Disrupted stimulus encoding shapes tactile perception in autism

Atypical sensory experience is a core characteristic of autism, significantly affecting daily life. Tactile perception is prominently impacted in autism, including difficulties in the detection and discrimination of low-level stimuli. However, we do not know the neural underpinnings of low-level tactile perception and how they change in autism. Using a translational perceptual task we recapitulate the multifaceted tactile features of autistic individuals in the Fmr1 ^-/y mouse model of autism and show tactile hyposensitivity, interindividual variability, and unreliable responses. Using concomitant population activity imaging of pyramidal neurons and GABAergic interneurons, we reveal weak stimulus encoding in the primary somatosensory cortex of Fmr1 ^-/y -hyposensitive mice. Disrupted encoding renders perception more vulnerable to the ongoing network state and impedes reliable response decoding. Increasing the number and reliability of stimulus-recruited neurons by targeting the large conductance calcium-activated potassium (BK _Ca ) channels improves tactile perception. Our work shows an evolutionarily conserved role for the primary somatosensory cortex in tactile detection and presents a highly translational approach for probing neuronal-perceptual changes in neurodevelopmental conditions.