Spatial recognition test: A novel cognition task for assessing topographical memory in mice

Abstract

Dysfunction in topographical memory is a core feature of several neurological disorders. There is a large unmet medical need to address learning and memory deficits as a whole in central nervous system disease. There are considerable efforts to identify pro-cognitive compounds but current methods are either lengthy or labour intensive. Our test used a two chamber apparatus and is based on the preference of rodents to explore novel environments. It was used firstly to assess topographical memory in mice at different retention intervals (RI) and secondly to investigate the effect of three drugs reported to be beneficial for cognitive decline associated with Alzheimer's disease, namely: donepezil, memantine and levetiracetam. Animals show good memory performance at all RIs tested under four hours. At the four-hour RI, animals show a significantly poorer memory performance which can be rescued using donepezil, memantine and levetiracetam. Using this test we established and validated a spatial recognition paradigm to address topographical memory in mice by showing a decremental time-induced forgetting response and reversing this decrease in performance using pharmacological tools. The spatial recognition test differs from more commonly used visuospatial laboratory tests in both throughput capability and potentially neuroanatomical substrate. This test has the potential to be used to assess cognitive performance in transgenic animals, disease models and to screen putative cognitive enhancers or depressors.

NMDA receptors containing GluN2C and GluN2D subunits have opposing roles in modulating neuronal oscillations; potential mechanism for bidirectional feedback

“…MK-801 is commonly used in the 0.05 to 0.25 mg/kg range, we found 0.2 mg/kg gave a reproducible, robust augmentation of oscillations. Memantine results in NMDAR-related behavioral effects in the 2.5 to 30 mg/kg range (Zhu et al, 2015;Havolli et al, 2017;Kakefuda et al, 2016). In our experiments, 20 mg/kg memantine gave clear augmentation of gamma oscillations comparable in magnitude with the other channel blockers.…”