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Neuronal correlates of asocial behavior in a BTBR T (+) Itpr3(tf)/J mouse model of autism.

Meyza K, Nikolaev T, Kondrakiewicz K, Blanchard DC, Blanchard RJ, Knapska E - Front Behav Neurosci (2015)

Bottom Line: Patients diagnosed with ASD are often devoid of empathy and impaired in understanding other people's emotional perspective.The neuronal correlates of this impairment are not fully understood.However, after Social Proximity exposure we observed a strong increase in c-Fos expression in the CA3 field of the hippocampus and two hypothalamic regions of BTBR brains.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Emotions' Neurobiology, Department of Neurophysiology, Nencki Institute of Experimental Biology PAS Warsaw, Poland.

ABSTRACT
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized, in part, by an inability to adequately respond to social cues. Patients diagnosed with ASD are often devoid of empathy and impaired in understanding other people's emotional perspective. The neuronal correlates of this impairment are not fully understood. Replicating such a behavioral phenotype in a mouse model of autism would allow us insight into the neuronal background of the problem. Here we tested BTBR T(+)Itpr3(tf)/J (BTBR) and c57BL/6J (B6) mice in two behavioral paradigms: the Transfer of Emotional Information test and the Social Proximity test. In both tests BTBR mice displayed asocial behavior. We analyzed c-Fos protein expression in several brain regions after each of these tests, and found that, unlike B6 mice, BTBR mice react to a stressed cagemate exposure in the Transfer of Emotional Information test with no increase of c-Fos expression in either the prefrontal cortex or the amygdala. However, after Social Proximity exposure we observed a strong increase in c-Fos expression in the CA3 field of the hippocampus and two hypothalamic regions of BTBR brains. This response was accompanied by a strong activation of periaqueductal regions related to defensiveness, which suggests that BTBR mice find unavoidable social interaction highly aversive.

No MeSH data available.


Related in: MedlinePlus

Transfer of Emotional Information—unlike c57BL/6J (B6) mice, BTBR T+Itpr3tf/J (BTBR) mice do not display prosocial behaviors towards their stressed cagemates. (A) The frequency of behaviors displayed by Observer mice during first 10 min of reunion with either non-stressed or stressed Demonstrators, (B) Duration of these behaviors, (C) Frequency of digging performed by both non-stressed and stressed Demonstrators and Observers, (D) Duration of these digging episodes. White bars represent non-stressed c57BL/6J (B6) mice, dark gray bars represent stressed B6 mice, light gray bars represent non-stressed BTBR T+Itpr3tf/J (BTBR) mice and black bars represent stressed BTBR mice. Values presented as mean. Error bars represent SEM. #p < 0.05 for within strain comparisons, *p < 0.05, **p < 0.01, for between strain comparisons.
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Figure 2: Transfer of Emotional Information—unlike c57BL/6J (B6) mice, BTBR T+Itpr3tf/J (BTBR) mice do not display prosocial behaviors towards their stressed cagemates. (A) The frequency of behaviors displayed by Observer mice during first 10 min of reunion with either non-stressed or stressed Demonstrators, (B) Duration of these behaviors, (C) Frequency of digging performed by both non-stressed and stressed Demonstrators and Observers, (D) Duration of these digging episodes. White bars represent non-stressed c57BL/6J (B6) mice, dark gray bars represent stressed B6 mice, light gray bars represent non-stressed BTBR T+Itpr3tf/J (BTBR) mice and black bars represent stressed BTBR mice. Values presented as mean. Error bars represent SEM. #p < 0.05 for within strain comparisons, *p < 0.05, **p < 0.01, for between strain comparisons.

Mentions: In response to a stressed cagemate the B6 Observer mice displayed an increase in the number and duration of social contacts (p < 0.05, Figures 2A,B), with special emphasis on the number of nose-to-nose contacts (p < 0.05, Figure 2A). The number of nose-to-tail contacts was also elevated, but the increase did not reach significance (p < 0.08). The number of nose-to-nose contacts made by B6 Observers exposed to a stressed cagemate was higher than that made by their BTBR counterparts (p < 0.01, Figure 2A) Similarly, B6 Observers exposed to a stressed cagemate made more and longer nose-to-tail contacts than the BTBR Observers in the same situation (p < 0.01, Figures 2A,B). Moreover, upon exposure to a stressed cagemate, BTBR mice inhibited rather than increased nose-to-tail contacts (p < 0.05, Figure 2B).


Neuronal correlates of asocial behavior in a BTBR T (+) Itpr3(tf)/J mouse model of autism.

Meyza K, Nikolaev T, Kondrakiewicz K, Blanchard DC, Blanchard RJ, Knapska E - Front Behav Neurosci (2015)

Transfer of Emotional Information—unlike c57BL/6J (B6) mice, BTBR T+Itpr3tf/J (BTBR) mice do not display prosocial behaviors towards their stressed cagemates. (A) The frequency of behaviors displayed by Observer mice during first 10 min of reunion with either non-stressed or stressed Demonstrators, (B) Duration of these behaviors, (C) Frequency of digging performed by both non-stressed and stressed Demonstrators and Observers, (D) Duration of these digging episodes. White bars represent non-stressed c57BL/6J (B6) mice, dark gray bars represent stressed B6 mice, light gray bars represent non-stressed BTBR T+Itpr3tf/J (BTBR) mice and black bars represent stressed BTBR mice. Values presented as mean. Error bars represent SEM. #p < 0.05 for within strain comparisons, *p < 0.05, **p < 0.01, for between strain comparisons.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4526814&req=5

Figure 2: Transfer of Emotional Information—unlike c57BL/6J (B6) mice, BTBR T+Itpr3tf/J (BTBR) mice do not display prosocial behaviors towards their stressed cagemates. (A) The frequency of behaviors displayed by Observer mice during first 10 min of reunion with either non-stressed or stressed Demonstrators, (B) Duration of these behaviors, (C) Frequency of digging performed by both non-stressed and stressed Demonstrators and Observers, (D) Duration of these digging episodes. White bars represent non-stressed c57BL/6J (B6) mice, dark gray bars represent stressed B6 mice, light gray bars represent non-stressed BTBR T+Itpr3tf/J (BTBR) mice and black bars represent stressed BTBR mice. Values presented as mean. Error bars represent SEM. #p < 0.05 for within strain comparisons, *p < 0.05, **p < 0.01, for between strain comparisons.
Mentions: In response to a stressed cagemate the B6 Observer mice displayed an increase in the number and duration of social contacts (p < 0.05, Figures 2A,B), with special emphasis on the number of nose-to-nose contacts (p < 0.05, Figure 2A). The number of nose-to-tail contacts was also elevated, but the increase did not reach significance (p < 0.08). The number of nose-to-nose contacts made by B6 Observers exposed to a stressed cagemate was higher than that made by their BTBR counterparts (p < 0.01, Figure 2A) Similarly, B6 Observers exposed to a stressed cagemate made more and longer nose-to-tail contacts than the BTBR Observers in the same situation (p < 0.01, Figures 2A,B). Moreover, upon exposure to a stressed cagemate, BTBR mice inhibited rather than increased nose-to-tail contacts (p < 0.05, Figure 2B).

Bottom Line: Patients diagnosed with ASD are often devoid of empathy and impaired in understanding other people's emotional perspective.The neuronal correlates of this impairment are not fully understood.However, after Social Proximity exposure we observed a strong increase in c-Fos expression in the CA3 field of the hippocampus and two hypothalamic regions of BTBR brains.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Emotions' Neurobiology, Department of Neurophysiology, Nencki Institute of Experimental Biology PAS Warsaw, Poland.

ABSTRACT
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized, in part, by an inability to adequately respond to social cues. Patients diagnosed with ASD are often devoid of empathy and impaired in understanding other people's emotional perspective. The neuronal correlates of this impairment are not fully understood. Replicating such a behavioral phenotype in a mouse model of autism would allow us insight into the neuronal background of the problem. Here we tested BTBR T(+)Itpr3(tf)/J (BTBR) and c57BL/6J (B6) mice in two behavioral paradigms: the Transfer of Emotional Information test and the Social Proximity test. In both tests BTBR mice displayed asocial behavior. We analyzed c-Fos protein expression in several brain regions after each of these tests, and found that, unlike B6 mice, BTBR mice react to a stressed cagemate exposure in the Transfer of Emotional Information test with no increase of c-Fos expression in either the prefrontal cortex or the amygdala. However, after Social Proximity exposure we observed a strong increase in c-Fos expression in the CA3 field of the hippocampus and two hypothalamic regions of BTBR brains. This response was accompanied by a strong activation of periaqueductal regions related to defensiveness, which suggests that BTBR mice find unavoidable social interaction highly aversive.

No MeSH data available.


Related in: MedlinePlus