Degraded tactile coding in the Cntnap2 mouse model of autism

Atypical sensory processing in autism involves altered neural circuit function and neural coding in sensory cortex, but the nature of coding disruption is poorly understood. We characterized neural coding in L2/3 of whisker somatosensory cortex (S1) of Cntnap2(−/−) mice, an autism model with pronounced hypofunction of parvalbumin (PV) inhibitory circuits. We tested for both excess spiking, which is often hypothesized in autism models with reduced inhibition, and alterations in somatotopic coding, using c-fos immunostaining and 2-photon calcium imaging in awake mice. In Cntnap2(−/−) mice, c-fos-(+) neuron density was elevated in L2/3 of S1 under spontaneous activity conditions, but comparable to control mice after whisker stimulation, suggesting that sensory-evoked spiking was relatively normal. 2-photon GCaMP8m imaging in L2/3 pyramidal cells revealed no increase in whisker-evoked response magnitude, but instead showed multiple signs of degraded somatotopic coding. These included broadening of whisker tuning curves, blurring of the whisker map, and blunting of the point representation of each whisker. These altered properties were more pronounced in noisy than sparse sensory conditions. Tuning instability, assessed over 2–3 weeks of longitudinal imaging, was also significantly increased in Cntnap2(−/−) mice. Thus, Cntnap2(−/−) mice show no excess spiking, but a degraded and unstable tactile code in S1.