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Transgenic rodent models of Alzheimer’s disease (AD) were designed to study mechanisms of pathogenesis and connect these mechanisms with cognitive decline. Measurements of cognition in rodents can be confounded, however, by human handling and interaction; the IntelliCage was created to circumvent these issues while measuring various facets of cognition in a social environment with water consumption as the primary motivator for task completion. Here, for the first time, we examined the behavioral performance of 3xTg-AD mice in the IntelliCage. Seven- to 9-month-old female 3xTg-AD and non-transgenic (NonTg) mice were tested for 29 days in the IntelliCage to measure prefrontal cortical and hippocampal function. We found that a higher percentage of NonTg mice (86.96%) were able to successfully complete the training (adaptation) phases compared to their 3xTg-AD (57.14%) counterparts. Furthermore, the 3xTg-AD mice showed impairments in attention and working memory. Interestingly, we found that differences in body and brain weight between NonTg and 3xTg-AD mice were associated with whether mice were able to complete the IntelliCage tasks. 3xTg-AD mice that completed IntelliCage tasks had lower cortical insoluble amyloid-β40 fractions than their 3xTg-AD counterparts who failed to complete the tasks. Collectively, these results demonstrate deficits in cognition in the 3xTg-AD mouse and inform scientists of important factors to consider when testing this transgenic model in the IntelliCage.

The hippocampus, which engages in the process of consolidating long-term memories and learning, shows active development during childhood and adolescence. The hippocampus also functionally influences attention. Based on the influence of hippocampal function on attention, it was expected that the volume of the hippocampus would be associated with the difference in attention during childhood and adolescence, in which the brain develops actively. Thus, this study examined the association between hippocampal volume and attention metrics measured by the continuous performance test (CPT) in 115 children and adolescents (mean age = 12.43 ± 3.0, 63 male and 52 female). In association studies with both auditory and visual attention, we found that the bilateral hippocampal volumes showed negative relationships with auditory omission errors. A smaller volume of the left hippocampus also led to a longer auditory response time. However, visual attention did not show any significant relationship with the hippocampal volume. These findings were consistent even after adjusting for the effects of the related covariates (e.g., age, insomnia, and depression). Taken together, this study suggested that the increase in hippocampal volume during childhood and adolescence was associated significantly with better auditory attention.

Post-Traumatic Stress Disorder (PTSD) is a complex condition that develops after experiencing a severe emotional trauma, with or without physical trauma. There is no known cure and evidence-based treatments, which are effective in reducing symptoms, have low retention rates. It is therefore important, in addition to seeking new therapeutics, to identify ways to reduce the likelihood of developing PTSD. The fact that some, but not all, individuals exposed to the same traumatic event develop PTSD suggests that there is individual susceptibility. Investigating susceptibility and underlying factors will be better guided if there is a coherent framework for such investigations. In this review, we propose that susceptibility is a dynamic state that is comprised of susceptibility factors (before trauma) and sequalae factors (during or after trauma, but before PTSD diagnosis). We define key features of susceptibility and sequalae factors as: (1) they are detectable before trauma (susceptibility factors) or during/shortly after trauma (sequalae factors), (2) they can be manipulated, and (3) manipulation of these factors alters the likelihood of developing PTSD, thus affecting resilience. In this review we stress the importance of investigating susceptibility to PTSD with appropriate animal models, because prospective human studies are expensive and manipulation of susceptibility and sequalae factors for study purposes may not always be feasible. This review also provides a brief overview of a subset of animal models that study PTSD-related behaviors and related alterations in endocrine and brain systems that focus on individual differences, peri- and post-trauma. Attention is drawn to the RISP model (Revealing Individual Susceptibility to a PTSD-like Phenotype) which assesses susceptibility before trauma. Using the RISP model and expression of plasticity-associated immediate early genes, Arc and Homer1a, we have identified impaired hippocampal function as a potential susceptibility factor. We further discuss other putative susceptibility factors and approaches to mitigate them. We assert that this knowledge will guide successful strategies for interventions before, during or shortly after trauma that can decrease the probability of developing PTSD.

Altres ajuts: "ICREA-Academia 2013" (to AF-T). IO is recipient of a PhD FI fellowship (DGR 2014) The present study evaluated the long-lasting effects of neonatal handling (NH; administered during the first 21 days of life) on unlearned and learned anxiety-related responses in inbred Roman High- (RHA-I) and Low-avoidance (RLA-I) rats. To this aim, untreated and neonatally-handled RHA-I and RLA-I rats of both sexes were tested in the following tests/tasks: a novel object exploration (NOE) test, the elevated zero maze (ZM) test, a "baseline acoustic startle" (BAS) test, a "context-conditioned fear" (CCF) test and the acquisition of two-way active-shuttle box-avoidance (SHAV). RLA-I rats showed higher unconditioned (novel object exploration test -"NOE"-, elevated zero maze test -"ZM"-, BAS), and conditioned (CCF, SHAV) anxiety. NH increased exploration of the novel object in the NOE test as well as exploration of the open sections of the ZM test in both rat strains and sexes, although the effects were relatively more marked in the (high anxious) RLA-I strain and in females. NH did not affect BAS, but reduced CCF in both strains and sexes, and improved shuttle box avoidance acquisition especially in RLA-I (and particularly in females) and in female RHA-I rats. These are completely novel findings, which indicate that even some genetically-based anxiety/fear-related phenotypes can be significantly modulated by previous environmental experiences such as the NH manipulation.