Subplate neurons are the first cortical neurons to respond to sensory stimuli.

In utero experience, such as maternal speech in humans, can shape later perception, although the underlying cortical substrate is unknown. In adult mammals, ascending thalamocortical projections target layer 4, and the onset of sensory responses in the cortex is thought to be dependent on the onset of thalamocortical transmission to layer 4 as well as the ear and eye opening. In developing animals, thalamic fibers do not target layer 4 but instead target subplate neurons deep in the developing white matter. We investigated if subplate neurons respond to sensory stimuli. Using electrophysiological recordings in young ferrets, we show that auditory cortex neurons respond to sound at very young ages, even before the opening of the ears. Single unit recordings showed that auditory responses emerged first in cortical subplate neurons. Subsequently, responses appeared in the future thalamocortical input layer 4, and sound-evoked spike latencies were longer in layer 4 than in subplate, consistent with the known relay of thalamic information to layer 4 by subplate neurons. Electrode array recordings show that early auditory responses demonstrate a nascent topographic organization, suggesting that topographic maps emerge before the onset of spiking responses in layer 4. Together our results show that sound-evoked activity and topographic organization of the cortex emerge earlier and in a different layer than previously thought. Thus, early sound experience can activate and potentially sculpt subplate circuits before permanent thalamocortical circuits to layer 4 are present, and disruption of this early sensory activity could be utilized for early diagnosis of developmental disorders.