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Muscarinic cholinergic receptors in the developing and mature basal ganglia

Nastuk, Mary Alden
Fonte: Massachusetts Institute of Technology Publicador: Massachusetts Institute of Technology
Tipo: Tese de Doutorado Formato: 202 leaves; 12587839 bytes; 12587599 bytes; application/pdf; application/pdf
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by Mary Alden Nastuk.; Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, 1988.; Title as it appeared in M.I.T. Graduate List, June 1988: Muscarinic cholinergic binding sites in the developing and mature basal ganglia.; Includes bibliographical references.

CaMKII at a central synapse : α-calcium/calmodium protien kinase II and synaptic plasticity at CA3 Schaffer collateral -- CA1 synapses in the mammalian hippocampus

Hinds, Heather L., 1969-
Fonte: Massachusetts Institute of Technology Publicador: Massachusetts Institute of Technology
Tipo: Tese de Doutorado Formato: 180 leaves; 21391079 bytes; 21390836 bytes; application/pdf; application/pdf
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Long term potentiation (LTP) of synaptic transmission at the CA3-CA1 hippocampal synapse is a model synaptic plasticity mechanism that may underlie hippocampal dependent learning and memory. Inhibition of post-synaptic calcium/calmodulin protein kinase II (CaMKII) has been shown to block LTP, and a global knockout of the highly expressed a isoform of CaMKII caused an impairment in LTP and hippocampus dependent learning. We examined the role of CaMKII in CA3-CA1 LTP by selectively deleting [alpha]-CaMKII in adult hippocampal CA1 or CA3 pyramidal cells using conditional gene targeting. With this approach, we could investigate the locus of change that underlies LTP expression, as both pre- (CA3) and post- (CA1) synaptic CaMKII dependent mechanisms have been implicated, and further examine how CaMKII dependent plasticity contributes to learning and memory in a background of normal brain development. CA3-CA1 LTP is reduced in CA1 [alpha]-CaMKII knockout mice, suggesting that post-synaptic CaMKII is required for normal LTP. These mice are strikingly reminiscent of the a-CaMKII global knockout mice, demonstrating comparable LTP impairments and abnormal behaviors. In contrast, CA3 [alpha]-CaMKII knockout mice have normal LTP at CA3-CA1 synapses...

Development of and proposed applications for tetrodes in functional mapping of rodent sensorimotor striatum

Iyengar, Deepa Radhakrishna, 1972-
Fonte: Massachusetts Institute of Technology Publicador: Massachusetts Institute of Technology
Tipo: Tese de Doutorado Formato: 66 leaves; 4569916 bytes; 4569721 bytes; application/pdf; application/pdf
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The Wilson-McNaughton tetrode preparation for awake, behaving rodents was adapted by a group of investigators for use in dorsolateral striatum. Measures were taken to improve the reliability of reaching the target area in the brain and the stability of the implanted tetrode drive over several weeks of recording. Novel methods were developed to confirm the dorsoventral level of tetrodes at intermediate stages of advancement during recording, and to reconstruct estimated directions and distances of recorded sources from tetrodes by post-hoc analysis. Alternative methods of source separation and data visualization were implemented. Additional refinements to improve unit separation within and across recording sessions are proposed. The resulting recording technique is expected to have considerable potential in clarifying behavioral and other functional correlates of systems of striatal anatomical compartmentalization. A set of experiments is proposed to investigate how dorsolateral striatal neuronal activity changes in correlation with learning of three stimulus-response tasks relative to three control tasks with similar sensory, motor and motivational aspects but different learning and memory requirements, and to localize task-responsive units with respect to striosomes and body part areas identified by neuronal responses to cutaneous stimulation/passive manipulation and anterograde anatomical tracers from primary motor cortex. Neuronal activity in the globus pallidus and substantia nigra pars reticulata...

Coherence in natural language : data structures and applications

Wolf, Florian, 1975-
Fonte: Massachusetts Institute of Technology Publicador: Massachusetts Institute of Technology
Tipo: Tese de Doutorado Formato: 150 leaves; 8749340 bytes; 8769604 bytes; application/pdf; application/pdf
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(cont.) baseline, and that some coherence-based approaches best predict the human data. However, coherence-based algorithms that operate on trees did not perform as well as coherence-based algorithms that operate on more general graphs. It is suggested that that might in part be due to the fact that more general graphs are more descriptively adequate than trees for representing discourse coherence.; The general topic of this thesis is coherence in natural language, where coherence refers to informational relations that hold between segments of a discourse. More specifically, this thesis aims to (1) develop criteria for a descriptively adequate data structure for representing discourse coherence; (2) test the influence of coherence on psycholinguistic processes, in particular, pronoun processing; (3) test the influence of coherence on the relative saliency of discourse segments in a text. In order to address the first aim, a method was developed for hand-annotating a database of naturally occurring texts for coherence structures. The thus obtained database of coherence structures was used to test assumptions about descriptively adequate data structures for representing discourse coherence. In particular, the assumption that discourse coherence can be represented in trees was tested...

cpg2 encodes a brain- and synapse-specific protein that regulates the endocytosis of glutamate receptors; Candidate plasticity gene 2 encodes a brain- and synapse-specific protein that regulates the endocytosis of glutamate receptors

Cottrell, Jeffrey Richard, 1975-
Fonte: Massachusetts Institute of Technology Publicador: Massachusetts Institute of Technology
Tipo: Tese de Doutorado Formato: 113 leaves; 4695448 bytes; 4695255 bytes; application/pdf; application/pdf
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Synaptic plasticity is the rearrangement of neuronal connections that likely underlies learning and memory. It requires the expression of a set of genes essential for the synaptic changes that occur during plasticity, candidate plasticity gene 2 (cpg2) was isolated in a screen for genes that effect synaptic plasticity. In this thesis, I analyze the regulation and function of cpg2 in neurons. I find that cpg2 is a splice-variant of the syne-1 gene that is expressed only in brain regions capable of plasticity and encodes a protein specifically localized to a postsynaptic endocytic zone of excitatory synapses, often in the vicinity of clathrin-coated pits. I further show that, through its C-terminal coiled-coil motifs, CPG2 binds to the actin cytoskeleton and to endophilin B2, a member of a family of proteins involved in membrane trafficking. RNAi-mediated knock-down of CPG2 increased the number of postsynaptic clathrin-coated vesicles, some of which trafficked NMDA receptors, and disrupted the internalization of glutamate receptors. In addition, alterations in its protein levels affected dendritic spine size, supporting a role for CPG2 in regulating membrane trafficking. These data suggest that CPG2 organizes a network of proteins at the postsynaptic endocytic zone critical for glutamate receptor internalization. Due to its unique expression profile and subcellular localization...

Memory systems of the human brain : dissociations among learning capacities in amnesia

Gabrieli, John D. E. (John David Elemer), 1955-
Fonte: Massachusetts Institute of Technology Publicador: Massachusetts Institute of Technology
Tipo: Tese de Doutorado Formato: 2 v. (340 leaves); 14508460 bytes; 14548931 bytes; application/pdf; application/pdf
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by John D. E. Gabrieli.; Thesis (Ph. D.)--Massachusetts Institute of Technology, Whitaker College of Health Sciences, Technology, and Management, Dept. of Brain and Cognitive Sciences, 1987.; MICROFICHE COPY AVAILABLE IN ARCHIVE AND SCIENCE.; Vita.; Bibliography: leaves 295-325.

Multiple spatial memories in the brain : decoding and modification using microstimulation

Histed, Mark H
Fonte: Massachusetts Institute of Technology Publicador: Massachusetts Institute of Technology
Tipo: Tese de Doutorado Formato: 97 leaves; 1510235 bytes; 1508087 bytes; application/pdf; application/pdf
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Sequential processing --- using multiple sensory stimuli to plan and control a set of ordered movements --- is a central aspect of human behavior. Because previous and future movements must be stored during the execution of any movement in a sequence, memory is an indispensable aspect of sequential behavior. To study how memory is used to link sensory inputs to sequential motor outputs, we have used the oculomotor system as a model. We trained monkeys to remember the location of two spatial cues over a brief delay, and then make two eye movements to the remembered locations in the order that they appeared. We explored the role of two different frontal eye movement areas, the frontal and supplementary eye fields (FEF and SEF) during this memory delay. While both the FEF and SEF have shown to be important for sequential behavior, their individual roles are unknown. Here, using physiology, we show that the FEF is important for storing the location of multiple cues and their order in memory. In the SEF, we show that memory period stimulation can affect the order of a sequence, changing the goal of the entire sequence but not the individual movement components.; (cont.) Thus, both areas appear to play complementary roles in sequential planning: the FEF stores target locations...

Learning a dictionary of shape-components in visual cortex : comparison with neurons, humans and machines

Serre, Thomas (Thomas R. G.)
Fonte: Massachusetts Institute of Technology Publicador: Massachusetts Institute of Technology
Tipo: Tese de Doutorado Formato: 211 p.; 6642161 bytes; 6639386 bytes; application/pdf; application/pdf
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In this thesis, I describe a quantitative model that accounts for the circuits and computations of the feedforward path of the ventral stream of visual cortex. This model is consistent with a general theory of visual processing that extends the hierarchical model of [Hubel and Wiesel, 1959] from primary to extrastriate visual areas. It attempts to explain the first few hundred milliseconds of visual processing and "immediate recognition". One of the key elements in the approach is the learning of a generic dictionary of shape components from V2 to IT, which provides an invariant representation to task-specific categorization circuits in higher brain areas. This vocabulary of shape-tuned units is learned in an unsupervised manner from natural images, and constitutes a large and redundant set of image features with different complexities and invariances. This theory significantly extends an earlier approach by [Riesenhuber and Poggio, 1999a] and builds upon several existing neurobiological models and conceptual proposals. First, I present evidence to show that the model can duplicate the tuning properties of neurons in various brain areas (e.g., V1, V4 and IT).; (cont.) In particular, the model agrees with data from V4 about the response of neurons to combinations of simple two-bar stimuli [Reynolds et al....

Characterization of CPG15 during cortical development and activity dependent plasticity

Harwell, Corey (Corey C.)
Fonte: Massachusetts Institute of Technology Publicador: Massachusetts Institute of Technology
Tipo: Tese de Doutorado Formato: 102 p.
ENG
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Regulation of gene transcription by neuronal activity is thought to be key to the translation of sensory experience into long-term changes in synaptic structure and function. Here we show that cgp15, a gene encoding an extracellular signaling molecule that promotes dendritic and axonal growth and synaptic maturation, is regulated in the somatosensory cortex by sensory experience capable of inducing cortical plasticity. Using in situ hybridization, we monitored cgp15 expression in 4-week-old mouse barrel cortex after trimming all whiskers except D1. We found that cpgl5 expression is depressed in the deprived barrels and enhanced in the barrel column corresponding to the spared D1 whisker. Induction of cpgl5 expression is significantly diminished in adolescent as well as adult CREB knockout mice. cgp15 spatio-temporal expression pattern and its regulation by CREB are consistent with a role in experience-dependent plasticity of cortical circuits. Our results suggest that local structural and/or synaptic changes may be a mechanism by which the adult cortex can adapt to peripheral manipulations. The balance between proliferation and apoptosis is critical for proper development of the nervous system.; (cont.) Yet, little is known about molecules that regulate apoptosis of proliferative neurons. Here we identify a soluble...

Principles underlying the development and organization of feature maps in the visual cortex

Farley, Brandon J. (Brandon James)
Fonte: Massachusetts Institute of Technology Publicador: Massachusetts Institute of Technology
Tipo: Tese de Doutorado Formato: 142 leaves
ENG
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A fundamental question in neuroscience is how sensory information is represented in the brain. In particular, what principles guide the spatial organization of neurons with regard to their receptive field properties, and how is this organization established mechanistically? The visual cortex serves as a model area to address these questions, but whether general principles can explain the layouts of cortical maps, such as those of visual space and of specific response features, remains unresolved. We find that in primary visual cortex of ferret, the layout of each map is inter-dependent with that of the others. First, we find a strong anisotropy in the visual map, such that receptive field positions change more rapidly along one axis of cortex; and importantly, along the axis where visual space changes rapidly, the feature maps of orientation, ocular dominance, and spatial frequency change slowly. Second, orientation, ocular dominance, and spatial frequency maps have local spatial relationships with each other: in areas of cortex where one feature changes rapidly, the other features change more slowly. Each of these relationships are well-explained by a dimension-reduction model of cortex.; (cont.) This suggests that the constraints which drive map formation in the model...

Comparison of frontal and parietal cortices in the control of visual attention

Buschman, Timothy J. (Timothy Joseph)
Fonte: Massachusetts Institute of Technology Publicador: Massachusetts Institute of Technology
Tipo: Tese de Doutorado Formato: 186 p.
ENG
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The ability to switch between tasks reflects a fundamental part of our intelligence. A foundation of this ability lies in perceiving and processing information pertinent to the situation at hand. It is our capacity to attend to specific objects and, more importantly, our ability to switch our attention from object to object, that supports complex cognitive behavior. Therefore, by understanding the neural mechanisms involved in directing attention we hope to better understand cognition. Previous work investigating the ability to control attention has suggested that attention is influenced from two sources -- attention can either be driven from external sources in an bottom-up, exogenous manner or directed internally in an top-down, endogenous manner.This project will utilize two different forms of visual search in order to emphasize these two different types of attentional control. Both the prefrontal and parietal regions are implicated as the source of this control. In order to investigate their relative roles we recorded simultaneously from both parietal cortex (specifically, the lateral intraparietal cortex) and prefrontal cortex (specifically, the frontal eye fields and dorsolateral prefrontal cortex). We address four main questions. First...

LGN activity patterns during ocular dominance plasticity in vivo; (cont.) These findings substantially alter the interpretation of previous studies and define the activity patterns that govern cortical plasticity in vivo. Furthermore, this work may have important implications for treatments of developmental disorders including ambylopia.

Linden, Monica L. (Monica Loryn)
Fonte: Massachusetts Institute of Technology Publicador: Massachusetts Institute of Technology
Tipo: Tese de Doutorado Formato: 155 p.
ENG
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Perturbations of sensory experience in young animals are known to cause lasting changes in adult brain function. For example, monocular visual deprivation by lid closure (MC) leads to a loss of cortical responsiveness of the deprived eye and a concomitant visual impairment. This ocular dominance (OD) plasticity is a well-studied model of experience-dependent cortical plasticity. While much is known about the anatomical, physiological and biochemical changes that occur in primary visual cortex following OD plasticity, the input patterns that lead to these changes have not been characterized. Visual input travels from the retina through the dorsal lateral geniculate nucleus (dLGN) of the thalamus and then into visual cortex. Several models of the thalamic activity patterns which drive OD plasticity have been proposed, but the assumptions about the pattern and amount of input activity from thalamus to cortex during deprivation have not been experimentally validated. Therefore, we performed extracellular recordings from the dLGN of animals during periods of visual manipulation. Contrary to previous hypotheses, the present findings demonstrate that MC does not alter the overall firing rate of neural activity in the dLGN. Instead, MC alters the pattern of neural spike trains such that there is a decrease in simultaneous firing of neighboring neurons. Moreover...

Controlling memory and resolving interference : prefrontal contributions to flexible behavior

Badre, David
Fonte: Massachusetts Institute of Technology Publicador: Massachusetts Institute of Technology
Tipo: Tese de Doutorado Formato: 207 p.; 11746277 bytes; 11759551 bytes; application/pdf; application/pdf
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Flow does the brain meet shifting task demands? The experiments and formal theoretical framework presented in this dissertation characterize the cognitive and neural processes by which flexible performance is enabled during task switching. Chapter 1 reviews major findings and controversies in the task switching literature, highlighting (1) evidence that behavioral switch costs may derive from proactive interference due to the facilitated retrieval of irrelevant competitors from long-term memory and (2) the consistent finding of activation in ventrolateral prefrontal cortex (VLPFC) during task switching. These observations motivate the hypothesis that left VLPFC may resolve proactive interference arising from long-term memory during a task switch. Chapters 2 and 3 describe three fMRI experiments conducted in experimental contexts independent of task switching that directly link left mid-VLPFC (Brodmann's Area 45; inferior frontal gyrus pars triangularis) to a post-retrieval selection process that resolves proactive interference from irrelevant representations retrieved from long-term memory. Chapter 4 introduces a computational model that derives its task switch cost from interference due to performance-dependent changes in its associative structure...

Cellular and molecular analysis of neuronal structure plasticity in the mammalian cortex

Lee, Wei-Chung Allen
Fonte: Massachusetts Institute of Technology Publicador: Massachusetts Institute of Technology
Tipo: Tese de Doutorado Formato: 100 p.; 5924494 bytes; 5924232 bytes; application/pdf; application/pdf
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Despite decades of evidence for functional plasticity in the adult brain, the role of structural plasticity in its manifestation remains unclear. cpg15 is an activity-regulated gene encoding a membrane-bound ligand that coordinately regulates growth of apposing dendritic and axonal arbors and the maturation of their synapses. Here we compare cpg15 expression during normal development of the rat visual system, with that seen in response to dark rearing, monocular retinal action potential blockade, or monocular deprivation. Our results show that: (1) cpg15 expression in visual cortex correlates with the electrophysiologically mapped critical period for development of eye-specific preference in the primary visual cortex. (2) Dark rearing elevates adult levels of expression. (3) A component of cpg15 expression is activity-dependent after the peak of the critical period. (4) At the peak of the critical period, monocular deprivation decreases cpg15 expression more than monocular TTX blockade. And (5) cpg15 expression is robust and regulated by light in the superficial layers of the adult visual cortex.; (cont.) This suggests that cpg15 is an excellent molecular marker for the visual system's capacity for plasticity and predicts that neural remodeling normally occurs in the extragranular layers of the adult visual cortex. To examine the extent of neuronal remodeling that occurs in the brain on a daily basis...

Seeking the neural basis of grammar : English noun and verb morphological processing investigated with rapid event-related fMRI and intracortical electrophysiology

Sahin, Nedim T. (Nedim Turan), 1975-
Fonte: Massachusetts Institute of Technology Publicador: Massachusetts Institute of Technology
Tipo: Tese de Doutorado Formato: 2 v. (271 leaves); 21714406 bytes; 21749390 bytes; application/pdf; application/pdf
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(cont.) the functionality of the fMRI data analysis and visualization tools used at Massachusetts General Hospital. I analyze and interpret an 18-subject fMRI experiment I ran using the new task design and software tools. Finally, I present preliminary findings on linguistic questions as well as the nature of fMRI signal, using direct Electrophysiological data recorded from electrodes implanted in the brains of two Epilepsy patients. These patients had electrodes implanted through or near classical language areas of their brains, as a necessary clinical step in locating and surgically removing the seizure-causing tissue. The main findings of this thesis are: 1.) Morphology alone can activate Broca's area, 2.) Other areas are involved, including BA47, anterior insula, and SMA, 3.) Broca's area and BA47 respond to application of abstract grammatical features, even without phonological manipulations, 4.) Morphophonological manipulation additionally recruits insula and SMA, 5.) While simply accessing nouns versus verbs may involve separable brain regions, inflectional processing of the two categories may be done by the same process, 6.) Regularly and Irregularly inflected verbs show a double dissociation of activation in frontal and medial regions...

Cognitive and neural correlates of memory retrieval in young and older adults

O'Kane, Gail, 1965-
Fonte: Massachusetts Institute of Technology Publicador: Massachusetts Institute of Technology
Tipo: Tese de Doutorado Formato: 154 p.; 9207814 bytes; 9228924 bytes; application/pdf; application/pdf
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(cont.) increased activity whenever recollection was attempted, independent of the level of recollection success. The results are consistent with the hypothesis that increased left-lateralized retrieval activity in older adults supports recollection attempt. Age deficits in semantic memory are more subtle than in episodic memory. However, older adults are impaired when automatic, data-driven processes are not sufficient to support the retrieval of conceptual knowledge. The fMRI study described in Chapter 3 used semantic repetition priming to test two theories of the role LIPC plays in semantic retrieval. Young adults exhibited repetition-related BOLD response reductions in LIPC that were specific to the particular semantic task engaged, consistent with the hypothesis that LIPC supports controlled semantic retrieval. Older adults, in contrast, exhibited repetition-related signal reductions even when the semantic judgment made about a word differed across the two exposures, consistent with the hypothesis that older adults fail to gate irrelevant semantic information from working memory during initial presentation of the word.; Older adults are impaired in episodic and semantic retrieval but the extent of these deficits and their neural correlates is unknown. In episodic memory...

Identification, improved modeling and integration of signals to predict constitutive and altering splicing

Yeo, Gene W. (Gene Wei-Ming), 1977-
Fonte: Massachusetts Institute of Technology Publicador: Massachusetts Institute of Technology
Tipo: Tese de Doutorado Formato: 259 p.; 13699870 bytes; 13734221 bytes; application/pdf; application/pdf
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(cont.) manipulation of intronic elements that enables fish genes to be spliced properly in mammalian cells; (iii) A computational analysis using EST data, genome sequence data, and microarray expression data of tissue- specific alternative splicing is conducted, which distinguishes human brain, testis and liver as having unusually high levels of AS, highlights differences in the types of AS occurring commonly in different tissues, and identifies candidate cis-regulatory elements and trans-factors likely to play important roles in tissue-specific AS in human cells; (iv) The identification of a set of discriminatory sequence features and their integration into a statistical machine-learning algorithm, ACEScan, which distinguishes exons subject to evolutionarily conserved alternative splicing from constitutively spliced or lineage-specifically-spliced exons is described; (v) The genome-wide search for and experimental validation of exon-skipping events using the combination of two silencing cis-elements, UAGG and GGGG.; The regulation of pre-messenger RNA splicing by the spliceosomal machinery via interactions between cis-regulatory elements and splicing trans-factors to generate a specific mRNA i.e. constitutive splicing, or sometimes many distinct mRNA isoforms i.e. alternative splicing...

Categorical representation of visual stimuli in the primate prefrontal and inferior temporal cortices

Freedman, David J. (David Jordan), 1975-
Fonte: Massachusetts Institute of Technology Publicador: Massachusetts Institute of Technology
Tipo: Tese de Doutorado Formato: 130 leaves; 9288319 bytes; 9288077 bytes; application/pdf; application/pdf
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The ability to group stimuli into meaningful categories is a fundamental cognitive process though little is known its neuronal basis. To address this issue, we trained monkeys to perform a categorization task in which they classified visual stimuli into well defined categories that were separated by a "category-boundary". We recorded from neurons in the prefrontal (PFC) and inferior temporal (ITC) cortices during task performance. This allowed the neuronal representation of category membership and stimulus shape to be independently examined. In the first experiment, monkeys were trained to classify the set of morphed stimuli into two categories, "cats" and "dogs". Recordings from the PFC of two monkeys revealed a large population of categorically tuned neurons. Their activity made sharp distinctions between categories, even for stimuli that were visually similar but from different classes. Likewise, these neurons responded similarly to stimuli from the same category even if they were visually dissimilar from one another. In the second experiment, one of the monkeys used in the first experiment was retrained to classify the same stimuli into three new categories. PFC recordings collected after the monkeys were retrained revealed that the population of neurons reflected the three new categories but not the previous (now irrelevant) two categories. In the third experiment...

Investigations of the cognitive and neural processes supporting memory for neutral and emotional words

Kensinger, Elizabeth A. (Elizabeth Ann), 1976-
Fonte: Massachusetts Institute of Technology Publicador: Massachusetts Institute of Technology
Tipo: Tese de Doutorado Formato: 141 leaves; 6270119 bytes; 6269927 bytes; application/pdf; application/pdf
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The cognitive and neural processes underlying memory formation may differ depending on the vividness, or detail, of information encoded. In Chapter 1, a divided attention paradigm was used to examine memory formation when resources are (a) devoted primarily to encoding and (b) directed away from encoding, and toward a secondary task. In condition (b) the memories formed often lacked vividness. The formation of these less detailed memories recruited right inferior prefrontal cortex (PFC) and left parahippocampal gyrus. The left inferior PFC and left anterior hippocampus were additionally recruited in condition (a) when vivid memories could be formed. Investigations of memories' vividness have typically included only neutral information. The studies in Chapter 2 revealed that emotional information is vividly remembered more frequently than information lacking emotional import. This enhancement occurred for words with valence only (i.e., negative words that did not elicit physiological arousal) as well as for arousing ("taboo") words, but was stronger for the arousing words. In Chapter 3 a divided attention paradigm was employed to investigate the contributions of automatic and controlled processing to the recollective enhancement for the emotional words. Automatic processes (unaffected by task manipulation) drove the enhancement for arousing words...

Consuming a diet enriched with choline, UMP, and DHA improves memory in rodents when these compounds increase phospholipids

Holguin, Sarah, Ph. D. Massachusetts Institute of Technology
Fonte: Massachusetts Institute of Technology Publicador: Massachusetts Institute of Technology
Tipo: Tese de Doutorado Formato: 74 leaves
ENG
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A new treatment tested in laboratory animals increases synaptic membrane and cholinergic neurotransmission. This treatment involves giving three compounds; DHA, a phosphatide precursor; choline, another phosphatide precursor present in the rodents' diets but not varied in this study; and UMP, a precursor of CTP, the rate-limiting compound in Kennedy Cycle production of phosphatides. Their administration increases the quantities of phosphatides, the major constituent of neuronal membrane, per brain cell, as well as specific synaptic proteins, the number of dendritic spines; and the expression of genes related to hippocampal glutamatergic neurotransmission. Since such membrane is the predominant component of synapses, the treatment might also ameliorate the loss of synapses occurring in the brains of Alzheimer's patients. My study involves assessing the behavioral effects of the treatment in individual rats or gerbils subsequently shown to manifest its neurochemical effects (i.e., increased phosphatides). My present findings show that the treatment improves performance on various tests of memory function. The largest improvements in memory function and increases in phosphatide levels are observed when DHA, choline, and UMP are consumed in combination.; by Sarah Holguin.; Thesis (Ph. D.)--Massachusetts Institute of Technology...