Abstract
Adolescence is a critical period for the development of higher-order cognitive functions. Unlike in humans, very limited tools are available to assess such cognitive abilities in adolescent rodents. We implemented a modified 5-Choice Serial Reaction Time Task (5CSRTT) to selectively measure attentiveness, impulsivity, broad monitoring, processing speed and distractibility in adolescent mice. 21-day old C57BL/6J mice reliably acquired this task with no sex-dependent differences in 10–12 days. A protocol previously used in adults was less effective to assess impulsiveness in adolescents, but revealed increased vulnerability in females. Next, we distinctively assessed selective, divided and broad monitoring attention modeling the human Spatial Attentional Resource Allocation Task (SARAT). Finally, we measured susceptibility to distractions using non-predictive cues that selectively disrupted attention. These paradigms were also applied to two genetically modified lines: the dopamine transporter (DAT) and catechol-O-methyltransferase (COMT) heterozygous. Adolescent DAT hypo-functioning mice showed attentional deficits and higher impulsivity as found in adults. In contrast to adults, adolescent COMT hypo-functioning mice showed decreased impulsivity and attentional resilience to distractors. These paradigms open new avenues to study the establishment of higher-order cognitive functions in mice, as well as an effective tool for drug-testing and genetic screenings focused on adolescence.
Highlights
The development of attentional control is crucial because this ability might strongly influence all other cognitive domains[7, 8]
The data reported here demonstrate that this modified 5-Choice Serial Reaction Time Task (5CSRTT) can effectively test attentional control abilities in adolescent mice
Different challenges in the test were able to detect in adolescent mice: (i) impulsive-like behaviors defined as the ability to refrain to make a preponderant response, (ii) the ability to maintain focused or broad attention when different pre-cue stimuli were presented (SARAT) and (iii) the attentional vulnerability to distractors
Summary
The development of attentional control is crucial because this ability might strongly influence all other cognitive domains[7, 8]. Studies dissecting the changes in brain circuits and molecular footprints in animal models, very limited behavioral tools that reliably assess higher order cognitive functions are available for adolescent rodents. Available tasks to assess higher-order cognitive functions have been designed and tested only in adult mice and rats[32,33,34,35] This is mostly due to the long periods required for training, which are incompatible with the very short duration of rodent adolescence. The novel automatic paradigms implemented are effective in differentially measuring multiple attentional functions such as selective and divided attention, broad monitoring, vulnerability to distractors, impulsivity, speed of processing and motivation in adolescent mice This was validated in both males and females as well as in two different genetically modified mouse lines (i.e. DAT and COMT), highlighting substantial divergences in performance between adolescents and adults. Combined with the advanced techniques currently available to study the impact of molecular-, circuital-, cell- and genetic-specific factors in mice, this new behavioral tool will help improve our understanding of adolescence
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