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1.
Nat Commun ; 10(1): 3970, 2019 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-31481701

RESUMO

Gamma is a ubiquitous brain rhythm hypothesized to support cognitive, perceptual, and mnemonic functions by coordinating neuronal interactions. While much correlational evidence supports this hypothesis, direct experimental tests have been lacking. Since gamma occurs as brief bursts of varying frequencies and durations, most existing approaches to manipulate gamma are either too slow, delivered irrespective of the rhythm's presence, not spectrally specific, or unsuitable for bidirectional modulation. Here, we overcome these limitations with an approach that accurately detects and modulates endogenous gamma oscillations, using closed-loop signal processing and optogenetic stimulation. We first show that the rat basolateral amygdala (BLA) exhibits prominent gamma oscillations during the consolidation of contextual memories. We then boost or diminish gamma during consolidation, in turn enhancing or impairing subsequent memory strength. Overall, our study establishes the role of gamma oscillations in memory consolidation and introduces a versatile method for studying fast network rhythms in vivo.


Assuntos
Complexo Nuclear Basolateral da Amígdala/fisiologia , Ritmo Gama/fisiologia , Memória Espacial/fisiologia , Animais , Comportamento Apetitivo/fisiologia , Aprendizagem da Esquiva/fisiologia , Masculino , Consolidação da Memória/fisiologia , Optogenética , Ratos Long-Evans
2.
Nat Commun ; 10(1): 3710, 2019 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-31420546

RESUMO

Despite strong evidence to the contrary in the literature, microsaccades are overwhelmingly described as involuntary eye movements. Here we show in both human subjects and monkeys that individual microsaccades of any direction can easily be triggered: (1) on demand, based on an arbitrary instruction, (2) without any special training, (3) without visual guidance by a stimulus, and (4) in a spatially and temporally accurate manner. Subjects voluntarily generated instructed "memory-guided" microsaccades readily, and similarly to how they made normal visually-guided ones. In two monkeys, we also observed midbrain superior colliculus neurons that exhibit movement-related activity bursts exclusively for memory-guided microsaccades, but not for similarly-sized visually-guided movements. Our results demonstrate behavioral and neural evidence for voluntary control over individual microsaccades, supporting recently discovered functional contributions of individual microsaccade generation to visual performance alterations and covert visual selection, as well as observations that microsaccades optimize eye position during high acuity visually-guided behavior.


Assuntos
Neurônios/fisiologia , Movimentos Sacádicos/fisiologia , Memória Espacial/fisiologia , Colículos Superiores/fisiologia , Adulto , Animais , Feminino , Humanos , Macaca mulatta , Masculino , Memória , Memória de Curto Prazo , Vias Neurais , Colículos Superiores/citologia , Adulto Jovem
3.
Acta Psychol (Amst) ; 199: 102895, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31377309

RESUMO

Spatial abilities associated with success in educational and occupational fields of Science, Technology, Engineering, and Mathematics (STEM) have been repeatedly shown to be gendered, with males demonstrating measurably better spatial abilities than females. Less is known about why this is, or about how experience with spatial systems (videogames, for example) affects these abilities. We conducted two experiments with 82 participants with varying degrees of videogame experience on measures of mental rotation, spatial learning, and spatial memory. Spatial learning and memory were tested in a Virtual Morris Water Maze. In the first experiment, the maze lacked proximal landmarks. Males proved faster and more accurate than females in learning the location of the hidden platform. As predicted males also outperformed females in mental rotation abilities. Mental rotation correlated with performance in the virtual maze, indicating that in the absence of proximal landmarks, participants relied on strategies requiring mental rotation. Experienced 3D videogame players did not demonstrate superior spatial learning and memory, but performed better than novices in mental rotation. In the second experiment, the maze had proximal cues, in the form of landmarks on the circumference of the virtual pool, and gender-based differences in navigational performance significantly diminished. Under these changed environmental conditions, mental rotation ability did not correlate with performance in the VMWM, suggesting that given proximal cues, the need for mental rotation diminishes. Differences between videogame novices and experts also decreased when proximal cues were provided. Females in particular obtained more discernible benefits from videogame experience. Together, these experiments reveal how the spatial abilities and strategies used to solve the Morris maze task vary with environmental design. Given the structural similarities between the virtual maze and videogame environments, these results offer insight into how spatial experience gained through videogame playing can affect aspects of spatial cognition, and can help identify design elements that contribute to their improvement.


Assuntos
Percepção Espacial/fisiologia , Aprendizagem Espacial/fisiologia , Jogos de Vídeo/psicologia , Realidade Virtual , Adolescente , Adulto , Feminino , Humanos , Masculino , Aprendizagem em Labirinto/fisiologia , Fatores Sexuais , Memória Espacial/fisiologia , Navegação Espacial/fisiologia , Adulto Jovem
4.
Psychon Bull Rev ; 26(5): 1657-1665, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31388836

RESUMO

Most studies on visual working memory (VWM) and spatial working memory (SWM) have employed visual stimuli presented at the fronto-parallel plane and few have involved depth perception. VWM is often considered as a memory buffer for temporarily holding and manipulating visual information that relates to visual features of an object, and SWM for holding and manipulating spatial information that concerns the spatial location of an object. Although previous research has investigated the effect of stereoscopic depth on VWM, the question of how depth positions are stored in working memory has not been systematically investigated, leaving gaps in the existing literature on working memory. Here, we explore working memory for depth by using a change detection task. The memory items were presented at various stereoscopic depth planes perpendicular to the line of sight, with one item per depth plane. Participants were asked to make judgments on whether the depth position of the target (one of the memory items) had changed. The results showed a conservative response bias that observers tended to make 'no change' responses when detecting changes in depth. In addition, we found that similar to VWM, the change detection accuracy degraded with the number of memory items presented, but the accuracy was much lower than that reported for VWM, suggesting that the storage for depth information is severely limited and less precise than that for visual information. The detection sensitivity was higher for the nearest and farthest depths and was better when the probe was presented along with the other items originally in the memory array, indicating that how well the to-be-stored depth can be stored in working memory depends on its relation with the other depth positions.


Assuntos
Percepção de Profundidade/fisiologia , Memória de Curto Prazo/fisiologia , Memória Espacial/fisiologia , Percepção Visual/fisiologia , Adulto , Feminino , Humanos , Masculino
5.
Brain Cogn ; 135: 103581, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31301590

RESUMO

Anatomic and molecular sex differences exist in the brain, which suggests there may be functional differences. The present functional magnetic resonance imaging (fMRI) investigation aimed to identify the similarities and differences in brain activity between females and males during item memory. During encoding, abstract shapes were presented to the left or right of fixation. During retrieval, old and new shapes were presented at fixation and participants made "old-left", "old-right", or "new" judgments. Item memory was isolated by contrasting correct "old" responses to old items (with incorrect spatial memory responses; item memory hits) and "new" responses to old items (item memory misses). For both sexes, item memory produced activity in regions associated with visual long-term memory including the prefrontal cortex, parietal cortex, and visual processing regions. A sex by accuracy interaction analysis within each sub-region of activity produced largely null results, supporting common patterns of brain activity. However, there was sex-specific (male > female) activity within default network regions, which suggests males may have been less engaged in the task, and there was evidence for greater activity for females than males in language processing cortex. The present findings indicate that females and males employ similar patterns of brain activity during item memory.


Assuntos
Encéfalo/diagnóstico por imagem , Memória Espacial/fisiologia , Adolescente , Mapeamento Encefálico , Feminino , Neuroimagem Funcional , Humanos , Imagem por Ressonância Magnética , Masculino , Estimulação Luminosa/métodos , Fatores Sexuais , Adulto Jovem
6.
PLoS Biol ; 17(6): e3000322, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31206519

RESUMO

Declarative memory encompasses representations of specific events as well as knowledge extracted by accumulation over multiple episodes. To investigate how these different sorts of memories are created, we developed a new behavioral task in rodents. The task consists of 3 distinct conditions (stable, overlapping, and random). Rodents are exposed to multiple sample trials, in which they explore objects in specific spatial arrangements, with object identity changing from trial to trial. In the stable condition, the locations are constant during all sample trials even though the objects themselves change; in the test trial, 1 object's location is changed. In the random condition, object locations are presented in the sample phase without a specific spatial pattern. In the overlapping condition, 1 location is shared (overlapping) between all trials, while the other location changes during sample trials. We show that in the overlapping condition, instead of only remembering the last sample trial, rodents form a cumulative memory of the sample trials. Here, we could show that both mice and rats can accumulate information across multiple trials and express a long-term abstracted memory.


Assuntos
Memória de Longo Prazo/fisiologia , Memória/fisiologia , Memória Espacial/fisiologia , Animais , Comportamento Animal/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Ratos , Ratos Wistar , Percepção Espacial/fisiologia
7.
Behav Processes ; 166: 103888, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31226335

RESUMO

Different personalities may lead to different ways of processing environmental information; however, the relationship between personality and cognition is not fully understood as studies on diverse species present contrasting results. As there is great within-flock variability of outdoor ranging behavior in free-range broiler chickens, we tested whether and how ranging behavior impacts on individual spatial memory abilities. The experiment was conducted on one flock (n = 200) reared in the same conditions throughout the study, to simulate on-farm situations. As the ranging behavior was stable over time, we compared two distinct groups of male chickens: one that visited the range more (High rangers) and one that was more prone to staying in the poultry house (Low rangers). To test the spatial memory, individuals (n = 30) went through two main phases in an arena with 8 cups. For the familiarization phase, individuals were submitted to one trial per day, for seven days, to a situation where all eight cups were baited with mealworms. Animals had to reach a criterion of 5 cups visited out of 8 to advance to the next phase. For the spatial test, only four cups were baited and systematically placed at the same location. This last phase comprised two trials per individual per day, for nine days. During these two phases, latency to visit cups and the number of visits and revisits of all cups were recorded. Low ranger chickens took less time to attain the pre-established threshold of visiting 5 cups out of 8, over the familiarization phase. During the spatial test, the latency to visit four cups decreased between the within-day trials for low ranger chickens and increased for high ranger chickens. Moreover, in the within-day trial analysis, low ranger chickens exhibited an improvement on spatial memory and better spatial memory compared to high ranger chickens. Different speed-accuracy trade-offs may explain these differences between low and high ranger chickens and the way individuals interact and solve the task. Our study strengthens the scientific evidence relating consistent individual differences in behavior, with the ranging behavior of free-range chickens, and cognitive performance during a spatial memory task.


Assuntos
Comportamento Animal/fisiologia , Galinhas/fisiologia , Comportamento Exploratório/fisiologia , Memória Espacial/fisiologia , Animais , Cognição/fisiologia , Masculino , Personalidade/fisiologia
8.
Ear Hear ; 40(4): 757-765, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31242136

RESUMO

OBJECTIVES: Hearing loss is considered an independent risk factor for dementia. Growing evidence in animal and human studies suggest that not only hearing loss but also vestibular loss might result in cognitive deficits. The objective of this study is to evaluate the presence of spatial and nonspatial cognitive deficits in patients with bilateral vestibulopathy. As different causes of bilateral vestibulopathy are associated with hearing loss, the objective is to evaluate if these cognitive deficits are due to the vestibular loss of the patients with bilateral vestibulopathy, or to their hearing loss, or both. DESIGN: We performed a systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. (1) Data sources: MEDLINE and the Cochrane Library. (2) Study selection: Cross-sectional studies investigating cognitive performances in human patients with bilateral vestibulopathy confirmed by quantitative vestibular testing. (3) Data extraction: Independent extraction of articles by three authors using predefined data fields, including patient- and control characteristics and cognitive outcomes. RESULTS: Ten studies reporting on 126 patients with bilateral vestibulopathy matched the inclusion criteria. Cognitive domains evaluated in patients with bilateral vestibulopathy included visuospatial abilities, memory, language, attention, and executive function. In only three studies, hearing performance of the included patients was briefly described. Nearly all studies demonstrated a significant impairment of spatial cognition in patients with bilateral vestibulopathy. In the few papers investigating nonspatial cognition, worse outcome was demonstrated in patients with bilateral vestibular loss performing cognitive tasks assessing attentional performance, memory, and executive function. CONCLUSIONS: Strong evidence exists that patients with bilateral vestibulopathy suffer from impaired spatial cognition. Recent studies even suggest impairment in other cognitive domains than spatial cognition. However, in all previous studies, conclusions on the link between cognitive performance and vestibular loss were drawn without taken hearing loss into consideration as a possible cause of the cognitive impairment.


Assuntos
Vestibulopatia Bilateral/fisiopatologia , Vestibulopatia Bilateral/psicologia , Cognição/fisiologia , Memória Espacial/fisiologia , Processamento Espacial/fisiologia , Humanos , Testes de Estado Mental e Demência , Navegação Espacial/fisiologia , Escala de Memória de Wechsler
9.
Braz J Med Biol Res ; 52(5): e8026, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31038577

RESUMO

Carassius auratus is a teleost fish that has been largely used in behavioral studies. However, little is known about potential environmental influences on its performance of learning and memory tasks. Here, we investigated this question in C. auratus, and searched for potential correlation between exercise and visuospatial enrichment with the total number of telencephalic glia and neurons. To that end, males and females were housed for 183 days in either an enriched (EE) or impoverished environment (IE) aquarium. EE contained toys, natural plants, and a 12-hour/day water stream for voluntary exercise, whereas the IE had none of the above. A third plus-maze aquarium was used for spatial and object recognition tests. Different visual clues in 2 of its 4 arms were used to guide fish to reach the criteria to complete the task. The test consisted of 30 sessions and was concluded when each animal performed three consecutive correct choices or seven alternated, each ten trials. Learning rates revealed significant differences between EE and IE fish. The optical fractionator was used to estimate the total number of telencephalic cells that were stained with cresyl violet. On average, the total number of cells in the subjects from EE was higher than those from subjects maintained in IE (P=0.0202). We suggest that environmental enrichment significantly influenced goldfish spatial learning and memory abilities, and this may be associated with an increase in the total number of telencephalic cells.


Assuntos
Proliferação de Células/fisiologia , Peixes/fisiologia , Aprendizagem Espacial/fisiologia , Memória Espacial/fisiologia , Telencéfalo/metabolismo , Animais , Comportamento Animal/fisiologia , Contagem de Células , Feminino , Masculino , Condicionamento Físico Animal
10.
Exp Brain Res ; 237(7): 1811-1820, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31055606

RESUMO

Herein, we investigate how the three types of mental spatial representation (landmark, route and survey) are reorganized to perform wayfinding and homing behaviour. We also investigate the contribution of visuo-spatial working memory in reaching and in vista space in performing the retracing of the path. For this purpose, we asked 68 healthy college students to learn and come back along an unknown path in a real environment and to perform two different forward and backward working memory tasks, one in the reaching space (Corsi Block-Tapping Test) and the other in a vista space (Walking Corsi Test). The results show that participants performed better when travelling the route forward (which corresponds to the originally learned direction) than when travelling the route backward (return path) and that working memory in vista space is crucial for both wayfinding and homing behaviour, while the working memory for reaching space contributes only to homing behaviour. Although homing behaviour is an early mechanism in navigation shared among many species, it represents a very complex behaviour that requires both topographic and visuo-spatial memory as well as the first two levels of environmental knowledge.


Assuntos
Planejamento Ambiental , Memória de Curto Prazo/fisiologia , Estimulação Luminosa/métodos , Memória Espacial/fisiologia , Navegação Espacial/fisiologia , Adulto , Feminino , Humanos , Masculino , Adulto Jovem
11.
Nat Hum Behav ; 3(5): 462-470, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31089296

RESUMO

Brain areas that control gaze are also recruited for covert shifts of spatial attention1-9. In the external space of perception, there is a natural ecological link between the control of gaze and spatial attention, as information sampled at covertly attended locations can inform where to look next2,10,11. Attention can also be directed internally to representations held within the spatial layout of visual working memory12-16. In such cases, the incentive for using attention to direct gaze disappears, as there are no external targets to scan. Here we investigate whether the oculomotor system of the brain also participates in attention focusing within the internal space of memory. Paradoxically, we reveal this participation through gaze behaviour itself. We demonstrate that selecting an item from visual working memory biases gaze in the direction of the memorized location of that item, despite there being nothing to look at and location memory never explicitly being probed. This retrospective 'gaze bias' occurs only when an item is not already in the internal focus of attention, and it predicts the performance benefit associated with the focusing of internal attention. We conclude that the oculomotor system also participates in focusing attention within memorized space, leaving traces all the way to the eyes.


Assuntos
Atenção/fisiologia , Fixação Ocular/fisiologia , Memória de Curto Prazo/fisiologia , Percepção Espacial/fisiologia , Memória Espacial/fisiologia , Percepção Visual/fisiologia , Adolescente , Adulto , Eletroencefalografia , Medições dos Movimentos Oculares , Feminino , Humanos , Masculino , Fatores de Tempo , Adulto Jovem
12.
Exp Brain Res ; 237(7): 1881-1888, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31093716

RESUMO

Numerous mental health disorders are characterized by cognitive impairments that result in poor vocational and social outcomes. Among the cognitive domains commonly affected, working memory deficits have been noted in patients with attention-deficit/hyperactivity disorder (Martinussen et al. in J Am Acad Child Adolesc Psychiatry 44:377-384, 2005), post-traumatic stress disorder (Honzel et al. in Cogn Affect Behav Neurosci 14:792-804, 2014), and consistently with schizophrenia patients (Callicott et al. in Cereb Cortex 10:1078-1092, 2000; Lewis et al. in Front Hum Neurosci 10:85, 2005; Amann et al. in Brain Res Bull 83:147-161, 2010; Limongi et al. in Schizophr Res 197:386-391, 2018). Oscillations in neural activity from electroencephalogram (EEG) recordings are decomposed by frequency, and band-specific decreases in gamma power (> 30 Hz) have been correlated with working memory ability. This study examined within-subject changes in power of frequency-specific bands during sample versus choice trials during a spatial working memory paradigm (T-maze). EEG was recorded using a relatively novel wireless EEG telemetry system fully implanted within the mouse, enabling uninhibited movement during behavioral tasks. No significant differences were found between sample and correct choice phases in the alpha, theta or gamma frequency ranges. Evoked power was significantly higher during the choice phase than the sample phase in the high-beta/low-gamma frequency range. This frequency range has been implicated in the propagation of cortical predictions to lower levels of stimuli encoding in a top-down hierarchical manner. Results suggest there is an increase in brain activity during correct trials when the mouse enters the opposite arm during the choice phase compared to the sample phase, likely due to prediction error resulting from a discrepancy between present and prior experience. Future studies should identify specific cortical networks involved and investigate neural activity at the neuronal level.


Assuntos
Ritmo beta/fisiologia , Ritmo Gama/fisiologia , Aprendizagem em Labirinto/fisiologia , Memória de Curto Prazo/fisiologia , Memória Espacial/fisiologia , Animais , Previsões , Camundongos , Camundongos Endogâmicos C57BL
13.
Neuroscience ; 408: 204-213, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-30999030

RESUMO

Aging causes various functional changes, including cognitive impairment and inflammatory responses in the brain. Transient receptor potential melastatin 2 (TRPM2), a Ca2+-permeable channel expressed abundantly in immune cells, exacerbates inflammatory responses. Previously, we reported that TRPM2 on resident microglia plays a critical role in exacerbating inflammation, white matter injury, and cognitive impairment during chronic cerebral hypoperfusion; however, the physiological or pathophysiological role of TRPM2 during age-associated inflammatory responses remains unclear. Therefore, we examined the effects of TRPM2 deletion in young (2-3 months) and older (12-24 months) mice. Compared with young wild-type (WT) mice, middle-aged (12-16 months) WT mice showed working and cognitive memory dysfunction and aged (20-24 months) WT mice exhibited impaired spatial memory. However, these characteristics were not seen in TRPM2 knockout (TRPM2-KO) mice. Consistent with the finding of cognitive impairment, aged WT mice exhibited white matter injury and hippocampal damage and an increase in the number of Iba1-positive cells and amounts of pro-inflammatory cytokines in the brain; these characteristics were not seen in TRPM2-KO mice. These findings suggest that TRPM2 plays a critical role in exacerbating inflammatory responses and cognitive dysfunction during aging.


Assuntos
Envelhecimento/metabolismo , Disfunção Cognitiva/metabolismo , Inflamação/metabolismo , Microglia/patologia , Memória Espacial/fisiologia , Canais de Cátion TRPM/metabolismo , Envelhecimento/patologia , Envelhecimento/psicologia , Animais , Proteínas de Ligação ao Cálcio/metabolismo , Disfunção Cognitiva/genética , Disfunção Cognitiva/patologia , Citocinas/metabolismo , Hipocampo/metabolismo , Hipocampo/patologia , Inflamação/patologia , Camundongos , Camundongos Knockout , Proteínas dos Microfilamentos/metabolismo , Microglia/metabolismo , Canais de Cátion TRPM/genética , Substância Branca/metabolismo , Substância Branca/patologia
14.
Braz J Med Biol Res ; 52(4): e8041, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30994731

RESUMO

Although normal aging has been related to several cognitive difficulties, other processes have been studied less, such as spatial memory. Our aim was to compare egocentric and allocentric memory in an elderly population using ecological tasks. Twenty-eight cognitively unimpaired participants performed Egocentric and Allocentric Spatial Memory Tasks, as well as Spatial Span from CANTAB, Benton's Judge of Line Orientation test (JoLO), and Montreal Cognitive Assessment test (MoCA). The results revealed that younger participants showed better performance than older participants on both the Egocentric and Allocentric Spatial Memory Tasks, although only the Egocentric test was able to discriminate between younger, middle, and older elderly participants. Learning effect was found in Allocentric Spatial Memory Task in younger and older groups, but not in the middle group. Allocentric and egocentric performance was not related to other visuospatial neuropsychological scores and gender did not influence performance in any task. Egocentric and Allocentric Spatial Memory Tasks may be useful tools in early screening for cognitive decline, as they are able to detect age differences in the cognitive unimpaired elderly population.


Assuntos
Envelhecimento Saudável/fisiologia , Envelhecimento Saudável/psicologia , Percepção Espacial/fisiologia , Memória Espacial/fisiologia , Análise e Desempenho de Tarefas , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/fisiologia , Envelhecimento/psicologia , Análise de Variância , Disfunção Cognitiva/fisiopatologia , Disfunção Cognitiva/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Fatores Sexuais , Navegação Espacial/fisiologia
15.
Neurobiol Learn Mem ; 161: 106-114, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30954674

RESUMO

We have previously reported cognitive impairments in both young and old mice, particularly in female mice expressing mouse Arg-61 apoE, with a point mutation to mimic the domain interaction feature of human apoE4, as compared to the wildtype mouse (C57BL/6J) apoE. In this study, we further evaluated water maze performance in the female Arg-61 mice at an additional time point and then investigated related hippocampal cyto-architecture in these young female Arg-61 apoE mice vs. the wildtype mice. The results of behavioral performance consistently support our previous report that the young female Arg-61 apoE showed cognitive impairment versus C57BL/6J at the same age. The cyto-architectural results showed that volume of the granular cell layer (GCL) was significantly larger in both 5- and 10-month old Arg-61 apoE mice versus C57BL/6J mice. While the number of newborn calretinin-positive neurons was greater in the sub-granular zone (SGZ) in 5-month old Arg-61 mice, this number dropped significantly in 10-month old Arg-61 mice to a lower level than in age-matched C57BL/6J mice. In addition, the amyloid ß species was significantly higher in 5-month old Arg-61 mice versus age-matched C57BL/6J mice. In conclusion, impaired cognitive functions in female Arg-61 apoE mice appear correlated with larger GCL volume and higher calretinin-positive cell number and suggest a compensatory cellular response that may be related to amyloid beta perturbations early in life. Therefore this study suggests a novel cyto-architectural mechanism of apoE4-dependent pathologies and increased susceptibility of APOEε4 subjects to Alzheimer's disease.


Assuntos
Peptídeos beta-Amiloides/metabolismo , Apolipoproteínas E/genética , Calbindina 2/metabolismo , Disfunção Cognitiva , Hipocampo , Neurogênese , Fatores Etários , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Doença de Alzheimer/fisiopatologia , Animais , Comportamento Animal/fisiologia , Disfunção Cognitiva/genética , Disfunção Cognitiva/fisiopatologia , Modelos Animais de Doenças , Feminino , Hipocampo/citologia , Hipocampo/metabolismo , Hipocampo/patologia , Aprendizagem em Labirinto/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Neurogênese/genética , Neurogênese/fisiologia , Memória Espacial/fisiologia
16.
Brain Struct Funct ; 224(4): 1659-1676, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30927056

RESUMO

The ventral midline thalamus contributes to hippocampo-cortical interactions supporting systems-level consolidation of memories. Recent hippocampus-dependent memories rely on hippocampal connectivity remodeling. Remote memories are underpinned by neocortical connectivity remodeling. After a ventral midline thalamus lesion, recent spatial memories are formed normally but do not last. Why these memories do not endure after the lesion is unknown. We hypothesized that a lesion could interfere with hippocampal and/or neocortical connectivity remodeling. To test this hypothesis, in a first experiment male rats were subjected to lesion of the reuniens and rhomboid (ReRh) nuclei, trained in a water maze, and tested in a probe trial 5 or 25 days post-acquisition. Dendritic spines were counted in the dorsal hippocampus and medial prefrontal cortex. Spatial learning resulted in a significant increase of mushroom spines in region CA1. This modification persisted between 5 and 25 days post-acquisition in Sham rats, not in rats with ReRh lesion. Furthermore, 25 days after acquisition, the number of mushroom spines in the anterior cingulate cortex (ACC) had undergone a dramatic increase in Sham rats; ReRh lesion prevented this gain. In a second experiment, the increase of c-Fos expression in CA1 accompanying memory retrieval was not affected by the lesion, be it for recent or remote memory. However, in the ACC, the lesion had reduced the retrieval-triggered c-Fos expression observed 25 days post-acquisition. These observations suggest that a ReRh lesion might disrupt spatial remote memory formation by preventing persistence of early remodeled hippocampal connectivity, and spinogenesis in the ACC.


Assuntos
Região CA1 Hipocampal/fisiologia , Espinhas Dendríticas/fisiologia , Núcleos da Linha Média do Tálamo/fisiologia , Plasticidade Neuronal , Córtex Pré-Frontal/fisiologia , Memória Espacial/fisiologia , Animais , Giro do Cíngulo/fisiologia , Masculino , Aprendizagem em Labirinto/fisiologia , Memória de Longo Prazo/fisiologia , Ratos Long-Evans
17.
Neuron ; 102(3): 683-693.e4, 2019 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-30871859

RESUMO

Little is known about the neural mechanisms that allow humans and animals to plan actions using knowledge of task contingencies. Emerging theories hypothesize that it involves the same hippocampal mechanisms that support self-localization and memory for locations. Yet limited direct evidence supports the link between planning and the hippocampal place map. We addressed this by investigating model-based planning and place memory in healthy controls and epilepsy patients treated using unilateral anterior temporal lobectomy with hippocampal resection. Both functions were impaired in the patient group. Specifically, the planning impairment was related to right hippocampal lesion size, controlling for overall lesion size. Furthermore, although planning and boundary-driven place memory covaried in the control group, this relationship was attenuated in patients, consistent with both functions relying on the same structure in the healthy brain. These findings clarify both the neural mechanism of model-based planning and the scope of hippocampal contributions to behavior.


Assuntos
Lobectomia Temporal Anterior , Epilepsia do Lobo Temporal/cirurgia , Hipocampo/cirurgia , Memória Espacial/fisiologia , Adulto , Estudos de Casos e Controles , Tomada de Decisões , Feminino , Hipocampo/diagnóstico por imagem , Hipocampo/fisiologia , Hipocampo/fisiopatologia , Humanos , Masculino , Aprendizagem Espacial/fisiologia , Análise e Desempenho de Tarefas
18.
Can J Exp Psychol ; 73(1): 37-46, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30883177

RESUMO

Broad individual differences exist in the ability to create a cognitive map of a new environment. The current studies investigated whether familiarizing participants with to-be-learned target landmarks (Experiment 1) or target landmarks plus the order they would be encountered along routes (Experiment 2) before exploring the Silcton virtual environment would increase performance on tasks assaying spatial memory of Silcton. Participants in both experiments were randomly assigned to be pre-exposed either to information about target landmarks in Silcton or control landmarks on the university campus. In both experiments, participants explored Silcton via four prescribed routes and then performed a direction estimation task and a map building task based on memory for the locations of the target landmarks. In addition, participants completed the Spatial Orientation Test of perspective-taking. Pre-exposure to Silcton landmarks versus control landmarks did not affect scores on Silcton-based tasks in either experiment. Some sex differences in direction estimation were observed in Experiment 1 but not Experiment 2. While facilitating familiarity with landmarks did not improve cognitive map accuracy, both sex and perspective taking ability were found to contribute to individual differences in the ability to create a cognitive map. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Assuntos
Individualidade , Percepção Espacial/fisiologia , Memória Espacial/fisiologia , Navegação Espacial/fisiologia , Adolescente , Adulto , Feminino , Humanos , Masculino , Adulto Jovem
19.
Nat Commun ; 10(1): 1365, 2019 03 25.
Artigo em Inglês | MEDLINE | ID: mdl-30911003

RESUMO

Triggering receptor expressed on myeloid cells 2 (TREM2) is a microglial surface receptor genetically linked to the risk for Alzheimer's disease (AD). A proteolytic product, soluble TREM2 (sTREM2), is abundant in the cerebrospinal fluid and its levels positively correlate with neuronal injury markers. To gain insights into the pathological roles of sTREM2, we studied sTREM2 in the brain of 5xFAD mice, a model of AD, by direct stereotaxic injection of recombinant sTREM2 protein or by adeno-associated virus (AAV)-mediated expression. We found that sTREM2 reduces amyloid plaque load and rescues functional deficits of spatial memory and long-term potentiation. Importantly, sTREM2 enhances microglial proliferation, migration, clustering in the vicinity of amyloid plaques and the uptake and degradation of Aß. Depletion of microglia abolishes the neuroprotective effects of sTREM2. Our study demonstrates a protective role of sTREM2 against amyloid pathology and related toxicity and suggests that increasing sTREM2 can be explored for AD therapy.


Assuntos
Doença de Alzheimer/terapia , Potenciação de Longa Duração/efeitos dos fármacos , Glicoproteínas de Membrana/genética , Microglia/efeitos dos fármacos , Placa Amiloide/terapia , Receptores Imunológicos/genética , Memória Espacial/efeitos dos fármacos , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/química , Peptídeos beta-Amiloides/metabolismo , Animais , Animais Recém-Nascidos , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologia , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Dependovirus/genética , Dependovirus/metabolismo , Modelos Animais de Doenças , Feminino , Expressão Gênica , Vetores Genéticos/química , Vetores Genéticos/metabolismo , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Humanos , Injeções Intraventriculares , Potenciação de Longa Duração/fisiologia , Masculino , Glicoproteínas de Membrana/administração & dosagem , Glicoproteínas de Membrana/metabolismo , Camundongos , Microglia/metabolismo , Microglia/patologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/metabolismo , Fenótipo , Placa Amiloide/genética , Placa Amiloide/metabolismo , Placa Amiloide/patologia , Cultura Primária de Células , Proteólise , Receptores Imunológicos/administração & dosagem , Receptores Imunológicos/metabolismo , Proteínas Recombinantes de Fusão/administração & dosagem , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Memória Espacial/fisiologia , Técnicas Estereotáxicas
20.
Psychopharmacology (Berl) ; 236(7): 2223-2232, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30911792

RESUMO

RATIONALE: Phencyclidine (PCP) could induce schizophrenia (Sz) like behavior in both humans and animals, therefore, has been widely utilized to establish Sz animal models. It induced cognitive deficits, the core symptom of Sz, mainly through influencing frontal dopaminergic function. Nonhuman primate (NHP) studies demonstrated impaired object retrieval detour (ORD) and spatial delayed response (SDR) task performance by acute or chronic PCP treatment. However, NHP investigations, continually monitoring SDR performance before, during and after PCP treatment, are lacking. OBJECTIVES: Present study investigated the long-term influence of chronic PCP treatment on SDR performance and the possible increase of SDR deficit severity and duration by the incremental dosing procedure in rhesus monkeys. METHODS: SDR task was performed repeatedly up to eight weeks after constant dosing procedure (i.m., 0.3 mg/kg, day 12-25), during which drug effects on locomotor activity and blood cortisol concentration were assessed. Incremental dosing procedure (starting dose 0.3 mg/kg, day 6-19) began five months later. RESULTS: Constant dosing procedure induced differential level of hyperactivity across testing days, without significant influence on blood cortisol concentration. It reduced SDR performance, until occurrence of the first and worst impairment on day 15 and 23 respectively. The impaired performance recovered to pretreatment level over one week after drug cessation. In contrast, incremental dosing procedure impaired SDR performance on the first treatment day, which recovered within treatment period. CONCLUSION: Results suggested increase of SDR deficit severity by repeated PCP administrations, whereas the incremental dosing procedure did not increase SDR deficit severity and duration.


Assuntos
Locomoção/efeitos dos fármacos , Memória de Curto Prazo/efeitos dos fármacos , Fenciclidina/administração & dosagem , Fenciclidina/toxicidade , Memória Espacial/efeitos dos fármacos , Animais , Antagonistas de Aminoácidos Excitatórios/administração & dosagem , Antagonistas de Aminoácidos Excitatórios/toxicidade , Locomoção/fisiologia , Macaca mulatta , Masculino , Memória de Curto Prazo/fisiologia , Desempenho Psicomotor/efeitos dos fármacos , Desempenho Psicomotor/fisiologia , Tempo de Reação/efeitos dos fármacos , Tempo de Reação/fisiologia , Esquizofrenia/induzido quimicamente , Memória Espacial/fisiologia
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