Odor Experience Stabilizes Glomerular Output Representations in Two Mouse Models of Autism

Area of Science:

• Neuroscience
• Autism Spectrum Disorder Research
• Sensory Processing

Background:

• Novel stimuli can be stressful for individuals with autism spectrum disorders (ASD).
• Repeated exposure can reduce the impact of novel stimuli.
• Mouse models of ASD, including Cntnap2-/- and Shank3B+/-, exhibit deficits in recognizing target odors when novel background odors are present.

Purpose of the Study:

• To investigate the neural mechanisms underlying behavioral improvements in odor recognition following training in ASD mouse models.
• To compare the neural responses to odors in ASD models versus wild-type (WT) mice before and after training.

Main Methods:

• Utilized wide-field calcium imaging to monitor olfactory bulb activity in Cntnap2-/- and Shank3B+/- mice, as well as WT mice.
• Assessed behavioral performance in odor recognition tasks.
• Analyzed neural discriminability and trial-to-trial variability of odor responses.

Main Results:

• Training enhanced both behavioral performance and neural discriminability of odor mixtures in all mouse groups.
• Naive ASD model mice exhibited higher neural variability than WT mice; training stabilized these responses.
• Training led to a significant reduction in olfactory bulb responses to background odors specifically in ASD models, not WT mice.

Conclusions:

• Despite comparable behavioral improvements to WT mice, Cntnap2-/- and Shank3B+/- mice utilize a distinct neural strategy.
• ASD models achieve enhanced olfactory coding in the presence of background odors through broad suppression of background odor responses.
• This highlights a unique neural adaptation in ASD models for processing complex olfactory environments.