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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

Social Proximity test—BTBR T+Itpr3tf/J (BTBR) mice do not display prosocial behaviors towards c57BL/6J (B6) mice. (A) Number of nose-to-nose, nose-to-face, nose-to-tail, crawl under, crawl over, allogrooming, selfgrooming and upright posture episodes, (B) the duration of these behaviors. White bars represent c57BL/6J (B6) mice, gray bars represent BTBR T+Itpr3tf/J (BTBR) mice. Values presented as mean. Error bars represent SEM. *p < 0.05 and **p < 0.01 for between strain comparisons.
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Figure 4: Social Proximity test—BTBR T+Itpr3tf/J (BTBR) mice do not display prosocial behaviors towards c57BL/6J (B6) mice. (A) Number of nose-to-nose, nose-to-face, nose-to-tail, crawl under, crawl over, allogrooming, selfgrooming and upright posture episodes, (B) the duration of these behaviors. White bars represent c57BL/6J (B6) mice, gray bars represent BTBR T+Itpr3tf/J (BTBR) mice. Values presented as mean. Error bars represent SEM. *p < 0.05 and **p < 0.01 for between strain comparisons.

Mentions: During solitary exposure to the novel environment (the empty arena), BTBR mice groomed themselves more than the B6 mice (p < 0.01, data not shown). In the Social Proximity test, where social interactions were inevitable, the BTBR mice displayed a decreased number and amount of time spent on Nose-to-Face contacts, Allogrooming and the Upright postures (Figures 4A,B). The number of Selfgrooming bouts was slightly higher (n.s.) in B6 mice, but the bouts were significantly longer in BTBR mice (Figure 4B). The B6 mice also displayed a greater variety of other (non-social) types of behavior during the 10 min test, but the duration of these behaviors was similar in both mouse strains (data not shown).


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)

Social Proximity test—BTBR T+Itpr3tf/J (BTBR) mice do not display prosocial behaviors towards c57BL/6J (B6) mice. (A) Number of nose-to-nose, nose-to-face, nose-to-tail, crawl under, crawl over, allogrooming, selfgrooming and upright posture episodes, (B) the duration of these behaviors. White bars represent c57BL/6J (B6) mice, gray bars represent BTBR T+Itpr3tf/J (BTBR) mice. Values presented as mean. Error bars represent SEM. *p < 0.05 and **p < 0.01 for between strain comparisons.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 4: Social Proximity test—BTBR T+Itpr3tf/J (BTBR) mice do not display prosocial behaviors towards c57BL/6J (B6) mice. (A) Number of nose-to-nose, nose-to-face, nose-to-tail, crawl under, crawl over, allogrooming, selfgrooming and upright posture episodes, (B) the duration of these behaviors. White bars represent c57BL/6J (B6) mice, gray bars represent BTBR T+Itpr3tf/J (BTBR) mice. Values presented as mean. Error bars represent SEM. *p < 0.05 and **p < 0.01 for between strain comparisons.
Mentions: During solitary exposure to the novel environment (the empty arena), BTBR mice groomed themselves more than the B6 mice (p < 0.01, data not shown). In the Social Proximity test, where social interactions were inevitable, the BTBR mice displayed a decreased number and amount of time spent on Nose-to-Face contacts, Allogrooming and the Upright postures (Figures 4A,B). The number of Selfgrooming bouts was slightly higher (n.s.) in B6 mice, but the bouts were significantly longer in BTBR mice (Figure 4B). The B6 mice also displayed a greater variety of other (non-social) types of behavior during the 10 min test, but the duration of these behaviors was similar in both mouse strains (data not shown).

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