Attentional Control in Adolescent Mice Assessed with a Modified Five Choice Serial Reaction Time Task

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.

DIY-NAMIC behavior: A high-throughput method to measure complex phenotypes in the homecage

“…We were able to use the rich data set collected to tease impulsivity apart from other behavioral parameters that may also be different during adolescence and could otherwise obscure or contaminate measures of impulsive behavior. For example, previous work has shown hyperactivity, increased motivation, and decreased attention in adolescent mice [46]. We were able to increase the sensitivity of the task to detect impulsivity by increasing the delay length [47].…”

“…Some of these studies have taken the strategy of eliminating mice that don't learn quickly enough to progress to increasingly complex behavioral paradigms, leading to potentially biased samples [45]. There has also been some progress in the development of new training paradigms that reduce training time to allow testing in adolescent mice [38,46], however they still require food deprivation which could be detrimental to growth and the maturation of feeding circuits during the adolescence. Inexpensive Arduino-based operant testing apparatus have also been developed, such as ROBucket [37], though these have also been used with the daily experimenter-initiated daily sessions.…”

Convergent neural substrates of inattention in bipolar disorder patients and dopamine transporter‐deficient mice using the 5‐choice CPT

“…Hence, while 0% is severely detrimental to learning such a task, 10% expression, as in the present study, can be beneficial to learning and performance of this standard target‐only task. In contrast, 50% expression as seen in heterozygous mice, resulted in reduced accurate target responding in the 5‐CSRTT in young and adult male mice, although overall %correct remained unaffected . The level of DAT expression could therefore negatively impact this target‐only task, and alters performance when nontarget stimuli are included, such as in the 5C‐CPT.…”

“…In contrast, 50% expression as seen in heterozygous mice, resulted in reduced accurate target responding in the 5-CSRTT in young and adult male mice, although overall %correct remained unaffected. 49,50 The level of DAT expression could therefore negatively impact this target-only task, and alters performance when nontarget stimuli are included, such as in the 5C-CPT. A systematic approach toward understanding attentional performance of mice across DAT expression will be useful in future studies.…”

Enhancing cognition through pharmacological and environmental interventions: Examples from preclinical models of neurodevelopmental disorders

“…For rodents, discrete elements of attentional processes such as sustained and focused attention, impulse control, perseverative and reactivity-related functions can be effectively studied. In particular, one of the most effective and extensively used task in rodents is the 5-Choice Serial Reaction Time Task (5-CSRTT) which allows for measures of general attention, impulse control and processing speed (Carli et al, 1983;Ciampoli et al, 2017;Huang et al, 2017;Mereu et al, 2017;Robbins et al, 1993;Robbins, 2002;Voon et al, 2014). Conversely, the Distractor Condition Sustained Attention Task (dSAT) and the 5-Choice Continuous Performance Test (5C-CPT) are operant -based tasks developed as signal-detection tasks first in rodents (Barnes et al, 2012;Bushnell, 1999;Ciampoli et al, 2017;Huang et al, 2017;McGaughy and Sarter, 1995;Mereu et al, 2017;Mohler et al, 2001;Nuechterlein et al, 2009;Young et al, 2009) and then redesigned for humans, providing clinical translatability (Demeter et al, 2008;Young et al, 2013).…”