Transient callosal projections of L4 neurons are eliminated for the acquisition of local connectivity

N S De León Reyes,I Varela,I Varela,L A Weiss,M J Galazo,G Perea,M Nieto,M Nieto,S Mederos

doi:10.1038/s41467-019-12495-w

Abstract

Interhemispheric axons of the corpus callosum (CC) facilitate the higher order functions of the cerebral cortex. According to current views, callosal and non-callosal fates are determined early after a neuron’s birth, and certain populations, such as cortical layer (L) 4 excitatory neurons of the primary somatosensory (S1) barrel, project only ipsilaterally. Using a novel axonal-retrotracing strategy and GFP-targeted visualization of Rorb+ neurons, we instead demonstrate that L4 neurons develop transient interhemispheric axons. Locally restricted L4 connectivity emerges when exuberant contralateral axons are refined in an area- and layer-specific manner during postnatal development. Surgical and genetic interventions of sensory circuits demonstrate that refinement rates depend on distinct inputs from sensory-specific thalamic nuclei. Reductions in input-dependent refinement result in mature functional interhemispheric hyperconnectivity, demonstrating the plasticity and bona fide callosal potential of L4 neurons. Thus, L4 neurons discard alternative interhemispheric circuits as instructed by thalamic input. This may ensure optimal wiring.

Highlights

Interhemispheric axons of the corpus callosum (CC) facilitate the higher order functions of the cerebral cortex
This latter scenario requires considerable structural rearrangement of axons. How these alternative circuits emerge is not well understood, nor is it understood why early postmitotic neurons exhibit greater plasticity upon molecular reprogramming[7]. We investigated these questions in the context of the selection of the neuronal populations that form the corpus callosum (CC)
Cats, and primates, in which axonal retrotracers were injected into the cortical plate of the opposite hemisphere of adult animals, found that the distribution of callosally projecting neurons (CPNs) varies within the functional areas, and that in most areas, CPNs are predominantly located in L2/3 and L5, and some in L6

Summary

Introduction

Interhemispheric axons of the corpus callosum (CC) facilitate the higher order functions of the cerebral cortex. These foundational studies in the CC, together with those in the retina[21] and with investigations describing cortical exuberant projections to subcortical targets[20,22], identified axonal refinement as being a principal mechanism during the wiring of the central nervous system These experiments determined that the increased number of CPN of developing brains were located preferentially in those layers that contain CPN in adults. Certain layers, such as L4, that contain few callosals in the adult, showed sparse retrotracer labeling in the embryo and young postnatal individuals[13,14,16,17,23,24] Studies interrogating how these restricted CPN distributions arise and how cortical callosal and non-callosal populations emerge concluded that restrictions to neuronal connectivity are established prior to axonal extension[16,20,25]. A dynamic acquisition of neuronal fates provides a more comprehensive account of how cortical neurons are specified and helps explain their early plasticity, but poses unanswered questions about how and when cortical neurons commit their dendritic and axonal structures during the process of fate determination

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Conclusion