crews. GCR are unique in their extremely high-energy particles. With current spacecraft shielding technology, some of the predominant particles astronauts would be exposed to are 1 H + 16 O. Radiation has been shown to cause cognitive deficits in mice. The hippocampus plays a key role in memory and cognitive tasks; it receives information from the cortex, undergoes dendritic-dependent processing and then relays information back to the cortex. In this study, we investigated the effects of combined 1 H + 16 O irradiation on cognition and dendritic structures in the hippocampus of adult male mice three months postirradiation. Six-month-old male C57BL/6 mice were irradiated first with 1 H (0.5 Gy, 150 MeV/n) and 1 h later with 16 O (0.1 Gy, 600 MeV/n) at the NASA Space Radiation Laboratory (Upton, NY). Three months after irradiation, animals were tested for hippocampus-dependent cognitive performance using the Y-maze. Upon sacrifice, molecular and morphological assessments were performed on hippocampal tissues. During Y-maze testing, the irradiated mice failed to distinguish the novel arm, spending approximately the same amount of time in all three arms during the retention trial relative to sham-treated controls. Irradiated animals also showed changes in expression of glutamate receptor subunits and synaptic density-associated proteins. 1 H + 16 O radiation compromised dendritic morphology in the cornu ammonis 1 and dentate gyrus within the hippocampus. These data indicate cognitive injuries due to 1 H + 16 O at three months postirradiation.

Piping inspection instrument carriage with precise and repeatable position control and location determination

DOEpatents

Hapstack, M.; Talarek, T.R.; Zollinger, W.T.; Heckendorn, F.M. II; Park, L.R.

1994-02-15

An instrument carriage for inspection of piping comprises front and rear leg assemblies for engaging the interior of the piping and supporting and centering the carriage therein, and an instrumentation arm carried by a shaft system running from the front to rear leg assemblies. The shaft system has a screw shaft for moving the arm axially and a spline gear for moving the arm azimuthally. The arm has a pair of air cylinders that raise and lower a plate in the radial direction. On the plate are probes including an eddy current probe and an ultrasonic testing probe. The ultrasonic testing probe is capable of spinning 360[degree] about its axis. The instrument carriage uses servo motors and pressurized air cylinders for precise actuation of instrument components and precise, repeatable actuation of position control mechanisms. 8 figures.

Piping inspection instrument carriage with precise and repeatable position control and location determination

DOEpatents

Hapstack, Mark; Talarek, Ted R.; Zollinger, W. Thor; Heckendorn, II, Frank M.; Park, Larry R.

1994-01-01

An instrument carriage for inspection of piping comprises front and rear leg assemblies for engaging the interior of the piping and supporting and centering the carriage therein, and an instrumentation arm carried by a shaft system running from the front to rear leg assemblies. The shaft system has a screw shaft for moving the arm axially and a spline gear for moving the arm azimuthally. The arm has a pair of air cylinders that raise and lower a plate in the radial direction. On the plate are probes including an eddy current probe and an ultrasonic testing probe. The ultrasonic testing probe is capable of spinning 360.degree. about its axis. The instrument carriage uses servo motors and pressurized air cylinders for precise actuation of instrument components and precise, repeatable actuation of position control mechanisms.

Synchrotron X-ray scattering characterization of the molecular structures of star polystyrenes with varying numbers of arms.

PubMed

Jin, Sangwoo; Higashihara, Tomoya; Jin, Kyeong Sik; Yoon, Jinhwan; Rho, Yecheol; Ahn, Byungcheol; Kim, Jehan; Hirao, Akira; Ree, Moonhor

2010-05-20

We have synthesized well-defined multiarmed star polystyrenes, with 6, 9, 17, 33, and 57 arms, and studied their molecular shapes and structural characteristics in a good solvent (tetrahydrofuran at 25 degrees C) and in a theta (Theta) solvent (cyclohexane at 35 degrees C) by small-angle X-ray scattering (SAXS) using a synchrotron radiation source. Analysis of the SAXS data provided a detailed characterization of the molecular shapes, including the contributions of the blob morphology of the arms, the radius of gyration, the paired distance distribution, the radial electron density distribution, and the Zimm-Stockmayer and Roovers g-factor, for the multiarmed star polystyrenes. In particular, the molecular shapes of the star polystyrenes were found to change from a fuzzy ellipsoid, for the 6-armed polystyrene, to a fuzzy sphere, for the 57-armed polystyrene, with an increasing number of arms. The ellipsoidal character of the star polystyrenes with fewer arms may originate from the extended anisotropically branched architecture at the center of the molecule. The arms of the star polystyrenes were found to be more extended than those of the linear polystyrenes. Furthermore, the degree of chain extension in the arms increased with the number of arms.

Gaia DR1 Evidence of Disrupting the Perseus Arm

NASA Astrophysics Data System (ADS)

Baba, Junichi; Kawata, Daisuke; Matsunaga, Noriyuki; Grand, Robert J. J.; Hunt, Jason A. S.

2018-02-01

We have discovered a clear sign of the disruption phase of the Perseus arm in the Milky Way using Cepheid variables, taking advantage of the accurately measured distances of Cepheids and the proper motions from Gaia Data Release 1. Both the Galactocentric radial and rotation velocities of 77 Cepheids within 1.5 kpc of the Perseus arm are correlated with their distances from the locus of the Perseus arm, as the trailing side is rotating faster and moving inward compared to the leading side. We also found a negative vertex deviation for the Cepheids on the trailing side, ‑27.°6 ± 2.°4, in contrast to the positive vertex deviation in the solar neighborhood. This is, to our knowledge, the first direct evidence that the vertex deviation around the Perseus arm is affected by the spiral arm. We compared these observational trends with our N-body/hydrodynamics simulations based on a static density-wave spiral scenario and with those based on a transient dynamic spiral scenario. Although our comparisons are limited to qualitative trends, they strongly favor the conclusion that the Perseus arm is in the disruption phase of a transient arm.

Differential long-term effects of haloperidol and risperidone on the acquisition and performance of tasks of spatial working and short-term memory and sustained attention in rats.

PubMed

Hutchings, Elizabeth J; Waller, Jennifer L; Terry, Alvin V

2013-12-01

A common feature of the neuropsychiatric disorders for which antipsychotic drugs are prescribed is cognitive dysfunction, yet the effects of long-term antipsychotic treatment on cognition are largely unknown. In the current study, we evaluated the effects of long-term oral treatment with the first-generation antipsychotic haloperidol (1.0 and 2.0 mg/kg daily) and the second-generation antipsychotic risperidone (1.25 and 2.5 mg/kg daily) on the acquisition and performance of two radial-arm maze (RAM) tasks and a five-choice serial reaction-time task (5C-SRTT) in rats during days 15-60 and 84-320 days of treatment, respectively. In the RAM, neither antipsychotic significantly affected the acquisition or performance of a spatial win shift or a delayed non-match-to-position task. Conversely, in the rats administered 5C-SRTT, haloperidol was associated with profound deficits in performance, and the subjects were not able to progress through all stages of task acquisition. Depending on the dose, risperidone was associated with a greater number of trials to meet specific performance criteria during task acquisition compared with vehicle-treated controls; however, most subjects were eventually able to achieve all levels of task acquisition. Both haloperidol and risperidone also increased the number of perseverative and time-out responses during certain stages of task acquisition, and the response and reward latencies were slightly higher than controls during several stages of the study. These results in rats suggest that while long-term treatment with haloperidol or risperidone may not significantly affect spatial working or short-term memory, both antipsychotics can (depending on dose) impair sustained attention, decrease psychomotor speed, increase compulsive-type behaviors, and impair cognitive flexibility.

Impairment of spatial working memory and oxidative stress induced by repeated crack cocaine inhalation in rats.

PubMed

Lipaus, Ingryd Fortes Souza; Gomes, Elisa Fraga; Martins, Cleciane Waldetário; E Silva, Cristina Martins; Pires, Rita Gomes Wanderley; Malgarin, Fernanda; Schuck, Patrícia Fernanda; Palacios, Ester Miyuki Nakamura; de Melo Rodrigues, Lívia Carla

2018-06-20

Crack cocaine is a highly toxic drug with great potential to induce addiction. It produces more intense effects than cocaine powder, with its use having grown worldwide. However, few studies have focused on the cognitive and biochemical consequences that result from crack cocaine inhalation. This study examined the effects of direct crack cocaine inhalation on spatial working memory and brain oxidative stress parameters in rats. Male adult Wistar rats, well-trained in an eight-arm radial maze (8-RM), underwent five sessions of crack cocaine inhalation (crack cocaine group) once a day or inhalation simulation (sham group), being tested in 1-h delayed tasks 24 h after the last inhalation. An additional inhalation session was carried out the following day, with the prefrontal cortex, hippocampus and striatum being removed five minutes afterwards in order to assess oxidative damage such as lipid peroxidation, thiobarbituric acid-reactive species (TBARS) levels, and advanced oxidation protein products (AOPP), as well as the activity of antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx). Animals from the crack cocaine group showed more errors (p <  0.01) in the 1-h post-delay performance in the 8-RM when compared to the sham group. The crack cocaine group showed decreased (p <  0.05) lipid peroxidation in the hippocampus and increased (p <  0.001) levels of AOPP and SOD activity (p < 0.05) in the striatum when compared to the sham group. Therefore, the repeated inhalation of crack cocaine impaired long-term spatial working memory and elicited oxidative stress in the hippocampus and striatum of rats. Copyright © 2018. Published by Elsevier B.V.

EFFECTS OF LONG-TERM MEMANTINE ON MEMORY AND NEUROPATHOLOGY IN TS65DN MICE, A MODEL FOR DOWN SYNDROME

PubMed Central

Lockrow, Jason; Boger, Heather; Bimonte-Nelson, Heather; Granholm, Ann-Charlotte

2010-01-01

Memantine is a partial NMDA receptor antagonist that has been shown to improve learning and memory in several animal models, and is approved for the treatment of Alzheimer’s disease. Chronic treatments using memantine in animal models of Alzheimer’s disease show disease-modifying effects and suggest a potential neuroprotective function. The present study assessed the effects of both short- and long-term memantine treatment in a mouse model of Down syndrome, the Ts65Dn mouse. The Ts65Dn mouse contains a partial trisomy of murine chromosome 16, and exhibits hippocampal-dependent memory deficits, as well as progressive degeneration of basal forebrain cholinergic neurons. Ts65Dn mice were treated with memantine for a period of six months, beginning at four months of age. At the end of treatment the mice underwent memory testing using novel object recognition and water radial arm maze tasks, and then histologically analyzed for markers of neurodegeneration. Memantine treatment improved spatial and recognition memory performance in the Ts65Dn mice, though not to the level of normosomic littermate controls. Despite these memory improvements, histological analysis found no morphological signs of neuroprotection of basal forebrain cholinergic or locus coeruleus neurons in memantine-treated Ts65Dn mice. However, memantine treatment of Ts65Dn mice gave rise to elevated brain-derived neurotrophic factor expression in the hippocampus and frontal cortex, suggesting a mechanism of behavioral modification. Thus, our findings provide further evidence for memory facilitation of memantine, but suggest pharmacological rather than neuroprotective effects of memantine both after acute and chronic treatment in this mouse model. PMID:20363261

Developmental neurotoxicity of Propylthiouracil (PTU) in rats: Relationship between transient hypothyroxinemia during development and long-lasting behavioural and functional changes

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

Axelstad, Marta; Hansen, Pernille Reimar; Boberg, Julie

2008-10-01

Markedly lowered thyroid hormone levels during development may influence a child's behaviour, intellect, and auditory function. Recent studies, indicating that even small changes in the mother's thyroid hormone status early in pregnancy may cause adverse effects on her child, have lead to increased concern for thyroid hormone disrupting chemicals in the environment. The overall aim of the study was therefore to provide a detailed knowledge on the relationship between thyroid hormone levels during development and long-lasting effects on behaviour and hearing. Groups of 16-17 pregnant rats (HanTac:WH) were dosed with PTU (0, 0.8, 1.6 or 2.4 mg/kg/day) from gestation daymore » (GD) 7 to postnatal day (PND) 17, and the physiological and behavioural development of rat offspring was assessed. Both dams and pups in the higher dose groups had markedly decreased thyroxine (T{sub 4}) levels during the dosing period, and the weight and histology of the thyroid glands were severely affected. PTU exposure caused motor activity levels to decrease on PND 14, and to increase on PND 23 and in adulthood. In the adult offspring, learning and memory was impaired in the two highest dose groups when tested in the radial arm maze, and auditory function was impaired in the highest dose group. Generally, the results showed that PTU-induced hypothyroxinemia influenced the developing rat brain, and that all effects on behaviour and loss of hearing in the adult offspring were significantly correlated to reductions in T{sub 4} during development. This supports the hypothesis that decreased T{sub 4} may be a relevant predictor for long-lasting developmental neurotoxicity.« less

Effects of Maternal Choline Supplementation on the Septohippocampal Cholinergic System in the Ts65Dn Mouse Model of Down Syndrome.

PubMed

Kelley, Christy M; Ash, Jessica A; Powers, Brian E; Velazquez, Ramon; Alldred, Melissa J; Ikonomovic, Milos D; Ginsberg, Stephen D; Strupp, Barbara J; Mufson, Elliott J

2016-01-01

Down syndrome (DS), caused by trisomy of chromosome 21, is marked by intellectual disability (ID) and early onset of Alzheimer's disease (AD) neuropathology including hippocampal cholinergic projection system degeneration. Here we determined the effects of age and maternal choline supplementation (MCS) on hippocampal cholinergic deficits in Ts65Dn mice compared to 2N mice sacrificed at 6-8 and 14-18 months of age. Ts65Dn mice and disomic (2N) littermates sacrificed at ages 6-8 and 14-18 mos were used for an aging study and Ts65Dn and 2N mice derived from Ts65Dn dams were maintained on either a choline-supplemented or a choline-controlled diet (conception to weaning) and examined at 14-18 mos for MCS studies. In the latter, mice were behaviorally tested on the radial arm Morris water maze (RAWM) and hippocampal tissue was examined for intensity of choline acetyltransferase (ChAT) immunoreactivity. Hippocampal ChAT activity was evaluated in a separate cohort. ChAT-positive fiber innervation was significantly higher in the hippocampus and dentate gyrus in Ts65Dn mice compared with 2N mice, independent of age or maternal diet. Similarly, hippocampal ChAT activity was significantly elevated in Ts65Dn mice compared to 2N mice, independent of maternal diet. A significant increase with age was seen in hippocampal cholinergic innervation of 2N mice, but not Ts65Dn mice. Degree of ChAT intensity correlated negatively with spatial memory ability in unsupplemented 2N and Ts65Dn mice, but positively in MCS 2N mice. The increased innervation produced by MCS appears to improve hippocampal function, making this a therapy that may be exploited for future translational approaches in human DS.

Exercise Preconditioning Improves Traumatic Brain Injury Outcomes

PubMed Central

Taylor, Jordan M.; Montgomery, Mitchell H.; Gregory, Eugene J.; Berman, Nancy E.J.

2015-01-01

Purpose To determine whether 6 weeks of exercise performed prior to traumatic brain injury (TBI) could improve post-TBI behavioral outcomes in mice, and if exercise increases neuroprotective molecules (vascular endothelial growth factor-A [VEGF-A], erythropoietin [EPO], and heme oxygenase-1 [HO-1]) in brain regions responsible for movement (sensorimotor cortex) and memory (hippocampus). Methods 120 mice were randomly assigned to one of four groups: 1) no exercise + no TBI (NOEX-NOTBI [n=30]), 2) no exercise + TBI (NOEX-TBI [n=30]), 3) exercise + no TBI (EX-NOTBI [n=30]), and 4) exercise + TBI (EX-TBI [n=30]). The gridwalk task and radial arm water maze were used to evaluate sensorimotor and cognitive function, respectively. Quantitative real time polymerase chain reaction and immunostaining were performed to investigate VEGF-A, EPO, and HO-1 mRNA and protein expression in the right cerebral cortex and ipsilateral hippocampus. Results EX-TBI mice displayed reduced post-TBI sensorimotor and cognitive deficits when compared to NOEX-TBI mice. EX-NOTBI and EX-TBI mice showed elevated VEGF-A and EPO mRNA in the cortex and hippocampus, and increased VEGF-A and EPO staining of sensorimotor cortex neurons 1 day post-TBI and/or post-exercise. EX-TBI mice also exhibited increased VEGF-A staining of hippocampal neurons 1 day post-TBI/post-exercise. NOEX-TBI mice demonstrated increased HO-1 mRNA in the cortex (3 days post-TBI) and hippocampus (3 and 7 days post-TBI), but HO-1 was not increased in mice that exercised. Conclusions Improved TBI outcomes following exercise preconditioning are associated with increased expression of specific neuroprotective genes and proteins (VEGF-A and EPO, but not HO-1) in the brain. PMID:26165153

Putative cognitive enhancers in preclinical models related to schizophrenia: the search for an elusive target.

PubMed

Barak, Segev; Weiner, Ina

2011-08-01

Several developments have converged to drive what may be called "the cognitive revolution" in drug discovery in schizophrenia (SCZ), including the emphasis on cognitive deficits as a core disabling aspect of SCZ, the increasing consensus that cognitive deficits are not treated satisfactorily by the available antipsychotic drugs (APDs), and the failure of animal models to predict drug efficacy for cognitive deficits in clinical trials. Consequently, in recent years, a paradigm shift has been encouraged in animal modeling, triggered by the NIMH sponsored Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) initiative, and intended to promote the development and use of behavioral measures in animals that can generate valid (clinically relevant) measures of cognition and thus promote the identification of cognition enhancers for SCZ. Here, we provide a non-exhaustive survey of the effects of putative cognition enhancers (PCEs) representing 10 pharmacological targets as well as antipsychotic drugs (APDs), on SCZ-mimetic drugs (NMDA antagonists, muscarinic antagonist scopolamine and dopaminergic agonist amphetamine), in several tasks considered to measure cognitive processes/domains that are disrupted in SCZ (the five choice serial reaction time task, sustain attention task, working and/or recognition memory (delayed (non)matching to sample, delayed alternation task, radial arm maze, novel object recognition), reversal learning, attentional set shifting, latent inhibition and spatial learning and memory). We conclude that most of the available models have no capacity to distinguish between PCEs and APDs and that there is a need to establish models based on tasks whose perturbations lead to performance impairments that are resistant to APDs, and/or to accept APDs as a "weak gold standard". Several directions derived from the surveyed data are suggested. Copyright © 2011 Elsevier Inc. All rights reserved.

Blocking leukotriene synthesis attenuates the pathophysiology of traumatic brain injury and associated cognitive deficits

PubMed Central

Corser-Jensen, Chelsea E.; Goodell, Dayton J.; Freund, Ronald K.; Serbedzija, Predrag; Murphy, Robert C.; Farias, Santiago E.; Dell'Acqua, Mark L.; Frey, Lauren C.; Serkova, Natalie; Heidenreich, Kim A.

2014-01-01

Neuroinflammation is a component of secondary injury following traumatic brain injury (TBI) that can persist beyond the acute phase. Leukotrienes are potent, pro-inflammatory lipid mediators generated from membrane phospholipids. In the absence of injury, leukotrienes are undetectable in brain, but after trauma they are rapidly synthesized by a transcellular event involving infiltrating neutrophils and endogenous brain cells. Here, we investigate the efficacy of MK-886, an inhibitor of 5-lipoxygenase activating protein (FLAP), in blocking leukotriene synthesis, secondary brain damage, synaptic dysfunction, and cognitive impairments after TBI. Male Sprague Dawley rats (9-11 weeks) received either MK-886 or vehicle after they were subjected to unilateral moderate fluid percussion injury (FPI) to assess the potential clinical use of FLAP inhibitors for TBI. MK-886 was also administered before FPI to determine the preventative potential of FLAP inhibitors. MK-886 given before or after injury significantly blocked the production of leukotrienes, measured by reverse-phase liquid chromatography coupled to tandem mass spectrometry (RP LC-MS/MS), and brain edema, measured by T2-weighted magnetic resonance imaging (MRI). MK-886 significantly attenuated blood-brain barrier disruption in the CA1 hippocampal region and deficits in long-term potentiation (LTP) at CA1 hippocampal synapses. The prevention of FPI-induced synaptic dysfunction by MK-886 was accompanied by fewer deficits in post-injury spatial learning and memory performance in the radial arms water maze (RAWM). These results indicate that leukotrienes contribute significantly to secondary brain injury and subsequent cognitive deficits. FLAP inhibitors represent a novel anti-inflammatory approach for treating human TBI that is feasible for both intervention and prevention of brain injury and neurologic deficits. PMID:24681156

Age- and gender-dependent impairments of neurobehaviors in mice whose mothers were exposed to lipopolysaccharide during pregnancy.

PubMed

Wang, Hua; Meng, Xiu-Hong; Ning, Huan; Zhao, Xian-Feng; Wang, Qun; Liu, Ping; Zhang, Heng; Zhang, Cheng; Chen, Gui-Hai; Xu, De-Xiang

2010-02-01

Lipopolysaccharide (LPS)-induced intrauterine infection has been associated with neurodevelopmental injury in rodents. The purpose of the present study was to analyze the dynamic changes of neurobehaviors in mice whose mothers were exposed to LPS during pregnancy. The pregnant mice were intraperitoneally (i.p.) injected with LPS (8 microg/kg) daily from gestational day (gd) 8 to gd 15. A battery of neurobehavioral tasks was performed in mice at postnatal day (PND) 70, 200, 400 and 600. Results showed that the spatial learning and memory ability, determined by radial six-arm water maze (RAWM), were obviously impaired in two hundred-day-old female mice and four hundred-day-old male mice whose mothers were exposed to LPS during pregnancy. Open field test showed that the number of squares crossed and peripheral time, a marker of anxiety and exploration activity, were markedly increased in two hundred-day-old female mice following prenatal LPS exposure. In addition, prenatal LPS exposure significantly shortened the latency to the first grid crossing in six hundred-day-old female offspring. Moreover, sensorimotor impairment in the beam walking was observed in two hundred-day-old female mice whose mothers were exposed to LPS during pregnancy. Species-typical behavior examination showed that prenatal LPS exposure markedly increased weight burrowed in seventy-day-old male offspring and six hundred-day-old female offspring. Correspondingly, prenatal LPS exposure significantly reduced weight hoarded in two hundred-day-old female offspring. Taken together, these results suggest that prenatal LPS exposure induces neurobehavioral impairments at adulthood in an age- and gender-dependent manner. 2009 Elsevier Ireland Ltd. All rights reserved.

Age- and sex-related disturbance in a battery of sensorimotor and cognitive tasks in Kunming mice.

PubMed

Chen, Gui-Hai; Wang, Yue-Ju; Zhang, Li-Qun; Zhou, Jiang-Ning

2004-12-15

A battery of tasks, i.e. beam walking, open field, tightrope, radial six-arm water maze (RAWM), novel-object recognition and olfactory discrimination, was used to determine whether there was age- and sex-related memory deterioration in Kunming (KM) mice, and whether these tasks are independent or correlated with each other. Two age groups of KM mice were used: a younger group (7-8 months old, 12 males and 11 females) and an older group (17-18 months old, 12 males and 12 females). The results showed that the spatial learning ability and memory in the RAWM were lower in older female KM mice relative to younger female mice and older male mice. Consistent with this, in the novel-object recognition task, a non-spatial cognitive task, older female mice but not older male mice had impairment of short-term memory. In olfactory discrimination, another non-spatial task, the older mice retained this ability. Interestingly, female mice performed better than males, especially in the younger group. The older females exhibited sensorimotor impairment in the tightrope task and low locomotor activity in the open-field task. Moreover, older mice spent a longer time in the peripheral squares of the open-field than younger ones. The non-spatial cognitive performance in the novel-object recognition and olfactory discrimination tasks was related to performance in the open-field, whereas the spatial cognitive performance in the RAWM was not related to performance in any of the three sensorimotor tasks. These results suggest that disturbance of spatial learning and memory, as well as selective impairment of non-spatial learning and memory, existed in older female KM mice.

Chronic stress impairs prefrontal cortex-dependent response inhibition and spatial working memory.

PubMed

Mika, Agnieszka; Mazur, Gabriel J; Hoffman, Ann N; Talboom, Joshua S; Bimonte-Nelson, Heather A; Sanabria, Federico; Conrad, Cheryl D

2012-10-01

Chronic stress leads to neurochemical and structural alterations in the prefrontal cortex (PFC) that correspond to deficits in PFC-mediated behaviors. The present study examined the effects of chronic restraint stress on response inhibition (using a response-withholding task, the fixed-minimum interval schedule of reinforcement, or FMI), and working memory (using a radial arm water maze, RAWM). Adult male Sprague-Dawley rats were first trained on the RAWM and subsequently trained on FMI. After acquisition of FMI, rats were assigned to a restraint stress (6h/d/28d in wire mesh restrainers) or control condition. Immediately after chronic stress, rats were tested on FMI and subsequently on RAWM. FMI results suggest that chronic stress reduces response inhibition capacity and motivation to initiate the task on selective conditions when sucrose reward was not obtained on the preceding trial. RAWM results suggest that chronic stress produces transient deficits in working memory without altering previously consolidated reference memory. Behavioral measures from FMI failed to correlate with metrics from RAWM except for one in which changes in FMI timing imprecision negatively correlated with changes in RAWM working memory errors for the controls, a finding that was not observed following chronic stress. Fisher's r-to-z transformation revealed no significant differences between control and stress groups with correlation coefficients. These findings are the first to show that chronic stress impairs both response inhibition and working memory, two behaviors that have never been directly compared within the same animals after chronic stress, using FMI, an appetitive task, and RAWM, a nonappetitive task. PsycINFO Database Record (c) 2012 APA, all rights reserved.

Adverse effect of combination of chronic psychosocial stress and high fat diet on hippocampus-dependent memory in rats.

PubMed

Alzoubi, K H; Abdul-Razzak, K K; Khabour, O F; Al-Tuweiq, G M; Alzubi, M A; Alkadhi, K A

2009-12-01

The combined effects of high fat diet (HFD) and chronic stress on the hippocampus-dependent spatial learning and memory were studied in rats using the radial arm water maze (RAWM). Chronic psychosocial stress and/or HFD were simultaneously administered for 3 months to young adult male Wister rats. In the RAWM, rats were subjected to 12 learning trials as well as short-term and long-term memory tests. This procedure was applied on a daily basis until the animal reaches days to criterion (DTC) in the 12th learning trial and in memory tests. DTC is the number of days that the animal takes to make zero error in two consecutive days. Groups were compared based on the number of errors per trial or test as well as on the DTC. Chronic stress, HFD and chronic stress/HFD animal groups showed impaired learning as indicated by committing significantly (P<0.05) more errors than untreated control group in trials 6 through 9 of day 4. In memory tests, chronic stress, HFD and chronic stress/HFD groups showed significantly impaired performance compared to control group. Additionally, the stress/HFD was the only group that showed significantly impaired performance in memory tests on the 5th training day, suggesting more severe memory impairment in that group. Furthermore, DTC value for above groups indicated that chronic stress or HFD, alone, resulted in a mild impairment of spatial memory, but the combination of chronic stress and HFD resulted in a more severe and long-lasting memory impairment. The data indicated that the combination of stress and HFD produced more deleterious effects on hippocampal cognitive function than either chronic stress or HFD alone.

Evaluation of the Effect of Moringa peregrina Extract on Learning and Memory: Role of Oxidative Stress.

PubMed

Alzoubi, Karem H; Rawashdeh, Nasab Q; Khabour, Omar F; El-Elimat, Tamam; Albataineh, Hanan; Al-Zghool, Hamzeh M; Alali, Feras Q

2017-12-01

Oxidative stress interferes with the functional roles of the hippocampus and results in cognitive decline. Antioxidant supplementation has a cognitive enhancing activity through protecting hippocampus brain cells from the damaging effects of the reactive oxygen species. The dried methanolic extract of the aboveground parts of Moringa peregrina (Forssk.) Fiori (Moringaceae) was hypothesized to have memory-enhancing activity via its antioxidative properties. HPLC and LC-MS methods were used for qualitative analysis of the marker compounds. Six major compounds of the methanolic extract of M. peregrina were identified, namely, rutin, myricetin, α-amyrin, β-amyrin, lupeol acetate, and β-sitosterol. Male Wistar rats were administered via oral gavage three dose levels (50, 100, and 500 mg/kg) of M. peregrina methanolic extract for 2 months. The radial arm water maze (RAWM) was used to test spatial learning and memory. In addition, ELISA was used to analyze the levels of brain-derived neurotrophic factor (BDNF) and to assess the level of some oxidative stress markers. M. peregrina (150 mg/kg) resulted in short- and long-term memory enhancement (P < 0.05). Moreover, M. peregrina administration elevated BDNF levels in the hippocampus (P < 0.05) and caused favorable changes in oxidative stress biomarkers. In particular, an increase in glutathione (GSH), a decrease in oxidized glutathione (GSSG), and an increase in the antioxidant enzyme glutathione peroxidase (GPx) levels in the hippocampus were elicited after treatment with M. peregrina. Taken together, our data show that oral administration of M. peregrina enhances both short- and long-term memory functions via combating oxidative stress and increasing BDNF levels in the hippocampus. Consuming this safe plant may thus help promote spatial learning and improve memory.

Maternal omega-3 fatty acid supplementation on vitamin B12 rich diet improves brain omega-3 fatty acids, neurotrophins and cognition in the Wistar rat offspring.

PubMed

Rathod, Richa; Khaire, Amrita; Kemse, Nisha; Kale, Anvita; Joshi, Sadhana

2014-11-01

The consequences of wide spread vegetarianism due to low vitamin B12 on brain development and functioning is gaining importance. However, there are no studies which have evaluated exclusively vitamin B12 supplementation during pregnancy on brain growth. A series of our animal studies have documented adverse effects of maternal micronutrient imbalance on brain neurotrophins and its amelioration by omega-3 fatty acids. Therefore, the present study investigated the effect of maternal supplementation with vitamin B12 alone and B12 plus omega-3 fatty acid on pup brain fatty acids and neurotrophins at birth and 3 mo of age. Pregnant Wistar rats and their male offspring were assigned to 3 dietary groups: Control (normal vitamin B12 (25 μg/kg), vitamin B12 supplemented (BS) (50 μg/kg), vitamin B12 supplemented with omega-3 fatty acid (BSO) till 3 month of age. Maternal vitamin B12 supplementation (BS) increased brain BDNF (protein and mRNA) and DHA levels in pups at birth and in the hippocampus at 3 month of age (BDNF only). These effects were further enhanced by omega-3 fatty acid supplementation to vitamin B12 supplemented group. The spatial memory performance was found to be enhanced in BSO group which was characterised by less number of errors in radial eight arm maze. Our results indicate that a combination of omega-3 fatty acid and vitamin B12 enriched diet may exert beneficial effects on synaptic plasticity and cognition, which may prove beneficial for mental health, particularly in preventing neurocognitive disorders. Copyright © 2013 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Artesunate restores spatial learning of rats with hepatic encephalopathy by inhibiting ammonia-induced oxidative damage in neurons and dysfunction of glutamate signaling in astroglial cells.

PubMed

Wu, Yuan-Bo; Zhang, Li; Li, Wen-Ting; Yang, Yi; Zhao, Jiang-Ming

2016-12-01

Artesunate (ART) is an antimalarial drug with potential anti-inflammatory effect. This study aimed to explore the potential protective role of ART in hepatic encephalopathy (HE), involving its function against ammonia toxicity. HE rats were induced by the administration of thioacetamide (TAA, 300mg/kg/day). Spatial learning ability was tested in both Morris water and eight-arm radial maze. Rat cerebellar granule neurons (CGNs) were prepared for ammonia treatment in vitro, in line with SH-SY5Y and C6 cells. ART was administrated at 50 or 100mg/kg/day in vivo or added at 50 or 100μM in vitro. Oxidative damages were evaluated by the changes of cell viability, reactive oxygen species (ROS) levels and glutathione (GSH) content, while glutamate uptake and release, and the activities of glutamine synthetase (GS) and Na + K + -ATPase were measured to indicate the dysfunction of glutamate signaling. Decreased escape latency and increased numbers of working errors were observed in TAA-induced HE rats, which could be significantly restored by ART at a dosage-dependent manner. Decreased cell viability and GSH content and increased ROS accumulation were detected in ammonia-treated SH-SY5Y and CGNs, while ammonia-treated C6 cells showed reduced glutamate uptake, increased glutamate release, and decrease of GSH content, GS and Na + K + -ATPase activity. In contrast, ART, especially at 100μM, strongly reversed all changes induced by ammonia, showing a similar dosage-dependent manner in vitro. This study revealed a new neuroprotective role of ART in the pathogenesis of HE, by protecting neurons and astroglial cells from ammonia-induced damages and dysfunctions. Copyright © 2016. Published by Elsevier Masson SAS.

Developmental neurotoxicity of propylthiouracil (PTU) in rats: relationship between transient hypothyroxinemia during development and long-lasting behavioural and functional changes.

PubMed

Axelstad, Marta; Hansen, Pernille Reimar; Boberg, Julie; Bonnichsen, Mia; Nellemann, Christine; Lund, Søren Peter; Hougaard, Karin Sørig; Hass, Ulla

2008-10-01

Markedly lowered thyroid hormone levels during development may influence a child's behaviour, intellect, and auditory function. Recent studies, indicating that even small changes in the mother's thyroid hormone status early in pregnancy may cause adverse effects on her child, have lead to increased concern for thyroid hormone disrupting chemicals in the environment. The overall aim of the study was therefore to provide a detailed knowledge on the relationship between thyroid hormone levels during development and long-lasting effects on behaviour and hearing. Groups of 16-17 pregnant rats (HanTac:WH) were dosed with PTU (0, 0.8, 1.6 or 2.4 mg/kg/day) from gestation day (GD) 7 to postnatal day (PND) 17, and the physiological and behavioural development of rat offspring was assessed. Both dams and pups in the higher dose groups had markedly decreased thyroxine (T(4)) levels during the dosing period, and the weight and histology of the thyroid glands were severely affected. PTU exposure caused motor activity levels to decrease on PND 14, and to increase on PND 23 and in adulthood. In the adult offspring, learning and memory was impaired in the two highest dose groups when tested in the radial arm maze, and auditory function was impaired in the highest dose group. Generally, the results showed that PTU-induced hypothyroxinemia influenced the developing rat brain, and that all effects on behaviour and loss of hearing in the adult offspring were significantly correlated to reductions in T(4) during development. This supports the hypothesis that decreased T(4) may be a relevant predictor for long-lasting developmental neurotoxicity.

Differential Long-Term Effects of Haloperidol and Risperidone on the Acquisition and Performance of Tasks of Spatial Working and Short-Term Memory and Sustained Attention in Rats

PubMed Central

Hutchings, Elizabeth J.; Waller, Jennifer L.

2013-01-01

A common feature of the neuropsychiatric disorders for which antipsychotic drugs are prescribed is cognitive dysfunction, yet the effects of long-term antipsychotic treatment on cognition are largely unknown. In the current study, we evaluated the effects of long-term oral treatment with the first-generation antipsychotic haloperidol (1.0 and 2.0 mg/kg daily) and the second-generation antipsychotic risperidone (1.25 and 2.5 mg/kg daily) on the acquisition and performance of two radial-arm maze (RAM) tasks and a five-choice serial reaction-time task (5C-SRTT) in rats during days 15–60 and 84–320 days of treatment, respectively. In the RAM, neither antipsychotic significantly affected the acquisition or performance of a spatial win shift or a delayed non–match-to-position task. Conversely, in the rats administered 5C-SRTT, haloperidol was associated with profound deficits in performance, and the subjects were not able to progress through all stages of task acquisition. Depending on the dose, risperidone was associated with a greater number of trials to meet specific performance criteria during task acquisition compared with vehicle-treated controls; however, most subjects were eventually able to achieve all levels of task acquisition. Both haloperidol and risperidone also increased the number of perseverative and time-out responses during certain stages of task acquisition, and the response and reward latencies were slightly higher than controls during several stages of the study. These results in rats suggest that while long-term treatment with haloperidol or risperidone may not significantly affect spatial working or short-term memory, both antipsychotics can (depending on dose) impair sustained attention, decrease psychomotor speed, increase compulsive-type behaviors, and impair cognitive flexibility. PMID:24042161

R-flurbiprofen improves tau, but not Aß pathology in a triple transgenic model of Alzheimer's disease.

PubMed

Carreras, Isabel; McKee, Ann C; Choi, Ji-Kyung; Aytan, Nurgul; Kowall, Neil W; Jenkins, Bruce G; Dedeoglu, Alpaslan

2013-12-06

We have previously reported that chronic ibuprofen treatment improves cognition and decreases intracellular Aß and phosphorylated-tau levels in 3xTg-AD mice. Ibuprofen is a non-steroidal anti-inflammatory drug (NSAID) that independently of its anti-inflammatory effects has anti-amyloidogenic activity as a gamma-secretase modulator (GSM) and both activities have the potential to decrease Aß pathology. To further understand the effects of NSAIDs in 3xTg-AD mice, we treated 3xTg-AD mice with R-flurbiprofen, an enantiomer of the NSAID flurbiprofen that maintains the GSM activity but has greatly reduced anti-inflammatory activity, and analyzed its effect on cognition, Aß, tau, and the neurochemical profile of the hippocampus. Treatment with R-flurbiprofen from 5 to 7 months of age resulted in improved cognition on the radial arm water maze (RAWM) test and decreased the level of hyperphosphorylated tau immunostained with AT8 and PHF-1 antibodies. No significant changes in the level of Aß (using 6E10 and NU-1 antibodies) were detected. Using magnetic resonance spectroscopy (MRS) we found that R-flurbiprofen treatment decreased the elevated level of glutamine in 3xTg-AD mice down to the level detected in non-transgenic mice. Glutamine levels correlated with PHF-1 immunostained hyperphosphorylated tau. We also found an inverse correlation between the concentration of glutamate and learning across all the mice in the study. Glutamine and glutamate, neurochemicals that shuttles between neurons and astrocytes to maintain glutamate homeostasis in the synapses, deserve further attention as MR markers of cognitive function. © 2013 Published by Elsevier B.V.

RNA-Sequencing Reveals Unique Transcriptional Signatures of Running and Running-Independent Environmental Enrichment in the Adult Mouse Dentate Gyrus.

PubMed

Grégoire, Catherine-Alexandra; Tobin, Stephanie; Goldenstein, Brianna L; Samarut, Éric; Leclerc, Andréanne; Aumont, Anne; Drapeau, Pierre; Fulton, Stephanie; Fernandes, Karl J L

2018-01-01

Environmental enrichment (EE) is a powerful stimulus of brain plasticity and is among the most accessible treatment options for brain disease. In rodents, EE is modeled using multi-factorial environments that include running, social interactions, and/or complex surroundings. Here, we show that running and running-independent EE differentially affect the hippocampal dentate gyrus (DG), a brain region critical for learning and memory. Outbred male CD1 mice housed individually with a voluntary running disk showed improved spatial memory in the radial arm maze compared to individually- or socially-housed mice with a locked disk. We therefore used RNA sequencing to perform an unbiased interrogation of DG gene expression in mice exposed to either a voluntary running disk (RUN), a locked disk (LD), or a locked disk plus social enrichment and tunnels [i.e., a running-independent complex environment (CE)]. RNA sequencing revealed that RUN and CE mice showed distinct, non-overlapping patterns of transcriptomic changes versus the LD control. Bio-informatics uncovered that the RUN and CE environments modulate separate transcriptional networks, biological processes, cellular compartments and molecular pathways, with RUN preferentially regulating synaptic and growth-related pathways and CE altering extracellular matrix-related functions. Within the RUN group, high-distance runners also showed selective stress pathway alterations that correlated with a drastic decline in overall transcriptional changes, suggesting that excess running causes a stress-induced suppression of running's genetic effects. Our findings reveal stimulus-dependent transcriptional signatures of EE on the DG, and provide a resource for generating unbiased, data-driven hypotheses for novel mediators of EE-induced cognitive changes.

Sucrose and naltrexone prevent increased pain sensitivity and impaired long-term memory induced by repetitive neonatal noxious stimulation: Role of BDNF and β-endorphin.

PubMed

Nuseir, Khawla Q; Alzoubi, Karem H; Alhusban, Ahmed; Bawaane, Areej; Al-Azzani, Mohammed; Khabour, Omar F

2017-10-01

Pain in neonates is associated with short and long-term adverse outcomes. Data demonstrated that long-term consequences of untreated pain are linked to the plasticity of the neonate's brain. Sucrose is effective and safe for reducing painful procedures from single events. However, the mechanism of sucrose-induced analgesia is not fully understood. The role of the opioid system in this analgesia using the opioid receptor antagonist Naltrexone was investigated, plus the long-term effects on learning and memory formation during adulthood. Pain was induced in rat pups via needle pricks of the paws. Sucrose solution and/or naltrexone were administered before the pricks. All treatments started on day one of birth and continued for two weeks. At the end of 8weeks, behavioral studies were conducted to test spatial learning and memory using radial arm water maze (RAWM), and pain threshold via foot-withdrawal response to a hot plate. The hippocampus was dissected; levels of brain derived neurotrophic factor (BDNF) and endorphins were assessed using ELISA. Acute repetitive neonatal pain increased pain sensitivity later in life, while naltrexone with sucrose decreased pain sensitivity. Naltrexone and/or sucrose prevented neonatal pain induced impairment of long-term memory, while neonatal pain decreased levels of BDNF in the hippocampus; this decrease was averted by sucrose and naltrexone. Sucrose with naltrexone significantly increased β-endorphin levels in noxiously stimulated rats. In conclusion, naltrexone and sucrose can reverse increased pain sensitivity and impaired long-term memory induced by acute repetitive neonatal pain probably by normalizing BDNF expression and increasing β-endorphin levels. Copyright © 2017 Elsevier Inc. All rights reserved.

Treadmill exercise ameliorates Alzheimer disease-associated memory loss through the Wnt signaling pathway in the streptozotocin-induced diabetic rats.

PubMed

Kim, Dae-Young; Jung, Sun-Young; Kim, Kijeong; Kim, Chang-Ju

2016-08-01

Diabetes mellitus is considered as a risk factor for Alzheimer disease. The aim of the present study was to evaluate the possibility whether treadmill exercise ameliorates Alzheimer disease-associated memory loss in the diabetes mellitus. For this study, the effects of treadmill exercise on short-term memory and spatial learning ability in relation with Wnt signaling pathway were evaluated using the streptozotocin (STZ)-induced diabetic rats. Diabetes was induced by intraperitoneal injection of STZ. Step-down avoidance task and 8-arm radial maze test were performed for the memory function. Immunohistochemistry for 5-bro-mo-2'-deoxyridine (BrdU) and doublecortin (DCX) and Western blot for Wnt3 and glycogen synthase kinase-3β (GSK-3β) were conducted. The rats in the exercise groups were made to run on the treadmill for 30 min per one day, 5 times a week, during 12 weeks. In the present results, short-term memory and spatial learning ability were deteriorated by induction of diabetes. Treadmill exercise improved short-term memory and spatial learning ability in the diabetic rats. The numbers of BrdU-positive and DCX-positive cells in the hippocampal dentate gyrus were decreased by induction of diabetes. Treadmill exercise increased these numbers in the diabetic rats. Wnt3 expression in the hippocampus was decreased and GSK-3β expression in the hippocampus was increased by induction of diabetes. Treadmill exercise increased Wnt3 expression and suppressed GSK-3β expression in the diabetic rats. The present study suggests that treadmill exercise alleviates Alzheimer disease-associated memory loss by increasing neurogenesis through activating Wnt signaling pathway in the diabetic rats.

Differential expression of molecular markers of synaptic plasticity in the hippocampus, prefrontal cortex, and amygdala in response to spatial learning, predator exposure, and stress-induced amnesia.

PubMed

Zoladz, Phillip R; Park, Collin R; Halonen, Joshua D; Salim, Samina; Alzoubi, Karem H; Srivareerat, Marisa; Fleshner, Monika; Alkadhi, Karim A; Diamond, David M

2012-03-01

We have studied the effects of spatial learning and predator stress-induced amnesia on the expression of calcium/calmodulin-dependent protein kinase II (CaMKII), brain-derived neurotrophic factor (BDNF) and calcineurin in the hippocampus, basolateral amygdala (BLA), and medial prefrontal cortex (mPFC). Adult male rats were given a single training session in the radial-arm water maze (RAWM) composed of 12 trials followed by a 30-min delay period, during which rats were either returned to their home cages or given inescapable exposure to a cat. Immediately following the 30-min delay period, the rats were given a single test trial in the RAWM to assess their memory for the hidden platform location. Under control (no stress) conditions, rats exhibited intact spatial memory and an increase in phosphorylated CaMKII (p-CaMKII), total CaMKII, and BDNF in dorsal CA1. Under stress conditions, rats exhibited impaired spatial memory and a suppression of all measured markers of molecular plasticity in dorsal CA1. The molecular profiles observed in the BLA, mPFC, and ventral CA1 were markedly different from those observed in dorsal CA1. Stress exposure increased p-CaMKII in the BLA, decreased p-CaMKII in the mPFC, and had no effect on any of the markers of molecular plasticity in ventral CA1. These findings provide novel observations regarding rapidly induced changes in the expression of molecular plasticity in response to spatial learning, predator exposure, and stress-induced amnesia in brainregions involved in different aspects of memory processing. Copyright © 2011 Wiley Periodicals, Inc.

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

Effects of Aged Garlic Extract on Cholinergic, Glutamatergic and GABAergic Systems with Regard to Cognitive Impairment in Aβ-Induced Rats

PubMed Central

Thorajak, Piyaporn; Pannangrong, Wanassanun; Umka Welbat, Jariya; Chaijaroonkhanarak, Wunnee; Sripanidkulchai, Kittisak; Sripanidkulchai, Bungorn

2017-01-01

Alzheimer’s disease (AD) has been linked to the degeneration of central cholinergic and glutamatergic transmission, which correlates with progressive memory loss and the accumulation of amyloid-β (Aβ). It has been claimed that aged garlic extract (AGE) has a beneficial effect in preventing neurodegeneration in AD. Therefore, the objective of this study was to investigate the effects of AGE on Aβ-induced cognitive dysfunction with a biochemical basis in the cholinergic, glutamatergic, and GABAergic systems in rats. Adult male Wistar rats were orally administered three doses of AGE (125, 250, and 500 mg/kg) daily for 65 days. At day 56, they were injected with 1 μL of aggregated Aβ (1–42) into each lateral ventricle, bilaterally. After six days of Aβ injection, the rats’ working and reference memory was tested using a radial arm maze. The rats were then euthanized to investigate any changes to the cholinergic neurons, vesicular glutamate transporter 1 and 2 proteins (VGLUT1 and VGLUT2), and glutamate decarboxylase (GAD) in the hippocampus. The results showed that AGE significantly improved the working memory and tended to improve the reference memory in cognitively-impaired rats. In addition, AGE significantly ameliorated the loss of cholinergic neurons and increased the VGLUT1 and GAD levels in the hippocampus of rat brains with Aβ-induced toxicity. In contrast, the VGLUT2 protein levels did not change in any of the treated groups. We concluded that AGE was able to attenuate the impairment of working memory via the modification of cholinergic neurons, VGLUT1, and GAD in the hippocampus of Aβ-induced rats. PMID:28671572

Short-term estradiol administration in aging ovariectomized rats provides lasting benefits for memory and the hippocampus: a role for insulin-like growth factor-I.

PubMed

Witty, Christine F; Gardella, Layne P; Perez, Maria C; Daniel, Jill M

2013-02-01

We previously demonstrated that aged ovariectomized rats that had received prior estradiol treatment in middle age exhibited enhanced spatial memory and increased levels of estrogen receptor (ER)-α in the hippocampus long after estradiol treatment was terminated. The implication for cognition of increased levels of ERα resulting from prior estradiol exposure is unknown. In the absence of estrogens, growth factors, including IGF-I, can induce ERα-mediated transcription through ligand-independent mechanisms. Our current goal was to determine whether IGF-I mediates the ability of short-term exposure to estradiol to exert long-term effects on cognition and the hippocampus of aging females. Ovariectomized middle-aged rats were implanted with estradiol or cholesterol vehicle capsules. After 40 days, all capsules were removed and drug treatments were initiated. Half of each hormone treatment group received chronic intracerebroventricular delivery of the IGF-I receptor antagonist JB1, and the other half received artificial cerebrospinal fluid vehicle. Rats were tested on a spatial memory radial-arm maze task and hippocampi were immunostained for proteins of interest by Western blotting. As expected, previous treatment with estradiol enhanced spatial memory and increased levels of ERα in the hippocampus. JB1 reversed these effects. Previous treatment with estradiol resulted in lasting increases in levels of IGF-I receptors and phosphorylation of ERK/MAPK, a downstream signaling molecule of both ERα and IGF-I receptors, and increased levels of the ERα-regulated protein, choline acetyltransferase. JB1 blocked effects on ERK/MAPK and choline acetyltransferase. Results indicate that activation of IGF-I receptors is necessary for prior estradiol exposure to exert lasting impact on the hippocampus and memory.

Exercise preconditioning improves traumatic brain injury outcomes.

PubMed

Taylor, Jordan M; Montgomery, Mitchell H; Gregory, Eugene J; Berman, Nancy E J

2015-10-05

To determine whether 6 weeks of exercise performed prior to traumatic brain injury (TBI) could improve post-TBI behavioral outcomes in mice, and if exercise increases neuroprotective molecules (vascular endothelial growth factor-A [VEGF-A], erythropoietin [EPO], and heme oxygenase-1 [HO-1]) in brain regions responsible for movement (sensorimotor cortex) and memory (hippocampus). 120 mice were randomly assigned to one of four groups: (1) no exercise+no TBI (NOEX-NOTBI [n=30]), (2) no exercise+TBI (NOEX-TBI [n=30]), (3) exercise+no TBI (EX-NOTBI [n=30]), and (4) exercise+TBI (EX-TBI [n=30]). The gridwalk task and radial arm water maze were used to evaluate sensorimotor and cognitive function, respectively. Quantitative real time polymerase chain reaction and immunostaining were performed to investigate VEGF-A, EPO, and HO-1 mRNA and protein expression in the right cerebral cortex and ipsilateral hippocampus. EX-TBI mice displayed reduced post-TBI sensorimotor and cognitive deficits when compared to NOEX-TBI mice. EX-NOTBI and EX-TBI mice showed elevated VEGF-A and EPO mRNA in the cortex and hippocampus, and increased VEGF-A and EPO staining of sensorimotor cortex neurons 1 day post-TBI and/or post-exercise. EX-TBI mice also exhibited increased VEGF-A staining of hippocampal neurons 1 day post-TBI/post-exercise. NOEX-TBI mice demonstrated increased HO-1 mRNA in the cortex (3 days post-TBI) and hippocampus (3 and 7 days post-TBI), but HO-1 was not increased in mice that exercised. Improved TBI outcomes following exercise preconditioning are associated with increased expression of specific neuroprotective genes and proteins (VEGF-A and EPO, but not HO-1) in the brain. Copyright © 2015 Elsevier B.V. All rights reserved.

The involvement of cholinergic and noradrenergic systems in behavioral recovery following oxotremorine treatment to chronically stressed rats.

PubMed

Srikumar, B N; Raju, T R; Shankaranarayana Rao, B S

2006-12-01

Chronic stress in rats has been shown to impair learning and memory, and precipitate several affective disorders like depression and anxiety. The mechanisms involved in these stress-induced disorders and the possible reversal are poorly understood, thus limiting the number of drugs available for their treatment. Our earlier studies suggest cholinergic dysfunction as the underlying cause in the behavioral deficits following stress. Muscarinic cholinergic agonist, oxotremorine is demonstrated to have a beneficial effect in reversing brain injury-induced behavioral dysfunction. In this study, we have evaluated the effect of oxotremorine treatment on chronic restraint stress-induced cognitive deficits. Rats were subjected to restraint stress (6 h/day) for 21 days followed by oxotremorine treatment for 10 days. Spatial learning and memory was assessed in a partially baited eight-arm radial maze task. Stressed rats exhibited impairment in performance, with decreased percentage of correct choices and an increase in the number of reference memory errors (RMEs). Oxotremorine treatment (0.1 or 0.2 mg/kg, i.p.) to stressed rats resulted in a significant increase in the percent correct choices and a decrease in the number of RMEs compared with stress as well as the stress+vehicle-treated groups. In the retention test, oxotremorine treated rats committed less RMEs compared with the stress group. Chronic restraint stress decreased acetylcholinesterase (AChE) activity in the hippocampus, frontal cortex and septum, which was reversed by both the doses of oxotremorine. Further, oxotremorine treatment also restored the norepinephrine levels in the hippocampus and frontal cortex. Thus, this study demonstrates the potential of cholinergic muscarinic agonists and the involvement of both cholinergic and noradrenergic systems in the reversal of stress-induced learning and memory deficits.

The preclinical pharmacological profile of WAY-132983, a potent M1 preferring agonist.

PubMed

Bartolomeo, A C; Morris, H; Buccafusco, J J; Kille, N; Rosenzweig-Lipson, S; Husbands, M G; Sabb, A L; Abou-Gharbia, M; Moyer, J A; Boast, C A

2000-02-01

Muscarinic M1 preferring agonists may improve cognitive deficits associated with Alzheimer's disease. Side effect assessment of the M1 preferring agonist WAY-132983 showed significant salivation (10 mg/kg i.p. or p.o.) and produced dose-dependent hypothermia after i. p. or p.o. administration. WAY-132983 significantly reduced scopolamine (0.3 mg/kg i.p.)-induced hyperswimming in mice. Cognitive assessment in rats used pretrained animals in a forced choice, 1-h delayed nonmatch-to-sample radial arm maze task. WAY-132983 (0.3 mg/kg i.p) significantly reduced scopolamine (0.3 mg/kg s.c.)-induced errors. Oral WAY-132983 attenuated scopolamine-induced errors; that is, errors produced after combining scopolamine and WAY-132983 (to 3 mg/kg p.o.) were not significantly increased compared with those of vehicle-treated control animals, whereas errors after scopolamine were significantly higher than those of control animals. With the use of miniosmotic pumps, 0.03 mg/kg/day (s.c.) WAY-132983 significantly reduced AF64A (3 nmol/3 microliter/lateral ventricle)-induced errors. Verification of AF64A cholinotoxicity showed significantly lower choline acetyltransferase activity in the hippocampi of AF64A-treated animals, with no significant changes in the striatal or frontal cortex. Cognitive assessment in primates involved the use of pretrained aged animals in a visual delayed match-to-sample procedure. Oral WAY-132983 significantly increased the number of correct responses during short and long delay interval testing. These effects were also apparent 24 h after administration. WAY-132983 exhibited cognitive benefit at doses lower than those producing undesirable effects; therefore, WAY-132983 is a potential candidate for improving the cognitive status of patients with Alzheimer's disease.

Altered synaptic marker abundance in the hippocampal stratum oriens of Ts65Dn mice is associated with exuberant expression of versican

PubMed Central

Howell, Matthew D; Gottschall, Paul E

2012-01-01

DS (Down syndrome), resulting from trisomy of chromosome 21, is the most common cause of genetic mental retardation; however, the molecular mechanisms underlying the cognitive deficits are poorly understood. Growing data indicate that changes in abundance or type of CSPGs (chondroitin sulfate proteoglycans) in the ECM (extracellular matrix) can influence synaptic structure and plasticity. The purpose of this study was to identify changes in synaptic structure in the hippocampus in a model of DS, the Ts65Dn mouse, and to determine the relationship to proteoglycan abundance and/or cleavage and cognitive disability. We measured synaptic proteins by ELISA and changes in lectican expression and processing in the hippocampus of young and old Ts65Dn mice and LMCs (littermate controls). In young (5 months old) Ts65Dn hippocampal extracts, we found a significant increase in the postsynaptic protein PSD-95 (postsynaptic density 95) compared with LMCs. In aged (20 months old) Ts65Dn hippocampus, this increase was localized to hippocampal stratum oriens extracts compared with LMCs. Aged Ts65Dn mice exhibited impaired hippocampal-dependent spatial learning and memory in the RAWM (radial-arm water maze) and a marked increase in levels of the lectican versican V2 in stratum oriens that correlated with the number of errors made in the final RAWM block. Ts65Dn stratum oriens PNNs (perineuronal nets), an extension of the ECM enveloping mostly inhibitory interneurons, were dispersed over a larger area compared with LMC mice. Taken together, these data suggest a possible association with alterations in the ECM and inhibitory neurotransmission in the Ts65Dn hippocampus which could contribute to cognitive deficits. PMID:22225533

Effects of Maternal Choline Supplementation on the Septohippocampal Cholinergic System in the Ts65Dn Mouse Model of Down Syndrome

PubMed Central

Kelley, Christy M.; Ash, Jessica A.; Powers, Brian E.; Velazquez, Ramon; Alldred, Melissa J.; Ikonomovic, Milos D.; Ginsberg, Stephen D.; Strupp, Barbara J.; Mufson, Elliott J.

2016-01-01

Down syndrome (DS), caused by trisomy of chromosome 21, is marked by intellectual disability (ID) and early onset of Alzheimer’s disease (AD) neuropathology including hippocampal cholinergic projection system degeneration. Here we determined the effects of age and maternal choline supplementation (MCS) on hippocampal cholinergic deficits in Ts65Dn mice. Ts65Dn mice and disomic (2N) littermates sacrificed at ages 6–8 and 14–18 mos were used for an aging study, and Ts65Dn and 2N mice derived from Ts65Dn dams were maintained on either a choline-supplemented or a choline-controlled diet (conception to weaning) and examined at 14–18 mos for MCS studies. In the latter, mice were behaviorally tested on the radial arm Morris water maze (RAWM) and hippocampal tissue was examined for intensity of choline acetyltransferase (ChAT) immunoreactivity. Hippocampal ChAT activity was evaluated in a separate cohort. ChAT-positive fiber innervation was significantly higher in the hippocampus and dentate gyrus in Ts65Dn mice compared with 2N mice, independent of age or maternal diet. Similarly, hippocampal ChAT activity was significantly elevated in TS65Dn mice compared to 2N mice, independent of maternal diet. A significant increase with age was seen in hippocampal cholinergic innervation of 2N mice, but not Ts65Dn mice. Degree of ChAT intensity correlated negatively with spatial memory ability in unsupplemented 2N and Ts65Dn mice, but positively in MCS 2N mice. The increased innervation produced by MCS appears to improve hippocampal function, making this a therapy that may be exploited for future translational approaches in human DS. PMID:26391045

Evaluation of Epidemiology and Animal Data for Risk Assessment: Chlorpyrifos Developmental Neurobehavioral Outcomes

PubMed Central

Li, Abby A.; Lowe, Kimberly A.; McIntosh, Laura J.; Mink, Pamela J.

2012-01-01

Developmental neurobehavioral outcomes attributed to exposure to chlorpyrifos (CPF) obtained from epidemiologic and animal studies published before June 2010 were reviewed for risk assessment purposes. For epidemiological studies, this review considered (1) overall strength of study design, (2) specificity of CPF exposure biomarkers, (3) potential for bias, and (4) Hill guidelines for causal inference. In the case of animal studies, this review focused on evaluating the consistency of outcomes for developmental neurobehavioral endpoints from in vivo mammalian studies that exposed dams and/or offspring to CPF prior to weaning. Developmental neuropharmacologic and neuropathologic outcomes were also evaluated. Experimental design and methods were examined as part of the weight of evidence. There was insufficient evidence that human developmental exposures to CPF produce adverse neurobehavioral effects in infants and children across different cohort studies that may be relevant to CPF exposure. In animals, few behavioral parameters were affected following gestational exposures to 1 mg/kg-d but were not consistently reported by different laboratories. For postnatal exposures, behavioral effects found in more than one study at 1 mg/kg-d were decreased errors on a radial arm maze in female rats and increased errors in males dosed subcutaneously from postnatal day (PND) 1 to 4. A similar finding was seen in rats exposed orally from PND 1 to 21 with incremental dose levels of 1, 2, and 4 mg/kg-d, but not in rats dosed with constant dose level of 1 mg/kg-d. Neurodevelopmental behavioral, pharmacological, and morphologic effects occurred at doses that produced significant brain or red blood cell acetylcholinesterase inhibition in dams or offspring. PMID:22401178

Ketogenic diet improves motor performance but not cognition in two mouse models of Alzheimer's pathology.

PubMed

Brownlow, Milene L; Benner, Leif; D'Agostino, Dominic; Gordon, Marcia N; Morgan, Dave

2013-01-01

Dietary manipulations are increasingly viewed as possible approaches to treating neurodegenerative diseases. Previous studies suggest that Alzheimer's disease (AD) patients present an energy imbalance with brain hypometabolism and mitochondrial deficits. Ketogenic diets (KDs), widely investigated in the treatment and prevention of seizures, have been suggested to bypass metabolic deficits present in AD brain by providing ketone bodies as an alternative fuel to neurons. We investigated the effects of a ketogenic diet in two transgenic mouse lines. Five months old APP/PS1 (a model of amyloid deposition) and Tg4510 (a model of tau deposition) mice were offered either a ketogenic or a control (NIH-31) diet for 3 months. Body weight and food intake were monitored throughout the experiment, and blood was collected at 4 weeks and 4 months for ketone and glucose assessments. Both lines of transgenic mice weighed less than nontransgenic mice, yet, surprisingly, had elevated food intake. The ketogenic diet did not affect these differences in body weight or food consumption. Behavioral testing during the last two weeks of treatment found that mice offered KD performed significantly better on the rotarod compared to mice on the control diet independent of genotype. In the open field test, both transgenic mouse lines presented increased locomotor activity compared to nontransgenic, age-matched controls, and this effect was not influenced by KD. The radial arm water maze identified learning deficits in both transgenic lines with no significant differences between diets. Tissue measures of amyloid, tau, astroglial and microglial markers in transgenic lines showed no differences between animals fed the control or the ketogenic diet. These data suggest that ketogenic diets may play an important role in enhancing motor performance in mice, but have minimal impact on the phenotype of murine models of amyloid or tau deposition.

The effects of memantine on recovery, cognitive functions, and pain after propofol anesthesia.

PubMed

Emik, Ulku; Unal, Yusuf; Arslan, Mustafa; Demirel, Cengiz Bekir

2016-01-01

Postoperative cognitive dysfunction refers to the problems associated with thought and memory that are often experienced after major surgery. The aim of this study is to evaluate the effects of intraperitoneally administered memantine on recovery, cognitive functions, and pain after propofol anesthesia. The study was conducted in Gazi University Animal Research Laboratory, Ankara, Turkey in January 2012. Twenty-four adult female Wistar Albino rats weighing 170-270g were educated for 300s in the radial arm maze (RAM) over three days. Group P was administered 150mgkg(-1) of intraperitoneal (IP) propofol; Group M was given 1mgkg(-1) of IP memantine; and Group MP was given 1mgkg(-1) of IP memantine before being administered 150mgkg(-1) of IP propofol. The control group received only IP saline. RAM and hot plate values were obtained after recovery from the groups that received propofol anesthesia and 30min after the administration of drugs in other two groups. The duration of recovery for Group MP was significantly shorter than Group P (p<0.001), and the number of entries and exits in the RAM by Group MP was significantly higher during the first hour when compared to Group P (p<0.0001). Hot plate values, on the other hand, were found to be significantly increased in all groups when compared to the control values, aside from Group C (p<0.0001). In this study, memantine provided shorter recovery times, better cognitive functions, and reduced postoperative pain. From this study, we find that memantine has beneficial effects on recovery, cognitive functions, and pain after propofol anesthesia. Copyright © 2015 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.

Effects of Electromagnetic Radiation from Smartphones on Learning Ability and Hippocampal Progenitor Cell Proliferation in Mice

PubMed Central

Choi, Yu-Jin; Choi, Yun-Sik

2015-01-01

Objectives Nonionizing radiation is emitted from electronic devices, such as smartphones. In this study, we intended to elucidate the effect of electromagnetic radiation from smartphones on spatial working memory and progenitor cell proliferation in the hippocampus. Methods Both male and female mice were randomly separated into two groups (radiated and control) and the radiated group was exposed to electromagnetic radiation for 9 weeks and 11 weeks for male and female mice, respectively. Spatial working memory was examined with a Y maze, and proliferation of hippocampal progenitor cells were examined by 5-bromo-2′-deoxyuridine administration and immunohistochemical detection. Results When spatial working memory on a Y maze was examined in the 9th week, there was no significant difference in the spontaneous alternation score on the Y maze between the two groups. In addition, there was no significant difference in hippocampal progenitor cell proliferation. However, immunoreactivity to glial fibrillary acidic protein was increased in exposed animals. Next, to test the effect of recovery following chronic radiation exposure, the remaining female mice were further exposed to electromagnetic radiation for 2 more weeks (total 11 weeks), and spontaneous alternation was tested 4 weeks later. In this experiment, although there was no significant difference in the spontaneous alternation scores, the number of arm entry was significantly increased. Conclusion These data indicate that although chronic electromagnetic radiation does not affect spatial working memory and hippocampal progenitor cell proliferation it can mediate astrocyte activation in the hippocampus and delayed hyperactivity-like behavior. PMID:26981337

Effects of acute or repeated paroxetine and fluoxetine treatment on affective behavior in male and female adolescent rats

PubMed Central

Amodeo, Leslie R.; Greenfield, Venuz Y.; Humphrey, Danielle E.; Varela, Veronica; Pipkin, Joseph A.; Eaton, Shannon E.; Johnson, Jelesa D.; Plant, Christopher P.; Harmony, Zachary R.; Wang, Li; Crawford, Cynthia A.

2015-01-01

Rationale The SSRI antidepressant fluoxetine is one of the few drugs that is effective at treating depression in adolescent humans. In contrast, the SSRI paroxetine has limited efficacy and is more at risk for inducing suicidal behavior. Objective The purpose of the present study was to more fully characterize the differential actions of paroxetine and fluoxetine. Methods In Experiment 1, male and female rats were injected with paroxetine (2.5 or 10 mg/kg), fluoxetine (10 mg/kg), or vehicle for 10 days starting on postnatal day (PD) 35, and affective behaviors were assessed using sucrose preference and elevated plus maze tasks. A separate set of rats were used to examine monoamine levels. In Experiment 2, rats were injected with paroxetine (2.5, 5 or 10 mg/kg), fluoxetine (5, 10 or 20 mg/kg), or vehicle during the same time frame as Experiment 1 and anxiety-like behaviors were measured using elevated plus maze, light/dark box, and acoustic startle. Results Repeated SSRI treatment failed to alter sucrose preference, although both paroxetine and fluoxetine reduced time spent in the open arms of the elevated plus maze and light compartment of the light/dark box. Paroxetine, but not fluoxetine, enhanced acoustic startle and interfered with habituation. Serotonin turnover was decreased by both acute and repeated fluoxetine treatment but unaltered by paroxetine administration. Discussion These results show that repeated treatment with paroxetine and fluoxetine has dissociable actions in adolescent rats. In particular, paroxetine, but not fluoxetine, increases acoustic startle at low doses and may increase sensitivity to environmental stressors. PMID:26141193

Anxiolytic-like effects of ursolic acid in mice.

PubMed

Colla, André R S; Rosa, Julia M; Cunha, Mauricio P; Rodrigues, Ana Lúcia S

2015-07-05

Ursolic acid is a pentacyclic triterpenoid that possesses several biological and neuropharmacological effects including antidepressant-like activity. Anxiety disorders represent common and disability psychiatric conditions that are often associated with depressive symptoms. This work investigated the anxiolytic-like effects of ursolic acid administration in different behavioral paradigms that evaluate anxiety in mice: open field test, elevated plus maze test, light/dark box test and marble burying test. To this end, mice were administered with ursolic acid (0.1, 1 and 10mg/kg, p.o.) or diazepam (2mg/kg, p.o.), positive control, and submitted to the behavioral tests. The results show that ursolic acid (10mg/kg) elicited an anxiolytic-like effect observed by the increased total time in the center and decreased number of rearings responses in the open field test and an increased percentage of entries and total time spent in the open arms of elevated plus maze, similarly to diazepam. No significant effects of ursolic acid were shown in the light/dark box and marble burying test. These data indicate that ursolic acid exhibits anxiolytic-like effects in the open field and elevated plus maze test, but not in the light/dark box and marble burying test, showing the relevance of testing several behavioral paradigms in the evaluation of anxiolytic-like actions. Of note, the results extend the understanding on the effects of ursolic acid in the central nervous system and suggest that it may be a novel approach for the management of anxiety-related disorders. Copyright © 2015. Published by Elsevier B.V.

Effects of acute or repeated paroxetine and fluoxetine treatment on affective behavior in male and female adolescent rats.

PubMed

Amodeo, Leslie R; Greenfield, Venuz Y; Humphrey, Danielle E; Varela, Veronica; Pipkin, Joseph A; Eaton, Shannon E; Johnson, Jelesa D; Plant, Christopher P; Harmony, Zachary R; Wang, Li; Crawford, Cynthia A

2015-10-01

The SSRI antidepressant fluoxetine is one of the few drugs that is effective at treating depression in adolescent humans. In contrast, the SSRI paroxetine has limited efficacy and is more at risk for inducing suicidal behavior. The purpose of the present study was to more fully characterize the differential actions of paroxetine and fluoxetine. In experiment 1, male and female rats were injected with paroxetine (2.5 or 10 mg/kg), fluoxetine (10 mg/kg), or vehicle for 10 days starting on postnatal day (PD) 35, and affective behaviors were assessed using sucrose preference and elevated plus maze tasks. A separate set of rats were used to examine monoamine levels. In experiment 2, rats were injected with paroxetine (2.5, 5, or 10 mg/kg), fluoxetine (5, 10, or 20 mg/kg), or vehicle during the same time frame as experiment 1, and anxiety-like behaviors were measured using elevated plus maze, light/dark box, and acoustic startle. Repeated SSRI treatment failed to alter sucrose preference, although both paroxetine and fluoxetine reduced time spent in the open arms of the elevated plus maze and light compartment of the light/dark box. Paroxetine, but not fluoxetine, enhanced acoustic startle and interfered with habituation. Serotonin turnover was decreased by both acute and repeated fluoxetine treatment but unaltered by paroxetine administration. These results show that repeated treatment with paroxetine and fluoxetine has dissociable actions in adolescent rats. In particular, paroxetine, but not fluoxetine, increases acoustic startle at low doses and may increase sensitivity to environmental stressors.

Sex differences in the neurochemical and functional effects of MDMA in Sprague-Dawley rats.

PubMed

Walker, Q David; Williams, Christina N; Jotwani, Rakesh P; Waller, Samuel T; Francis, Reynold; Kuhn, Cynthia M

2007-01-01

3,4-Methylenedioxymethamphetamine (MDMA; "Ecstasy") use has been associated with acute toxicities and persistent depletion of the neurotransmitter serotonin (5-HT). This study investigates whether sex differences in the acute and long-term effects of MDMA exist. Male and female rats received saline or 15 mg/kg MDMA, ip, bid for 4 days. Temperature was monitored on days 1 and 4. Locomotor activity was measured in a second cohort of animals on days 1 and 4 and after recovery on day 14. The effects of MDMA on performance in a plus maze task and brain levels of serotonin (5-HT) and the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) were determined in a third cohort of animals 2 weeks after the last MDMA treatment. Locomotor activity and temperature increased after MDMA administration on day 1. The drug-induced increases in temperature but not locomotion attenuated with repeated MDMA administration. Male and female MDMA-treated rats spent less time in the open arms of the elevated plus maze and had less 5-HT and 5-HIAA in all brain regions 2 weeks after the end of treatment. Temperature effects of MDMA and persistent effects on plus maze and brain serotonin content were similar in males and females. In contrast, females exhibited markedly greater locomotor stimulation after acute MDMA and also showed sensitization to an acute challenge 2 weeks later. MDMA elicits substantially greater locomotor activation in female rats than in males, but persistent effects on anxiety and serotonin content were similar in males and females.

Intermittent ethanol exposure increases long-lasting behavioral and neurochemical effects of MDMA in adolescent mice.

PubMed

Rodríguez-Arias, Marta; Maldonado, Concepción; Vidal-Infer, Antonio; Guerri, Consuelo; Aguilar, María A; Miñarro, José

2011-11-01

Heavy binge drinking is increasingly frequent among adolescents, while ethanol (EtOH) is often used in combination with 3,4-methylenedioxymethamphetamine (MDMA). The long-lasting effects of intermittent exposure to EtOH and MDMA during adolescence on motor activity, anxiety, and social behavior were evaluated in adult mice. The concentration of brain monoamines in the striatum, cortex, and hippocampus was measured following the behavioral test. Adolescent OF1 mice were exposed to ethanol (1.25 g/kg) on two consecutive days at 48-h intervals over a 14-day period (from PND 29 to 42). A total of eight injections of MDMA (10 or 20 mg/kg) were administered twice daily at 4-h intervals over two consecutive days, and this schedule was repeated 6 days later (PND 33, 34, 41, and 42). Behavioral tests and analysis of brain monoamines took place on PND 64 to 67. Exposure to MDMA during adolescence increased the anxiogenic response in the elevated plus maze, with adult mice spending less time in the open arms of the maze and exhibiting lower concentrations of DA in the striatum. A pattern of ethanol administration modeling binge drinking during adolescence enhanced these effects and undermined the hyperthermic response induced by MDMA. Passive avoidance was affected only when EtOH was administered alone. Juvenile administration of MDMA and alcohol was found to cause a decrease in monoamine levels in adulthood, as well as changes in social interaction behaviors, locomotor activity, increase measures of anxiety in the elevated plus maze (EPM), and decrease step-through latencies in passive avoidance test.

Rapamycin blocks the antidepressant effect of ketamine in task-dependent manner.

PubMed

Holubova, Kristina; Kleteckova, Lenka; Skurlova, Martina; Ricny, Jan; Stuchlik, Ales; Vales, Karel

2016-06-01

The aim of our study was to test whether ketamine produces an antidepressant effect in animal model of olfactory bulbectomy and assess the role of mammalian target of rapamycin (mTOR) pathway in ketamine's antidepressant effect. Bulbectomized (OBX) rats and sham controls were assigned to four subgroups according to the treatment they received (ketamine, saline, ketamine + rapamycin, and saline + rapamycin). The animals were subjected to open field (OF), elevated plus maze (EPM), passive avoidance (PA), Morris water maze (MWM), and Carousel maze (CM) tests. Blood samples were collected before and after drug administration for analysis of phosphorylated mTOR level. After behavioral testing, brains were removed for evaluation of brain-derived neurotrophic factor (BDNF) in prefrontal cortex (PFC) and hippocampus. Ketamine normalized hyperactivity of OBX animals in EPM and increased the time spent in open arms. Rapamycin pretreatment resulted in elimination of ketamine effect in EPM test. In CM test, ketamine + rapamycin administration led to cognitive impairment not observed in saline-, ketamine-, or saline + rapamycin-treated OBX rats. Prefrontal BDNF content was significantly decreased, and level of mTOR was significantly elevated in OBX groups. OBX animals significantly differed from sham controls in most of the tests used. Treatment had more profound effect on OBX phenotype than controls. Pretreatment with rapamycin eliminated the anxiolytic and antidepressant effects of ketamine in task-dependent manner. The results indicate that ketamine + rapamycin application resulted in impaired stress responses manifested by cognitive deficits in active place avoidance (CM) test. Intensity of stressor (mild vs. severe) used in the behavioral tests had opposite effect on controls and on OBX animals.

HSP90 and pCREB alterations are linked to mancozeb-dependent behavioral and neurodegenerative effects in a marine teleost

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

Zizza, Merylin

The pesticide mancozeb (mz) is recognized as a potent inducer of oxidative stress due to its ability to catalyze the production of reactive oxygen species plus inhibiting mitochondrial respiration thus becoming an environmental risk for neurodegenerative diseases. Despite numerous toxicological studies on mz have been directed to mammals, attention on marine fish is still lacking. Thus, it was our intention to evaluate neurobehavioral activities of ornate wrasses (Thalassoma pavo) exposed to 0.2 mg/l of mz after a preliminary screening test (0.07–0.3 mg/l). Treated fish exhibited an evident (p < 0.001) latency to reach T-maze arms (> 1000%) while exploratory attitudesmore » (total arm entries) diminished (− 50%; p < 0.05) versus controls during spontaneous exploration tests. Moreover, they showed evident enhancements (+ 111%) of immobility in the cylinder test. Contextually, strong (− 88%; p < 0.01) reductions of permanence in light zone of the Light/Dark apparatus along with diminished crossings (− 65%) were also detected. Conversely, wrasses displayed evident enhancements (160%) of risk assessment consisting of fast entries in the dark side of this apparatus. From a molecular point of view, a notable activation (p < 0.005) of the brain transcription factor pCREB occurred during mz-exposure. Similarly, in situ hybridization supplied increased HSP90 mRNAs in most brain areas such as the lateral part of the dorsal telencephalon (Dl; + 68%) and valvula of the cerebellum (VCe; + 35%) that also revealed evident argyrophilic signals. Overall, these first indications suggest a possible protective role of the early biomarkers pCREB and HSP90 against fish toxicity. - Highlights: • Fish exposed to mancozeb exhibited an evident latency to reach T-maze arms. • Mancozeb caused immobility and reduction of explorative attitudes. • Fish exposed to mancozeb showed anxiogenic performances in the Light/Dark apparatus. • The brain of fish exposed to mancozeb supplied pCREB plus HSP90 mRNA up-regulations. • Some brain areas of fish exposed to mancozeb revealed an evident neurodegeneration.« less

Effects of interleukin-1beta and lipopolysaccharide on behavior of mice in the elevated plus-maze and open field tests.

PubMed

Swiergiel, Artur H; Dunn, Adrian J

2007-04-01

It has been postulated that infections, inflammatory processes and resulting cytokines may be causative factors in emotional disorders, including depression and anxiety. Support for this possibility has been sought in studies of animal behavior following administration of interleukin-1 (IL-1) and lipopolysaccharide (LPS). However, such treatments induce a variety of behavioral responses, collectively known as sickness behavior, some of which could affect the performance in tests used to assess anxiety and depression. Thus the effects of peripheral administration of IL-1beta and LPS on the behavior of mice were studied in the elevated plus-maze (EPM) and the open field (OF). Mouse IL-1beta (30, 100, 300, and 1000 ng) was injected intraperitoneally 30 or 60 min, and LPS (0.5, 1 and 5 microg) 120 min before the tests. IL-1beta and LPS induced dose-dependent decreases in open arm entries and the time spent on the open arms in the EPM, effects considered to reflect anxiety-like behavior. However, entries to all arms were also reduced in a dose-dependent manner, indicating a decrease in general activity. In the OF, IL-1beta and LPS decreased the number of line crossings in the center of the field, that can also be considered to reflect anxiety-like behavior. However, this effect was accompanied by a similar decrease in line crossings in the periphery, as well as in rears and climbs. Thus the doses of IL-1beta and LPS necessary to induce these effects also decreased locomotor activity in the EPM and OF. Therefore, the behavioral responses induced by IL-1beta and LPS in the EPM and the OF considered to reflect anxiety must be interpreted in the light of this reduction in overall activity. Thus the results do not provide unequivocal support for the suggestion that LPS or IL-1 mediate anxiety. Nevertheless, because infections, endotoxins, and the ensuing cytokines cause alterations in CNS norepinephrine and serotonin, they may contribute to emotionality, and perhaps to anxiety.

How does a planet excite multiple spiral arms?

NASA Astrophysics Data System (ADS)

Bae, Jaehan; Zhu, Zhaohuan

2018-01-01

Protoplanetary disk simulations show that a single planet excites multiple spiral arms in the background disk, potentially supported by the multi-armed spirals revealed with recent high-resolution observations in some disks. The existence of multiple spiral arms is of importance in many aspects. It is empirically found that the arm-to-arm separation increases as a function of the planetary mass, so one can use the morphology of observed spiral arms to infer the mass of unseen planets. In addition, a spiral arm opens a radial gap as it steepens into a shock, so when a planet excites multiple spiral arms it can open multiple gaps in the disk. Despite the important implications, however, the formation mechanism of multiple spiral arms has not been fully understood by far.In this talk, we explain how a planet excites multiple spiral arms. The gravitational potential of a planet can be decomposed into a Fourier series, a sum of individual azimuthal modes having different azimuthal wavenumbers. Using a linear wave theory, we first demonstrate that appropriate sets of Fourier decomposed waves can be in phase, raising a possibility that constructive interference among the waves can produce coherent structures - spiral arms. More than one spiral arm can form since such constructive interference can occur at different positions in the disk for different sets of waves. We then verify this hypothesis using a suite of two-dimensional hydrodynamic simulations. Finally, we present non-linear behavior in the formation of multiple spiral arms.

Visualization of 3D elbow kinematics using reconstructed bony surfaces

NASA Astrophysics Data System (ADS)

Lalone, Emily A.; McDonald, Colin P.; Ferreira, Louis M.; Peters, Terry M.; King, Graham J. W.; Johnson, James A.

2010-02-01

An approach for direct visualization of continuous three-dimensional elbow kinematics using reconstructed surfaces has been developed. Simulation of valgus motion was achieved in five cadaveric specimens using an upper arm simulator. Direct visualization of the motion of the ulna and humerus at the ulnohumeral joint was obtained using a contact based registration technique. Employing fiducial markers, the rendered humerus and ulna were positioned according to the simulated motion. The specific aim of this study was to investigate the effect of radial head arthroplasty on restoring elbow joint stability after radial head excision. The position of the ulna and humerus was visualized for the intact elbow and following radial head excision and replacement. Visualization of the registered humerus/ulna indicated an increase in valgus angulation of the ulna with respect to the humerus after radial head excision. This increase in valgus angulation was restored to that of an elbow with a native radial head following radial head arthroplasty. These findings were consistent with previous studies investigating elbow joint stability following radial head excision and arthroplasty. The current technique was able to visualize a change in ulnar position in a single DoF. Using this approach, the coupled motion of ulna undergoing motion in all 6 degrees-of-freedom can also be visualized.

Clinical and Radiographic Outcomes of Unipolar and Bipolar Radial Head Prosthesis in Patients with Radial Head Fracture: A Systemic Review and Meta-Analysis.

PubMed

Chen, Hongwei; Wang, Ziyang; Shang, Yongjun

2018-06-01

To compare clinical outcomes of unipolar and bipolar radial head prosthesis in the treatment of patients with radial head fracture. Medline, Cochrane, EMBASE, Google Scholar databases were searched until April 18, 2016 using the following search terms: radial head fracture, elbow fracture, radial head arthroplasty, implants, prosthesis, unipolar, bipolar, cemented, and press-fit. Randomized controlled trials, retrospective, and cohort studies were included. The Mayo elbow performance score (MEPS), disabilities of the arm, shoulder, and hand (DASH) score, radiologic assessment, ROM, and grip strength following elbow replacement were similar between prosthetic devices. The pooled mean excellent/good ranking of MEPS was 0.78 for unipolar and 0.73 for bipolar radial head arthroplasty, and the pooled mean MEPS was 86.9 and 79.9, respectively. DASH scores for unipolar and bipolar prosthesis were 19.0 and 16.3, respectively. Range of motion outcomes were similar between groups, with both groups have comparable risk of flexion arc, flexion, extension deficit, rotation arc, pronation, and supination (p values <0.001 for both unipolar and bipolar prosthesis). However, bipolar radial head prosthesis was associated with an increased chance of heterotopic ossification and lucency (p values ≤0.049) while unipolar prosthesis was not (p values ≥0.088). Both groups had risk for development of capitellar osteopenia or erosion/wear (p values ≤0.039). Unipolar and bipolar radial head prostheses were similar with respect to clinical outcomes. Additional comparative studies are necessary to further compare different radial head prostheses used to treat radial head fracture.

Radial access for cerebrovascular procedures: Case report and technical note.

PubMed

Satti, Sudhakar R; Vance, Ansar Z; Sivapatham, Thinesh

2016-04-01

Advantages of radial access over brachial/axillary or femoral access have been well described for several decades and include decreased cost, patient preference, and decreased major access site complications. Despite these advantages, radial access is rarely employed or even considered for neurointerventional procedures. This attitude should be reconsidered given several recent large, randomized, controlled trials from the cardiovascular literature proving that radial access is associated with statistically lower costs, decreased incidence of myocardial infarctions, strokes, and even decreased mortality. Radial access is now considered the standard of care for percutaneous coronary interventions in most US centers. Although radial access has been described for neurovascular procedures in the past, overall experience is limited. The two major challenges are the unique anatomy required to access the cerebral vasculature given very acute angles between the arm and craniocervical vessels and limitations in available technology. We present a simplified approach to radial access for cerebrovascular procedures and provide a concise step-by-step approach for patient selection, ultrasound-guided single-wall access, recommended catheters/wires, and review of patent hemostasis. Additionally, we present a complex cerebrovascular intervention in which standard femoral access was unsuccessful, while radial access was quickly achieved to highlight the importance of familiarity with the radial approach for all neurointerventionalists. We have found that the learning curve is not too steep and that the radial access approach can be adopted smoothly for a large percentage of diagnostic and interventional neuroradiologic procedures. Radial access should be considered in all patients undergoing a cerebrovascular procedure. © The Author(s) 2015.

Spontaneous radial nerve palsy subsequent to non-traumatic neuroma.

PubMed

Ebrahimpour, Adel; Nazerani, Shahram; Tavakoli Darestani, Reza; Khani, Salim

2013-09-01

Spontaneous radial palsy is a not rare finding in hand clinics. The anatomy of the radial nerve renders it prone to pressure paralysis as often called "Saturday night palsy". This problem is a transient nerve lesion and an acute one but the case presented here is very unusual in that it seems this entity can also occur as an acute on chronic situation with neuroma formation. A 61 year-old man presented with the chief complaint of inability to extend the wrist and the fingers of the left hand which began suddenly the night before admission, following a three-week history of pain, numbness and tingling sensation of the affected extremity. He had no history of trauma to the extremity. Electromyography revealed a severe conductive defect of the left radial nerve with significant axonal loss at the upper arm. Surgical exploration identified a neuroma of the radial nerve measuring 1.5 cm in length as the cause of the paralysis. The neuroma was removed and an end-to-end nerve coaption was performed. Complete recovery of the hand and finger extension was achieved in nine months.

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.

Studies on cerebral protection of digoxin against hypoxic-ischemic brain damage in neonatal rats.

PubMed

Peng, Kaiwei; Tan, Danfeng; He, Miao; Guo, Dandan; Huang, Juan; Wang, Xia; Liu, Chentao; Zheng, Xiangrong

2016-08-17

Hypoxic-ischemic brain damage (HIBD) is a major cause of neonatal acute deaths and chronic nervous system damage. Our present study was designed to investigate the possible neuroprotective effect of digoxin-induced pharmacological preconditioning after hypoxia-ischemia and underlying mechanisms. Neonatal rats were assigned randomly to control, HIBD, or HIBD+digoxin groups. Pharmacological preconditioning was induced by administration of digoxin 72 h before inducing HIBD by carotid occlusion+hypoxia. Behavioral assays, and neuropathological and apoptotic assessments were performed to examine the effects; the expression of Na/K ATPase was also assessed. Rats in the HIBD group showed deficiencies on the T-maze, radial water maze, and postural reflex tests, whereas the HIBD+digoxin group showed significant improvements on all behavioral tests. The rats treated with digoxin showed recovery of pathological conditions, increased number of neural cells and proliferative cells, and decreased number of apoptotic cells. Meanwhile, an increased expression level of Na/K ATPase was observed after digoxin preconditioning treatment. The preconditioning treatment of digoxin contributed toward an improved functional recovery and exerted a marked neuroprotective effect including promotion of cell proliferation and reduction of apoptosis after HIBD, and the neuroprotective action was likely associated with increased expression of Na/K ATPase.

Nootropic and anxiolytic activity of saponins of Albizzia lebbeck leaves.

PubMed

Une, H D; Sarveiya, V P; Pal, S C; Kasture, V S; Kasture, S B

2001-01-01

The effect of saponin containing, n-butanolic fraction (BF), extracted from dried leaves of Albizzia lebbeck, was studied on cognitive behavior and anxiety in albino mice. The elevated plus maze was used for assessment of both nootropic and anxiolytic activity. The nootropic activity was evaluated by recording the effect of BF (0, 10, 25, and 50 mg/kg) on the transfer latency, whereas anxiolytic activity was assessed by studying its effect on the duration of occupancy in the closed arm. Results showed significant improvement in the retention ability of the normal and amnesic mice as compared to their respective controls. Animals treated with BF (25 mg/kg) spent more time in the open arm in a dose-dependent manner. The BF was without any significant effect on motor coordination. However, it significantly inhibited passivity and hypothermia induced by baclofen (10 mg/kg), a GABA(B) agonist. The data emanated in the present study suggests involvement of gamma-aminobutyric acid (GABA) in the nootropic and anxiolytic activity of saponins obtained from A. lebbeck.

Morphological and functional consequences of transradial coronary angiography on the radial artery: implications for its use as a bypass conduit.

PubMed

Gaudino, Mario; Leone, Alessandro; Lupascu, Andrea; Toesca, Amelia; Mazza, Andrea; Ponziani, Francesca Romana; Flore, Roberto; Tondi, Paolo; Massetti, Massimo

2015-09-01

To assess the degree of damage to the radial artery (RA) in coronary artery bypass grafting (CABG) patients who underwent preoperative transradial coronary angiography (RA-CA). From May 2012 to October 2013, 50 consecutive CABG patients who underwent RA-CA were prospectively enrolled in the study. All patients underwent echo-Doppler evaluation of the RA of the catheterized arm; the contralateral RA was used as control. The distal segment of the RA was submitted to immunohistochemical assessment of endothelial integrity. Patients were divided in three groups according to the time interval from angiography to evaluation: ≤24 h, >24 h to <7 days and ≥7 days. Baseline RA median diameters were 0.25 ± 0.04 cm in the cannulated arm and 0.22 ± 0.04 cm in the non-cannulated arm (P = 0.01). The flow-mediated dilatation (FMD) in the RA in the catheterized arm and in the control arm were 11.6 ± 7.9 and 14.2 ± 8.9 (P = 0.01), respectively. A statistically significant correlation was found between FMD of the catheterized RA and the time from RA-CA (Pearson's r = 0.348). Linear regression analysis confirmed that the FMD of the catheterized RA was dependent on days elapsed from the procedure (P = 0.032; OR 1.11, CI 0.009-0.203). Immunohistochemical evaluation showed extensive endothelial lesion in all examined RAs, with a trend towards reduction of the damage with time. Endothelial function and integrity of the cannulated arm did not reach those of the control arm in any of the study patients. RA-CA produces extensive damage to the RA. The lesions tend to heal with time but incomplete recovery of endothelial integrity and function is still present more than 30 days after the procedure. After RA-CA, the cannulated RA should not be used for CABG. © The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Effects of palmitoylethanolamide and luteolin in an animal model of anxiety/depression.

PubMed

Crupi, Rosalia; Paterniti, Irene; Ahmad, Akbar; Campolo, Michela; Esposito, Emanuela; Cuzzocrea, Salvatore

2013-11-01

The antidepressant effect of a compound formed by co-ultramicronized palmitoylethanolamide (PEA) and luteolin (PEA+luteolin) was investigated in a mouse model of anxiety/depressive-like behavior. 129Sv/Ev mice were subjected to 6 weeks of corticosterone administration, and then behavior, neurogenesis, neuroplasticity, neurotrophic and apoptotic proteins expression were evaluated. The effect of PEA+luteolin compound treatment (1mg/kg, i.p.), on depression-like behaviour was assessed using different paradigms such as open field, novelty suppressed feeding, forced swim test and elevated plus maze. In particular in the open field, novelty suppressed feeding and elevated plus maze the time spent in the open arm was employed as an indicator of anxiety; forced swim test was used to evaluate the antidepressant capacity of PEA+luteolin on immobility time as an indicator of depression. Adult hippocampal neurogenesis and neuroplasticity were evaluated by immunohistochemical techniques; brain-derived neurotrophic factor and apoptotic protein (Bax and Bcl2) expression were studied by immunostaining and Western blot analysis. For the first time we demonstrated that PEA+luteolin compound exerts a significant antidepressant effect a low dose and may be considered as a novel therapeutic strategy in depression.

Protective effect of rutin on cognitive impairment caused by phenytoin

PubMed Central

Dubey, Shagun; Ganeshpurkar, Aditya; Bansal, Divya; Dubey, Nazneen

2015-01-01

Objective: To study the effect of the co-administration of phenytoin (PHT) and rutin in comparison with PHT and piracetam (PIM) on seizure control, cognitive, and motor functions in mice. Materials and Methods: Increasing current electroshock seizure (ICES) test was used to evaluate the effect of the co-administration of PHT and PIM on convulsions. Cognitive functions in mice were assessed by a spontaneous alternation in behavior on a plus maze while motor functions were screened using rolling roller apparatus and by counting the number of arms entries on a plus maze. Brain acetyl-cholinesterase (AChE) activity was also estimated. Statistical Analysis: The expression of data was done as mean ± standard error of the mean. The normally distributed data were subjected to one-way ANOVA followed by Dunnett's test. P < 0.05 was considered significant. Results: The study showed that rutin when co-administered with PHT, significantly reversed PHT-induced reduction in spontaneous alternation without altering the efficacy of PHT against ICES, in both acute and chronic studies. Further, it also reversed PHT-induced increase in AChE activity. Conclusion: Rutin alleviated the PHT-induced cognitive impairment without compromising its antiepileptic efficacy. PMID:26729954

Valeriana officinalis root extracts have potent anxiolytic effects in laboratory rats.

PubMed

Murphy, K; Kubin, Z J; Shepherd, J N; Ettinger, R H

2010-07-01

Valerian root (Valeriana officinalis) is a popular and widely available herbal supplement, primarily used to treat insomnia and anxiety. Until recently, its mechanism of action has remained unknown. Neurobiological research has begun to show that the herb, with its active valerenic acid, interacts with the GABA(A)-ergic system, a mechanism of action similar to the benzodiazepine drugs. This series of experiments sought to corroborate these findings with behavioral measures, compare them to the benzodiazepine diazepam, and to analyze the chemical composition of Valeriana officinalis. Rats were administered either ethanol (1 ml/kg), diazepam (1mg/kg), valerian root extract (3 ml/kg), valerenic acid (3mg/kg), or a solution of valerenic acid and exogenous GABA (75 microg/kg and 3.6 microg/kg, respectively) and assessed for the number of entries and time spent on the open arms of an elevated plus maze. Results showed that there was a significant reduction in anxious behavior when valerian extract or valerenic acid exposed subjects were compared to the ethanol control group. The evidence supports Valeriana officinalis as a potential alternative to the traditional anxiolytics as measured by the elevated plus maze. (c) 2009 Elsevier GmbH. All rights reserved.

Acute behavioural and neurotoxic effects of MDMA plus cocaine in adolescent mice.

PubMed

Daza-Losada, M; Rodríguez-Arias, M; Maldonado, C; Aguilar, M A; Guerri, C; Miñarro, J

2009-01-01

The poly-drug pattern is the most common among those observed in MDMA users, with cocaine being a frequently associated drug. This study evaluates the acute effects of MDMA (5, 10 and 20 mg/kg), alone or in combination with cocaine (25 mg/kg), on motor activity, anxiety (elevated plus maze and social interaction test), memory and brain monoamines in adolescent mice. Both drugs, administered alone or concurrently, produced hyperactivity and a decrease in social contacts. However, an anxiolytic effect, studied by means of the elevated plus maze and expressed as an increase in the time spent on the open arms, was observed only in those animals treated with cocaine and MDMA. The passive avoidance task was affected only with the highest MDMA dose (20 mg/kg). Mice treated with MDMA did not present significant changes in brain monoamines, while those receiving MDMA and cocaine showed a decrease in DA in the striatum, which was accompanied by an increase in the serotonin concentration in the striatum and cortex 30 min after acute administration. In conclusion, the combined use of MDMA and cocaine produces a predominance of serotonin over DA, which is associated with an anxiolytic profile, defensive behaviours and fewer social contacts.

Evaluation of neuroprotective, anticonvulsant, sedative and anxiolytic activity of citicoline in rats.

PubMed

Abdolmaleki, Arash; Moghimi, Ali; Ghayour, Mohammad B; Rassouli, Morteza B

2016-10-15

Citicoline (cytidine-5'-diphosphocholine) is a neuroprotective agent that is administered following ischemic and traumatic brain injuries. There is little information about the antiseizure and anxiolytic effects of citicoline, which are therefore addressed in the present study. For evaluating the anticonvulsant effect of citicoline in the pentylentetrazole seizure model, a single intraperitoneal dose of citicoline was administered at 50, 100 or 150mg/kg. Sedative and anxiolytic effects of citicoline were examined via elevated plus maze and pentobarbital induced sleep tests. Results show that citicoline at the doses of 100 and 150mg/kg significantly delayed the latent period compared with the control (P<0.05). Citicoline at the doses of 100 and 150mg/kg significantly decreased total locomotion compared with the control (P<0.05). Additionally, citicoline at the doses of 100 and 150mg/kg significantly increased both percentage of entry and time spent in the open arms in the elevated plus maze test (P<0.05). The pentobarbital induced sleep test showed that citicoline significantly reduced the latency to sleep (P<0.05). Our results suggest that acute administration of citicoline has anticonvulsant activity and sedative effect. Copyright © 2016 Elsevier B.V. All rights reserved.

Global enhancement and structure formation of the magnetic field in spiral galaxies

NASA Astrophysics Data System (ADS)

Khoperskov, Sergey A.; Khrapov, Sergey S.

2018-01-01

In this paper we study numerically large-scale magnetic field evolution and its enhancement in gaseous disks of spiral galaxies. We consider a set of models with the various spiral pattern parameters and the initial magnetic field strength with taking into account gas self-gravity and cooling and heating processes. In agreement with previous studies we find out that galactic magnetic field is mostly aligned with gaseous structures, however small-scale gaseous structures (spurs and clumps) are more chaotic than the magnetic field structure. In spiral arms magnetic field often coexists with the gas distribution, in the inter-arm region we see filamentary magnetic field structure. These filaments connect several isolated gaseous clumps. Simulations reveal the presence of the small-scale irregularities of the magnetic field as well as the reversal of magnetic field at the outer edge of the large-scale spurs. We provide evidences that the magnetic field in the spiral arms has a stronger mean-field component, and there is a clear inverse correlation between gas density and plasma-beta parameter, compared to the rest of the disk with a more turbulent component of the field and an absence of correlation between gas density and plasma-beta. We show the mean field growth up to >3-10 μG in the cold gas during several rotation periods (>500-800 Myr), whereas ratio between azimuthal and radial field is equal to >4/1. We find an enhancement of random and ordered components of the magnetic field. Mean field strength increases by a factor of >1.5-2.5 for models with various spiral pattern parameters. Random magnetic field component can reach up to 25% from the total strength. By making an analysis of the time-dependent evolution of the radial Poynting flux, we point out that the magnetic field strength is enhanced more strongly at the galactic outskirts which is due to the radial transfer of magnetic energy by the spiral arms pushing the magnetic field outward. Our results also support the presence of sufficient conditions for the development of magnetorotational instability at distances >11 kpc after >300 Myr of evolution.

The RMS survey: galactic distribution of massive star formation

NASA Astrophysics Data System (ADS)

Urquhart, J. S.; Figura, C. C.; Moore, T. J. T.; Hoare, M. G.; Lumsden, S. L.; Mottram, J. C.; Thompson, M. A.; Oudmaijer, R. D.

2014-01-01

We have used the well-selected sample of ˜1750 embedded, young, massive stars identified by the Red MSX Source (RMS) survey to investigate the Galactic distribution of recent massive star formation. We present molecular line observations for ˜800 sources without existing radial velocities. We describe the various methods used to assign distances extracted from the literature and solve the distance ambiguities towards approximately 200 sources located within the solar circle using archival H I data. These distances are used to calculate bolometric luminosities and estimate the survey completeness (˜2 × 104 L⊙). In total, we calculate the distance and luminosity of ˜1650 sources, one third of which are above the survey's completeness threshold. Examination of the sample's longitude, latitude, radial velocities and mid-infrared images has identified ˜120 small groups of sources, many of which are associated with well-known star formation complexes, such as G305, G333, W31, W43, W49 and W51. We compare the positional distribution of the sample with the expected locations of the spiral arms, assuming a model of the Galaxy consisting of four gaseous arms. The distribution of young massive stars in the Milky Way is spatially correlated with the spiral arms, with strong peaks in the source position and luminosity distributions at the arms' Galactocentric radii. The overall source and luminosity surface densities are both well correlated with the surface density of the molecular gas, which suggests that the massive star formation rate per unit molecular mass is approximately constant across the Galaxy. A comparison of the distribution of molecular gas and the young massive stars to that in other nearby spiral galaxies shows similar radial dependences. We estimate the total luminosity of the embedded massive star population to be ˜0.76 × 108 L⊙, 30 per cent of which is associated with the 10 most active star-forming complexes. We measure the scaleheight as a function of the Galactocentric distance and find that it increases only modestly from ˜20-30 pc between 4 and 8 kpc, but much more rapidly at larger distances.

Radial nerve palsy in mid/distal humeral fractures: is early exploration effective?

PubMed

Keighley, Geffrey; Hermans, Deborah; Lawton, Vidya; Duckworth, David

2018-03-01

Radial nerve palsies are a common complication with displaced distal humeral fractures. This case series examines the outcomes of early operative exploration and decompression of the nerve with fracture fixation with the view that this provides a solid construct for optimisation of nerve recovery. A total of 10 consecutive patients with a displaced distal humeral fracture and an acute radial nerve palsy were treated by the senior author by open reduction and internal fixation of the distal humerus and exploration and decompression of the radial nerve. Motor function and sensation of the radial nerve was assessed in the post-operative period every 2 months or until full recovery of the radial nerve function had occurred. All patients (100%) had recovery of motor and sensation function of their upper limb in the radial nerve distribution over a 12-month period. Recovery times ranged between 4 and 32 weeks, with the median time to recovery occurring at 26 weeks and the average time to full recovery being 22.9 weeks. Wrist extension recovered by an average of 3 months (range 2-26 weeks) and then finger extension started to recover 2-6 weeks after this. Disability of the arm, shoulder and hand scores ranged from 0 to 11.8 at greater than 1 year post-operatively. Our study demonstrated that early operative exploration of the radial nerve when performing an open stabilization of displaced distal humeral fractures resulted in a 100% recovery of the radial nerve. © 2017 Royal Australasian College of Surgeons.

Piping inspection carriage having axially displaceable sensor

DOEpatents

Zollinger, W.T.; Treanor, R.C.

1994-12-06

A pipe inspection instrument carriage is described for use with a pipe crawler for performing internal inspections of piping surfaces. The carriage has a front leg assembly, a rear leg assembly and a central support connecting the two assemblies and for mounting an instrument arm having inspection instruments. The instrument arm has a Y-arm mounted distally thereon for axially aligning the inspection instrumentation and a mounting block, a linear actuator and axial movement arm for extending the inspection instruments radially outward to operably position the inspection instruments on the piping interior. Also, the carriage has a rotation motor and gear assembly for rotating the central support and the front leg assembly with respect to the rear leg assembly so that the inspection instruments azimuthally scan the piping interior. The instrument carriage allows performance of all piping inspection operations with a minimum of moving parts, thus decreasing the likelihood of performance failure. 4 figures.

Piping inspection carriage having axially displaceable sensor

DOEpatents

Zollinger, William T.; Treanor, Richard C.

1994-01-01

A pipe inspection instrument carriage for use with a pipe crawler for performing internal inspections of piping surfaces. The carriage has a front leg assembly, a rear leg assembly and a central support connecting the two assemblies and for mounting an instrument arm having inspection instruments. The instrument arm has a y-arm mounted distally thereon for axially aligning the inspection instrumentation and a mounting block, a linear actuator and axial movement arm for extending the inspection instruments radially outward to operably position the inspection instruments on the piping interior. Also, the carriage has a rotation motor and gear assembly for rotating the central support and the front leg assembly with respect to the rear leg assembly so that the inspection instruments azimuthally scan the piping interior. The instrument carriage allows performance of all piping inspection operations with a minimum of moving parts, thus decreasing the likelihood of performance failure.

A Pilot Study of a Novel Automated Somatosensory Evoked Potential (SSEP) Monitoring Device for Detection and Prevention of Intraoperative Peripheral Nerve Injury in Total Shoulder Arthroplasty Surgery.

PubMed

Chui, Jason; Murkin, John M; Drosdowech, Darren

2018-05-21

Peripheral nerve injury is a potentially devastating complication after total shoulder arthroplasty (TSA) surgery. This pilot study aimed to assess the feasibility of using an automated somatosensory evoked potential (SSEP) device to provide a timely alert/intervention to minimize intraoperative nerve insults during TSA surgery. A prospective, single-arm, observational study was conducted in a single university hospital. The attending anesthesiologist monitored the study participants using the EPAD automated SSEP device and an intervention was made if there was an alert during TSA surgery. The median, radial, and ulnar nerve SSEP on the operative arm, as well as the median nerve SSEP of the nonoperative arm were monitored for each patient. All patients were evaluated for postoperative neurological deficits 6 weeks postoperatively. In total, 21 patients were consented and were successfully monitored. In total, 4 (19%) patients developed intraoperative abnormal SSEP signal changes in the operative arm, in which 3 were reversible and 1 was irreversible till the end of surgery. Median and radial nerves were mostly involved (3/4 patients). The mean cumulative duration of nerve insult (abnormal SSEP) was 21.7±26.2 minutes. Univariate analysis did not identify predictor of intraoperative nerve insults. No patients demonstrated postoperative peripheral neuropathy at 6 weeks. A high incidence (19%) of intraoperative nerve insult was observed in this study demonstrating the feasibility of using an automated SSEP device to provide a timely alert and enable an intervention in order to minimize peripheral nerve injury during TSA. Further randomized studies are warranted.

A common neural element receiving rhythmic arm and leg activity as assessed by reflex modulation in arm muscles

PubMed Central

Tazoe, Toshiki; Nakajima, Tsuyoshi; Futatsubashi, Genki; Ohtsuka, Hiroyuki; Suzuki, Shinya; Zehr, E. Paul; Komiyama, Tomoyoshi

2016-01-01

Neural interactions between regulatory systems for rhythmic arm and leg movements are an intriguing issue in locomotor neuroscience. Amplitudes of early latency cutaneous reflexes (ELCRs) in stationary arm muscles are modulated during rhythmic leg or arm cycling but not during limb positioning or voluntary contraction. This suggests that interneurons mediating ELCRs to arm muscles integrate outputs from neural systems controlling rhythmic limb movements. Alternatively, outputs could be integrated at the motoneuron and/or supraspinal levels. We examined whether a separate effect on the ELCR pathways and cortico-motoneuronal excitability during arm and leg cycling is integrated by neural elements common to the lumbo-sacral and cervical spinal cord. The subjects performed bilateral leg cycling (LEG), contralateral arm cycling (ARM), and simultaneous contralateral arm and bilateral leg cycling (A&L), while ELCRs in the wrist flexor and shoulder flexor muscles were evoked by superficial radial (SR) nerve stimulation. ELCR amplitudes were facilitated by cycling tasks and were larger during A&L than during ARM and LEG. A low stimulus intensity during ARM or LEG generated a larger ELCR during A&L than the sum of ELCRs during ARM and LEG. We confirmed this nonlinear increase in single motor unit firing probability following SR nerve stimulation during A&L. Furthermore, motor-evoked potentials following transcranial magnetic and electrical stimulation did not show nonlinear potentiation during A&L. These findings suggest the existence of a common neural element of the ELCR reflex pathway that is active only during rhythmic arm and leg movement and receives convergent input from contralateral arms and legs. PMID:26961103

Learning Under Stress: The Inverted-U-Shape Function Revisited

ERIC Educational Resources Information Center

Salehi, Basira; Cordero, M. Isabel; Sandi, Carmen

2010-01-01

Although the relationship between stress intensity and memory function is generally believed to follow an inverted-U-shaped curve, strikingly this phenomenon has not been demonstrated under the same experimental conditions. We investigated this phenomenon for rats' performance in a hippocampus-dependent learning task, the radial arm water maze…

Wood Programs. Courseware Evaluation for Vocational and Technical Education.

ERIC Educational Resources Information Center

Kaylor, Robert; And Others

This courseware evaluation rates the Wood Programs software developed by the Iowa Department of Public Instruction. (These programs--not contained in this document--include understanding board feet, wood characteristics, wood safety drill, wood dimensions, wood moisture, operating the table saw, radial arm, measurement drill, fraction drill, and…

ENU-mutagenesis mice with a non-synonymous mutation in Grin1 exhibit abnormal anxiety-like behaviors, impaired fear memory, and decreased acoustic startle response

PubMed Central

2013-01-01

Background The Grin1 (glutamate receptor, ionotropic, NMDA1) gene expresses a subunit of N-methyl-D-aspartate (NMDA) receptors that is considered to play an important role in excitatory neurotransmission, synaptic plasticity, and brain development. Grin1 is a candidate susceptibility gene for neuropsychiatric disorders, including schizophrenia, bipolar disorder, and attention deficit/hyperactivity disorder (ADHD). In our previous study, we examined an N-ethyl-N-nitrosourea (ENU)-generated mutant mouse strain (Grin1Rgsc174/Grin1+) that has a non-synonymous mutation in Grin1. These mutant mice showed hyperactivity, increased novelty-seeking to objects, and abnormal social interactions. Therefore, Grin1Rgsc174/Grin1+ mice may serve as a potential animal model of neuropsychiatric disorders. However, other behavioral characteristics related to these disorders, such as working memory function and sensorimotor gating, have not been fully explored in these mutant mice. In this study, to further investigate the behavioral phenotypes of Grin1Rgsc174/Grin1+ mice, we subjected them to a comprehensive battery of behavioral tests. Results There was no significant difference in nociception between Grin1Rgsc174/Grin1+ and wild-type mice. The mutants did not display any abnormalities in the Porsolt forced swim and tail suspension tests. We confirmed the previous observations that the locomotor activity of these mutant mice increased in the open field and home cage activity tests. They displayed abnormal anxiety-like behaviors in the light/dark transition and the elevated plus maze tests. Both contextual and cued fear memory were severely deficient in the fear conditioning test. The mutant mice exhibited slightly impaired working memory in the eight-arm radial maze test. The startle amplitude was markedly decreased in Grin1Rgsc174/Grin1+ mice, whereas no significant differences between genotypes were detected in the prepulse inhibition (PPI) test. The mutant mice showed no obvious deficits in social behaviors in three different social interaction tests. Conclusions This study demonstrated that the Grin1Rgsc174/Grin1+ mutation causes abnormal anxiety-like behaviors, a deficiency in fear memory, and a decreased startle amplitude in mice. Although Grin1Rgsc174/Grin1+ mice only partially recapitulate symptoms of patients with ADHD, schizophrenia, and bipolar disorder, they may serve as a unique animal model of a certain subpopulation of patients with these disorders. PMID:23688147

Uncovering the origins of spiral structure through the measurement of pattern speeds and their radial variation

NASA Astrophysics Data System (ADS)

Meidt, Sharon E.

At the intersection of galactic dynamics, evolution and global structure, unresolved issues in the nature and origin of spirals can be addressed through the characterization of the angular speeds of the patterns and their possible radial variation. In this thesis I describe the development, testing, and application of the Radial Tremaine-Weinberg (TWR) Method, a generalized version of the continuity-based TW method wherein the pattern speed is allowed to vary arbitrarily with radius. I will address the utility of, and caveats in applying, the TWR calculation together with a standard regularization technique in a series of tests on N- body simulations. The regularization, which smooths otherwise intrinsically noisy solutions based on a priori assumptions for the radial dependence of the pattern speed, proves to be essential for achieving the radial precision necessary for accurate measurement. I also present results from applications of the TWR method to observations of real galaxies, where the possible sources and sinks in the continuity equation are well understood. Using CO observations of the grand design galaxy M51, the TWR method reveals a heretofore un-measured inner spiral pattern speed for the bright two-armed spiral structure, with a value significantly higher than conventional estimates. In addition, the radial dependence implied in the TWR solution suggests a possible resonant link between the inner and outer regions of the bright spiral arms. These findings signify an advance in observational investigations into the nature and origin of grand-design spiral structure. By analyzing high-quality HI and CO data cubes available for four other spiral galaxies, the characteristic signatures of the processes that drive spiral structure are likewise identifiable; within this small sample, the first direct evidence for the presence of resonant coupling of multiple distinct patterns is found in some galaxies, while a simple single pattern speed is measured in others. I conclude with a summary of future avenues for investigation with the TWR method and propose additional modifications of the TW calculation with which the influence of bar and spiral structure on the evolution of galaxy disks can be directly characterized.

Differences in wrist mechanics during the golf swing based on golf handicap.

PubMed

Fedorcik, Gregory G; Queen, Robin M; Abbey, Alicia N; Moorman, Claude T; Ruch, David S

2012-05-01

Variation in swing mechanics between golfers of different skill levels has been previously reported. To investigate if differences in three-dimensional wrist kinematics and the angle of golf club descent between low and high handicap golfers. A descriptive laboratory study was performed with twenty-eight male golfers divided into two groups, low handicap golfers (handicap = 0-5, n = 15) and high handicap golfers (handicap ≥ 10, n = 13). Bilateral peak three-dimensional wrist mechanics, bilateral wrist mechanics at ball contact (BC), peak angle of descent from the end of the backswing to ball contact, and the angle of descent when the forearm was parallel to the ground (DEC-PAR) were determined using an 8 camera motion capture system. Independent t-tests were completed for each study variable (α = 0.05). Pearson correlation coefficients were determined between golf handicap and each of the study variables. The peak lead arm radial deviation (5.7 degrees, p = 0.008), lead arm radial deviation at ball contact (7.1 degrees, p = 0.001), and DEC-PAR (15.8 degrees, p = 0.002) were significantly greater in the high handicap group. In comparison with golfers with a low handicap, golfers with a high handicap have increased radial deviation during the golf swing and at ball contact. Copyright © 2011 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

High resolution infrared astronomy satellite observations of a selected spiral galaxy

NASA Technical Reports Server (NTRS)

Kulkarni, S. R.

1991-01-01

The H I, infrared, CO, H alpha and H beta band observations of M51, the prototypical grand-design spiral galaxy, are used to study the consequences of star formation for the distribution of H I and dust. Using the new Very Large Array (VLA) map of 21 cm emission, the Owens Valley Radio Observatory CO mosaic map, and an H alpha imate, new tests were performed with the idea of Tilanus and Allen that the H I is largely a photodissociation product in star-forming regions. It is confirmed that the H I spiral arms are generally coincident with the H II region arms, and offset downstream from the CO arms. The radial distributions of total gas, H alpha and H I surface density have a simple explanation in the dissociation picture. The distributions also demonstrate how the surface density of H I might be related to the star formation efficiency in molecule-rich galaxies. The large width of the H I regions along the arms compared to that of the giant H II regions can be understood in terms of a simple calculation of the expected size of an H I region associated with a typical giant H II region. The longer lifetime of the stars producing dissociating radiation vs. those producing ionizing radiation and the relatively long molecular formation timescale will also contribute to the greater width of the H I arms if stars are continuously forming on the arms. The lack of detailed coincidence of the H I and H II regions along the inner arms has a variety of possible explanations. Two simple tests were performed to probe the origins of the IRAS emission in M51. First, it was found that the infrared excess (IFE) of M51 is 24, suggesting that a substantial fraction of the infrared emission arises from dust heated by photons which do not originate in massive star-formaing regions. Second, radial cuts through the IRAS bands show that at 12, 25, and 60 microns, the arm-interarm contrast of the IRAS emission is substantially less than that of the H alpha emission, providing further evidence for the explanation and for the existence of a broadly distributed dust component. Deconvolved IRAS maps have improved resolution but do not change this finding.

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

Baba, Junichi; Saitoh, Takayuki R.; Wada, Keiichi, E-mail: babajn@geo.titech.ac.jp

In order to understand the physical mechanisms underlying non-steady stellar spiral arms in disk galaxies, we analyzed the growing and damping phases of their spiral arms using three-dimensional N-body simulations. We confirmed that the spiral arms are formed due to a swing amplification mechanism that reinforces density enhancement as a seeded wake. In the damping phase, the Coriolis force exerted on a portion of the arm surpasses the gravitational force that acts to shrink the portion. Consequently, the stars in the portion escape from the arm, and subsequently they form a new arm at a different location. The time-dependent naturemore » of the spiral arms originates in the continual repetition of this nonlinear phenomenon. Since a spiral arm does not rigidly rotate, but follows the galactic differential rotation, the stars in the arm rotate at almost the same rate as the arm. In other words, every single position in the arm can be regarded as the corotation point. Due to interaction with their host arms, the energy and angular momentum of the stars change, thereby causing radial migration of the stars. During this process, the kinetic energy of random motion (random energy) of the stars does not significantly increase, and the disk remains dynamically cold. Owing to this low degree of disk heating, short-lived spiral arms can recurrently develop over many rotational periods. The resultant structure of the spiral arms in the N-body simulations is consistent with the observational nature of spiral galaxies. We conclude that the formation and structure of spiral arms in isolated disk galaxies can be reasonably understood by nonlinear interactions between a spiral arm and its constituent stars.« less

The effect of neonatal handling on adult feeding behavior is not an anxiety-like behavior.

PubMed

Silveira, P P; Portella, A K; Clemente, Z; Gamaro, G D; Dalmaz, C

2005-02-01

Brief periods of handling during the neonatal period have been shown to have profound and long-lasting physiological consequences. Previous studies performed in our laboratory have demonstrated that handling the pups during the neonatal period leads to increased sweet food ingestion in adult life. The objective of this study is to verify if this effect could be explained by the enhanced anxiety levels in these animals. Litters were divided in: (1) intact; (2) handled (10 min in an incubator/day) and (3) handled + tactile stimulation (10 min/day). Procedures were performed on days 1-10 after birth. When adults, rats were tested in the elevated plus maze apparatus, light dark exploration test and open field test. They were also tested for sweet food ingestion, being injected with 2 mg/kg diazepam or vehicle 60 min before the test. Handling and handling + tactile stimulation do not alter performance in the plus maze test, but handled rats presented more crossings in the light/dark exploration test and open field (two-way ANOVA). Females also spent more % time in the open arms in the plus maze and more time in the lit compartment in the light/dark test, presenting more crossings in both tests. Both treated rats (handled and handled + tactile stimulation groups) consumed more sweet food than intact ones (two-way ANOVA). When diazepam was injected prior to the measurement of sweet food ingestion, there was no effect of the drug. We suggest that handling during the neonatal period leads to plastic alterations in the central nervous system of these animals, causing an increased ingestion of palatable food in adult life, and this alteration does not express an anxiety-like behavior.

Effects of N-acetyl-cysteine treatment on glutathione depletion and a short-term spatial memory deficit in 2-cyclohexene-1-one-treated rats.

PubMed

Choy, Kwok Ho Christopher; Dean, Olivia; Berk, Michael; Bush, Ashley I; van den Buuse, Maarten

2010-12-15

Glutathione (GSH) is the primary antioxidant in the body and is present in high levels in the brain. Levels of GSH and other antioxidants are significantly altered in major psychiatric illnesses, such as schizophrenia. Recent clinical trials have demonstrated that chronic treatment with N-acetyl-l-cysteine (NAC), a GSH precursor, improved symptoms in individuals with this illness. We previously showed in rats and mice that depletion of GSH by treatment with 2-cyclohexene-1-one (CHX) induced short-term spatial memory deficits in the Y-maze test. The aim of present study was to characterise the effect of NAC in this CHX-induced glutathione depletion model. Consistent with our previous studies, CHX treatment induced approximately 50% reduction of GSH levels in striatum, hippocampus and frontal cortex tissue. GSH depletion was significantly rescued by either 1.2 g/kg or 1.6 g/kg of NAC administration, with a full recovery observed in the frontal cortex after the high dose of NAC. CHX treatment also induced a disruption in short-term spatial recognition memory in Y-maze test, as measured by the duration of time spent in the novel arm. This disruption was reversed by treatment with 1.6 g/kg of NAC. In conclusion, this study suggests that rescue of depleted levels of GSH in the brain restores cognitive deficits, as measured by the Y-maze. These effects appear to be dose-dependent and region-specific. These results may be relevant to the understanding and management of the cognitive symptoms of schizophrenia and bipolar disorder. Copyright © 2010 Elsevier B.V. All rights reserved.

Dilantin therapy in an experimental model of traumatic brain injury: effects of limited versus daily treatment on neurological and behavioral recovery.

PubMed

Darrah, Shaun D; Darrah, Shaun H; Chuang, Jerry; Mohler, Laura M; Chen, Xiangbai; Cummings, Erin E; Burnett, Tiffany; Reyes-Littaua, M Christina; Galang, Gary N; Wagner, Amy K

2011-01-01

The mechanisms by which Dilantin confers anticonvulsant benefits may also be neuroprotective by attenuating the acute excitatory insult in cortical and subcortical structures when the drug is given in the acute phase after traumatic brain injury (TBI). However, when Dilantin is used for prolonged periods, we hypothesized that it may impede recovery, synaptic plasticity may be impaired, and neuroprotective benefits may be lost. As such, we assessed the effect of daily chronic administration (75 mg/kg day 0 followed by 50 mg/kg daily i.p.) and acute administration (75 mg/kg day 0 followed by 50 mg/kg i.p. day 1) of Dilantin in young adult male rats on motor performance, y-maze exploration, Morris Water Maze (MWM), hippocampal (HC) cell survival, contusion size, and regional expression of neuroplasticity markers after controlled cortical impact (CCI) injury. Chronic daily Dilantin administration resulted in beam walking impairments on day 6, whereas acute Dilantin administration resulted in beam walking impairments on days 3 and 4. Chronic Dilantin administration also resulted in worse MWM performance, more HC cell loss and no increases in neuroplasticity markers compared to rats with CCI receiving chronic vehicle. Conversely, rats receiving acute Dilantin administration exhibited more novel arm exploration in the y-maze, greater HC cell sparing, and greater growth-associated protein 43 (GAP-43) expression in the HC ipsilateral to the CCI, compared to injured rats receiving vehicle. MWM was not influenced by acute Dilantin administration. These results suggest that there are beneficial effects of limited acute Dilantin therapy after TBI, and that extended daily Dilantin therapy has deleterious effects on neural recovery. These findings support clinical guidelines for limited use of Dilantin in seizure prophylaxis after TBI.

Endogenous IL-1 in Cognitive Function and Anxiety: A Study in IL-1RI−/− Mice

PubMed Central

Murray, Carol L.; Obiang, Pauline; Bannerman, David; Cunningham, Colm

2013-01-01

Interleukin-1 (IL-1) is a key pro-inflammatory cytokine, produced predominantly by peripheral immune cells but also by glia and some neuronal populations within the brain. Its signalling is mediated via the binding of IL-1α or IL-1β to the interleukin-1 type one receptor (IL-1RI). IL-1 plays a key role in inflammation-induced sickness behaviour, resulting in depressed locomotor activity, decreased exploration, reduced food and water intake and acute cognitive deficits. Conversely, IL-1 has also been suggested to facilitate hippocampal-dependent learning and memory: IL-1RI−/− mice have been reported to show deficits on tasks of visuospatial learning and memory. We sought to investigate whether there is a generalised hippocampal deficit in IL-1RI−/− animals. Therefore, in the current study we compared wildtype (WT) mice to IL-1RI−/− mice using a variety of hippocampal-dependent learning and memory tasks, as well as tests of anxiety and locomotor activity. We found no difference in performance of the IL-1RI−/− mice compared to WT mice in a T-maze working memory task. In addition, the IL-1RI−/− mice showed normal learning in various spatial reference memory tasks including the Y-maze and Morris mater maze, although there was a subtle deficit in choice behaviour in a spatial discrimination, beacon watermaze task. IL-1RI−/− mice also showed normal memory for visuospatial context in the contextual fear conditioning paradigm. In the open field, IL-1RI−/− mice showed a significant increase in distance travelled and rearing behaviour compared to the WT mice and in the elevated plus-maze spent more time in the open arms than did the WT animals. The data suggest that, contrary to prior studies, IL-1RI−/− mice are not robustly impaired on hippocampal-dependent memory and learning but do display open field hyperactivity and decreased anxiety compared to WT mice. The results argue for a careful evaluation of the roles of endogenous IL-1 in hippocampal and limbic system function. PMID:24205219

Fatigue modulates dopamine availability and promotes flexible choice reversals during decision making.

PubMed

Iodice, Pierpaolo; Ferrante, Claudio; Brunetti, Luigi; Cabib, Simona; Protasi, Feliciano; Walton, Mark E; Pezzulo, Giovanni

2017-04-03

During decisions, animals balance goal achievement and effort management. Despite physical exercise and fatigue significantly affecting the levels of effort that an animal exerts to obtain a reward, their role in effort-based choice and the underlying neurochemistry are incompletely known. In particular, it is unclear whether fatigue influences decision (cost-benefit) strategies flexibly or only post-decision action execution and learning. To answer this question, we trained mice on a T-maze task in which they chose between a high-cost, high-reward arm (HR), which included a barrier, and a low-cost, low-reward arm (LR), with no barrier. The animals were parametrically fatigued immediately before the behavioural tasks by running on a treadmill. We report a sharp choice reversal, from the HR to LR arm, at 80% of their peak workload (PW), which was temporary and specific, as the mice returned to choose the HC when the animals were successively tested at 60% PW or in a two-barrier task. These rapid reversals are signatures of flexible choice. We also observed increased subcortical dopamine levels in fatigued mice: a marker of individual bias to use model-based control in humans. Our results indicate that fatigue levels can be incorporated in flexible cost-benefits computations that improve foraging efficiency.

Planet-driven Spiral Arms in Protoplanetary Disks. II. Implications

NASA Astrophysics Data System (ADS)

Bae, Jaehan; Zhu, Zhaohuan

2018-06-01

We examine whether various characteristics of planet-driven spiral arms can be used to constrain the masses of unseen planets and their positions within their disks. By carrying out two-dimensional hydrodynamic simulations varying planet mass and disk gas temperature, we find that a larger number of spiral arms form with a smaller planet mass and a lower disk temperature. A planet excites two or more spiral arms interior to its orbit for a range of disk temperatures characterized by the disk aspect ratio 0.04≤slant {(h/r)}p≤slant 0.15, whereas exterior to a planet’s orbit multiple spiral arms can form only in cold disks with {(h/r)}p≲ 0.06. Constraining the planet mass with the pitch angle of spiral arms requires accurate disk temperature measurements that might be challenging even with ALMA. However, the property that the pitch angle of planet-driven spiral arms decreases away from the planet can be a powerful diagnostic to determine whether the planet is located interior or exterior to the observed spirals. The arm-to-arm separations increase as a function of planet mass, consistent with previous studies; however, the exact slope depends on disk temperature as well as the radial location where the arm-to-arm separations are measured. We apply these diagnostics to the spiral arms seen in MWC 758 and Elias 2–27. As shown in Bae et al., planet-driven spiral arms can create concentric rings and gaps, which can produce a more dominant observable signature than spiral arms under certain circumstances. We discuss the observability of planet-driven spiral arms versus rings and gaps.

A common neural element receiving rhythmic arm and leg activity as assessed by reflex modulation in arm muscles.

PubMed

Sasada, Syusaku; Tazoe, Toshiki; Nakajima, Tsuyoshi; Futatsubashi, Genki; Ohtsuka, Hiroyuki; Suzuki, Shinya; Zehr, E Paul; Komiyama, Tomoyoshi

2016-04-01

Neural interactions between regulatory systems for rhythmic arm and leg movements are an intriguing issue in locomotor neuroscience. Amplitudes of early latency cutaneous reflexes (ELCRs) in stationary arm muscles are modulated during rhythmic leg or arm cycling but not during limb positioning or voluntary contraction. This suggests that interneurons mediating ELCRs to arm muscles integrate outputs from neural systems controlling rhythmic limb movements. Alternatively, outputs could be integrated at the motoneuron and/or supraspinal levels. We examined whether a separate effect on the ELCR pathways and cortico-motoneuronal excitability during arm and leg cycling is integrated by neural elements common to the lumbo-sacral and cervical spinal cord. The subjects performed bilateral leg cycling (LEG), contralateral arm cycling (ARM), and simultaneous contralateral arm and bilateral leg cycling (A&L), while ELCRs in the wrist flexor and shoulder flexor muscles were evoked by superficial radial (SR) nerve stimulation. ELCR amplitudes were facilitated by cycling tasks and were larger during A&L than during ARM and LEG. A low stimulus intensity during ARM or LEG generated a larger ELCR during A&L than the sum of ELCRs during ARM and LEG. We confirmed this nonlinear increase in single motor unit firing probability following SR nerve stimulation during A&L. Furthermore, motor-evoked potentials following transcranial magnetic and electrical stimulation did not show nonlinear potentiation during A&L. These findings suggest the existence of a common neural element of the ELCR reflex pathway that is active only during rhythmic arm and leg movement and receives convergent input from contralateral arms and legs. Copyright © 2016 the American Physiological Society.

Combination downflow-upflow vapor-liquid separator

DOEpatents

Kidwell, John H.; Prueter, William P.; Eaton, Andrew M.

1987-03-10

An improved vapor-liquid separator having a vertically disposed conduit for flow of a mixture. A first, second and third plurality of curved arms penetrate and extend within the conduit. A cylindrical member is radially spaced from the conduit forming an annulus therewith and having perforations and a retaining lip at its upper end.

Reevaluation of the superior radial collateral artery in the human upper arm.

PubMed

Ichimura, Koichiro; Kinose, Shota; Kawasaki, Yuto; Kato, Kota; Sakai, Tatsuo

2018-01-01

The superior radial collateral artery (SRCA) was described in well-established anatomy textbooks published in the 1800s. According to those textbooks, the SRCA originates from the brachial artery, passes transversely between the coracobrachialis and the humerus, and distributes to the most distal portion of the deltoid. The SRCA is not listed in the international standard on anatomical terminology, Terminologia Anatomica, or in modern anatomy textbooks. In the present study, we reevaluated the anatomical features of the SRCA by cadaveric dissection. We found that two kinds of SRCAs were consistently present in the upper arm. One was similar to the previous descriptions of the SRCA in terms of origin and course, but the distribution was somewhat different. The other was similar to the previous descriptions in terms of the distribution, although it differed in origin and course. The discrepancy between the description of the SRCA in classical textbooks and the actual morphologies of the SRCA presumably prompted previous anatomists to question the existence of the SRCA, resulting in its absence from anatomical textbooks after a particular time point.

Quantification of human upper extremity nerves and fascicular anatomy.

PubMed

Brill, Natalie A; Tyler, Dustin J

2017-09-01

In this study we provide detailed quantification of upper extremity nerve and fascicular anatomy. The purpose is to provide values and trends in neural features useful for clinical applications and neural interface device design. Nerve cross-sections were taken from 4 ulnar, 4 median, and 3 radial nerves from 5 arms of 3 human cadavers. Quantified nerve features included cross-sectional area, minor diameter, and major diameter. Fascicular features analyzed included count, perimeter, area, and position. Mean fascicular diameters were 0.57 ± 0.39, 0.6 ± 0.3, 0.5 ± 0.26 mm in the upper arm and 0.38 ± 0.18, 0.47 ± 0.18, 0.4 ± 0.27 mm in the forearm of ulnar, median, and radial nerves, respectively. Mean fascicular diameters were inversely proportional to fascicle count. Detailed quantitative anatomy of upper extremity nerves is a resource for design of neural electrodes, guidance in extraneural procedures, and improved neurosurgical planning. Muscle Nerve 56: 463-471, 2017. © 2016 Wiley Periodicals, Inc.

KINEMATIC ANALYSIS OF NUCLEAR SPIRALS: FEEDING THE BLACK HOLE IN NGC 1097

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

Van de Ven, Glenn; Fathi, Kambiz, E-mail: glenn@mpia.d, E-mail: kambiz@astro.su.s

2010-11-01

We present a harmonic expansion of the observed line-of-sight velocity field as a method to recover and investigate spiral structures in the nuclear regions of galaxies. We apply it to the emission-line velocity field within the circumnuclear star-forming ring of NGC 1097, obtained with the GMOS-IFU spectrograph. The radial variation of the third harmonic terms is well described by a logarithmic spiral, from which we interpret that the gravitational potential is weakly perturbed by a two-arm spiral density wave with an inferred pitch angle of 52{sup 0} {+-} 4{sup 0}. This interpretation predicts a two-arm spiral distortion in the surfacemore » brightness, as hinted by the dust structures in central images of NGC 1097, and predicts a combined one-arm and three-arm spiral structure in the velocity field, as revealed in the non-circular motions of the ionized gas. Next, we use a simple spiral perturbation model to constrain the fraction of the measured non-circular motions that is due to radial inflow. We combine the resulting inflow velocity with the gas density in the spiral arms, inferred from emission-line ratios, to estimate the mass inflow rate as a function of radius, which reaches about 0.011 M{sub sun} yr{sup -1} at a distance of 70 pc from the center. This value corresponds to a fraction of about 4.2 x 10{sup -3} of the Eddington mass accretion rate onto the central black hole in this LINER/Seyfert1 galaxy. We conclude that the line-of-sight velocity can not only provide a cleaner view of nuclear spirals than the associated dust, but that the presented method also allows the quantitative study of these possibly important links in fueling the centers of galaxies, including providing a constraint on the mass inflow rate as a function of radius.« less

Reciprocal inhibition in writer's cramp.

PubMed

Chen, R S; Tsai, C H; Lu, C S

1995-09-01

We studied the inhibition of median H-reflexes by conditioning stimuli on the radial nerve in 13 patients with writer's cramp, eight of the simple type and five of the dystonic type, and in 14 normal volunteers. The patients and controls were right-handed, and their right arms were studied. Asymptomatic left arms were also studied in nine of 13 patients. In the control group we identified three periods of inhibition, with maximum peaks at conditioning-test intervals of 0 ms (41 +/- 17%), 20 ms (40 +/- 13%), and 100 ms (36 +/- 20%). In the patient group, the amplitudes of inhibition of these three periods in both arms were significantly less than those in the control group. However, there were no significant differences in the amplitudes of inhibition of these three periods between symptomatic and asymptomatic arms. There were also no significant differences between simple and dystonic writer's cramps. Our results indicate that the attenuation of reciprocal inhibition was present not only in symptomatic arms but also in asymptomatic arms of patients with writer's cramp. The defect of reciprocal inhibition in the asymptomatic hand has never been documented. We suggest that the preexistent electrophysiological abnormality may provide an explanation for the development of hand cramp after shifted writing.

Streaming motions and kinematic distances to molecular clouds

NASA Astrophysics Data System (ADS)

Ramón-Fox, F. G.; Bonnell, Ian A.

2018-02-01

We present high-resolution smoothed particle hydrodynamics simulations of a region of gas flowing in a spiral arm and identify dense gas clouds to investigate their kinematics with respect to a Milky Way model. We find that, on average, the gas in the arms can have a net radial streaming motion of vR ≈ -9 km s-1 and rotate ≈ 6 km s-1 slower than the circular velocity. This translates to average peculiar motions towards the Galaxy centre and opposite to Galactic rotation. These results may be sensitive to the assumed spiral arm perturbation, which is ≈ 3 per cent of the disc potential in our model. We compare the actual distance and the kinematic estimate and we find that streaming motions introduce systematic offsets of ≈1 kpc. We find that the distance error can be as large as ±2 kpc, and the recovered cloud positions have distributions that can extend significantly into the inter-arm regions. We conclude that this poses a difficulty in tracing spiral arm structure in molecular cloud surveys.

Molecular architecture of inner dynein arms in situ in Chlamydomonas reinhardtii flagella

PubMed Central

Bui, Khanh Huy; Sakakibara, Hitoshi; Movassagh, Tandis; Oiwa, Kazuhiro; Ishikawa, Takashi

2008-01-01

The inner dynein arm regulates axonemal bending motion in eukaryotes. We used cryo-electron tomography to reconstruct the three-dimensional structure of inner dynein arms from Chlamydomonas reinhardtii. All the eight different heavy chains were identified in one 96-nm periodic repeat, as expected from previous biochemical studies. Based on mutants, we identified the positions of the AAA rings and the N-terminal tails of all the eight heavy chains. The dynein f dimer is located close to the surface of the A-microtubule, whereas the other six heavy chain rings are roughly colinear at a larger distance to form three dyads. Each dyad consists of two heavy chains and has a corresponding radial spoke or a similar feature. In each of the six heavy chains (dynein a, b, c, d, e, and g), the N-terminal tail extends from the distal side of the ring. To interact with the B-microtubule through stalks, the inner-arm dyneins must have either different handedness or, more probably, the opposite orientation of the AAA rings compared with the outer-arm dyneins. PMID:19029338

Upper extremity sensorimotor control among collegiate football players.

PubMed

Laudner, Kevin G

2012-03-01

Injuries stemming from shoulder instability are very common among athletes participating in contact sports, such as football. Previous research has shown that increased laxity negatively affects the function of the sensorimotor system potentially leading to a pathological cycle of shoulder dysfunction. Currently, there are no data detailing such effects among football players. Therefore, the purpose of this study was to examine the differences in upper extremity sensorimotor control among football players compared with that of a control group. Forty-five collegiate football players and 70 male control subjects with no previous experience in contact sports participated. All the subjects had no recent history of upper extremity injury. Each subject performed three 30-second upper extremity balance trials on each arm. The balance trials were conducted in a single-arm push-up position with the test arm in the center of a force platform and the subjects' feet on a labile device. The trials were averaged, and the differences in radial area deviation between groups were analyzed using separate 1-way analyses of variance (p < 0.05). The football players showed significantly more radial area deviation of the dominant (0.41 ± 1.23 cm2, p = 0.02) and nondominant arms (0.47 ± 1.63 cm2, p = 0.03) when compared with the control group. These results suggest that football players may have decreased sensorimotor control of the upper extremity compared with individuals with no contact sport experience. The decreased upper extremity sensorimotor control among the football players may be because of the frequent impacts accumulated during football participation. Football players may benefit from exercises that target the sensorimotor system. These findings may also be beneficial in the evaluation and treatment of various upper extremity injuries among football players.

A Randomized Controlled Trial to Evaluate if Computerized Cognitive Rehabilitation Improves Neurocognition in Ugandan Children with HIV.

PubMed

Boivin, Michael J; Nakasujja, Noeline; Sikorskii, Alla; Opoka, Robert O; Giordani, Bruno

2016-08-01

Clinically stable children with HIV can have neuromotor, attention, memory, visual-spatial, and executive function impairments. We evaluated neuropsychological and behavioral benefits of computerized cognitive rehabilitation training (CCRT) in Ugandan HIV children. One hundred fifty-nine rural Ugandan children with WHO Stage I or II HIV disease (6 to 12 years; 77 boys, 82 girls; M = 8.9, SD = 1.86 years) were randomized to one of three treatment arms over a 2-month period. The CCRT arm received 24 one-hour sessions over 2 months, using Captain's Log (BrainTrain Corporation) programmed for games targeting working memory, attention, and visual-spatial analysis. These games progressed in difficulty as the child's performance improved. The second arm was a "limited CCRT" with the same games rotated randomly from simple to moderate levels of training. The third arm was a passive control group receiving no training. All children were assessed at enrollment, 2 months (immediately following CCRT), and 3 months after CCRT completion. The CCRT group had significantly greater gains through 3 months of follow-up compared to passive controls on overall Kaufman Assessment Battery for Children-second edition (KABC-II) mental processing index (p < .01), planning (p = .04), and knowledge (p = .03). The limited CCRT group performed better than controls on learning (p = .05). Both CCRT arms had significant improvements on CogState Groton maze learning (p < .01); although not on CogState attention/memory, TOVA/impulsivity, or behavior rating inventory for executive function and child behavior checklist (psychiatric behavior/symptom problems) ratings by caregiver. CCRT intervention can be effective for neurocognitive rehabilitation in children with HIV in low-resource settings, especially in children who are clinically stable on ARV treatment.

Origin of three-armed rifts in volcanic islands: the case of El Hierro (Canary Islands)

NASA Astrophysics Data System (ADS)

Galindo Jiménez, Inés; Becerril Carretero, Laura; Martí Molist, Joan; Gudmundsson, Agust

2015-04-01

Rifts zones in volcanic oceanic islands are common structures that have been explained through several theories/models. However, despite all these models it is as yet unclear whether it is the intense intrusive activity or the sector collapses that actually control the structural evolution and geometry of oceanic-island rift zones. Here we provide a new hypothesis to explain the origin and characteristics of the feeding system of oceanic-island rift zones based on the analysis of more than 1700 surface, subsurface (water galleries), and submarine structural data from El Hierro (Canary Islands). El Hierro's geological structure is primarily controlled by a three-armed rift-zone, the arms striking NE, WSW and S. Between the rift axes there are three valleys formed during huge landslides: El Golfo, El Julan, and Las Playas. Our results show: (1) a predominant NE-SW strike of structural elements, which coincides with the main regional trend of the Canary Archipelago as a whole; (2) a clear radial strike distribution of structural elements for the whole volcanic edifice (including submarine flanks) with respect to the centre of the island; (3) that the rift zones are mainly subaerial structures and do not propagate through the submarine edifice; (4) that it is only in the NE rift that structures have a general strike similar to that of the rift as a whole, and; (5) that in the W and S rifts there is not clear main direction, showing the structural elements in the W rift a fan distribution coinciding with the general radial pattern in the island as a whole. Based on these data, we suggest that the radial-striking structures reflect comparatively uniform stress fields that operated during the constructive episodes, mainly conditioned by the combination of overburden pressure, gravitational spreading, and magma-induced stresses. By contrast, in the shallower parts of the edifice, that is, the NE-SW, N-S and WNW-ESE-striking structures, reflect local stress fields related to the formation of mega-landslides and mask the general radial pattern. Thus, the rift zones on El Hierro are shallow structures that commonly capture and divert ascending magma towards different parts of the island but do not condition magma ascent at depth.

Arm coordination in octopus crawling involves unique motor control strategies.

PubMed

Levy, Guy; Flash, Tamar; Hochner, Binyamin

2015-05-04

To cope with the exceptional computational complexity that is involved in the control of its hyper-redundant arms [1], the octopus has adopted unique motor control strategies in which the central brain activates rather autonomous motor programs in the elaborated peripheral nervous system of the arms [2, 3]. How octopuses coordinate their eight long and flexible arms in locomotion is still unknown. Here, we present the first detailed kinematic analysis of octopus arm coordination in crawling. The results are surprising in several respects: (1) despite its bilaterally symmetrical body, the octopus can crawl in any direction relative to its body orientation; (2) body and crawling orientation are monotonically and independently controlled; and (3) contrasting known animal locomotion, octopus crawling lacks any apparent rhythmical patterns in limb coordination, suggesting a unique non-rhythmical output of the octopus central controller. We show that this uncommon maneuverability is derived from the radial symmetry of the arms around the body and the simple pushing-by-elongation mechanism by which the arms create the crawling thrust. These two together enable a mechanism whereby the central controller chooses in a moment-to-moment fashion which arms to recruit for pushing the body in an instantaneous direction. Our findings suggest that the soft molluscan body has affected in an embodied way [4, 5] the emergence of the adaptive motor behavior of the octopus. Copyright © 2015 Elsevier Ltd. All rights reserved.

Unilateral block of NMDA receptors in the amygdala prevents predator stress-induced lasting increases in anxiety-like behavior and unconditioned startle--effective hemisphere depends on the behavior.

PubMed

Adamec, R E; Burton, P; Shallow, T; Budgell, J

Lasting increases in anxiety-like behavior (ALB) in the elevated plus-maze are produced by a single 5-min exposure of a rat to a cat. Rats become more anxious in the plus-maze for up to 3 weeks after the exposure. The first study in this series demonstrated that blockade of NMDA receptors in rats with MK-801, AP7, or CPP, given systemically 30 min prior to exposure to a cat prevents the increase in ALB assessed 1 week later in the elevated plus-maze. To localize the site of action of systemic MK-801, MK-801 was injected in the amygdala 30 min prior to predator stress. Injections were given either unilaterally in either hemisphere, or bilaterally in both hemispheres. The target of the injection was the basolateral amygdala. The effects of injection depended on both the type of behavior and the hemisphere of injection. Injections of MK-801 in a variety of sites in the basolateral amygdala had no effect on the suppression of open-arm exploration produced by predator stress. Other amygdala nuclei or other limbic sites likely mediate the effects of systemically administered MK-801 on this behavior. In contrast, NMDA receptors in the left lateral amygdala mediate lasting suppression of risk assessment. MK-801, in a variety of sites in the left but not right lateral amygdala, blocked the effects of predator stress on risk assessment. This is clear evidence of separability of neural mechanisms controlling open-arm exploration and risk assessment. Different NMDA-dependent amygdala circuitry mediated effects of predator stress on unconditioned acoustic startle 1 week after cat exposure. The data indicate that integrity of the left lateral amygdala is necessary for potentiation of startle amplitude by predator stress, though NMDA receptors are not involved in this function. Nevertheless, NMDA receptors in the right, but not the left lateral amygdala, mediate initiation of changes in startle. The data also suggest that the right amygdala action is "downstream" from the left amygdala contribution. These findings are consistent with the view that NMDA receptors are involved in initiation, but not maintenance, of neural changes mediating lasting increases in anxiety following severe stress. Finally, the findings of the importance of the right amygdala in stress-induced enhancement of the startle response provides neurobiological face validity to predator stress as a model of aspects of posttraumatic stress disorder.

Long-lasting changes in stress-induced corticosterone response and anxiety-like behaviors as a consequence of neonatal maternal separation in Long-Evans rats.

PubMed

Kalinichev, Mikhail; Easterling, Keith W; Plotsky, Paul M; Holtzman, Stephen G

2002-08-01

Early neonatal environmental factors appear to have powerful and long-lasting influences on an organism's physiology and behavior. Long-Evans male rats separated from their dam for 3 h daily over the first 2 weeks of life (maternally separated, MS rats) when tested as adults exhibit exaggerated behavioral and neuroendocrine responses to stress compared to 15-min separated (handled, H) animals. The purpose of this study was to compare male and female adult rats that were MS, H or were undisturbed (nonhandled, NH) as neonates in anxiety-like behaviors, in the elevated plus-maze, and in response to startle-inducing auditory stimuli. We confirmed that MS males oversecrete corticosterone (CORT; 2.5-5 times) in response to mild handling stress. MS males and females were less likely to explore open arms of the plus-maze. MS males exhibited 35% higher startle amplitudes compared to controls. Furthermore, MS males were more likely to emit ultrasonic vocalizations in response to startle than were H controls. However, MS and control females did not differ in auditory startle response or in startle-induced ultrasonic vocalizations. Therefore, experiencing maternal separation results in a long-lasting increase in anxiety-like behaviors that occurs in a sex-dependent manner.

Canagliflozin prevents scopolamine-induced memory impairment in rats: Comparison with galantamine hydrobromide action.

PubMed

Arafa, Nadia M S; Ali, Elham H A; Hassan, Mohamed Kamel

2017-11-01

Canagliflozin (CAN) is a sodium-glucose co-transporter 2 (SGLT2) inhibitor indicated to improve glycemic control in adults with type 2 diabetes mellitus. There is a little information about its effect on the cholinergic system that proposed mechanism for memory improvement occurring by SGLT2 drugs. This study aimed to estimate the effect of CAN as compared to galantamine (GAL) treatments for two weeks on scopolamine hydrobromide (SCO)-induced memory dysfunction in experimental rats. Animals divided into six groups; control (CON), CAN, GAL, SCO, SCO + CAN and SCO + GAL. Results indicated significant decrease in body weights of the CAN groups as compared to control values. Moreover, in the SCO + CAN and SCO + GAL the number of arm entry and number of correct alternation in Y maze task increased and showed improvement in the water maze task, acetylcholinesterase (AChE) activities decreased significantly, while monoamines levels significantly increased compared with the SCO group values. Results also recorded acetylcholine M1 receptor (M1 mAChR) in SCO + CAN or SCO + GAL groups in comparison with the SCO group. The study suggested that canagliflozin might improve memory dysfunction induced by scopolamine hydrobromide via cholinergic and monoamines system. Copyright © 2017 Elsevier B.V. All rights reserved.