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Reduced Social Interaction, Behavioural Flexibility and BDNF Signalling in the BTBR T+TF/J Strain, a Mouse Model of Autism

Thursday, 2 May 2013: 09:00-13:00
Banquet Hall (Kursaal Centre)
M. L. Scattoni1, A. Martire2, A. Ferrante2, G. Cartocci1 and L. Ricceri3, (1)Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy, (2)Therapeutic Research and Medicine Evaluation, Istituto Superiore di Sanità, Rome, Italy, (3)Dept. Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy
Background: The inbred BTBR T+tf/J (BTBR) strain, a putative mouse model of autism, exhibits low levels of social interactions, high repetitive self-grooming levels and unusual pattern of vocalizations when compared to other mouse strains (e.g. the commonly used C57BL/6J strain).

Objectives: In male BTBR and C57BL/6J mice assessment of: i) responsiveness to social and non social cues at adolescence;  ii) adult learning and memory of a conditioned fear response; iii)  status of BDNF signalling in the hippocampus.

 Methods: i) in BTBR and C57BL/6J adolescent mice (30-35-day old) two behavioural tasks involving either social investigation (including evaluation of ultrasonic vocalization rates) in the presence of same strain partner or investigation of inanimate objects; ii) in BTBR and C57BL/6J adult mice fear conditioning test to evaluate learning, memory (and within session extinction) of a fear response; iii) Brain Derived Neurotrophic Factor (BDNF)-induced potentiation in hippocampal slices to evaluate synaptic plasticity, ELISA and western Blot to evaluate protein levels of BDNF and its receptor tyrosine kinase (TrkB) in cortical and hippocampal regions.

 Results: BTBR mice showed a reduction of investigation of the social partner, due to a selective reduction of head sniffing, associated with a decrease in ultrasonic vocalizations. No strain differences were detected in object investigation. During fear conditioning, data from contextual retest indicate a BTBR deficit in extinction of the fear response. Subsequent electrophysiological analysis revealed a significant reduction of synaptic transmission in BTBR mice. BDNF and tyrosine kinase B (TrkB) protein levels measured in the hippocampal region were lower in BTBR as compared to C57BL/6J mice.

 Conclusions: These data confirm at adolescence the low levels of social interactions in the BTBR strain. At adulthood BTBR mice show a behavioural flexibility deficit (in extinction of the fear response), whereas both biochemical and electrophysiological data point to decreased BDNF signalling (likely due to a reduction in TrkB levels) in the hippocampus of this mouse strain, possibly related to the observed fear extinction deficit.

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