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Touchscreen response technology and the power of stimulus‐based approaches in freely behaving animals

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Learning about stimuli that predict rewards, their locations, and the actions needed to procure rewards requires a diverse set of neural and genetic substrates. The systems that support behavior in… Click to show full abstract

Learning about stimuli that predict rewards, their locations, and the actions needed to procure rewards requires a diverse set of neural and genetic substrates. The systems that support behavior in natural environments evolved in freely moving animals, and yet these same systems are probed with increasing frequency in head-fixed animals using methods that enable more control and several benefits, including precise stimulus viewing, reduction of movement artifact during neural recordings, and collection of thousands of trials from each animal, to name a few. Along with the capacity to image and record from hundreds to thousands of neurons across extended periods of time and in multiple brain regions, the ethological validity of the behavior should also be an important consideration in data interpretation. Indeed, learning paradigms in freely moving and behaving animals such as those utilizing touchscreen-based operant systems simulate more naturalistic foraging behavior with the addition of an appreciable level of experimental control, and while animals have the option to engage in the task (or not), as in the real world. Freely moving and body/head-fixed behavioral methods may reveal the same underlying process, but there are also important and potentially growing examples of divergence. The touchscreen response system is an increasingly widely used platform for behavioral and systems neuroscience. In this Special Issue, Dumont et al provide an overview of the rise in popularity and worldwide appeal of this technology. Some key advantages of touchscreen-response methods in experimental animals include: face validity to human cognitive testing, high throughput automation, task flexibility (including wide spatial ranges of stimulus presentation), and compatibility with recording and imaging technology in rodents. Apropos to the important consideration of ethological validity in freely behaving animals, in this issue Mosser and colleagues provide an open source and standardized framework for integrating miniscope technology and touchscreen responding in freely moving rodents. Increasingly, the availability of standardized tests and tools from the McGill-Mouse-Miniscope (M3) Platform, inspired by and adapted from the UCLA Miniscope project (www.miniscope.org), is making this integration more accessible to laboratories globally. Sharing of methods, codes, data, and symposia for touchscreen users are also made possible by centralized resources described in this issue by Sullivan et al as the Mouse Translational Research Accelerator Platform (MouseTRAP). This platform will continue to help touchscreen users in addressing the increasingly prevalent journal and funding agency requirements to include evidence of rigor and reproducibility in experiments, as well as data and resource sharing. Taking a bird's eye view of the reports included in this Special Issue, at least two (albeit not mutually exclusive) categories of benefits afforded by the use of touchscreen response systems are highlighted: the possibility of a “test battery” and a “subprocess” approach. Investigators using a test battery design often compare the performance of a touchscreen-based response task with another; usually the comparison is with an analogous manual (maze) task or a complementary behavioral assay also using touchscreen response methods (the latter more common than the former). As a first example of the test battery approach, Van den Broeck and colleagues investigated a mouse model of Alzheimer's disease, the APP/PS1-21 mouse, on performance of spatial learning in the Morris Water Maze and discrimination learning using automated touchscreen methods. Authors found touchscreen-based reversal learning to be much more sensitive to early prefrontal cortex dysfunction than maze performance and further, that older subjects needed many more sessions of experience in pairwise discrimination and, more prominently, reversal learning than younger subjects. The results of this experiment provide information on the desired baseline sensitivity of tasks in preclinical research on Alzheimer's Disease. Using a similar test battery approach, Olguin et al probed the effects of rodent prenatal alcohol exposure on two tasks: the 5-choice serial reaction time task (5-CSRTT) and this group's recently established 5-choice continuous performance task (5C-CPT). Authors discovered 5C-CPT to be impaired and 5-CSRTT to be intact following alcohol exposure, suggesting a vigilance and cognitive control impairment that could not be accounted for by a gross motor impairment. These findings have relevance to our understanding of fetal alcohol spectrum disorders in humans. Taken together, by comparing and contrasting complementary behaviors on different tasks, investigators may glean a more precise behavioral phenotype relevant to human disease. Researchers using more of a subprocess approach may operationally distinguish behaviors observed within a single touchscreen-based task, in a more fine-grained way (e.g., motor responding versus attention to stimuli), rather than reporting omnibus measures alone (e.g., sessions required to reach criterion, total errors). An example of the use of touchscreen-response methods with subprocess sensitivity is the study by Aarde et al. These authors used the Four Core Genotypes mouse model to probe the extent to which sex biasing factors of gonadal hormones and/or sex chromosome complement (SCC, XX DOI: 10.1111/gbb.12720

Keywords: task; touchscreen response; response; technology; behaving animals

Journal Title: Genes
Year Published: 2020

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