Summary An increasingly popular method of assessing cognitive functions in rodents is the automated touchscreen platform, on which a number of different cognitive tests can be run in a manner very similar to touchscreen methods currently used to test human subjects. This methodology is low stress (using appetitive, rather than aversive reinforcement), has high translational potential, and lends itself to a high degree of standardisation and throughput. Applications include the study of cognition in rodent models of psychiatric and neurodegenerative diseases (e.g., Alzheimer’s disease, schizophrenia, Huntington’s disease, frontotemporal dementia), and characterisation of the role of select brain regions, neurotransmitter systems and genes in rodents. This protocol describes how to perform four touchscreen assays of learning and memory: Visual Discrimination, Object-Location Paired-Associates Learning, Visuomotor Conditional Learning and Autoshaping. It is accompanied by two further protocols using the touchscreen platform to assess executive function, working memory and pattern separation.

Summary This protocol details a subset of assays developed within the touchscreen platform to measure aspects of executive function in rodents. Three main procedures are included: Extinction, measuring the rate and extent of curtailing a response that was previously, but is no longer, associated with reward; Reversal Learning, measuring the rate and extent of switching a response toward a visual stimulus that was previously not, but has become, associated with reward (and away from a visual stimulus that was previously, but is no longer, rewarded); and the 5-Choice Serial Reaction Time (5-CSRT) task, gauging the ability to selectively detect and appropriately respond to briefly presented, spatially unpredictable visual stimuli. These methods were designed to assess both complimentary and overlapping constructs including selective and divided visual attention, inhibitory control, flexibility, impulsivity and compulsivity. The procedures comprise part of a wider touchscreen test battery assessing cognition in rodents with high potential for translation to human studies.

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The wettability of electrospun poly(epsilon-caprolactone) (PCL) mats was improved by co-electrospinning with poly(vinyl alcohol) (PVA), by double-spinneret electrospinning method. The improved hydrophilicity of the hybrid PCL/PVA mats was confirmed by water contact angle measurement. The in vitro cell attachment on the hydrophobic PCL and hydrophilically modified PCL/PVA mats was compared by culture studies using human prostate epithelial cells (HPECs). The stability of water-soluble PVA component in the electrospun PCL/PVA mats was checked by thermogravimetric analysis and intensity of fluorescence material after immersion in water for 7 days. The images from scanning electron microscopy, field emission scanning electron microscopy, and optical microscopy showed that the attachment and proliferation rate of HPECs were improved by introducing PVA into the electrospun PCL mats.

IntroductionWe conducted a phase 1 clinical trial in nine patients with mild-to-moderate Alzheimer's disease to evaluate the safety and dose-limiting toxicity of stereotactic brain injection of human umbilical cord blood–derived mesenchymal stem cells (hUCB-MSCs).MethodsThe low- (n = 3) and high-dose (n = 6) groups received a total of 3.0 × 106 cells/60 μL and 6.0 × 106 cells/60 μL, respectively, into the bilateral hippocampi and right precuneus.ResultsNo patient showed serious adverse events including fever during the 24-month follow-up period. During the 12-week follow-up period, the most common acute adverse event was wound pain from the surgical procedure (n = 9), followed by headache (n = 4), dizziness (n = 3), and postoperative delirium (n = 3). There was no dose-limiting toxicity.DiscussionAdministration of hUCB-MSCs into the hippocampus and precuneus by stereotactic injection was feasible, safe, and well tolerated. Further trials are warranted to test the efficacy.Clinical Trial RegistrationClinicalTrial.gov identifier NCT01297218 and NCT01696591.

Our findings suggest that although deep CMBs are mainly linked to subcortical SVD, both subcortical SVD and amyloid-related pathologies (eg, CAA) contribute to the pathogenesis of lobar CMBs, at least in subjects with mixed lobar and deep CMBs. Furthermore, subcortical SVD and amyloid-related pathologies interact to increase the risk of lobar CMBs.

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RationaleContinuous performance tests (CPTs) are widely used to assess attentional processes in a variety of disorders including Alzheimer’s disease and schizophrenia. Common human CPTs require discrimination of sequentially presented, visually patterned ‘target’ and ‘non-target’ stimuli at a single location.ObjectivesThe aims of this study were to evaluate the performance of three popular mouse strains on a novel rodent touchscreen test (rCPT) designed to be analogous to common human CPT variants and to investigate the effects of donepezil, a cholinesterase inhibitor and putative cognitive enhancer.MethodsC57BL/6J, DBA/2J and CD1 mice (n = 15–16/strain) were trained to baseline performance using four rCPT training stages. Then, probe tests assessed the effects of parameter changes on task performance: stimulus size, duration, contrast, probability, inter-trial interval or inclusion of flanker distractors. rCPT performance was also evaluated following acute administration of donepezil (0–3 mg/kg, i.p.).ResultsC57BL/6J and DBA/2J mice showed similar acquisition rates and final baseline performance following rCPT training. On probe tests, rCPT performance of both strains was sensitive to alteration of visual and/or attentional demands (stimulus size, duration, contrast, rate, flanker distraction). Relative to C57BL/6J, DBA/2J mice exhibited (1) decreasing sensitivity (d′) across the 45-min session, (2) reduced performance on probes where the appearance of stimuli or adjacent areas were changed (size, contrast, flanking distractors) and (3) larger dose- and stimulus duration-dependent changes in performance following donepezil administration. In contrast, CD1 mice failed to acquire rCPT (stage 3) and pairwise visual discrimination tasks.ConclusionsrCPT is a potentially useful translational tool for assessing attention in mice and for detecting the effects of nootropic drugs.