Measuring Motivation and Reward‐Related Decision Making in the Rodent Operant Touchscreen System

Heath, Christopher; Phillips, Benjamin U.; Bussey, Timothy J.; Saksida, Lisa M.

doi:10.1002/0471142301.ns0834s74

Cited by 43 publications

(44 citation statements)

References 29 publications

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“…Notably, whilst the aforementioned faster reward collection of Dlg4 +/− mice in the Visual Discrimination and Paired‐Associates Learning tasks could simply be indicative of superior learning about reward delivery, it might reflect a greater motivation for reward which, in turn, could have stimulated faster learning throughout our battery of appetitively motivated touch screen tasks. The latter mechanism could be investigated using the recently developed touch screen‐based Progressive Ratio assay of motivation (Heath et al ., ).…”

Section: Discussionmentioning

confidence: 97%

Enhanced cognition and dysregulated hippocampal synaptic physiology in mice with a heterozygous deletion of PSD‐95

Horner

McLaughlin

Afinowi

et al. 2018

Eur J of Neuroscience

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PSD-95 is one of the most abundant proteins of the postsynaptic density of excitatory synapses. It functions as the backbone of protein supercomplexes that mediate signalling between membrane glutamate receptors and intracellular pathways. Homozygous deletion of the Dlg4 gene encoding PSD-95 was previously found to cause a profound impairment in operant and Pavlovian conditioning in Dlg4 mice studied in touch screen chambers that precluded evaluation of PSD-95's role in shaping more subtle forms of learning and memory. In this study, using a battery of touch screen tests, we investigated cognitive behaviour of mice with a heterozygous Dlg4 mutation. We found that in contrast to learning deficits of Dlg4 mice, Dlg4 animals demonstrated enhanced performance in the Visual Discrimination, Visual Discrimination Reversal and Paired-Associates Learning touch screen tasks. The divergent directions of learning phenotypes observed in Dlg4 and Dlg4 mice also contrasted with qualitatively similar changes in the amplitude and plasticity of field excitatory postsynaptic potentials recorded in the CA1 area of hippocampal slices from both mutants. Our results have important repercussions for the studies of genetic models of human diseases, because they demonstrate that reliance on phenotypes observed solely in homozygous mice may obscure qualitatively different changes in heterozygous animals and potentially weaken the validity of translational comparisons with symptoms seen in heterozygous human carriers.

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Section: Discussionmentioning

confidence: 97%

Enhanced cognition and dysregulated hippocampal synaptic physiology in mice with a heterozygous deletion of PSD‐95

Horner

McLaughlin

Afinowi

et al. 2018

Eur J of Neuroscience

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“…The ratio schedule we used here was designed to study motivation [23,32,45]. The canonical interpretation of elevated breakpoints is increased motivation.…”

Section: Discussionmentioning

confidence: 99%

“…Testing was conducted in standard Bussey-Saksida mouse touchscreen chambers (Campden Instruments Ltd., Loughborough, UK) that have been described in detail elsewhere [15,16,18,20,23]. These consist of an operant arena housed within a sound-and light-attenuating chamber.…”

Section: Apparatusmentioning

confidence: 99%

“…The general FR task procedure in the touchscreen was previously described [15,23]. Following initial training, animals progressed to FR training.…”

Section: Fr/pr Taskmentioning

confidence: 99%

“…PR schedules that require increasing numbers of responses for a reinforcer over successive sessions are commonly used to assess behavioural motivation [15,23,32]. They are sensitive, however, to "non-motivational" influences such as perseverative behaviour [33,34,35].…”

Section: Mglur5 Ko Performance On Touchscreen Fr and Pr Schedules Is mentioning

confidence: 99%

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Assessment of mGluR5 KO mice under conditions of low stress using a rodent touchscreen apparatus reveals impaired behavioural flexibility driven by perseverative responses

et al. 2019

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Genetic and pharmacological manipulations targeting metabotropic glutamate receptor 5 (mGluR5) affect performance in behavioural paradigms that depend on cognitive flexibility. Many of these studies involved exposing mice to highly stressful conditions including electric foot shocks or water immersion and forced swimming. Because mGluR5 is also implicated in resilience and stress responses, however, apparent impairments in inhibitory learning may have been an artifact of manipulation-induced changes in affective state. To address this, we present here a characterization of cognitive flexibility in mGluR5 knockout (KO) mice conducted with a rodent touchscreen cognitive assessment apparatus in which the animals experience significantly less stress. Our results indicate a significant reversal learning impairment relative to wild-type (WT) controls in the two-choice Visual Discrimination-Reversal (VDR) paradigm. Upon further analysis, we found that this deficit is primarily driven by a prolonged period of perseveration in the early phase of reversal. We also observed a similar perseveration phenotype in the KO mice in the Extinction (EXT) paradigm. In addition, mGluR5 KO mice show higher breakpoints in the touchscreen Progressive Ratio (PR) and altered decision making in the Effort-related Choice (ERC) tasks. Interestingly, this impairment in PR is an additional manifestation of an increased propensity to perseverate on the emission of relatively simplistic behavioural outputs. Together, these findings suggest that under conditions of low stress, mGluR5 KO mice exhibit a pronounced perseverative phenotype that blunts cognitive flexibility.

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Evaluating Sequential Response Learning in the Rodent Operant Touchscreen System

et al. 2021

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Sequential and cue-directed response learning in rodents have been previously shown to depend on intact striatal signaling. In particular, these behaviors rely on striatal dopamine and acetylcholine release, with an impairment of sequential response learning evident in animal models with alterations in the two systems. Here we provide a protocol for testing sequential response/response chain learning using the rodent touchscreen system. Specifically, the present protocol is designed to implement the heterogeneous sequence task, adapted from Keeler et al. ( 2014), in the rodent touchscreen apparatus. This task has been used previously to assess complex motor learning and response selection in mice. In the following protocol, the task is performed in touchscreen-based automated chambers with five response locations using food reinforcers to maintain performance. The sequence task requires the subject to make five nose pokes to white square stimuli appearing in five different locations sequentially from left to right.

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Measuring Motivation and Reward‐Related Decision Making in the Rodent Operant Touchscreen System

Cited by 43 publications

References 29 publications

Enhanced cognition and dysregulated hippocampal synaptic physiology in mice with a heterozygous deletion of PSD‐95

Enhanced cognition and dysregulated hippocampal synaptic physiology in mice with a heterozygous deletion of PSD‐95

Assessment of mGluR5 KO mice under conditions of low stress using a rodent touchscreen apparatus reveals impaired behavioural flexibility driven by perseverative responses

Evaluating Sequential Response Learning in the Rodent Operant Touchscreen System

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