Autism is a neurodevelopmental disorder characterized by social and 
communication impairments and repetitive behaviours. The inbred BTBR T+ tf/J 
(BTBR) strain, a putative mouse model of autism, exhibits lower social 
interactions, higher repetitive self-grooming levels and unusual pattern of 
vocalizations as compared to C57BL/6J strain. First aim of the present study was 
to evaluate at adolescence (postnatal days 30-35) male BTBR and C57BL/6J 
performances in two different tasks involving either investigation of social 
cues (same strain partners) or non social ones (inanimate objects). In the 
social interaction test, 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. By contrast, no strain differences were 
detected in object investigations. Second aim of the study was to evaluate adult 
male BTBR and C57BL/6J performances in a fear conditioning task. Strain 
differences were evident during contextual retest: these strain differences 
primarily suggested a lack of behavioural flexibility in BTBR mice (i.e., 
realizing the occurrence of changes in the experimental paradigm). Subsequent 
electrophysiological analysis in hippocampal slices from adult BTBR and C57BL/6J 
mice revealed a significant reduction of Brain Derived Neurotrophic Factor 
(BDNF)-induced potentiation of synaptic transmission in BTBR mice. BDNF and 
tyrosine kinase B (TrkB) protein levels measured in the hippocampal region were 
also lower in BTBR as compared to C57BL/6J mice. These data confirm the presence 
of low levels of direct interaction with social stimuli in BTBR mice at 
adolescence, in the absence of any strain difference as for investigation of 
physical objects. At adulthood in BTBR mice clear signs of behavioural 
inflexibility were evident 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.