Gap junction networks can generate both ripple‐like and fast ripple‐like oscillations

Abstract

Fast ripples (FRs) are network oscillations, defined variously as having frequencies of > 150 to > 250 Hz, with a controversial mechanism. FRs appear to indicate a propensity of cortical tissue to originate seizures. Here, we demonstrate field oscillations, at up to 400 Hz, in spontaneously epileptic human cortical tissue in vitro, and present a network model that could explain FRs themselves, and their relation to ‘ordinary’ (slower) ripples. We performed network simulations with model pyramidal neurons, having axons electrically coupled. Ripples (< 250 Hz) were favored when conduction of action potentials, axon to axon, was reliable. Whereas ripple population activity was periodic, firing of individual axons varied in relative phase. A switch from ripples to FRs took place when an ectopic spike occurred in a cell coupled to another cell, itself multiply coupled to others. Propagation could then start in one direction only, a condition suitable for re-entry. The resulting oscillations were > 250 Hz, were sustained or interrupted, and had little jitter in the firing of individual axons. The form of model FR was similar to spontaneously occurring FRs in excised human epileptic tissue. In vitro, FRs were suppressed by a gap junction blocker. Our data suggest that a given network can produce ripples, FRs, or both, via gap junctions, and that FRs are favored by clusters of axonal gap junctions. If axonal gap junctions indeed occur in epileptic tissue, and are mediated by connexin 26 (recently shown to mediate coupling between immature neocortical pyramidal cells), then this prediction is testable.

A semi-automated method for rapid detection of ripple events on interictal voltage discharges in the scalp electroencephalogram

“…Experimental observations in animal models suggest that these fast oscillations reflect rapid inhibitory postsynaptic potentials (IPSPs) on the somata of pyramidal cells during simultaneous excitation of the pyramidal cells and surrounding interneurons (Bragin et al, 1999). An alternative mechanism - axo-axonal gap junctions between pyramidal cells - has also been proposed to support ripple band activity (Traub et al, 2001; Simon et al, 2014). Ripple oscillations have been observed in healthy tissue and may reflect normal physiological processes that contribute to the synaptic remodeling that underlies information processing, memory transference and consolidation (Buzsaki and Silva, 2012).…”

Advances of Intracranial Electroencephalography in Localizing the Epileptogenic Zone

“…There is little evidence that single neurons can fire at frequencies [300 Hz. Fast ripples have also been proposed to emerge from outof-phase firing within small groups of neurons, perhaps through coupling via axonal gap junctions [34]. Several studies have examined the pre-ictal and ictal changes of HFOs [4,35,36].…”

Electrophysiological Biomarkers of Epilepsy

“…Recent computational models provide evidence for the role of axonal gap junctions during fast ripple-frequency HFOs, as well as ripple-frequency and ripple-to-fast ripple transition [56]. Others have proposed that fast ripplefrequency HFOs emerge from the out-of-phase firing between small groups of neurons with individual neurons discharging at low frequencies and rarely firing during successive waves of the HFO [48,52,57].…”