Decreased amplitude and reliability of odor-evoked responses in two mouse models of autism.

Sensory processing deficits are increasingly recognized as core symptoms of autism spectrum disorders (ASDs). However the molecular and circuit mechanisms that lead to sensory deficits are unknown. We show that two molecularly disparate mouse models of autism display similar deficits in sensory-evoked responses in the mouse olfactory system. We find that both Cntnap2- and Shank3-deficient mice of both sexes exhibit reduced response amplitude and trial-to-trial reliability during repeated odor presentation. Mechanistically, we show that both mouse models have weaker and fewer synapses between olfactory sensory nerve (OSN) terminals and olfactory bulb tufted cells and weaker synapses between OSN terminals and inhibitory periglomerular cells. Consequently, deficits in sensory processing provide an excellent candidate phenotype for analysis in ASDs.NEW & NOTEWORTHY The genetics of autism spectrum disorder (ASD) are complex. How the many risk genes generate the similar sets of symptoms that define the disorder is unknown. In particular, little is understood about the functional consequences of these genetic alterations. Sensory processing deficits are important aspects of the ASD diagnosis and may be due to unreliable neural circuits. We show that two mouse models of autism, Cntnap2- and Shank3-deficient mice, display reduced odor-evoked response amplitudes and reliability. These data suggest that altered sensory-evoked responses may constitute a circuit phenotype in ASDs.