Strict control over the initiation of action potentials is the primary task of a neuron. One way to lose proper spike control is to create several spikes, a burst, when only one should be initiated. We describe a new site for burst initiation in rat hippocampal CA3 neurons: the Schaffer collateral axons. These axons lack myelin, are long, extremely thin, and form synapses along their entire paths, features typical for many, if not most cortical axons in the mammalian brain. We used hippocampal slices and recorded from individual Schaffer collateral axons. We found that single action potentials were converted into bursts of two to six action potentials after blocking 4-aminopyridine (4-AP) sensitive K(+) channels. The CA3 somata and initial part of their axons were surgically removed in these experiments, leading to the conclusion that the bursts were initiated far out in the axons. This conclusion was supported by two additional kinds of experiments. First, local application of 4-AP to one out of two stimulated axonal branches of the same neuron showed bursting only at the 4-AP exposed branch. Second, intracellular recordings from CA3 somata showed that some spontaneously occurring bursts were resistant to somatic hyperpolarization. We then investigated a hyperexcitable period that follows individual spikes in the Schaffer collaterals. With extracellular excitability testing, we showed that the time course of this hyperexcitability was compatible with that of the bursts, so this hyperexcitability could be the underlying cause of the bursts. Furthermore, the hyperexcitability was enhanced by low doses of 4-AP (20 microM), alpha-dendrotoxin (alpha-DTX) or margatoxin (MgTX). Kv1.2 containing channels may therefore dampen the hyperexcitability, but because bursting was observed only at high 4-AP concentration (1 mM), other channels may be needed to prevent axonal bursting.
展开▼
