Earliest experience of a relatively rare sound but not a frequent sound causes long term changes in the adult auditory cortex

Sensory experience during a critical period alters sensory cortical responses and organization. We find that the earliest sound driven activity in the mouse auditory cortex (ACX) starts before ear-canal opening (ECO). Effects of auditory experience before ECO on ACX development are unknown. We find that mouse ACX subplate neurons (SPNs), crucial in thalamocortical maturation, respond to sounds before ECO showing oddball selectivity. Before ECO, SPNs are more selective to oddball sounds in auditory streams than thalamo-recipient layer 4 (L4) neurons and not after ECO. We hypothesize that SPNs’ oddball selectivity can direct development of L4 responses before ECO. Exposing mice before ECO with a rarely occurring tone in a stream of another tone occurring frequently leads to the strengthening of the adult cortical representation of the rare tone, but not that of the frequent tone. Results of control exposure experiments at multiple developmental windows and also with only a single tone corroborate the observations. A computational network model of known thalamic inputs to SPNs and L4 explains the observed developmental plasticity. Information-theoretic analysis with sparse coding assumptions also predicts the observations. Thus, salient low probability sounds in the earliest auditory environment cause long term changes in the ACX.