Transgenic expression of the FTDP-17 tauV337M mutation in brain dissociates components of executive function in mice

• Published in: Neurobiology of learning and memory Vol. 104; pp. 73 - 81
• Main Authors: Reichelt, A.C., Killcross, S., Wilkinson, L.S., Humby, T., Good, M.A.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01.09.2013; Elsevier; Elsevier BV
• Subjects: Acoustic Stimulation; Adult and adolescent clinical studies; Animals; Behavioral psychophysiology; Biological and medical sciences; Chromosomes, Human, Pair 17; Cognition & reasoning; Cognitive control; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Dementia; Disease Models, Animal; Executive Function - physiology; Frontotemporal dementia; Frontotemporal Dementia - genetics; Frontotemporal Dementia - physiopathology; Fundamental and applied biological sciences. Psychology; Gene expression; Humans; Instrumental responding; Male; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Transgenic; Mutation; Neurobiology; Neurology; Organic mental disorders. Neuropsychology; Photic Stimulation; Prefrontal cortex; Prefrontal Cortex - physiology; Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Psychopathology. Psychiatry; Response conflict; Tau; tau Proteins - genetics; tau Proteins - metabolism; Instrumental responding; Tau; Prefrontal cortex; Frontotemporal dementia; Response conflict; Cognitive control; Nervous system diseases; Executive function; Rodentia; Central nervous system; Transgenic animal; Cerebral disorder; Encephalon; Vertebrata; Mammalia; Tau protein; Mouse; Conflict; Central nervous system disease; Degenerative disease; Mutation
• ISSN: 1074-7427; 1095-9564
• DOI: 10.1016/j.nlm.2013.05.005

•A mouse response conflict task was used that is analogous to the human Stroop task.•Performance was impaired by prefrontal cortex lesions in mice.•The tauV337M mutation – a model of the frontotemporal dementia had no effect.•The tauV337M mice were impaired at goal-directed responding following devaluation.•TauV337M mutation may disrupt structures involved in goal-directed actions. Frontotemporal lobe dementia (FTD) is a heterogeneous range of disorders, a subset of which arise from fully penetrant, autosomal dominant point mutations in the gene coding for the microtubule associated protein tau. These genetic tauopathies are associated with complex behavioural/cognitive disturbances, including compromised executive function. In the present study, we modelled the effects of the FTD with Parkinsonism linked to chromosome 17 (FTDP-17) tauV337M mutation (known as the Seattle Family A mutation) expressed in mice on executive processes using a novel murine analogue of the Stroop task. Employing biconditional discrimination procedures, Experiment 1 showed that normal mice, but not mice with excitotoxic lesions of the medial prefrontal cortex, were able to use context cues to resolve response conflict generated by incongruent stimulus compounds. In contrast to predictions, response conflict resolution was not disrupted by the tauV337M mutation (Experiment 2). However, while context appropriate actions were goal-directed in wild-type mice, performance of tauV337M mice was not goal-directed (Experiment 3). The results indicate that the tauV337M mutation in mice disrupts, selectively, a subset of processes related to executive function.