Performance of C57BL/6J and DBA/2J mice on a touchscreen-based attentional set-shifting task

Abstract

Attentional set-shifting deficits are a feature of multiple psychiatric disorders. However, the neurogenetic mechanisms underlying these deficits are largely unknown. In the present study we assessed performance of C57BL/6J and DBA/2J mice on a touchscreen-based attentional set-shifting task similar to those used with humans and non-human primates. In experiment 1, mice discriminated simple white lines followed by compound stimuli composed of white lines superimposed on grey shapes. Although performance of the two strains was largely equivalent during early stages of the task, DBA/2J mice committed significantly more errors compared to C57BL/6J mice on the extra-dimensional shift. Additionally, performance of mice as a group declined across the three compound discrimination reversals. In experiment 2 we assessed salience of the shapes and lines dimensions and determined if dimensional salience, a variable previously shown to affect set-shifting abilities in humans and non-human primates, could be systematically manipulated. Findings from experiment 2 suggested that strain differences during the extra-dimensional shift in experiment 1 were most parsimoniously explained by a consistently impaired ability in DBA/2J mice to discriminate a subset of the compound stimuli. Additionally, unlike maze-based tasks, the relative salience of the two dimensions could be manipulated by systematically altering the width of lines exemplars while retaining other potentially-relevant attributes of the compound stimuli. These findings reveal unique and in some cases strain-dependent phenomena related to discriminations of simple and multidimensional visual stimuli which may facilitate future efforts to identify and fully characterize visual discrimination, reversal learning, and attentional set-shifting deficits in mice.

Cerebellar contribution to higher and lower order rule learning and cognitive flexibility in mice

“…These data suggest that the cerebellum contributes to higher-order cognitive flexibility. It is also possible that altered perception of stimulus salience in the low Purkinje cell group contributed to the EDS performance deficit (Dickson et al, 2014). The use of a counterbalanced design in which some mice learn to shift attention from shapes to lines and other mice learn to shift attention from lines to shapes would enable fully dissociating the effect of the cerebellum on stimulus salience attribution and attentional set-shifting.…”

“…Mice were individually housed the day before training began and were trained for at least 7 days prior to the beginning of the simple discrimination phase. Mice were tested on ten IED stages as previously described (Dickson et al, 2014). Visual stimuli used at each stage of the IED task are provided in Figure 1.…”

“…The lines dimension was relevant during the SD – IDS4R stages, and the shapes dimension was relevant during the EDS – EDSR stages. As we have done in previous studies, we prevented the development of side bias by using a correction procedure (Dickson et al, 2010, Dickson et al, 2013, Dickson et al, 2014). Sessions lasted for 60 minutes or until the mouse completed 64 trials.…”

“…To assess the contribution of the cerebellum to higher- and lower-order rule learning and cognitive flexibility, we tested lurcher↔wildtype aggregation chimeras (Martin et al, 2003, Martin et al, 2004, Martin et al, 2006, Dickson et al, 2010, Martin et al, 2010) on a touchscreen version of the IED task that we (Dickson et al, 2014) and others (Brigman et al, 2005, Brigman et al, 2006) have adapted for mice. Purkinje cells, the sole output of the cerebellar cortex, die during the first month of development in lurcher mutants as a result of a gain-of-function mutation in Grid2 (Caddy and Biscoe, 1979, Zuo et al, 1997).…”

The NEWMEDS rodent touchscreen test battery for cognition relevant to schizophrenia

“…Furthermore, we and others have made strides towards a rodent intra-and extra-dimensional set shifting task in the touchscreen using two visual dimensions (Brigman et al 2005;Dickson et al 2014), a valuable contribution for cross-species comparisons with both monkey (e.g. Roberts et al 1988) and human literature (e.g.…”