Enhanced fear limits behavioral flexibility in Shank2-deficient mice

Area of Science:

• Neuroscience
• Behavioral Science
• Genetics

Background:

• Autism spectrum disorder (ASD) is characterized by repetitive and restrictive behaviors, potentially stemming from cognitive or behavioral inflexibility.
• Shank2-knockout mice, a common model for ASD, are used to investigate the underlying mechanisms of these behavioral traits.

Purpose of the Study:

• To investigate behavioral flexibility in Shank2-knockout mice, an animal model of autism spectrum disorder (ASD).
• To determine if and how behavioral flexibility is compromised in this ASD model.

Main Methods:

• Utilized reversal learning in a probabilistic classical trace conditioning paradigm to compare Shank2-knockout mice with wild-type littermates.
• Assessed behavioral performance using appetitive (water) and aversive (air puff) stimuli, and measured air puff-induced eye closure responses.

Main Results:

• Male Shank2-knockout mice exhibited impaired reversal learning with a strong air puff, suggesting enhanced fear may underlie this deficit.
• Female Shank2-knockout mice did not show the same impairment, indicating sex-specific effects.
• Reversal learning was intact in males when the air puff was mild or absent, supporting the role of fear.

Conclusions:

• Enhanced fear significantly suppresses reversal learning in Shank2-knockout mice, despite intact learning of cue-outcome contingencies.
• Abnormal emotional responses, particularly fear, may critically limit behavioral flexibility in individuals with ASD.