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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 increase of c-Fos protein expression in response to direct or socially transmitted stress in: (A) prelimbic cortex, (B) infralimbic cortex (IL), (C) basal/basolateral nucleus (BLA) of the amygdala, (D) LA of the amygdala, (E) lateral part of the central nucleus of the amygdala, (F) medial part of the central nucleus of the amygdala, (G) medial nucleus of the amygdala, (H) cortical nucleus of the amygdala, (I) CA1 field of the ventral hippocampus, (J) CA3 field of the ventral hippocampus, (K) dentate gyrus (DG) of the ventral hippocampus. D—Demonstrators, O—Observers. Light gray bars represent non-stressed pairs, dark gray bars represent stressed pairs. Values presented as mean. Error bars represent SEM. #p < 0.05, ##p < 0.01, ###p < 0.001 for within strain comparisons, and *p < 0.05, **p < 0.01 for between strain comparisons.
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Figure 3: Transfer of Emotional Information—unlike c57BL/6J (B6) mice, BTBR T+Itpr3tf/J (BTBR) mice do not display increase of c-Fos protein expression in response to direct or socially transmitted stress in: (A) prelimbic cortex, (B) infralimbic cortex (IL), (C) basal/basolateral nucleus (BLA) of the amygdala, (D) LA of the amygdala, (E) lateral part of the central nucleus of the amygdala, (F) medial part of the central nucleus of the amygdala, (G) medial nucleus of the amygdala, (H) cortical nucleus of the amygdala, (I) CA1 field of the ventral hippocampus, (J) CA3 field of the ventral hippocampus, (K) dentate gyrus (DG) of the ventral hippocampus. D—Demonstrators, O—Observers. Light gray bars represent non-stressed pairs, dark gray bars represent stressed pairs. Values presented as mean. Error bars represent SEM. #p < 0.05, ##p < 0.01, ###p < 0.001 for within strain comparisons, and *p < 0.05, **p < 0.01 for between strain comparisons.

Mentions: The expression of c-Fos protein in the prelimbic cortex (PrL) was analyzed for between strain (B6 and BTBR) and between conditions (non-stressed vs. stressed Demonstrator in a given pair) separately. In B6 mice both the stressed Demonstrators and Observers exhibit an increase in c-Fos protein expression, as compared with their non-stressed peers (p < 0.01, Figure 3A). No such reaction was observed in BTBR mice. Moreover, upon stressing of the Demonstrators, the B6 mice (both the Demonstrators and Observers) displayed much higher expression of c-Fos protein than BTBR mice (both p < 0.01, Figure 3A). There was also an initial difference between non-stressed B6 and BTBR Observers, with the latter showing fewer c-Fos positive nuclei in the PrL region (p < 0.05, Figure 3A).


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 increase of c-Fos protein expression in response to direct or socially transmitted stress in: (A) prelimbic cortex, (B) infralimbic cortex (IL), (C) basal/basolateral nucleus (BLA) of the amygdala, (D) LA of the amygdala, (E) lateral part of the central nucleus of the amygdala, (F) medial part of the central nucleus of the amygdala, (G) medial nucleus of the amygdala, (H) cortical nucleus of the amygdala, (I) CA1 field of the ventral hippocampus, (J) CA3 field of the ventral hippocampus, (K) dentate gyrus (DG) of the ventral hippocampus. D—Demonstrators, O—Observers. Light gray bars represent non-stressed pairs, dark gray bars represent stressed pairs. Values presented as mean. Error bars represent SEM. #p < 0.05, ##p < 0.01, ###p < 0.001 for within strain comparisons, and *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 3: Transfer of Emotional Information—unlike c57BL/6J (B6) mice, BTBR T+Itpr3tf/J (BTBR) mice do not display increase of c-Fos protein expression in response to direct or socially transmitted stress in: (A) prelimbic cortex, (B) infralimbic cortex (IL), (C) basal/basolateral nucleus (BLA) of the amygdala, (D) LA of the amygdala, (E) lateral part of the central nucleus of the amygdala, (F) medial part of the central nucleus of the amygdala, (G) medial nucleus of the amygdala, (H) cortical nucleus of the amygdala, (I) CA1 field of the ventral hippocampus, (J) CA3 field of the ventral hippocampus, (K) dentate gyrus (DG) of the ventral hippocampus. D—Demonstrators, O—Observers. Light gray bars represent non-stressed pairs, dark gray bars represent stressed pairs. Values presented as mean. Error bars represent SEM. #p < 0.05, ##p < 0.01, ###p < 0.001 for within strain comparisons, and *p < 0.05, **p < 0.01 for between strain comparisons.
Mentions: The expression of c-Fos protein in the prelimbic cortex (PrL) was analyzed for between strain (B6 and BTBR) and between conditions (non-stressed vs. stressed Demonstrator in a given pair) separately. In B6 mice both the stressed Demonstrators and Observers exhibit an increase in c-Fos protein expression, as compared with their non-stressed peers (p < 0.01, Figure 3A). No such reaction was observed in BTBR mice. Moreover, upon stressing of the Demonstrators, the B6 mice (both the Demonstrators and Observers) displayed much higher expression of c-Fos protein than BTBR mice (both p < 0.01, Figure 3A). There was also an initial difference between non-stressed B6 and BTBR Observers, with the latter showing fewer c-Fos positive nuclei in the PrL region (p < 0.05, Figure 3A).

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