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. We thank the members of the Kanold laboratory for valuable discussions on the project. We also thank the Johns Hopkins Transgenic Core Laboratory, led by Chip Hawkins, for their support in generating the Cplx3-CreER mouse line.

This work was supported by the National Institutes of Health (R01DC009607 to P.O.K.) and an NIH NRSA F32 fellowship (F32DC019842 to T.A.B.). These authors contributed equally: Travis A. Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA Travis A.

Babola, Minzi Chang, Rachel Jun, Marina Cardoso de Oliveira, Yunru Chen, Lillian Choi, Dave R. Kanold Division of Neonatal-Perinatal Medicine, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA Kavli Neuroscience Discovery Institute, Johns Hopkins University, Baltimore, MD, USA The authors declare no competing interests. Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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