1,720,963 research outputs found
Analysis of visual cortical function and circuits in a mouse model of Rett- Syndrome
No full textRett Syndrome (RTT), a neurodevelopmental disorder, is caused by de novo mutation of MECP2 gene on X- chromosome and it is characterized by regression during the first few years of life. Specifically in the mouse visual cortex, evidence has shown that lack of Mecp2 disrupts development of inhibitory interneuron systems, leading to compromised balance of inhibitory and excitatory cortical neuronal function.
In my thesis, I worked on Mecp2-heterozygous females, which are considered a closer model of the human condition. I performed visual evoked potential (VEP) in adult Mecp2 Het that exhibited either mild or severe RTT-like symptoms, according to the 12-point RTT phenotypic score (Guy et al., 2001). Mecp2 Het mice displayed a significant decrease in the amplitude of VEP response in comparison with their wild-type (WT) littermates. Interestingly, such defect was already present in Mecp2 Het mice with mild symptomatology and worsened with the disorder progression. Moreover, VEP response to high spatial frequencies was lost, resulting in a shift down in the spatial frequency (SF) tuning curve and significantly lower spatial resolution.
I then tested whether administration of low dosage of NMDAR antagonist, ketamine (8mg/kg, ip) for six weeks (two weeks on/two weeks off) was sufficient to ameliorate the visual function in Mecp2 Het mice. I found an increase in the VEP amplitude in comparison with the Het treated with vehicle. In addition, we observed this increase in the response to all stimuli resulting in an amelioration of the visual acuity. Finally I characterized the inhibitory/excitatory imbalance in visual cortex using immunohistochemistry., finding an increase in the thalamic excitatory markers that precedes the full onset of the regression. Together our results indicate that visual processing is impaired across Mecp2 mouse models and provide further evidence that targeting NMDAR function is a feasible and an effective therapeutic treatment for Rett Syndrome
Early Social Enrichment Improves Social Motivation and Skills in a Monogenic Mouse Model of Autism, the Oprm1 -/- Mouse
Full text linkEnvironmental enrichment has been proven to have positive effects on both behavioral and physiological phenotypes in rodent models of mental and neurodevelopmental disorders. In this study, we used mice lacking the µ-opioid receptor gene (Oprm1−/−), which has been shown to have deficits in social competence and communication, to assess the hypothesis that early enrichment can ameliorate sociability during development and adulthood. Due to the immaturity of sensory-motor capabilities of young pups, we chose as environmental stimulation a second lactating female, who provided extra maternal care and stimulation from birth. The results show that double mothering normalized the abnormal response to maternal separation in Oprm1−/− pups and increased social motivation in juveniles and adult knockout mice. Additionally, we observed that Oprm1−/− mice act as less attractive social partners than wild types, which suggests that social motivation can be modulated by the stimulus employed. This experiment supports previous findings suggesting that early social environmental stimulation has profound and long-term beneficial effects, encouraging the use of nonpharmacological interventions for the treatment of social defects in neurodevelopmental diseases
The neural substrate of spatial memory stabilization depends on the distribution of the training sessions
Full text linkDistributed training is known to lead to more robust memory formation as compared to training experiences with short intervals. Although this phenomenon, termed distributed practice effect, ubiquitous over a wide variety of tasks and organisms, has long been known by psychologists, its neurobiological underpinning is still poorly understood. Using the striatum as a model system here we tested the hypothesis that the ability of distributed training to optimize memory might depend upon the recruitment of different neural substrates compared to those engaged by massed training. First, by contrasting the medial and the lateral domains of the dorsal striatum after massed and distributed training we demonstrated that neuronal activity, as assessed using c-Fos expression, is differentially affected by the training protocol in the two striatal subregions. Next, by blocking the AMPA receptors before recall we provide evidence to support a selective role of the medial and the lateral striatum in the storage of information acquired respectively by massed and distributed training. Finally, we found that optogenetic stimulation of the dorsolateral striatum during massed training enables the formation of an enduring memory similarly to what is observed with distributed learning. Overall, these findings identify a possible mechanism for the distributed practice effect, a still poorly understood aspect of learning
Chronic Administration of the N-Methyl-D-Aspartate Receptor Antagonist Ketamine Improves Rett Syndrome Phenotype
No full textDistinct roles of medial prefrontal cortex subregions in the consolidation and recall of remote spatial memories
Full text linkIt is a common belief that memories, over time, become progressively independent of the hippocampus and are gradually stored in cortical areas. This view is mainly based on evidence showing that prefrontal cortex (PFC) manipulations impair the retrieval of remote memories, while hippocampal inhibition does not. More controversial is whether activity in the medial PFC is required immediately after learning to initiate consolidation. Another question concerns functional differences among PFC subregions in forming and storing remote memories. To address these issues, we directly contrasted the effects of loss-of-function manipulations of the anterior cingulate cortex (aCC) and the ventromedial PFC, which includes the infralimbic (IL) and prelimbic (PL) cortices, before testing and immediately after training on the ability of CD1 mice to recall the hidden platform location in the Morris water maze. We injected an AAV carrying the hM4Di receptor into the PL-IL or aCC. Interestingly, pretest administrations of clozapine-N-oxide (CNO; 3 mg/kg) revealed that the aCC, but not the PL-IL, was necessary to recall remote spatial information. Furthermore, systemic post-training administration of CNO impaired memory recall at remote, but not recent, time points in both groups. These findings revealed a functional dissociation between the two prefrontal areas, demonstrating that both the PL-IL and the aCC are involved in early consolidation of remote spatial memories, but only the aCC is engaged in their recall
Specific patterns of neural activity in the hippocampus after massed or distributed spatial training
Full text linkAbstract Training with long inter-session intervals, termed distributed training, has long been known to be superior to training with short intervals, termed massed training. In the present study we compared c-Fos expression after massed and distributed training protocols in the Morris water maze to outline possible differences in the learning-induced pattern of neural activation in the dorsal CA1 in the two training conditions. The results demonstrate that training and time lags between learning opportunities had an impact on the pattern of neuronal activity in the dorsal CA1. Mice trained with the distributed protocol showed sustained neuronal activity in the postero-distal component of the dorsal CA1. In parallel, in trained mice we found more active cells that tended to constitute spatially restricted clusters, whose degree increased with the increase in the time lags between learning trials. Moreover, activated cell assemblies demonstrated increased stability in their spatial organization after distributed as compared to massed training or control condition. Finally, using a machine learning algorithm we found that differences in the number of c-Fos positive cells and their location in the dorsal CA1 could be predictive of the training protocol used. These results suggest that the topographic organization and the spatial location of learning activated cell assemblies might be critical to promote the increased stability of the memory trace induced by distributed training
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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