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1.
Zebrafish ; 21(2): 92-100, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38621209

RESUMO

Zebrafish have been used as an education tool for students of all ages and can be used in many learning environments to teach different fields of science. In this study, we focus on the biology of zebrafish. We describe an educational program within a weeklong science camp for students between 12 and 14 years old. The methodology described is based on running annual science camps over an 11-year period. In these camps, students learnt about the developmental stages of zebrafish, as well as general zebrafish biology, husbandry, ecology, behavior, and reproduction. This article describes how to provide students and educators with an educational program to explore, discover, and contribute to the ever-evolving landscape of biological understanding through active and visual learning. We describe the methodology, the evaluation, revisions to our program over time, and future directions for expansion.


Assuntos
Estudantes , Peixe-Zebra , Animais , Humanos , Pesquisa , Aprendizagem Espacial , Ensino
2.
PLoS One ; 19(3): e0298670, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38527080

RESUMO

Statistical Learning (SL) refers to human's ability to detect regularities from environment Kirkham, N. Z. (2002) & Saffran, J. R. (1996). There has been a growing interest in understanding how sensitivity to statistical regularities influences learning to read. The current study systematically examined whether and how non-linguistic SL, Chinese SL, and English SL contribute to Chinese and English word reading among native Chinese-speaking 4th, 6th and 8th graders who learn English as a second language (L2). Children showed above-chance learning across all SL tasks and across all grades. In addition, developmental improvements were shown across at least two of the three grade ranges on all SL tasks. In terms of the contribution of SL to reading, non-linguistic auditory SL (ASL), English visual SL (VSL), and Chinese ASL accounted for a significant amount of variance in English L2 word reading. Non-linguistic ASL, Chinese VSL, English VSL, and English ASL accounted for a significant amount of variance in Chinese word reading. Our results provide clear and novel evidence for cross-linguistic contribution from Chinese SL to English reading, and from English SL to Chinese reading, highlighting a bi-directional relationship between SL in one language and reading in another language.


Assuntos
Multilinguismo , Leitura , Criança , Humanos , Idioma , Linguística , Aprendizagem Espacial
3.
J Psychiatry Neurosci ; 49(2): E96-E108, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38490646

RESUMO

BACKGROUND: The assessment of deep brain stimulation (DBS) as a therapeutic alternative for treating Alzheimer disease (AD) is ongoing. We aimed to determine the effects of intracranial self-stimulation at the medial forebrain bundle (MFB-ICSS) on spatial memory, neurodegeneration, and serum expression of microRNAs (miRNAs) in a rat model of sporadic AD created by injection of streptozotocin. We hypothesized that MFB-ICSS would reverse the behavioural effects of streptozotocin and modulate hippocampal neuronal density and serum levels of the miRNAs. METHODS: We performed Morris water maze and light-dark transition tests. Levels of various proteins, specifically amyloid-ß precurser protein (APP), phosphorylated tau protein (pTAU), and sirtuin 1 (SIRT1), and neurodegeneration were analyzed by Western blot and Nissl staining, respectively. Serum miRNA expression was measured by reverse transcription polymerase chain reaction. RESULTS: Male rats that received streptozotocin had increased hippocampal levels of pTAU S202/T205, APP, and SIRT1 proteins; increased neurodegeneration in the CA1, dentate gyrus (DG), and dorsal tenia tecta; and worse performance in the Morris water maze task. No differences were observed in miRNAs, except for miR-181c and miR-let-7b. After MFB-ICSS, neuronal density in the CA1 and DG regions and levels of miR-181c in streptozotocin-treated and control rats were similar. Rats that received streptozotocin and underwent MFB-ICSS also showed lower levels of miR-let-7b and better spatial learning than rats that received streptozotocin without MFB-ICSS. LIMITATIONS: The reversal by MFB-ICSS of deficits induced by streptozotocin was fairly modest. CONCLUSION: Spatial memory performance, hippocampal neurodegeneration, and serum levels of miR-let-7b and miR-181c were affected by MFB-ICSS under AD-like conditions. Our results validate the MFB as a potential target for DBS and lend support to the use of specific miRNAs as promising biomarkers of the effectiveness of DBS in combatting AD-associated cognitive deficits.


Assuntos
Doença de Alzheimer , MicroRNAs , Ratos , Masculino , Animais , Ratos Wistar , Autoestimulação/fisiologia , Estreptozocina/toxicidade , Aprendizagem Espacial , Doença de Alzheimer/terapia , Sirtuína 1/farmacologia , Hipocampo , MicroRNAs/genética , Aprendizagem em Labirinto
4.
Behav Pharmacol ; 35(2-3): 79-91, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38451022

RESUMO

Remarkable performance improvements occur at the end of the third postnatal week in rodents tested in various tasks that require navigation according to spatial context. While alterations in hippocampal function at least partially subserve this cognitive advancement, physiological explanations remain incomplete. Previously, we discovered that developmental modifications to hippocampal glutamatergic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in juvenile rats was related to more mature spontaneous alternation behavior in a symmetrical Y-maze. Moreover, a positive allosteric modulator of AMPA receptors enabled immature rats to alternate at rates seen in older animals, suggesting an excitatory synaptic limitation to hippocampal maturation. We then validated the Barnes maze for juvenile rats in order to test the effects of positive AMPA receptor modulation on a goal-directed spatial memory task. Here we report the effects of the AMPA receptor modulator, CX614, on spatial learning and memory in the Barnes maze. Similar to our prior report, animals just over 3 weeks of age display substantial improvements in learning and memory performance parameters compared to animals just under 3 weeks of age. A moderate dose of CX614 enabled immature animals to move more directly to the goal location, but only after 1 day of training. This performance improvement was observed on the second day of training with drug delivery or during a memory probe trial performed without drug delivery after the second day of training. Higher doses created more search errors, especially in more mature animals. Overall, CX614 provided modest performance benefits for immature rats in a goal-directed spatial memory task.


Assuntos
Receptores de AMPA , Aprendizagem Espacial , Ratos , Animais , Ácido alfa-Amino-3-hidroxi-5-metil-4-isoxazol Propiônico/farmacologia , Memória Espacial , Cognição
5.
Sci Rep ; 14(1): 5644, 2024 03 07.
Artigo em Inglês | MEDLINE | ID: mdl-38453977

RESUMO

Visual perceptual learning is traditionally thought to arise in visual cortex. However, typical perceptual learning tasks also involve systematic mapping of visual information onto motor actions. Because the motor system contains both effector-specific and effector-unspecific representations, the question arises whether visual perceptual learning is effector-specific itself, or not. Here, we study this question in an orientation discrimination task. Subjects learn to indicate their choices either with joystick movements or with manual reaches. After training, we challenge them to perform the same task with eye movements. We dissect the decision-making process using the drift diffusion model. We find that learning effects on the rate of evidence accumulation depend on effectors, albeit not fully. This suggests that during perceptual learning, visual information is mapped onto effector-specific integrators. Overlap of the populations of neurons encoding motor plans for these effectors may explain partial generalization. Taken together, visual perceptual learning is not limited to visual cortex, but also affects sensorimotor mapping at the interface of visual processing and decision making.


Assuntos
Córtex Visual , Percepção Visual , Humanos , Percepção Visual/fisiologia , Movimentos Oculares , Córtex Visual/fisiologia , Aprendizagem Espacial , Generalização Psicológica
6.
J Vis Exp ; (204)2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38436361

RESUMO

Hippocampus-dependent spatial learning in rodents has been tested using a variety of methods. These include the Morris water maze (MWM), Y-maze, and novel object location (NOL) tasks. More recently, the active place avoidance (APA) task has been developed as an alternative to these more traditional approaches. In the APA task, mice must use spatial cues placed around a rotating arena to avoid a stationary shock zone. Due to the multiple parameters that can be adjusted, the APA task has been demonstrated to be a very versatile approach. It lends itself to being used longitudinally and repeatedly for the same cohort of mice. Here, we provide a detailed protocol to successfully conduct the APA task. We also highlight alternative APA approaches that can be used to examine different components of spatial learning. We describe the data collection and analysis processes. Critical steps during the APA task are discussed to increase the likelihood of successfully conducting the test. The APA task has several advantages over more traditional spatial navigation tests. It is appropriate to use with aged mice or those with disease phenotypes such as Alzheimer's disease. The complexity of the task can be easily altered, allowing a wide range of mouse strains to be tested. Further, the APA task is suitable for testing animals that have undergone surgery or experimental interventions that may have affected motor or neural function, such as stroke or traumatic brain injury.


Assuntos
Doença de Alzheimer , Lesões Encefálicas Traumáticas , Humanos , Animais , Camundongos , Aprendizagem Espacial , Sinais (Psicologia) , Coleta de Dados
7.
J Alzheimers Dis ; 98(3): 925-940, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38517786

RESUMO

Background: Caloric restriction (CR) has been recognized for its benefits in delaying age-related diseases and extending lifespan. While its effects on amyloid pathology in Alzheimer's disease (AD) mouse models are well-documented, its effects on tauopathy, another hallmark of AD, are less explored. Objective: To assess the impact of a short-term 30% CR regimen on age-dependent spatial learning deficits and pathological features in a tauopathy mouse model. Methods: We subjected male PS19 tau P301S (hereafter PS19) and age-matched wildtype mice from two age cohorts (4.5 and 7.5 months old) to a 6-week 30% CR regimen. Spatial learning performance was assessed using the Barnes Maze test. Tau pathology, neuroinflammation, hippocampal cell proliferation, and neurogenesis were evaluated in the older cohort by immunohistochemical staining and RT-qPCR. Results: CR mitigated age-dependent spatial learning deficits in PS19 mice but exhibited limited effects on tau pathology and the associated neuroinflammation. Additionally, we found a decrease in hippocampal cell proliferation, predominantly of Iba1+ cells. Conclusions: Our findings reinforce the cognitive benefits conferred by CR despite its limited modulation of disease pathology. Given the pivotal role of microglia in tau-driven pathology, the observed reduction in Iba1+ cells under CR suggests potential therapeutic implications, particularly if CR would be introduced early in disease progression.


Assuntos
Doença de Alzheimer , Tauopatias , Camundongos , Masculino , Humanos , Animais , Proteínas tau/genética , Proteínas tau/farmacologia , Aprendizagem Espacial , Camundongos Transgênicos , Restrição Calórica , Doenças Neuroinflamatórias , Doença de Alzheimer/patologia , Tauopatias/patologia , Aprendizagem em Labirinto , Modelos Animais de Doenças
8.
J Exp Child Psychol ; 241: 105864, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38335709

RESUMO

Acquiring sequential information is of utmost importance, for example, for language acquisition in children. Yet, the long-term storage of statistical learning in children is poorly understood. To address this question, 27 7-year-olds and 28 young adults completed four sessions of visual sequence learning (Year 1). From this sample, 16 7-year-olds and 20 young adults participated in another four equivalent sessions after a 12-month-delay (Year 2). The first three sessions of each year used Stimulus Set 1, and the last session used Stimulus Set 2 to investigate transfer effects. Each session consisted of alternating learning and test phases in a modified artificial grammar learning task. In Year 1, 7-year-olds and adults learned the regularities and showed transfer to Stimulus Set 2. Both groups retained their final performance level over the 1-year period. In Year 2, children and adults continued to improve with Stimulus Set 1 but did not show additional transfer gains. Adults overall outperformed children, but transfer effects were indistinguishable between both groups. The current results suggest that long-term memory traces are formed from repeated sequence learning that can be used to generalize sequence rules to new visual input. However, the current study did not provide evidence for a childhood advantage in learning and remembering sequence rules.


Assuntos
Desenvolvimento da Linguagem , Linguística , Criança , Adulto Jovem , Humanos , Aprendizagem Espacial , Rememoração Mental
9.
J Exp Child Psychol ; 241: 105870, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38354447

RESUMO

Geometrical knowledge is typically taught to children through a combination of vision and repetitive drawing (i.e. haptics), yet our understanding of how different spatial senses contribute to geometric perception during childhood is poor. Studies of line orientation suggest a dominant role of vision affecting the calibration of haptics during development; however, the associated multisensory interactions underpinning angle perception are unknown. Here we examined visual, haptic, and bimodal perception of angles across three age groups of children: 6 to 8 years, 8 to 10 years, and 10 to 12 years, with age categories also representing their class (grade) in primary school. All participants first learned an angular shape, presented dynamically, in one of three sensory tracing conditions: visual only, haptic only, or bimodal exploration. At test, which was visual only, participants selected a target angle from four possible alternatives with distractor angle sizes varying relative to the target angle size. We found a clear improvement in accuracy of angle perception with development for all learning modalities. Angle perception in the youngest group was equally poor (but above chance) for all modalities; however, for the two older child groups, visual learning was better than haptics. Haptic perception did not improve to the level of vision with age (even in a comparison adult group), and we found no specific benefit for bimodal learning over visual learning in any age group, including adults. Our results support a developmental increment in both spatial accuracy and precision in all modalities, which was greater in vision than in haptics, and are consistent with previous accounts of cross-sensory calibration in the perception of geometric forms.


Assuntos
Percepção do Tato , Percepção Visual , Adulto , Criança , Humanos , Adolescente , Tecnologia Háptica , Visão Ocular , Aprendizagem Espacial , Conhecimento
10.
Sci Rep ; 14(1): 3757, 2024 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-38355712

RESUMO

Many species learn temporal regularities in their visual environment, demonstrating visual statistical learning. In this study, we explored the sensitivity of macaque inferior temporal (IT) cortical neurons to transition probabilities of sequentially presented visual images, presented at different locations in the visual field. We exposed monkeys to sequences of two images, where the first image was presented either foveally or peripherally, and the second image was consistently presented foveally. Following several weeks of exposure, we recorded IT responses to assess differences between the exposed (Fixed) and new, Deviant sequences, where the identity of the first image in a sequence differed from the exposure phase. While enhanced responses to Deviant sequences were observed when both images of a pair were foveally presented during exposure, no such deviant responses were present when the first image was presented peripherally. This finding challenges the notion that mere exposure to image sequences always leads to deviant responses in macaque IT. The results highlight the complexity of the mechanisms underlying statistical learning in primates, particularly in the context of peripheral image presentations, emphasizing the need for further investigation into the origins of these responses in the IT cortex.


Assuntos
Lobo Temporal , Campos Visuais , Animais , Macaca mulatta , Lobo Temporal/diagnóstico por imagem , Lobo Temporal/fisiologia , Neurônios/fisiologia , Estimulação Luminosa , Aprendizagem Espacial
11.
Sci Rep ; 14(1): 3247, 2024 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-38332042

RESUMO

A reciprocal relationship between perceptual learning and functional brain changes towards perceptual learning effectiveness has been demonstrated previously; however, the underlying neural correlates remain unclear. Further, visual perceptual learning (VPL) is implicated in visual field defect (VFD) recovery following chronic stroke. We investigated resting-state functional connectivity (RSFC) in the visual cortices associated with mean total deviation (MTD) scores for VPL-induced VFD recovery in chronic stroke. Patients with VFD due to chronic ischemic stroke in the visual cortex received 24 VPL training sessions over 2 months, which is a dual discrimination task of orientation and letters. At baseline and two months later, the RSFC in the ipsilesional, interhemispheric, and contralesional visual cortices and MTD scores in the affected hemi-field were assessed. Interhemispheric visual RSFC at baseline showed the strongest correlation with MTD scores post-2-month VPL training. Notably, only the subgroup with high baseline interhemispheric visual RSFC showed significant VFD improvement following the VPL training. The interactions between the interhemispheric visual RSFC at baseline and VPL led to improvement in MTD scores and largely influenced the degree of VFD recovery. The interhemispheric visual RSFC at baseline could be a promising brain biomarker for the effectiveness of VPL-induced VFD recovery.


Assuntos
Acidente Vascular Cerebral , Córtex Visual , Humanos , Campos Visuais , Aprendizagem Espacial , Encéfalo , Córtex Visual/diagnóstico por imagem , Dano Encefálico Crônico , Imageamento por Ressonância Magnética
12.
Peptides ; 175: 171169, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38340898

RESUMO

The goal of the present study is to investigate the role of intraamygdaloid oxytocin in learning-related mechanisms. Oxytocin is a neuropeptide which is involved in social bonding, trust, emotional responses and various social behaviors. By conducting passive avoidance and Morris water maze tests on male Wistar rats, the role of intraamygdaloid oxytocin in memory performance and learning was investigated. Oxytocin doses of 10 ng and 100 ng were injected into the central nucleus of the amygdala. Our results showed that 10 ng oxytocin significantly reduced the time required to locate the platform during the Morris water maze test while significantly increasing the latency time in the passive avoidance test. However, the 100 ng oxytocin experiment failed to produce a significant effect in either of the tests. Wistar rats pretreated with 20 ng oxytocin receptor antagonist (L-2540) were administered 10 ng of oxytocin into the central nucleus of the amygdala and were also subjected to the aforementioned tests to highlight the role of oxytocin receptors in spatial- and avoidance learning. Results suggest that oxytocin supports memory processing during both the passive avoidance and the Morris water maze tests. Oxytocin antagonists can however block the effects of oxytocin in both tests. The results substantiate that oxytocin uses oxytocin receptors to enhance memory and learning performance.


Assuntos
Ocitocina , Receptores de Ocitocina , Ratos , Animais , Masculino , Ratos Wistar , Ocitocina/farmacologia , Aprendizagem Espacial , Aprendizagem da Esquiva , Aprendizagem em Labirinto
13.
Neuroscience ; 544: 28-38, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38423162

RESUMO

Our previous study revealed that acupuncture may exhibit therapeutic effects on Alzheimer's disease (AD) through the activation of metabolism in memory-related brain regions. However, the underlying functional mechanism remains poorly understood and warrants further investigation. In this study, we used resting-state functional magnetic resonance imaging (rsfMRI) to explore the potential effect of electroacupuncture (EA) on the 5xFAD mouse model of AD. We found that the EA group exhibited significant improvements in the number of platforms crossed and the time spent in the target quadrant when compared with the Model group (p < 0.05). The functional connectivity (FC) of left hippocampus (Hip) was enhanced significantly among 12 regions of interest (ROIs) in the EA group (p < 0.05). Based on the left Hip as the seed point, the rsfMRI analysis of the entire brain revealed increased FC between the limbic system and the neocortex in the 5xFAD mice after EA treatment. Additionally, the expression of amyloid-ß(Aß) protein and deposition in the Hip showed a downward trend in the EA group compared to the Model group (p < 0.05). In conclusion, our findings indicate that EA treatment can improve the learning and memory abilities and inhibit the expression of Aß protein and deposition of 5xFAD mice. This improvement may be attributed to the enhancement of the resting-state functional activity and connectivity within the limbic-neocortical neural circuit, which are crucial for cognition, motor function, as well as spatial learning and memory abilities in AD mice.


Assuntos
Doença de Alzheimer , Eletroacupuntura , Neocórtex , Camundongos , Animais , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/terapia , Doença de Alzheimer/metabolismo , Eletroacupuntura/métodos , Peptídeos beta-Amiloides/metabolismo , Hipocampo/metabolismo , Neocórtex/diagnóstico por imagem , Neocórtex/metabolismo , Aprendizagem Espacial , Modelos Animais de Doenças , Camundongos Transgênicos
14.
Neurotoxicology ; 101: 82-92, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38346645

RESUMO

Recent evidence showed that general anesthesia produces long-term neurotoxicity and cognitive dysfunction. However, it remains unclear whether maternal non-obstetric surgery under ketamine anesthesia during second trimester causes cognitive impairment in offspring. The present study assigned pregnant rats into three groups: 1) normal control group receiving no anesthesia and no surgery, 2) ketamine group receiving ketamine anesthesia for 2 h on the 14th day of gestation but no surgery, and 3) surgery group receiving abdominal surgery under ketamine anesthesia on the 14th day of gestation. On postnatal day 1, the offspring rats in Ketamine group and surgery group were assigned to receive intra-peritoneal injection of Senegenin (15 mg/kg), once per day for consecutive 14 days. The offspring's spatial perception, anxiety-like behavior, and learning and memory were evaluated. Then the offspring's hippocampal tissues were collected. The offspring of the surgery group were impaired in the spatial perception in the cliff avoidance test and the spatial learning and memory in the Morris water maze test. Accordingly, the activity of histone deacetylases increased, the protein levels of NEDD9, BDNF, p-TrkB, Syn and PSD-95 decreased, and the density of dendritic spines reduced in the hippocampus of the offspring of the surgery group, and such effects were not seen in the offspring of the ketamine group, neither in the offspring of control group. Senegenin alleviated the learning and memory impairment, and increased the protein levels of NEDD9, BDNF, p-TrkB, Syn and PSD-95 and the density of dendritic spines in the offspring of the surgery group. ketamine anesthesia plus surgery during second trimester impairs hippocampus-dependent learning and memory, and the deficits could be rescued by treatment with Senegenin.


Assuntos
Anestesia , Ketamina , Gravidez , Feminino , Ratos , Animais , Ketamina/toxicidade , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Aprendizagem Espacial , Hipocampo , Dendritos , Aprendizagem em Labirinto
15.
Behav Brain Res ; 461: 114845, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38184206

RESUMO

Biological sex influences decision-making processes in significant ways, differentiating the responses animals choose when faced with a range of stimuli. The neurobiological underpinnings that dictate sex differences in decision-making tasks remains an important open question, yet single-sex studies of males form most studies in behavioural neuroscience. Here we used female and male BALB/c mice on two spatial learning and memory tasks and examined the expression of perineuronal nets (PNNs) and parvalbumin interneurons (PV) in regions correlated with spatial memory. Mice underwent the aversive active place avoidance (APA) task or the appetitive trial-unique nonmatching-to-location (TUNL) touchscreen task. Mice in the APA cohort learnt to avoid the foot-shock and no differences were observed on key measures of the task nor in the number and intensity of PNNs and PV. On the delay but not separation manipulation in the TUNL task, females received more incorrect trials and less correct trials compared to males. Furthermore, females in this cohort exhibited higher intensity PNNs and PV cells in the agranular and granular retrosplenial cortex, compared to males. These data show that female and male mice perform similarly on spatial learning tasks. However, sex differences in neural circuitry may underly differences in making decisions under conditions of uncertainty on an appetitive task. These data emphasise the importance of using mice of both sexes in studies of decision-making neuroscience.


Assuntos
Interneurônios , Neurônios , Animais , Feminino , Masculino , Camundongos , Matriz Extracelular , Interneurônios/metabolismo , Neurônios/metabolismo , Parvalbuminas/metabolismo , Aprendizagem Espacial , Incerteza
16.
Brain Res ; 1828: 148764, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38242524

RESUMO

Mesenchymal stem cells therapy provides a new perspective of therapeutic approaches in the treatment of neurodegenerative diseases. The present study aimed to investigate the effects of intranasally transplanted human "olfactory ecto-mesenchymal stem cells" (OE-MSCs) in Alzheimer's disease (AD) rats. In this study, we isolated OE-MSCs from human olfactory lamina propria and phenotypically characterized them using immunocytochemistry and flow cytometry. The undifferentiated OE-MSCs were transplanted either by intranasal (IN) or intrahippocampal (IH) injection to rat models of AD, which were induced by injecting amyloid-beta (Aß) intrahippocampally. Behavioral, histological, and molecular assessments were performed after a three-month recovery period. Based on the results, intranasal administration of OE-MSCs significantly reduced Aß accumulation and neuronal loss, improved learning and memory impairments, and increased levels of BDNF (brain-derived neurotrophic factor) and NMDAR (N-methyl-D-Aspartate receptors) in the AD rat model. These changes were more significant in animals who received OE-MSCs by intranasal injection. The results of this study suggest that OE-MSCs have the potential to enhance cognitive function in AD, possibly mediated by BDNF and the NMDA receptors.


Assuntos
Doença de Alzheimer , Células-Tronco Mesenquimais , Humanos , Ratos , Animais , Doença de Alzheimer/patologia , Aprendizagem Espacial , Fator Neurotrófico Derivado do Encéfalo , Administração Intranasal , Peptídeos beta-Amiloides , Transtornos da Memória/terapia , Células-Tronco Mesenquimais/fisiologia , Modelos Animais de Doenças
17.
Cognition ; 244: 105711, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38224649

RESUMO

Humans leverage compositionality to efficiently learn new concepts, understanding how familiar parts can combine together to form novel objects. In contrast, popular computer vision models struggle to make the same types of inferences, requiring more data and generalizing less flexibly than people do. Here, we study these distinctively human abilities across a range of different types of visual composition, examining how people classify and generate "alien figures" with rich relational structure. We also develop a Bayesian program induction model which searches for the best programs for generating the candidate visual figures, utilizing a large program space containing different compositional mechanisms and abstractions. In few shot classification tasks, we find that people and the program induction model can make a range of meaningful compositional generalizations, with the model providing a strong account of the experimental data as well as interpretable parameters that reveal human assumptions about the factors invariant to category membership (here, to rotation and changing part attachment). In few shot generation tasks, both people and the models are able to construct compelling novel examples, with people behaving in additional structured ways beyond the model capabilities, e.g. making choices that complete a set or reconfigure existing parts in new ways. To capture these additional behavioral patterns, we develop an alternative model based on neuro-symbolic program induction: this model also composes new concepts from existing parts yet, distinctively, it utilizes neural network modules to capture residual statistical structure. Together, our behavioral and computational findings show how people and models can produce a variety of compositional behavior when classifying and generating visual objects.


Assuntos
Formação de Conceito , Redes Neurais de Computação , Humanos , Teorema de Bayes , Generalização Psicológica , Aprendizagem Espacial
18.
J Vis ; 24(1): 10, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38285454

RESUMO

The primate visual cortex contains various regions that exhibit specialization for different stimulus properties, such as motion, shape, and color. Within each region, there is often further specialization, such that particular stimulus features, such as horizontal and vertical orientations, are over-represented. These asymmetries are associated with well-known perceptual biases, but little is known about how they influence visual learning. Most theories would predict that learning is optimal, in the sense that it is unaffected by these asymmetries. However, other approaches to learning would result in specific patterns of perceptual biases. To distinguish between these possibilities, we trained human observers to discriminate between expanding and contracting motion patterns, which have a highly asymmetrical representation in the visual cortex. Observers exhibited biased percepts of these stimuli, and these biases were affected by training in ways that were often suboptimal. We simulated different neural network models and found that a learning rule that involved only adjustments to decision criteria, rather than connection weights, could account for our data. These results suggest that cortical asymmetries influence visual perception and that human observers often rely on suboptimal strategies for learning.


Assuntos
Aprendizagem Espacial , Córtex Visual , Animais , Humanos , Viés , Movimento (Física) , Redes Neurais de Computação
19.
Exp Neurol ; 374: 114688, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38216110

RESUMO

Proprotein convertase subtilisin/kexin type 6 (PCSK6) is a calcium-dependent serine proteinase that regulates the proteolytic activity of various precursor proteins and facilitates protein maturation. Dysregulation of PCSK6 expression or function has been implicated in several pathological processes including nervous system diseases. However, whether and how PCSK6 is involved in the pathogenesis of Alzheimer's disease (AD) remains unclear. In this study, we reported that the expression of PCSK6 was significantly increased in the brain tissues of postmortem AD patients and APP23/PS45 transgenic AD model mice, as well as N2AAPP cells. Genetic knockdown of PCSK6 reduced amyloidogenic processing of APP in N2AAPP cells by suppressing the activation of membrane-type 5-matrix metalloproteinase (MT5-MMP), referred to as η-secretase. We further found that PCSK6 cleaved and activated MT5-MMP by recognizing the RRRNKR sequence in its N-terminal propeptide domain in N2A cells. The mutation or knockout of this cleavage motif prevented PCSK6 from interacting with MT5-MMP and performing cleavage. Importantly, genetic knockdown of PCSK6 with adeno-associated virus (AAV) reduced Aß production and ameliorated hippocampal long-term potentiation (LTP) and long-term spatial learning and memory in APP23/PS45 transgenic mice. Taken together, these results demonstrate that genetic knockdown of PCSK6 effectively alleviate AD-related pathology and cognitive impairments by inactivating MT5-MMP, highlighting its potential as a novel therapeutic target for AD treatment.


Assuntos
Doença de Alzheimer , Animais , Humanos , Camundongos , Doença de Alzheimer/metabolismo , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Modelos Animais de Doenças , Camundongos Transgênicos , Pró-Proteína Convertases/genética , Pró-Proteína Convertases/metabolismo , Proteólise , Serina Endopeptidases/metabolismo , Aprendizagem Espacial
20.
Res Dev Disabil ; 146: 104673, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38280272

RESUMO

BACKGROUND: Rule learning (RL) is the ability to extract and generalize higher-order repetition-based structures. Children with Developmental Dyslexia (DD) often report difficulties in learning complex regularities in sequential stimuli, which might be due to the complexity of the rule to be learned. Learning high-order repetition-based rules represents a building block for the development of language skills. AIMS: This study investigates the ability to extract and generalize simple, repetition-based visual rules (e.g., ABA) in 8-11-year-old children without (TD) and with a diagnosis of Development Dyslexia (DD) and its relationship with language and reading skills. METHOD: Using a forced-choice paradigm, children were first exposed to a visual sequence containing a repetition-based rule (e.g., ABA) and were then asked to recognize familiar and novel rules generated by new visual elements. Standardized language and reading tests were also administered to both groups. RESULTS: The accuracy in recognizing rules was above chance for both groups, even though DD children were less accurate than TD children, suggesting a less efficient RL mechanism in the DD group. Moreover, visual RL was positively correlated with both language and reading skills. CONCLUSION: These results further confirm the crucial role of RL in the acquisition of linguistic skills and mastering reading abilities.


Assuntos
Dislexia , Criança , Humanos , Dislexia/diagnóstico , Leitura , Cognição , Idioma , Aprendizagem Espacial
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