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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.