The attentional set shifting task: a measure of cognitive flexibility in mice.
Cognitive impairment, particularly involving dysfunction of circuitry within the prefrontal cortex (PFC), represents a core feature of many neuropsychiatric and neurodevelopmental disorders, including depression, post-traumatic stress disorder, schizophrenia and autism spectrum disorder. Deficits in cognitive function also represent the most difficult symptom domain to successfully treat, as serotonin reuptake inhibitors and tricyclic antidepressants have only modest effects. Functional neuroimaging studies and postmortem analysis of human brain tissue implicate the PFC as being a primary region of dysregulation in patients with these disorders. However, preclinical behavioral assays used to assess these deficits in mouse models which can be readily manipulated genetically and could provide the basis for studies of new treatment avenues have been underutilized. Here we describe the adaptation of a behavioral assay, the attentional set shifting task (AST), to be performed in mice to assess prefrontal cortex mediated cognitive deficits. The neural circuits underlying behavior during the AST are highly conserved across humans, nonhuman primates and rodents, providing excellent face, construct and predictive validity.
Department of Pharmacology, University of Texas Health Science Center at San Antonio.
Jillian M
JM
Heisler
Department of Pharmacology, University of Texas Health Science Center at San Antonio.
Juan
J
Morales
Department of Pharmacology, University of Texas Health Science Center at San Antonio.
Jennifer J
JJ
Donegan
Department of Pharmacology, University of Texas Health Science Center at San Antonio.
Julianne D
JD
Jett
Department of Pharmacology, University of Texas Health Science Center at San Antonio.
Laney
L
Redus
Department of Pharmacology, University of Texas Health Science Center at San Antonio; Audie L. Murphy VA Hospital, South Texas Veteran's Health Care System; oconnorj@uthscsa.edu.
Jason C
JC
O'Connor
D000818:Animals; D001288:Attention; D001522:Behavior, Animal / Q000502:physiology; D003071:Cognition / Q000502:physiology; D003072:Cognition Disorders / Q000175:diagnosis / Q000503:physiopathology*; D004193:Discrimination Learning; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017397:Prefrontal Cortex / Q000503:physiopathology*; D012559:Schizophrenia / Q000503:physiopathology; D013313:Stress Disorders, Post-Traumatic / Q000503:physiopathology; D013647:Task Performance and Analysis