A schizophrenia relevant 5-Choice Serial Reaction Time Task for mice assessing broad monitoring, distractibility and impulsivity
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The 5-Choice Serial Reaction Time Task (5-CSRTT) is an automated test for rodents allowing the assessment of multiple cognitive measures. Originally designed to assess cognitive deficits relevant to attention deficit hyperactivity disorder, it has been widely used in the investigation of neural systems of attention. In the current study, we have set up a modified version, which reduced the training phase to only 8–9 days with minimal food deprivation and without single-housing. Furthermore, based on evidence that patients with schizophrenia are more impaired in broad monitoring abilities than in sustained attention, we successfully developed a protocol replicating the Spatial Attentional Resource Allocation Task (SARAT), used in humans to assess broad monitoring. During this task, when the target appeared at a single pre-cued location, mice selectively responded faster. Instead, increasing the number of validly cued locations proportionately decreased accuracy. We then validated a protocol which is relevant for neuropsychiatric disorders in which additional irrelevant pre-cue lights selectively disrupted attention (distractibility). Finally, we improved previously used protocols changing inter-trial intervals from 5 to 7 s by randomly presenting this shift only in 20% of the trials. This resulted in a selective effect on premature responses (impulsivity), with important implications for schizophrenia as well as for other mental disorders. Therefore, this revised 5-CSRTT reduced training and stress on the animals while selectively measuring different cognitive functions with translational validity to schizophrenia and other psychiatric disorders.
KeywordsAttentional control Cognition Behaviour Operant task Schizophrenia
We thank Dr. M. Morini, C. Chiabrera, A. Parodi, R. Navone and T. Luchetta for their excellent technical assistance.
Compliance with ethical standards
All procedures were approved by the Italian Ministry of Health (permit n. 230/2009-B) and strictly adhere to the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health.
Funding and disclosure
This research was supported by the Istituto Italiano di Tecnologia, the 2015 NARSAD Independent Investigator Grant and the RPF Roche program. The authors declare that they have no financial conflicts of interest and that they have nothing to disclose.
Conflict of interest
The authors declare that they have no conflict of interest.
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