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Reduced social interaction, behavioural flexibility and BDNF signalling in the BTBR T+ tf/J strain, a mouse model of autism.
Behav Brain Res 2013; 251:35-40BB

Abstract

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.

Authors+Show Affiliations

Department of Cell Biology and Neuroscience, Istituto Superiore di Sanità, Viale Regina Elena, 299 I-00161 Rome, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23270976

Citation

Scattoni, M L., et al. "Reduced Social Interaction, Behavioural Flexibility and BDNF Signalling in the BTBR T+ tf/J Strain, a Mouse Model of Autism." Behavioural Brain Research, vol. 251, 2013, pp. 35-40.
Scattoni ML, Martire A, Cartocci G, et al. Reduced social interaction, behavioural flexibility and BDNF signalling in the BTBR T+ tf/J strain, a mouse model of autism. Behav Brain Res. 2013;251:35-40.
Scattoni, M. L., Martire, A., Cartocci, G., Ferrante, A., & Ricceri, L. (2013). Reduced social interaction, behavioural flexibility and BDNF signalling in the BTBR T+ tf/J strain, a mouse model of autism. Behavioural Brain Research, 251, pp. 35-40. doi:10.1016/j.bbr.2012.12.028.
Scattoni ML, et al. Reduced Social Interaction, Behavioural Flexibility and BDNF Signalling in the BTBR T+ tf/J Strain, a Mouse Model of Autism. Behav Brain Res. 2013 Aug 15;251:35-40. PubMed PMID: 23270976.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Reduced social interaction, behavioural flexibility and BDNF signalling in the BTBR T+ tf/J strain, a mouse model of autism. AU - Scattoni,M L, AU - Martire,A, AU - Cartocci,G, AU - Ferrante,A, AU - Ricceri,L, Y1 - 2012/12/25/ PY - 2012/08/01/received PY - 2012/12/07/revised PY - 2012/12/17/accepted PY - 2012/12/29/entrez PY - 2012/12/29/pubmed PY - 2013/10/22/medline KW - 5HTT KW - ACSF KW - ASD KW - B6 KW - BDNF-induced potentiation KW - BTBR KW - BTBR T+tf/J KW - C57BL6/j KW - Object exploration KW - PND KW - TrkB KW - Ultrasonic vocalizations KW - artificial cerebrospinal fluid KW - autism spectrum disorders KW - postnatal day KW - serotonin transporter KW - trkB KW - tyrosine receptor kinase B SP - 35 EP - 40 JF - Behavioural brain research JO - Behav. Brain Res. VL - 251 N2 - 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. SN - 1872-7549 UR - https://www.unboundmedicine.com/medline/citation/23270976/Reduced_social_interaction_behavioural_flexibility_and_BDNF_signalling_in_the_BTBR_T+_tf/J_strain_a_mouse_model_of_autism_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0166-4328(12)00810-8 DB - PRIME DP - Unbound Medicine ER -