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

Abstract

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.

Stress facilitates late reversal learning using a touchscreen-based visual discrimination procedure in male Long Evans rats

“…The visual discrimination and reversal learning procedures closely followed those recommended by the manufacturer and optimized in Professor Timothy Bussey's laboratory [18,19,21]. Following the third day of food restriction, rats were put in the touchscreen operant chambers and habituated for 30 min.…”

“…Previous studies have used two operant paradigms for assessing the effects of acute stress on reversal learning. In two studies [11,12], a touchscreen-based discrimination task [17][18][19] that took several weeks to complete was used in mice. After being trained on a discrimination task for food reward and before initiating a reversal of the discrimination, mice were subjected to 3 days of swim stress.…”

Chemogenetic Inactivation of Dorsal Anterior Cingulate Cortex Neurons Disrupts Attentional Behavior in Mouse

“…We next assessed accurate and omitted trials as stimulus duration decreased in both groups upon CNO administration (Bari et al, 2008;Mar et al, 2013). Compared with vehicle delivery, CNO administration significantly increased the number of trials omitted in both hSyn-hM4Di and CaMKII-hM4Di mice.…”

“…Because an increase in omission can also arise because of altered motor function and decreased motivation to obtain a reward, we next sought to evaluate motivation and motor deficits through latency to collect rewards as well as the open field test (Bari et al, 2008;Mar et al, 2013). Although we observed a significant lengthening of latency to produce a correct response in hSyn-hM4Di mice (po0.05), but not in CaMK2-hM4Di mice (p = 0.13), CNO administration did not affect latency to collect reward (hSyn-hM4Di, p = 0.40; CaMKII-hM4Di, p = 0.13) (Figure 3a-d).…”

“…Addressing these concerns, we expressed hM4Di in dACC neurons and subjected mice to the five-choice serial reaction time task (5CSRTT) that measures sustained visuospatial attention alongside processing speed and response control (Bari et al, 2008;Robbins, 2002). Our study was conducted in Bussey-Saksida touch-screen operant chambers with a high degree of automation and standardization, applying similar stimulus and response characteristics to those used by the analogous Cambridge Neuropsychological Test Automated Battery in humans and non-human primates (Bussey et al, 2012;Mar et al, 2013;Romberg et al, 2011;Silverman et al, 2013). By coupling DREADD technology to attentional behavior for the first time, we demonstrated that the dACC neurons play an important causal role in attention to relevant stimuli.…”