A Novel Posner-Style Cueing Task to Assess Attention Orienting in Mouse Models of Autism

Background: A deficit in attention orienting may be one of the earliest features in people with Autism Spectrum Disorder (ASD). Attention orienting is comprised of two components - exogenous and endogenous orienting. Exogenous orienting of attention is a stimulus-driven process in which one’s attention is drawn automatically to salient external stimuli. Endogenous orienting of attention represents a goal-directed process in which expectations and/or knowledge of an individual determine where and when one’s attention is given. To date, the neural mechanisms underlying the atypical attention orienting in autism remain unclear.

Genetic mouse models are useful tools to investigate the neurobiology of cognition, but a well-established assessment of attention orienting in mice is missing. The Posner cueing task is a widely used visual-spatial orienting task in humans. It has been adapted in studies of rats and fish, but rarely used in mice. It is important to develop a mouse version of the Posner cueing task before investigating the association between attention orienting and ASD-associated genetic mutations.

Objectives: Our objective was to adapt the human Posner cueing task for use in mice using recently developed touchscreen technology. This mouse paradigm will be used to investigate attention orienting in mouse models expressing ASD-associated genetic mutations.

Methods: Thirty-two C57BL/6 mice were trained and tested in automated touchscreen chambers. Several versions of the exogenous and endogenous cueing tasks were piloted. The mice were randomly assigned to the exogenous (n = 16) and endogenous task (n = 16).

Mice were trained to sustain their nose-poke to a central dim square until the display of a peripheral target (a bright square). They were rewarded with strawberry milkshake for nose-poking the target. The targets were either validly or invalidly cued. In the exogenous tasks, the cue was a flash of light in the peripheral square. In the endogenous tasks, the cue was a centrally-presented spatially-predictive grating – 145 degree gratings predicted the target on the left, while 45 degree gratings predicted the target on the right. The validity of cues were 50% in the exogenous tasks, and above 80% in the endogenous tasks.

Results: In both the exogenous and endogenous tasks, mice showed higher accuracy and shorter response times in the validly cued trials, compared to invalidly cued trials. This effect is consistent with results in the human Posner task. While mice were able to maintain their nose-poke at centre, this was negatively correlated with increased stimulus-onset asynchrony (SOA).

Conclusions: In this study, we have successfully adapted the human Posner task to mice. Mice responded faster to validly cued stimuli, in line with results in humans. This mouse Posner task can be used to assess attention orienting in mice containing ASD-associated genetic mutations. This approach will enable a greater understanding of neural mechanisms underlying deficits of attention orienting in ASD.