Activity-Dependent Development of Callosal Projections in the Somatosensory Cortex

Abstract

The corpus callosum is the largest commissural system in the mammalian brain, but the mechanisms underlying its development are not well understood. Here we report that neuronal activity is necessary for the normal development and maintenance of callosal projections in the mouse somatosensory cortex. We labeled a subpopulation of layer II/III callosal neurons via in utero electroporation and traced their axons in the contralateral cortex at different postnatal stages. Callosal axons displayed region-and layer-specific projection patterns within the first 2 weeks postnatally. Prenatal suppression of neuronal excitation was achieved via electroporation-induced overexpression of the inward rectifying potassium channel Kir2.1 in layer II/III cortical neurons. This resulted in abnormal callosal projections with many axons extending beyond layers II-III to terminate in layer I. Others failed to terminate at the border between the primary and secondary somatosensory cortices. Blocking synaptic transmission via expression of the tetanus toxin light chain (TeNT-LC) in these axons produced a more pronounced reduction in the projections to the border region, and the eventual disappearance of callosal projections over the entire somatosensory cortex. When Kir2.1 and TeNT-LC were coexpressed, callosal axon targeting exhibited a more severe phenotype that appeared to represent the addition of the effects produced by individual expression of Kir2.1 and TeNT-LC. These results underscore the importance of activity in regulating the developing neural connections and suggest that neuronal and synaptic activities are involved in regulating different aspects of the development of callosal projection.

X-linked microtubule-associated protein, Mid1, regulates axon development

“…3C and Fig. S4C), consistent with previous report (19). In Mid1-depleted neurons, however, the axon projection to the S1/ S2 border was largely decreased, and a dense collection of axon terminals was observed in S2 and Ect (Fig.…”

CaMKK–CaMKI Signaling Pathways Differentially Control Axon and Dendrite Elongation in Cortical Neurons: Figure 1.

“…The progression of axons in CaMKI␣ knockdown animals at P16 described by Ageta-Ishihara et al (2009) is comparable to that of wild-type P8 animals in a study by Wang et al (2007). This latter study, which used similar electroporation methods, demonstrated that hyperpolarization of developing somatosensory axons through overexpression of Kir2.1, an inward rectifying K ϩ channel, delayed midline crossing (Wang et al, 2007). The results of Ageta-Ishihara et al (2009) suggest that hyperpolarization would block CaMKI␣ signaling, thus, it is possible that the two studies produce similar effects on axon growth.…”

“…An important alternative hypothesis, however, is that knockdown of CaMKI␣ delays axon midline crossing. The progression of axons in CaMKI␣ knockdown animals at P16 described by Ageta-Ishihara et al (2009) is comparable to that of wild-type P8 animals in a study by Wang et al (2007). This latter study, which used similar electroporation methods, demonstrated that hyperpolarization of developing somatosensory axons through overexpression of Kir2.1, an inward rectifying K ϩ channel, delayed midline crossing (Wang et al, 2007).…”

Role of pre- and postsynaptic activity in thalamocortical axon branching

“…Previous studies using neuronal silencing with Kir2.1 have suggested that presynaptic activity plays a dominant role in axon branching (27,29,30). In particular, competitive interactions between a retinal ganglion cell and adjacent cells have been suggested to be crucial in retinotectal axon branching (27).…”