A touch screen-automated cognitive test battery reveals impaired attention, memory abnormalities, and increased response inhibition in the TgCRND8 mouse model of Alzheimer's disease

Abstract

Transgenic mouse models of Alzheimer's disease (AD) with abundant β-amyloid develop memory impairments. However, multiple nonmnemonic cognitive domains such as attention and executive control are also compromised early in AD individuals, but have not been routinely assessed in animal models. Here, we assessed the cognitive abilities of TgCRND8 mice—a widely used model of β-amyloid pathology—with a touch screen-based automated test battery. The test battery comprises highly translatable tests of multiple cognitive constructs impaired in human AD, such as memory, attention, and response control, as well as appropriate control tasks. We found that familial AD mutations affect not only memory, but also cause significant alterations of sustained attention and behavioral flexibility. Because changes in attention and response inhibition may affect performance on tests of other cognitive abilities including memory, our findings have important consequences for the assessment of disease mechanisms and therapeutics in animal models of AD. A more comprehensive phenotyping with specialized, multicomponent cognitive test batteries for mice might significantly advance translation from preclinical mouse studies to the clinic.

The touchscreen operant platform for assessing executive function in rats and mice

“…The time it takes and the extent to which animals suppress their responding provide the basic indices of extinction learning. Variants of this protocol have been used to test extinction in various mutant mouse lines 40-44 and genetic strains 45-46 . We have only recently started using this procedure in rats, and no major issues have been observed or are expected in translating this relatively straightforward task.…”

Strain-dependent effects on acquisition and reversal of visual and spatial tasks in a rat touchscreen battery of cognition

“…Possibly the largest benefit of a rodent touchscreen platform is that it may facilitate a translational approach from animal to human by allowing cognition in the rodent to be measured in a similar fashion as to how it is measured in human. Rodent touchscreens have already been used to study the effects of genetic [3,25], pharmacological and region specific manipulations on cognitive performance using rats and mice [19,24,26,31]. Despite this, surprisingly little is known about the influence of background strain on task performance or on common challenge models within a touchscreen setting, despite it being well established that strain can substantially influence performance on cognitive tasks [6,10,11,15,18,36].…”

Touchscreen tasks in mice to demonstrate differences between hippocampal and striatal functions

“…Furthermore, the 91 touchscreen technology can be used to test the implication of the 92 HPC in other aspects of cognition, such as associating a particular 93 stimulus to a particular place (Barker & Warburton, 2011). Since 94 it offers the possibility to dynamically manipulate the nature and 95 spatial location of stimuli visualized on the screen across trials 96 Romberg, Horner, Bussey, & Saksida, 2013), 97 this approach seems particularly adapted to assess the formation 98 of associative memories resulting from the establishment of a rela-99 tionship between visual stimuli and their paired spatial location. 100 Paired Associates Learning (PAL) paradigms appealing to such 101 ''object-in-place'' associations are generally HPC-dependent 102 (Gilbert & Kesner, 2002;Lee & Solivan, 2008;Yoon, Seo, Kim, & 103 Lee, 2012).…”