Dynamic interplay between thalamic activity and Cajal-Retzius cells regulates the wiring of cortical layer 1

Cortical wiring relies on guidepost cells and activity-dependent processes that are thought to act sequentially. Here, we show that the construction of layer 1 (L1), a main site of top-down integration, is regulated by crosstalk between transient Cajal-Retzius cells (CRc) and spontaneous activity of the thalamus, a main driver of bottom-up information. While activity was known to regulate CRc migration and elimination, we found that prenatal spontaneous thalamic activity and NMDA receptors selectively control CRc early density, without affecting their demise. CRc density, in turn, regulates the distribution of upper layer inter neurons and excitatory synapses, thereby drastically impairing the apical dendrite activity of output pyramidal neurons. In contrast, postnatal sensory-evoked activity had a limited impact on L1 and selectively perturbed basal dendrites synaptogenesis. Collectively, our study highlights a remarkable interplay between thalamic activity and CRc in L1 functional wiring, with major implications for our understanding of cortical development.

Automated summary

This study reveals the interaction between thalamic activity and Cajal-Retzius cells (CRc) in the construction of the cortical layer 1 (L1). Thalamic activity and NMDA receptors regulate the early density of CRc, which in turn affects the distribution of upper layer interneurons and excitatory synapses, resulting in a significant impact on the activity of output pyramidal neuron dendrites.