Involvement of synapse formation in activity-dependent thalamocortical axon branching

Naoyuki Matsumoto, Maki Hoshiko, Nobuhiko Yamamoto
Grad. Sch. Of Frontier BioSci., Osaka Univ., Japan,

During development, thalamocortical (TC) axons are known to remodel in responding to neuronal activity. Here, we investigated the role of synapse formation in activity-dependent TC axon branching. TC axon branching and synapse formation was examined in organotypic coculture preparations in different conditions of neuronal activity. To do this, intrinsic neuronal activity of thalamic cells was either suppressed by expressing Kir2.1, an inward rectifying potassium channel or promoted by expressing NaChBac, a bacterial voltage-gated sodium channel. In addition, thalamic cells were transfected with synaptophysin (SYP)-EGFP and DsRed expression plasmids to observe axonal projection and presynaptic sites. We found that TC axon branching was strongly inhibited by Kir2.1 expression and considerably promoted by NaChBac expression. In contrast, the density of SYP-positive puncta was not altered by NaChBac expression although decreased by Kir2.1 expression. Time-lapse imaging of TC axons at 2 hr intervals further showed that branches emerged mostly from SYP-positive puncta in the control axons but frequently appeared from the locations other than SYP-positive puncta in NaChBac-expressing axons, indicating that accelerated activity promotes axon branching at non-synaptic sites. These results suggest that increased neuronal activity results in a shift of the axon branching mechanism to a synapse-independent manner.

KAKENHI: No. 23300118 and Scientific Research on Innovative Areas "Mesoscopic Neurocircuitry" (No. 23115102)