A new behavioural apparatus to reduce animal numbers in multiple types of spontaneous object recognition paradigms in rats

Standard object recognition procedures assess animals’ memory through their spontaneous exploration of novel objects or novel configurations of objects with other aspects of their environment. Such tasks are widely used in memory research, but also in pharmaceutical companies screening new drug treatments. However, behaviour in these tasks may be driven by influences other than novelty such as stress from handling which can subsequently influence performance. This extra-experimental variance means that large numbers of animals are required to maintain power. In addition, accumulation of data is time consuming as animals typically perform only one trial per day. The present study aimed to explore how effectively recognition memory could be tested with a new continual trials apparatus which allows for multiple trials within a session and reduced handling stress through combining features of delayed nonmatching-to-sample and spontaneous object recognition tasks. In this apparatus Lister hooded rats displayed performance significantly above chance levels in object recognition tasks (Experiments 1 and 2) and in tasks of object-location (Experiment 3) and object-in-context memory (Experiment 4) with data from only five animals or fewer per experimental group. The findings indicated that the results were comparable to those of previous reports in the literature and maintained statistical power whilst using less than a third of the number of animals typically used in spontaneous recognition paradigms. Overall, the results highlight the potential benefit of the continual trials apparatus to reduce the number of animals used in recognition memory tasks

Moving beyond standard procedures to assess spontaneous recognition memory

This review will consider how spontaneous tasks have been applied alongside neuroscientific techniques to test complex forms of recognition memory for objects and their environmental features, e.g. the spatial location of an object or the context in which it is presented. We discuss studies that investigate the roles of the perirhinal cortex and the hippocampus in recognition memory using standard testing paradigms, and consider how these findings contribute to the ongoing debate about whether recognition memory is a single unitary process or multiple processes that can be dissociated anatomically and functionally. Due to the wide use of spontaneous tasks, the need for improved procedures that reduce animal use is acknowledged, with multiple trial paradigms discussed as a novel way of reducing variability and animal numbers in these tasks. The importance of improving translation of animal models to humans is highlighted, with emphasis on a shift away from relying on the phenomenological experience of human subjects

Incidental context information increases recollection

The current study describes a receiver-operating characteristic (ROC) task for human participants based on the spontaneous recognition memory paradigms typically used with rodents. Recollection was significantly higher when an object was in the same location and background as at encoding, a combination used to assess episodic-like memory in animals, but not when only one of these task-irrelevant cues was present. The results show that incidentally encoded cue information can determine the degree of recollection, and opens up the possibility of assessing recollection across species in a single experimental paradigm, allowing better understanding of the cognitive and biological mechanisms at play

Differential perivascular microglial activation in the deep white matter in vascular dementia developed post‐stroke

With the hypothesis that perivascular microglia are involved as neuroinflammatory components of the gliovascular unit contributing to white matter hyperintensities on MRI and pathophysiology, we assessed their status in stroke survivors who develop dementia. Immunohistochemical and immunofluorescent methods were used to assess the distribution and quantification of total and perivascular microglial cell densities in 68 brains focusing on the frontal lobe WM and overlying neocortex in post-stroke dementia (PSD), post-stroke non-dementia (PSND) and similar age control subjects. We primarily used CD68 as a marker of phagocytic microglia, as well as other markers of microglia including Iba-1 and TMEM119, and the myeloid cell marker TREM2 to assess dementia-specific changes. We first noted greater total densities of CD68+ and TREM2+ cells per mm2 in the frontal WM compared to the overlying cortex across the stroke cases and controls (p = 0.001). PSD subjects showed increased percentage of activated perivascular CD68+ cells distinct from ramified or primed microglia in the WM (p 70%) between them in both the WM and the cortex. CD68 and Iba-1 or CD68 and TMEM119 markers were colocalised by ~55%. Within the deep WM, ~30% of CD68+ cells were co-localised with fragments of degraded myelin basic protein. Among fragmented CD68+ cells in adjacent WM of PSD subjects, >80% of the cells expressed cleaved caspase-3. Our observations suggest although the overall repertoire of perivascular microglial cells is not changed in the parenchyma, PSD subjects accrue more perivascular-activated CD68+ microglia rather than TREM2+ cells. This implies there is a subset of CD68+ cells, which are responsible for the differential response in perivascular inflammation within the gliovascular unit of the deep WM