A schizophrenia relevant 5-Choice Serial Reaction Time Task for mice assessing broad monitoring, distractibility and impulsivity

Huiping Huang, Simone Guadagna, Maddalena Mereu, Mariasole Ciampoli, Giacomo Pruzzo, Theresa Ballard, Francesco Papaleo

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.