Spatial representation and low vision: two studies on the content, accuracy and utility of mental representations

The paper reports on two studies being conducted with students from Dorton College - Royal London Society for the Blind (RLSB) in Kent. The first experiment will examine the content and accuracy of mental representations of a well-known environment. Students will walk a route around the college campus and learn the position of ten buildings or structures. They will then be asked to make heading judgments, estimate distances, complete a spatial cued model and sequentially visit a series of locations. The second experiment will examine the strategies and coding heuristics used to explore a complex novel environment. Students will be asked to explore a maze and learn the location of different places. Their search patterns will be digitally tracked, coded and analyzed using GIS software.Students will be tested using the same methods as in the first experiment and their performance level will be correlated with their exploratory patterns. Throughout the paper we are reminded that construct validity can only be secured by employing multiple converging techniques in the collection and analysis of cognitive data. Methods should be designed to test content and accuracy as well as the utility of mental representations

Early Cognitive/Social Deficits and Late Motor Phenotype in Conditional Wild-Type TDP-43 Transgenic Mice

Frontotemporal Dementia (FTD) and amyotrophic lateral sclerosis (ALS) are two neurodegenerative diseases associated to mislocalization and aggregation of TAR DNA-binding protein 43 (TDP-43). To investigate in depth the behavioral phenotype associated with this proteinopathy, we used as a model transgenic (Tg) mice conditionally overexpressing human wild-type TDP 43 protein (hTDP-43-WT) in forebrain neurons. We previously characterized these mice at the neuropathological level and found progressive neurodegeneration and other features that evoke human TDP-43 proteinopathies of the FTD/ALS spectrum. In the present study we analyzed the behavior of mice at multiple domains, including motor, social and cognitive performance. Our results indicate that young hTDP-43-WT Tg mice (1 month after post-weaning transgene induction) present a normal motor phenotype compared to control littermates, as assessed by accelerated rotarod performance, spontaneous locomotor activity in the open field test and a mild degree of spasticity shown by a clasping phenotype. Analysis of social and cognitive behavior showed a rapid installment of deficits in social interaction, working memory (Y-maze test) and recognition memory (novel object recognition test) in the absence of overt motor abnormalities. To investigate if the motor phenotype worsen with age, we analyzed the behavior of mice after long-term (up to 12 months) transgene induction. Our results reveal a decreased performance on the rotarod test and in the hanging wire test, indicating a motor phenotype that was absent in younger mice. In addition, long-term hTDP-43-WT expression led to hyperlocomotion in the open field test. In sum, these results demonstrate a time-dependent emergence of a motor phenotype in older hTDP-43-WT Tg mice, recapitulating aspects of clinical FTD presentations with motor involvement in human patients, and providing a complementary animal model for studying TDP-43 proteinopathies.Fil: Alfieri, Julio Armando. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Silva Pinto, Pablo Roberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Müller Igaz, Lionel Ivan. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentin

SOVEREIGN: An Autonomous Neural System for Incrementally Learning Planned Action Sequences to Navigate Towards a Rewarded Goal

How do reactive and planned behaviors interact in real time? How are sequences of such behaviors released at appropriate times during autonomous navigation to realize valued goals? Controllers for both animals and mobile robots, or animats, need reactive mechanisms for exploration, and learned plans to reach goal objects once an environment becomes familiar. The SOVEREIGN (Self-Organizing, Vision, Expectation, Recognition, Emotion, Intelligent, Goaloriented Navigation) animat model embodies these capabilities, and is tested in a 3D virtual reality environment. SOVEREIGN includes several interacting subsystems which model complementary properties of cortical What and Where processing streams and which clarify similarities between mechanisms for navigation and arm movement control. As the animat explores an environment, visual inputs are processed by networks that are sensitive to visual form and motion in the What and Where streams, respectively. Position-invariant and sizeinvariant recognition categories are learned by real-time incremental learning in the What stream. Estimates of target position relative to the animat are computed in the Where stream, and can activate approach movements toward the target. Motion cues from animat locomotion can elicit head-orienting movements to bring a new target into view. Approach and orienting movements are alternately performed during animat navigation. Cumulative estimates of each movement are derived from interacting proprioceptive and visual cues. Movement sequences are stored within a motor working memory. Sequences of visual categories are stored in a sensory working memory. These working memories trigger learning of sensory and motor sequence categories, or plans, which together control planned movements. Predictively effective chunk combinations are selectively enhanced via reinforcement learning when the animat is rewarded. Selected planning chunks effect a gradual transition from variable reactive exploratory movements to efficient goal-oriented planned movement sequences. Volitional signals gate interactions between model subsystems and the release of overt behaviors. The model can control different motor sequences under different motivational states and learns more efficient sequences to rewarded goals as exploration proceeds.Riverside Reserach Institute; Defense Advanced Research Projects Agency (N00014-92-J-4015); Air Force Office of Scientific Research (F49620-92-J-0225); National Science Foundation (IRI 90-24877, SBE-0345378); Office of Naval Research (N00014-92-J-1309, N00014-91-J-4100, N00014-01-1-0624, N00014-01-1-0624); Pacific Sierra Research (PSR 91-6075-2

The Combined Impact Of IgLON Family Proteins Lsamp And Neurotrimin On Developing Neurons And Behavioral Profiles In Mouse

Cell surface neural adhesion proteins are critical components in the complex orchestration of cell proliferation, apoptosis, and neuritogenesis essential for proper brain construction and behavior. We focused on the impact of two plasticity-associated IgLON family neural adhesion molecules, Neurotrimin (Ntm) and Limbic system associated membrane protein (Lsamp), on mouse behavior and its underlying neural development. Phenotyping neurons derived from the hippocampi of Lsamp−/−, Ntm−/− and Lsamp−/−Ntm−/− mice was performed in parallel with behavioral testing. While the anatomy of mutant brains revealed no gross changes, the Ntm−/− hippocampal neurons exhibited premature sprouting of neurites and manifested accelerated neurite elongation and branching. We propose that Ntm exerts an inhibitory impact on neurite outgrowth, whereas Lsamp appears to be an enhancer of the said process as premature neuritogenesis in Ntm−/− neurons is apparent only in the presence of Lsamp. We also show interplay between Lsamp and Ntm in regulating tissue homeostasis: the impact of Ntm on cellular proliferation was dependent on Lsamp, and Lsamp appeared to be a positive regulator of apoptosis in the presence of Ntm. Behavioral phenotyping indicated test-specific interactions between Lsamp and Ntm. The phenotypes of single mutant lines, such as reduced swimming speed in Morris water maze and increased activity in the elevated plus maze, were magnified in Lsamp−/−Ntm−/− mice. Altogether, evidence both from behavioral experiments and cultured hippocampal cells show combined and differential interactions between Ntm and Lsamp in the formation of hippocampal circuits and behavioral profiles. We demonstrate that mutual interactions between IgLON molecules regulate the initiation of neurite sprouting at very early ages, and even cell-autonomously, independent of their regulation of cell-cell adhesion

Neural mechanisms of affective instability and cognitive control in substance use

Objective: We explored the impact of affect on cognitive control as this relates to individual differences in affective instability and substance use. Toward this end, we examined how different dimensions of affective instability interact to predict substance misuse and the effect of this on two event-related potential components, the reward positivity and the late positive potential, which are said to reflect the neural mechanisms of reward and emotion processing, respectively. Methods: We recorded the ongoing electroencephalogram from undergraduate students as they navigated two T-maze tasks in search of rewards. One of the tasks included neutral, pleasant, and unpleasant pictures from the International Affective Picture System. Participants also completed several questionnaires pertaining to substance use and personality. Results: A principal components analysis revealed a factor related to affective instability, which we named reactivity. This factor significantly predicted increased substance use. Individuals reporting higher levels of affective reactivity also displayed a larger reward positivity following stimuli with emotional content. Conclusion: The current study uncovered a group of high-risk substance users who were characterized by greater levels of affective reactivity and context-specific increased sensitivity to rewards. Significance: These results help to elucidate the complex factors underlying substance use and may facilitate the creation of individually-tailored treatment programs for those struggling with substance use disorders

The dimensions of personality in humans and other animals: A comparative and evolutionary perspective

This paper considers the structure and proximate mechanisms of personality in humans and other animals. Significant similarities were found between personality structures and mechanisms across species in at least two broad traits: Extraversion and Neuroticism. The factor space tapped by these personality dimensions is viewed as a general integrative framework for comparative and evolutionary studies of personality in humans and other animals. Most probably, the cross-species similarities between the most broad personality dimensions like Extraversion and Neuroticism as well as other Big Five factors reflect conservative evolution: constrains on evolution imposed by physiological, genetic and cognitive mechanisms. Lower-order factors, which are more species- and situation-specific, would be adaptive, reflecting correlated selection on and trade-offs between many traits

Serotonin 2a Receptor and Serotonin 1a Receptor Interact Within the Medial Prefrontal Cortex During Recognition Memory in Mice

Episodic memory, can be defined as the memory for unique events. The serotonergic system one of the main neuromodulatory systems in the brain appears to play a role in it. The serotonin 2a receptor (5-HT2aR) one of the principal post-synaptic receptors for 5-HT in the brain, is involved in neuropsychiatric and neurological disorders associated with memory deficits. Recognition memory can be defined as the ability to recognize if a particular event or item was previously encountered and is thus considered, under certain conditions, a form of episodic memory. As human data suggest that a constitutively decrease of 5-HT2A signaling might affect episodic memory performance we decided to compare the performance of mice with disrupted 5-HT2aR signaling (htr2a−/−) with wild type (htr2a+/+) littermates in different recognition memory and working memory tasks that differed in the level of proactive interference. We found that ablation of 5-HT2aR signaling throughout development produces a deficit in tasks that cannot be solved by single item strategy suggesting that 5-HT2aR signaling is involved in interference resolution. We also found that in the absence of 5-HT2aR signaling serotonin has a deleterious effect on recognition memory retrieval through the activation of 5-HT1aR in the medial prefrontal cortex.Fil: Morici, Juan Facundo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Ciccia, Lucia Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Malleret, Gael. Université Claude Bernard Lyon 1; FranciaFil: Gingrich, Jay. Columbia University; Estados Unidos. New York State Psychiatric Institute; Estados UnidosFil: Bekinschtein, Pedro Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Weisstaub, Noelia V.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentin

A phenotypic and molecular characterization of the fmr1-tm1Cgr Fragile X mouse

Fragile X Syndrome is the most common form of\ud inherited mental retardation. It is also known for having\ud a substantial behavioral morbidity, including autistic features. In humans, Fragile X Syndrome is almost always\ud caused by inactivation of the X-linked FMR1 gene. A\ud single knockout mouse model, fmr1-tm1Cgr, exists. In\ud this report we further characterize the cognitive and\ud behavioral phenotype of the fmr1-tm1Cgr Fragile X\ud mouse through the use of F1 hybrid mice derived from\ud two inbred strains (FVB/NJ and C57BL/6J). Use of F1\ud hybrids allows focus on the effects of the fmr1-tm1Cgr\ud allele with reduced influence from recessive alleles\ud present in the parental inbred strains. We find that the\ud cognitive phenotype of fmr1-tm1Cgr mice, including\ud measures of working memory and learning set formation\ud that are known to be seriously impacted in humans with\ud Fragile X Syndrome, are essentially normal. Further testing of inbred strains supports this conclusion. Thus, any\ud fmr1-tm1Cgr cognitive deficit is surprisingly mild or\ud absent. There is, however, clear support presented for a\ud robust audiogenic seizure phenotype in all strains tested,\ud as well as increased entries into the center of an open\ud field. Finally, a molecular examination of the fmr1-tm1Cgr\ud mouse shows that, contrary to common belief, it is not a\ud molecular null. Implications of this finding for interpretation of the phenotype are discussed.\u

Mutant Tau knock-in mice display frontotemporal dementia relevant behaviour and histopathology

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