Search

Memory loss is a usual consequence of ageing. In aged brains, perineuronal nets (PNNs), which limit neuroplasticity and are implicated in memory, become inhibitory due to decreased 6-sulphation of their glycan chains (C6S). Aged mice show progressive deficits in memory tasks, but removal of PNNs or digestion of their glycans rescued age-related memory loss. Reduction of permissive C6S by transgenic deletion of 6-sulfotransferase led to very early memory loss. However, restoring C6S levels in aged animals by AAV delivery or transgenic expression of 6-sulfotransferase restored memory. Low C6S levels caused loss of cortical long-term potentiation, which was restored by AAV-mediated 6-sulfotransferase delivery. The study shows that loss of C6S in the aged brain leads to declining memory and cognition, which can be restored by C6S replacement. One sentence summary Sulphation changes in perineuronal nets lead to age-related memory loss; correction of sulphation restores memory.

Neuroscience is undergoing an open-access revolution. Repositories in areas such as neuroimaging and genomics have provided a paradigm shift in the way we are now able to analyze, share, and re-use vast amounts of data from multiple laboratories. Unfortunately, one area that is far behind in this respect is behavioural evaluation of animal models. Thanks to a new set of automated tests based on touchscreen technology [1], there is potential for standardized outputs in animal behavioral neuroscience that are consistent with open-access sharing. However, there is currently no mechanism to provide quality control for such data or to deposit them in an open access repository for reuse, like approaches used in the imaging and genomics fields. In order to enable cognitive data, obtained using the highly translatable and automated touchscreen technology to join the open-access revolution, we have developed MouseBytes, a web-based repository that enables researchers to store, share, visualize, and analyze cognitive data. We envision that MouseBytes will be the premier platform to allow cognitive data to become open access, searchable and to be reused. Furthermore, MouseBytes will support the innovative integration of standardized behavioural with MRI and RNA-sequencing, allowing comprehensive multi-modal information in mouse models of disease.

Attention is the cognitive processing that facilitates the ability to target and attend to relevant environmental stimuli, while filtering out irrelevant or distracting stimuli. Control over selective attention is theorized to be dependent on organized neural communication that stems from the medial prefrontal cortex (mPFC). To evaluate selective and sustained attention, mice were trained on the novel touchscreen rodent continuous performance task (rCPT), a task designed to emulate the human CPT. In the rodent version, images are continuously presented on a touchscreen, where mice have been trained to selectively respond to one image type while suppressing responses to all others. Following training on the rCPT, bilateral cannulas were implanted into the prelimbic region of the mPFC. Immediately prior to cognitive testing, a mixture of GABA A and B agonists were infused into the prelimbic to temporarily inactivate the structure. Inactivating the prelimbic cortex significantly impaired performance on this task, resulting in a reduced ability to discriminate the target from non-target images, as well as a reduction in speed and overall responding. Currently, mice expressing optogenetic receptors are being used to evaluate how parvalbumin interneuron activity within the prelimbic cortex influences attentional performance on the rCPT. As the parvalbumin interneuron population is heavily implicated in generating coordinated neuronal activity and supporting cognition, it is predicted that inhibiting these interneurons and altering synchronous prelimbic activity will impair rCPT performance.

The translational gap between animal models and clinical trials is a longstanding, yet largely unresolved, limitation in the study of cognition. This discrepancy is largely due to the differences in how cognition is assessed in animal models compared to those in clinical populations. In the stimulus-response (S-R) learning literature, for example, the techniques used to assess the acquisition of habitual behaviour differ greatly across species, leading to poor cross-species translation and often conflicting results. As a result, we set out to optimize a S-R learning task in mice using the touchscreen-based operant technologies. Similar to human studies, this touchscreen technique encourages animals to respond to visual stimuli displayed on a touchscreen according to a specific rule. Allowing for very similar, if not identical, cognitive assays in mice and men, this technique promotes high translational potential and a high degree of standardisation. Originally developed for rats, the Visuomotor Conditional Learning (VMCL) task encourages animals to learn arbitrary associations between visual stimuli and motor responses. In naïve C57BL/6 mice, we sought to optimize VMCL task parameters to promote better and more efficient responding, identifying the length of inter-trial intervals and the limited hold period as two potential candidates. The validation of this task will provide a novel means through which to study the neural correlates of S-R learning, and its use in conjunction with fiber photometry recordings may be provided.

An important link exists between intact metabolic processes and normal cognitive functioning; however, the underlying mechanisms remain unknown. There is accumulating evidence that the gut hormone ghrelin, an orexigenic peptide that is elevated during calorie restriction (CR) and known primarily for stimulating growth hormone release, has important extra-hypothalamic functions, such as enhancing synaptic plasticity and hippocampal neurogenesis. The present study was designed to evaluate the long-term effects of elevating acyl-ghrelin levels, albeit within the physiological range, on the number of new adult born neurons in the dentate gyrus (DG) and performance on the Spontaneous Location Recognition (SLR) task, previously shown to be DG-dependent and sensitive to manipulations of plasticity mechanisms and cell proliferation. The results revealed that peripheral treatment of rats with acyl-ghrelin enhanced both adult hippocampal neurogenesis and performance on SLR when measured 8-10 days after the end of acyl-ghrelin treatment. Our data show that systemic administration of physiological levels of acyl-ghrelin can produce long-lasting improvements in spatial memory that persist following the end of treatment. As ghrelin is potentially involved in regulating the relationship between metabolic and cognitive dysfunction in ageing and neurodegenerative disease, elucidating the underlying mechanisms holds promise for identifying novel therapeutic targets and modifiable lifestyle factors that may have beneficial effects on the brain. Fil: Kent, Brianne A.. University of Cambridge; Reino Unido Fil: Beynon, Amy L.. Swansea University; Reino Unido Fil: Hornsby, Amanda K. E.. Swansea University; Reino Unido Fil: Bekinschtein, Pedro Alejandro. University of Cambridge; Reino Unido. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Bussey, Timothy J.. University of Cambridge; Reino Unido Fil: Davies, Jeffrey S.. Swansea University; Reino Unido Fil: Saksida, Lisa M.. University of Cambridge; Reino Unido

The original version of the above article contained a mistake in the equation found in page 3953. Correct equation should be: c = -z(HR)+z(FAR)/2 Responsivityindex(RI) = HR+FAR-1/1-(HR-FAR)2.

Rationale\ud The hippocampus is implicated in many of the cognitive impairments observed in conditions such as Alzheimer’s disease (AD) and schizophrenia (SCZ). Often, mice are the species of choice for models of these diseases and the study of the relationship between brain and behaviour more generally. Thus, automated and efficient hippocampal-sensitive cognitive tests for the mouse are important for developing therapeutic targets for these diseases, and understanding brain-behaviour relationships. One promising option is to adapt the touchscreen-based trial-unique nonmatching-to-location (TUNL) task that has been shown to be sensitive to hippocampal dysfunction in the rat. \ud Objectives\ud This study aims to adapt the TUNL task for use in mice and to test for hippocampus-dependency of the task. \ud Methods\ud TUNL training protocols were altered such that C57BL/6 mice were able to acquire the task. Following acquisition, dysfunction of the dorsal hippocampus (dHp) was induced using a fibre-sparing excitotoxin, and the effects of manipulation of several task parameters were examined. \ud Results\ud Mice could acquire the TUNL task using training optimised for the mouse (experiments 1). TUNL was found to be sensitive to dHp dysfunction in the mouse (experiments 2, 3 and 4). In addition, we observed that performance of dHp dysfunction group was somewhat consistently lower when sample locations were presented in the centre of the screen. \ud Conclusions\ud This study opens up the possibility of testing both mouse and rat models on this flexible and hippocampus-sensitive touchscreen task.