Gap Junctions, Fast Oscillations and the Initiation of Seizures

In this chapter, we shall review evidence that gap junctions can contribute to epileptogenesis in the hippocampus and cortex—but not just any gap junctions. Rather, we shall argue for a role for a newly described sort of gap junction, located between the proximal axons of principal neurons. Such axon-axon gap junctions promote epileptogenesis not so much by enhancing synchrony, as by providing pathways for the direct spread of action potentials between neurons. A by-product of such spread is the ability of axonally-coupled neurons to generate oscillations at very high frequencies (>~70 Hz). It is of note that seizure activity, both in vivo and in vitro, has been observed to begin with very high-frequency oscillations. If such oscillations can be shown to initiate the seizure discharge, and not just be an epiphenomenon, then targeting gap junction conductances may prove useful as an anticonvulsant strategy.