Pre-synaptic and post-synaptic neuronal activity supports the axon development of callosal projection neurons during different post-natal periods in the mouse cerebral cortex.
Callosal projection neurons, one of the major types of projection neurons in the mammalian cerebral cortex, require neuronal activity for their axonal projections [H. Mizuno et al. (2007) J. Neurosci., 27, 6760-6770; C. L. Wang et al. (2007) J. Neurosci., 27, 11334-11342]. Here we established a method to label a few callosal axons with enhanced green fluorescent protein in the mouse cerebral cortex and examined the effect of pre-synaptic/post-synaptic neuron silencing on the morphology of individual callosal axons. Pre-synaptic/post-synaptic neurons were electrically silenced by Kir2.1 potassium channel overexpression. Single axon tracing showed that, after reaching the cortical innervation area, green fluorescent protein-labeled callosal axons underwent successive developmental stages: axon growth, branching, layer-specific targeting and arbor formation between post-natal day (P)5 and P9, and the subsequent elaboration of axon arbors between P9 and P15. Reducing pre-synaptic neuronal activity disturbed axon growth and branching before P9, as well as arbor elaboration afterwards. In contrast, silencing post-synaptic neurons disturbed axon arbor elaboration between P9 and P15. Thus, pre-synaptic neuron silencing affected significantly earlier stages of callosal projection neuron axon development than post-synaptic neuron silencing. Silencing both pre-synaptic and post-synaptic neurons impaired callosal axon projections, suggesting that certain levels of firing activity in pre-synaptic and post-synaptic neurons are required for callosal axon development. Our findings provide in-vivo evidence that pre-synaptic and post-synaptic neuronal activities play critical, and presumably differential, roles in axon growth, branching, arbor formation and elaboration during cortical axon development.
Mizuno
Hidenobu
H
Department of Biophysics, Kyoto University Graduate School of Science, Sakyo-ku, Kyoto, Japan.
Hirano
Tomoo
T
Tagawa
Yoshiaki
Y
D000818:Animals; D000831:Animals, Newborn; D001369:Axons / Q000502:physiology* / Q000648:ultrastructure; D048430:Cell Shape; D002540:Cerebral Cortex / Q000166:cytology / Q000254:growth & development; D003337:Corpus Callosum / Q000033:anatomy & histology / Q000502:physiology; D018274:Electroporation; D005260:Female; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009434:Neural Pathways / Q000033:anatomy & histology / Q000502:physiology; D009476:Neurons, Efferent / Q000166:cytology / Q000502:physiology; D024661:Potassium Channels, Inwardly Rectifying / Q000378:metabolism; D011247:Pregnancy; D009435:Synaptic Transmission / Q000502:physiology
C489461:Kir2.1 channel; D024661:Potassium Channels, Inwardly Rectifying; D049452:Green Fluorescent Proteins