Evaluation of Touchscreen Chambers To Assess Cognition in Adult Mice: Effect of Training and Mild Traumatic Brain Injury

Abstract

Cognitive impairments are often experienced after a mild traumatic brain injury (mTBI). In the clinical arena, neuropsychological assessments are used frequently to detect cognitive deficits. Animal models of mTBI, however, rely on an assortment of behavioral tasks to assess cognitive outcome. Computer-based touchscreen systems have been developed for rodents and are hypothesized to offer a translational approach to evaluate cognitive function because of the similarities of tasks performed in rodents to those implemented in humans. While these touchscreen systems have been used in pre-clinical models of neurodegenerative diseases and psychiatric disorders, their use in assessing cognitive impairment after mTBI has not been investigated. We hypothesized that mTBI would result in impaired cognitive performance on touchscreen tasks, particularly those with hippocampal-based learning components, including the paired associate learning (PAL) task and the location discrimination (LD) task. Adult male, C57BL/6 mice received a single impact-acceleration mTBI. We found that training mice before injury to perform to criteria is arduous and that performance is sensitive to many environmental variables. Despite extensive optimization and training, mice failed to perform better than chance in the PAL paradigm. Alternatively, mice demonstrated some capacity to learn in the LD paradigm, but only with the easier stages of the task. The mTBI did not affect performance in the LD paradigm, however. Thus, we concluded that under the conditions presented here, the PAL and LD touchscreen tasks are not robust outcome measures for the evaluation of cognitive performance in C57BL/6 mice after a single impact-acceleration mTBI.

Repeated mild traumatic brain injuries impair visual discrimination learning in adolescent mice

“…However, RmTBI significantly impaired pairwise discrimination learning. Our results with a single mTBI are in agreement with previous findings using a similar touchscreen-based discrimination task 49 . In a previous study using the 5-choice continuous performance touchscreen-based tasks, they did not find significant deficits in attention and/or cognition 50 .…”

Extended Erythropoietin Treatment Prevents Chronic Executive Functional and Microstructural Deficits Following Early Severe Traumatic Brain Injury in Rats

“…Touchscreen operant chamber platforms for rodents offer an opportunity to use analogous testing paradigms in humans and preclinical models ( 34 , 56 ). Touchscreen platforms have been used in humans and rodents to test cognitive deficits related to genetic mutations ( 38 , 39 , 57 , 58 ), psychiatric disorders ( 56 , 59 ) and adult TBI ( 60 , 61 ). However, to our knowledge, use of touchscreen platforms has not been previously been reported for assessing cognition in pediatric TBI.…”

Touchscreen learning deficits in Ube3a, Ts65Dn and Mecp2 mouse models of neurodevelopmental disorders with intellectual disabilities

“…Here we focus on operant touchscreen learning and memory approaches that could circumvent many procedural confounds. The small operant chambers require minimum locomotion, the sensitive touchscreen requires minimal motor skills, enhanced visual images can be used for low-vision mice who are not completely blind, software programs can define the training schedules to vary the levels of cognitive challenge, and available tasks can interrogate specific brain regions and neuroanatomical circuitry (Bussey et al, 1997; Brigman and Rothblat 2008; Brigman et al, 2005, 2008; Talpos et al, 2010; Bussey et al, 2012; McTighue et al, 2013; Silverman et al, 2015; Yang et al, 2015; Leach et al, 2016; Nichols et al, 2017; Buscher et al, 2017). …”

“…The small operant chambers require minimum locomotion, the sensitive touchscreen requires minimal motor skills, enhanced visual images can be used for low-vision mice who are not completely blind, software programs can define the training schedules to vary the levels of cognitive challenge, and available tasks can interrogate specific brain regions and neuroanatomical circuitry. [24][25][26][27][28][29][30][31][32][33][34][35] We tested 3 mouse models of neurodevelopmental disorders with intellectual disabilities on a touchscreen visual discrimination task, in concert with other learning and memory tasks, along with measures of rotarod motor coordination and balance and open field exploratory locomotion. (1) Angelman syndrome is caused by a maternally inherited deletion at chromosome 15q11-q13, in which the key mutation is in the UBE3A gene, [36][37][38] which codes for an E3 ubiquitin ligase.…”