The occurrence of a deficit in contextual fear extinction in adult amyloid-over-expressing TASTPM mice is independent of the strength of conditioning but can be prevented by mild novel cage stress

• Published in: Behavioural brain research Vol. 200; no. 1; pp. 83 - 90
• Main Authors: Rattray, Ivan, Scullion, Gillian A., Soulby, Andrew, Kendall, David A., Pardon, Marie-Christine
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier B.V 08-06-2009; Elsevier
• Subjects: Adult and adolescent clinical studies; Age Factors; Alzheimer's disease; Amyloid; Amyloid beta-Peptides - genetics; Amyloid beta-Peptides - metabolism; Amyloid beta-Protein Precursor - genetics; Analysis of Variance; Animals; Behavioral psychophysiology; Biological and medical sciences; Body Weight; Conditioning, Classical - physiology; Contextual fear-conditioning; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Disease Models, Animal; Electroshock - adverse effects; Exploratory Behavior - physiology; Extinction; Extinction, Psychological - physiology; Fear; Freezing Reaction, Cataleptic - physiology; Fundamental and applied biological sciences. Psychology; Humans; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Transgenic; Motor Activity - genetics; Mutation - genetics; Neurology; Organic mental disorders. Neuropsychology; Presenilin-1 - genetics; Psychological stress; Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Psychopathology. Psychiatry; Reconsolidation; Stress, Psychological - genetics; Stress, Psychological - physiopathology; Transgenic mice; Psychological stress; Reconsolidation; Extinction; Transgenic mice; Amyloid; Alzheimer's disease; Contextual fear-conditioning; Affect affectivity; Alzheimer disease; Transgenic animal; Gene overexpression; Adult; Degenerative disease; Conditioning; Human; Nervous system diseases; Rodentia; Emotion emotionality; Stress; Cerebral disorder; Fear; Vertebrata; Mammalia; Mouse; Central nervous system disease; Strength
• ISSN: 0166-4328; 1872-7549
• DOI: 10.1016/j.bbr.2008.12.037

In the amyloid over-expressing TASTPM mouse model of Alzheimer's disease, impaired contextual fear memory occurs early, and is preceded, at 4 months of age, by a deficit in extinction of contextual fear that is resistant to improvement by repeated mild novel cage stress. The first aim of this study was thus to establish whether the extinction deficit could be prevented if the novel cage procedure was applied prior to its onset. The second aim was to establish whether the occurrence of the extinction deficit was dependent on the robustness of the conditioning protocol. We first compared 3-month-old wild-type and TASTPM mice for acquisition, retention and extinction of contextual fear and then, looked at the impact of 5 weeks of novel cage stress (4
×
1
h/week) applied from 3 months onwards, on age-related changes in these behaviours evaluated at 4.5 months of age. In another experiment, we compared 4-month-old TASTPM and wild-type mice for the impact of a 2 and 5-pairing conditioning procedure on the three phases of contextual fear conditioning. In 4.5-month-old TASTPM mice, the deficit in extinction was alleviated by repeated novel cage stress, applied from prior to its onset at 3 months. At 4 months of age, the occurrence of an extinction deficit was independent of the strength of the conditioning procedure, in TASTPM mice, which even showed an increase in aversive memory under the 2-pairing condition. The robust early impairment in the extinction of contextual fear seen in adult TASTPM mice suggests that a deficit in cognitive flexibility is the first sign of behavioural pathology in this model of Alzheimer's disease.