Abnormal fear conditioning and amygdala processing in an animal model of autism

Kamila Markram; Tania Rinaldi; Deborah La Mendola; Carmen Sandi; Henry Markram; Tania Rinaldi Barkat

doi:10.1038/sj.npp.1301453

Abnormal fear conditioning and amygdala processing in an animal model of autism

Kamila Markram, Tania Rinaldi, Deborah La Mendola, Carmen Sandi, Henry Markram, Tania Rinaldi Barkat

211 Citations (Scopus)

Abstract

A core feature of autism spectrum disorders is the impairment in social interactions. Among other brain regions, a deficit in amygdala processing has been suggested to underlie this impairment, but whether the amygdala is processing fear abnormally in autism, is yet not clear. We used the valproic acid (VPA) rat model of autism to (a) screen for autism-like symptoms in rats, (b) test for alterations in amygdala-dependent fear processing, and (c) evaluate neuronal reactivity and synaptic plasticity in the lateral amygdala by means of in vitro single-cell electrophysiological recordings. VPA-treated animals displayed several symptoms common to autism, among them impaired social interactions and increased repetitive behaviors. Furthermore, VPA-treated rats were more anxious and exhibited abnormally high and longer lasting fear memories, which were overgeneralized and harder to extinguish. On the cellular level, the amygdala was hyperreactive to electrical stimulation and displayed boosted synaptic plasticity as well as a deficit in inhibition. We show for the first time enhanced, overgeneralized and resistant conditioned fear memories in an animal model of autism. Such hyperfear could be caused by the hyperreactivity and hyperplasticity found in the lateral amygdala, which may in turn be due to a deficit in the inhibitory system of the amygdala. We hypothesize an 'aversive world' syndrome that could, even if not a primary cause of the disorder itself, underlie some core symptoms in autism, such as impairments in social interactions and resistance to rehabilitation.

Original language	English
Journal	Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
Volume	33
Issue number	4
Pages (from-to)	901-12
Number of pages	12
DOIs	https://doi.org/10.1038/sj.npp.1301453
Publication status	Published - Mar 2008

Keywords

Amygdala
Analysis of Variance
Animals
Animals, Newborn
Anticonvulsants
Autistic Disorder
Behavior, Animal
Conditioning (Psychology)
Disease Models, Animal
Electric Stimulation
Embryo, Mammalian
Fear
Female
Interpersonal Relations
Long-Term Potentiation
Male
Maze Learning
Neurons
Patch-Clamp Techniques
Pregnancy
Rats
Rats, Wistar
Valproic Acid

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10.1038/sj.npp.1301453

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Abnormal fear conditioning and amygdala processing in an animal model of autism. / Markram, Kamila; Rinaldi, Tania; La Mendola, Deborah et al.

In: Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, Vol. 33, No. 4, 03.2008, p. 901-12.

Research output: Contribution to journal › Journal article › Research › peer-review

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abstract = "A core feature of autism spectrum disorders is the impairment in social interactions. Among other brain regions, a deficit in amygdala processing has been suggested to underlie this impairment, but whether the amygdala is processing fear abnormally in autism, is yet not clear. We used the valproic acid (VPA) rat model of autism to (a) screen for autism-like symptoms in rats, (b) test for alterations in amygdala-dependent fear processing, and (c) evaluate neuronal reactivity and synaptic plasticity in the lateral amygdala by means of in vitro single-cell electrophysiological recordings. VPA-treated animals displayed several symptoms common to autism, among them impaired social interactions and increased repetitive behaviors. Furthermore, VPA-treated rats were more anxious and exhibited abnormally high and longer lasting fear memories, which were overgeneralized and harder to extinguish. On the cellular level, the amygdala was hyperreactive to electrical stimulation and displayed boosted synaptic plasticity as well as a deficit in inhibition. We show for the first time enhanced, overgeneralized and resistant conditioned fear memories in an animal model of autism. Such hyperfear could be caused by the hyperreactivity and hyperplasticity found in the lateral amygdala, which may in turn be due to a deficit in the inhibitory system of the amygdala. We hypothesize an 'aversive world' syndrome that could, even if not a primary cause of the disorder itself, underlie some core symptoms in autism, such as impairments in social interactions and resistance to rehabilitation.",

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author = "Kamila Markram and Tania Rinaldi and {La Mendola}, Deborah and Carmen Sandi and Henry Markram and {Rinaldi Barkat}, Tania",

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AB - A core feature of autism spectrum disorders is the impairment in social interactions. Among other brain regions, a deficit in amygdala processing has been suggested to underlie this impairment, but whether the amygdala is processing fear abnormally in autism, is yet not clear. We used the valproic acid (VPA) rat model of autism to (a) screen for autism-like symptoms in rats, (b) test for alterations in amygdala-dependent fear processing, and (c) evaluate neuronal reactivity and synaptic plasticity in the lateral amygdala by means of in vitro single-cell electrophysiological recordings. VPA-treated animals displayed several symptoms common to autism, among them impaired social interactions and increased repetitive behaviors. Furthermore, VPA-treated rats were more anxious and exhibited abnormally high and longer lasting fear memories, which were overgeneralized and harder to extinguish. On the cellular level, the amygdala was hyperreactive to electrical stimulation and displayed boosted synaptic plasticity as well as a deficit in inhibition. We show for the first time enhanced, overgeneralized and resistant conditioned fear memories in an animal model of autism. Such hyperfear could be caused by the hyperreactivity and hyperplasticity found in the lateral amygdala, which may in turn be due to a deficit in the inhibitory system of the amygdala. We hypothesize an 'aversive world' syndrome that could, even if not a primary cause of the disorder itself, underlie some core symptoms in autism, such as impairments in social interactions and resistance to rehabilitation.

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KW - Electric Stimulation

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KW - Patch-Clamp Techniques

KW - Pregnancy

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KW - Rats, Wistar

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SP - 901

EP - 912

JO - Neuropsychopharmacology

JF - Neuropsychopharmacology

IS - 4

ER -

Abnormal fear conditioning and amygdala processing in an animal model of autism

Abstract

Keywords

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