Neuronal signaling in central nervous system.

A new method of axon recording through axon bleb has boosted the studies on the functional role of central nervous system (CNS) axons. Using this method, we have revealed the mechanisms underlying the initiation and propagation of the digital-mode signal, all-or-none action potentials (APs), in neocortical pyramidal neurons. Accumulation of the low-threshold Na(+) channel subtype Na(v)1.6 at the distal end of the axon initial segment (AIS) determines the lowest threshold for AP initiation, whereas accumulation of the high-threshold subtype Na(v)1.2 at the proximal region of the AIS promotes AP backpropagation to the soma and dendrites. Through dual recording from the soma and the axon, we have showed that subthreshold membrane potential (V(m)) fluctuations in the soma propagate along the axon to a long distance and probably reach the axon terminals. Paired recording from cortical neurons has revealed that these V(m) changes in the soma modulate AP-triggered synaptic transmission. This new V(m)-dependent mode of synaptic transmission is called analog communication. Unique properties of axonal K(+) channels (K(v)1 channels) may contribute to shaping the AP waveform, particularly its duration, and thus controlling synaptic strength at different levels of presynaptic V(m). The level of background Ca(2+) may also participate in mediating the analog signaling. Together, these findings enrich our knowledge on the principles of neuronal signaling in the CNS and help understand how the brain works.