The Ultimate Intra-/Extra-Dimensional Attentional Set-Shifting Task for Mice

Scheggia, Diego; Bebensee, Audrey; Weinberger, Daniel R.; Papaleo, Francesco

doi:10.1016/j.biopsych.2013.05.021

Cited by 58 publications

(79 citation statements)

References 46 publications

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“…In contrast to already established set-shifting procedures in mice (Garner et al, 2006; Endo et al, 2011; Bissonette and Powell, 2012; Scheggia et al, 2014), the strength of the present approach is twofold: First, it has a high translational value as it is derived from a behavioral paradigm for humans, and second, it is conceptually based on a biophysically plausible neurocomputational theory that has the potential of linking animal and human behavior across species.…”

Section: Introductionmentioning

confidence: 85%

Touchscreen-paradigm for mice reveals cross-species evidence for an antagonistic relationship of cognitive flexibility and stability

Richter

Vogel

Ueltzhöffer

et al. 2014

Front. Behav. Neurosci.

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The abilities to either flexibly adjust behavior according to changing demands (cognitive flexibility) or to maintain it in the face of potential distractors (cognitive stability) are critical for adaptive behavior in many situations. Recently, a novel human paradigm has found individual differences of cognitive flexibility and stability to be related to common prefrontal networks. The aims of the present study were, first, to translate this paradigm from humans to mice and, second, to test conceptual predictions of a computational model of prefrontal working memory mechanisms, the Dual State Theory, which assumes an antagonistic relation between cognitive flexibility and stability. Mice were trained in a touchscreen-paradigm to discriminate visual cues. The task involved “ongoing” and cued “switch” trials. In addition distractor cues were interspersed to test the ability to resist distraction, and an ambiguous condition assessed the spontaneous switching between two possible responses without explicit cues. While response times did not differ substantially between conditions, error rates (ER) increased from the “ongoing” baseline condition to the most complex condition, where subjects were required to switch between two responses in the presence of a distracting cue. Importantly, subjects switching more often spontaneously were found to be more distractible by task irrelevant cues, but also more flexible in situations, where switching was required. These results support a dichotomy of cognitive flexibility and stability as predicted by the Dual State Theory. Furthermore, they replicate critical aspects of the human paradigm, which indicates the translational potential of the testing procedure and supports the use of touchscreen procedures in preclinical animal research.

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Section: Introductionmentioning

confidence: 85%

Touchscreen-paradigm for mice reveals cross-species evidence for an antagonistic relationship of cognitive flexibility and stability

Richter

Vogel

Ueltzhöffer

et al. 2014

Front. Behav. Neurosci.

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“…This task places heavier emphasis on response conflicts and shares features similar to the operant conditioning tasks previously established to assess cognitive flexibility in rodents (Floresco et al 2008; Haluk and Floresco 2009; Brigman et al 2010; Scheggia et al 2014) and the Wisconsin Card Sorting Task in humans (Monchi et al 2001). Briefly, animals were autoshaped on a FR-1 schedule of reinforcement to acquire the lever press response and subsequent reward (10µl of .066% saccharin solution).…”

Section: Methodsmentioning

confidence: 99%

Impact of partial dopamine depletion on cognitive flexibility in BDNF heterozygous mice

et al. 2016

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Rationale Cognitive flexibility is a key component of executive function and is disrupted in major psychiatric disorders. Brain-derived neurotrophic factor (BDNF) exerts neuromodulatory effects on synaptic transmission and cognitive/affective behaviors. However the causal mechanisms linking BDNF hypofunction with executive deficits are not well understood. Objectives Here, we assessed the consequences of BDNF hemizygosity on cognitive flexibility in mice performing an operant conditioning task. As dopaminergic-glutamatergic interaction in the striatum is important for cognitive processing, and BDNF heterozygous (BDNF+/−) mice display a higher dopamine tone in the dorsal striatum, we also assessed the effects of partial striatal dopamine depletion on task performance and glutamate release. Results BDNF+/− mice acquired discrimination learning as well as new rule learning during set-shifting as efficiently as wild-type mice. However, partial removal of striatal dopaminergic inputs with 6-hydroxydopamine (6-OHDA) impaired these cognitive processes by impeding the maintenance of a new learning strategy in both genotypes. BDNF mutants exhibited performance impairments during reversal learning and these deficits were associated with increased perseveration to the previously acquired strategy. Partial dopamine depletion of the striatum reversed these cognitive impairments. Additionally, reduction in depolarization-evoked glutamate release noted in the dorsal striatum of BDNF+/− mice was not observed in 6-OHDA-infused BDNF mutants indicating normalization of glutamatergic transmission in these animals. Conclusions Our data illustrate that BDNF signaling regulates cognitive control processes presumably by maintaining striatal dopamine-glutamate balance. Moreover, aberrations in BDNF signaling may act as a common neurobiological substrate that accounts for executive dysfunction observed in multiple psychiatric conditions.

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“…We also found improved cognition in Dcc heterozygous mice in the attentional set-shifting test [63], a test of cognitive flexibility. Cognitive or behavioural flexibility is the ability to make adaptive responses to a changing environment and is specifically tested by the extradimensional set-shifting component of the attentional set-shifting test [29,63,64]. Performance on this component of the test is enhanced in Dcc heterozygous mice [29].…”

Section: Dcc-mediated Wiring Of Mesocortical Dopamine Circuitry Determentioning

confidence: 99%

Making Dopamine Connections in Adolescence

Hoops

Flores

2017

Trends in Neurosciences

116

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A dramatic maturational process ongoing in adolescence is prefrontal cortex development, including its dopamine innervation. Dopamine axons grow from the striatum to the prefrontal cortex, the only known case of long-distance axon growth during adolescence. This is coordinated by the Netrin-1 guidance cue receptor DCC, which in turn controls the intrinsic development of the prefrontal cortex itself. Stimulant drugs in adolescence alter DCC in dopamine neurons and in turn prefrontal cortex maturation, impacting cognitive abilities. Variations in DCC expression are linked to psychiatric conditions of prefrontal cortex dysfunction, and microRNA regulation of DCC may be key to determining adolescent vulnerability or resilience. Since early interventions are proving to effectively ameliorate disease outcome, the Netrin-1 system is a promising therapeutic target.

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The Ultimate Intra-/Extra-Dimensional Attentional Set-Shifting Task for Mice

Cited by 58 publications

References 46 publications

Touchscreen-paradigm for mice reveals cross-species evidence for an antagonistic relationship of cognitive flexibility and stability

Touchscreen-paradigm for mice reveals cross-species evidence for an antagonistic relationship of cognitive flexibility and stability

Impact of partial dopamine depletion on cognitive flexibility in BDNF heterozygous mice

Making Dopamine Connections in Adolescence

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