A topographic protomap in mouse subplate neurons precedes the onset of sensory experience

Within sensory systems, thalamic projections to layer 4 (L4) neurons establish precise neocortical topography. During development, thalamic axons first synapse onto subplate neurons (SPNs) beneath the cortical plate, however, how thalamic inputs are organized within the subplate is unknown. To examine SPN organization and activity, we generated an inducible Cplx3-CreER mouse driver line to examine SPNs during development. Before sensory onset, we found that Cplx3⁺ SPNs in the auditory and visual cortices exhibited topographically organized spontaneous activity. Stimulating thalamocortical afferents evoked robust responses in auditory cortex SPNs, indicating functional thalamic input, while cochlear ablation or enucleation dramatically reduced spontaneous activity among Cplx3⁺ SPNs, indicating that peripherally-generated activity propagates to the subplate. After ear canal opening, Cplx3⁺ SPNs responded reliably to sound with coarse tonotopy. Thus, Cplx3⁺ SPNs receive topographically organized input and integrate spontaneous and sensory-driven activity, which may shape refinement of nascent brain circuits.