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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 test—experimental design. D—Demonstrators, O—Observers, are housed in fixed, same-strain pairs for at least 3 weeks prior to the onset of the test. After 2 weeks of habituation to being moved to the experimental room, handling by the experimenter and 10 min separation, on test day Demonstrators from the stressed group (D s) are exposed to 10 × 0.6 mA shocks an then reunited with Observers (O s). In the non-stressed group (D and O ns) the Demonstrators are placed in the conditioning chamber but no shocks are applied.
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Figure 1: Transfer of Emotional Information test—experimental design. D—Demonstrators, O—Observers, are housed in fixed, same-strain pairs for at least 3 weeks prior to the onset of the test. After 2 weeks of habituation to being moved to the experimental room, handling by the experimenter and 10 min separation, on test day Demonstrators from the stressed group (D s) are exposed to 10 × 0.6 mA shocks an then reunited with Observers (O s). In the non-stressed group (D and O ns) the Demonstrators are placed in the conditioning chamber but no shocks are applied.

Mentions: The animals bred and housed at the animal facilities of the Faculty of Biology, University of Warsaw, Poland (BTBR n = 24, B6 n = 28) were transferred to the Animal House of the Nencki Institute of Experimental Biology, Warsaw, Poland approximately 3 weeks before the onset of the experiment. The housing conditions were identical to those at the Faculty of Biology, University of Warsaw, Poland with one difference. Upon transfer the animals were separated into weight-matched pairs and housed in these pairs, in standard (35 × 17 × 13 cm) macrolon cages until the end of the experiment. After about a week of acclimatization, the habituation to the experimental room and handling by the experimenters started. During that time (10 days) the animals were transported to the experimental room and briefly separated (10 min) daily. By marking the tail of the animal taken away from the home cage we ensured that the same animal was removed from the home cage on every occasion. Later this animal will serve as a Demonstrator. The other animal (Observer) was left undisturbed in the home cage throughout the entire habituation. On the testing day the Demonstrator was placed in the fear conditioning apparatus (MED-Associates) and either left there undisturbed for 10 min or exposed to ten 0.6 mA footshocks. After the return of the Demonstrator to the home cage the behavior and ultrasonic vocalization of both animals (the Demonstrator and the Observer, Figure 1) were recorded for 10 min with the use of a digital camera hung above the home cage and an ultrasonic microphone connected to the UltraSoundGate device (Avisoft, Germany).


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 test—experimental design. D—Demonstrators, O—Observers, are housed in fixed, same-strain pairs for at least 3 weeks prior to the onset of the test. After 2 weeks of habituation to being moved to the experimental room, handling by the experimenter and 10 min separation, on test day Demonstrators from the stressed group (D s) are exposed to 10 × 0.6 mA shocks an then reunited with Observers (O s). In the non-stressed group (D and O ns) the Demonstrators are placed in the conditioning chamber but no shocks are applied.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 1: Transfer of Emotional Information test—experimental design. D—Demonstrators, O—Observers, are housed in fixed, same-strain pairs for at least 3 weeks prior to the onset of the test. After 2 weeks of habituation to being moved to the experimental room, handling by the experimenter and 10 min separation, on test day Demonstrators from the stressed group (D s) are exposed to 10 × 0.6 mA shocks an then reunited with Observers (O s). In the non-stressed group (D and O ns) the Demonstrators are placed in the conditioning chamber but no shocks are applied.
Mentions: The animals bred and housed at the animal facilities of the Faculty of Biology, University of Warsaw, Poland (BTBR n = 24, B6 n = 28) were transferred to the Animal House of the Nencki Institute of Experimental Biology, Warsaw, Poland approximately 3 weeks before the onset of the experiment. The housing conditions were identical to those at the Faculty of Biology, University of Warsaw, Poland with one difference. Upon transfer the animals were separated into weight-matched pairs and housed in these pairs, in standard (35 × 17 × 13 cm) macrolon cages until the end of the experiment. After about a week of acclimatization, the habituation to the experimental room and handling by the experimenters started. During that time (10 days) the animals were transported to the experimental room and briefly separated (10 min) daily. By marking the tail of the animal taken away from the home cage we ensured that the same animal was removed from the home cage on every occasion. Later this animal will serve as a Demonstrator. The other animal (Observer) was left undisturbed in the home cage throughout the entire habituation. On the testing day the Demonstrator was placed in the fear conditioning apparatus (MED-Associates) and either left there undisturbed for 10 min or exposed to ten 0.6 mA footshocks. After the return of the Demonstrator to the home cage the behavior and ultrasonic vocalization of both animals (the Demonstrator and the Observer, Figure 1) were recorded for 10 min with the use of a digital camera hung above the home cage and an ultrasonic microphone connected to the UltraSoundGate device (Avisoft, Germany).

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