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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

Summary of c-Fos protein expression patterns related to asocial behavior for: (A) c57BL/6J (B6) mice and BTBR T+Itpr3tf/J (BTBR) mice Observers exposed to a stressed cagemate in the Transfer of Emotional Information test and (B) B6 and BTBR mice exposed to a social stimulus (unfamiliar B6 male) during Social proximity test.
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Figure 5: Summary of c-Fos protein expression patterns related to asocial behavior for: (A) c57BL/6J (B6) mice and BTBR T+Itpr3tf/J (BTBR) mice Observers exposed to a stressed cagemate in the Transfer of Emotional Information test and (B) B6 and BTBR mice exposed to a social stimulus (unfamiliar B6 male) during Social proximity test.

Mentions: In the Transfer of Emotional Information test, stressed B6 Demonstrator mice showed increased c-Fos expression in the medial prefrontal cortex (both PrL and IL parts), the amygdala (basolateral, central medial, central lateral, and medial nuclei) and the CA1 field of the ventral hippocampus. B6 Observers exposed to a stressed Demonstrator also showed increases in the number of c-Fos positive nuclei in the PrL and IL medial prefrontal cortex, basolateral nucleus of amygdala and the CA3 field of the ventral hippocampus. In contrast, the exposure to neither direct stress (experienced by the Demonstrators) nor remote stress (experienced by the Observers) produced an increase in c-Fos protein expression in any of the brain regions analyzed in the BTBR mice (Figure 5A). Instead, such behavioral challenge decreased c-Fos protein expression in the lateral, medial, and cortical nuclei of the amygdala and in the CA1 field and the DG of the ventral hippocampus in BTBR Demonstrators as well as in the CA1 field of the ventral hippocampus in BTBR Observers. Whether lower c-Fos expression in these amygdalar and hippocampal structures in stressed BTBR Demonstrators is linked to their inability to learn the context associated with aversive, unconditioned stimuli during fear conditioning (MacPherson et al., 2008; Scattoni et al., 2013; Stapley et al., 2013) is an intriguing possibility. In sum, the comparison of results for the two strains indicates that BTBR mice showed a widespread decrease, opposite to that observed in the B6 strain, of c-Fos protein expression during direct or transferred stress.


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)

Summary of c-Fos protein expression patterns related to asocial behavior for: (A) c57BL/6J (B6) mice and BTBR T+Itpr3tf/J (BTBR) mice Observers exposed to a stressed cagemate in the Transfer of Emotional Information test and (B) B6 and BTBR mice exposed to a social stimulus (unfamiliar B6 male) during Social proximity test.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 5: Summary of c-Fos protein expression patterns related to asocial behavior for: (A) c57BL/6J (B6) mice and BTBR T+Itpr3tf/J (BTBR) mice Observers exposed to a stressed cagemate in the Transfer of Emotional Information test and (B) B6 and BTBR mice exposed to a social stimulus (unfamiliar B6 male) during Social proximity test.
Mentions: In the Transfer of Emotional Information test, stressed B6 Demonstrator mice showed increased c-Fos expression in the medial prefrontal cortex (both PrL and IL parts), the amygdala (basolateral, central medial, central lateral, and medial nuclei) and the CA1 field of the ventral hippocampus. B6 Observers exposed to a stressed Demonstrator also showed increases in the number of c-Fos positive nuclei in the PrL and IL medial prefrontal cortex, basolateral nucleus of amygdala and the CA3 field of the ventral hippocampus. In contrast, the exposure to neither direct stress (experienced by the Demonstrators) nor remote stress (experienced by the Observers) produced an increase in c-Fos protein expression in any of the brain regions analyzed in the BTBR mice (Figure 5A). Instead, such behavioral challenge decreased c-Fos protein expression in the lateral, medial, and cortical nuclei of the amygdala and in the CA1 field and the DG of the ventral hippocampus in BTBR Demonstrators as well as in the CA1 field of the ventral hippocampus in BTBR Observers. Whether lower c-Fos expression in these amygdalar and hippocampal structures in stressed BTBR Demonstrators is linked to their inability to learn the context associated with aversive, unconditioned stimuli during fear conditioning (MacPherson et al., 2008; Scattoni et al., 2013; Stapley et al., 2013) is an intriguing possibility. In sum, the comparison of results for the two strains indicates that BTBR mice showed a widespread decrease, opposite to that observed in the B6 strain, of c-Fos protein expression during direct or transferred stress.

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