GABA-enhanced collective behavior in neuronal axons underlies persistent gamma-frequency oscillations

TLDR

Gamma oscillations (30–80 Hz) are cognitively relevant, with in‑vitro studies revealing transient and persistent forms; the persistent form is thought to involve gap‑junction communication between axons, but its precise relationship to neuronal activity remains unclear. The study aims to demonstrate that gamma oscillations coexist with high‑frequency (>90 Hz) oscillations. High‑frequency oscillations arise in the axonal plexus independently of pyramidal somata and are amplified and organized by interneurons into a coherent network rhythm. These oscillations are enhanced by nonsomatic GABA_A receptor activation, modulated by perisomatic GABA_A input to principal cells, and provide the phasic drive to interneurons that sustain persistent gamma, originating from random axonal activity.

Abstract

Gamma (30–80 Hz) oscillations occur in mammalian electroencephalogram in a manner that indicates cognitive relevance. In vitro models of gamma oscillations demonstrate two forms of oscillation: one occurring transiently and driven by discrete afferent input and the second occurring persistently in response to activation of excitatory metabotropic receptors. The mechanism underlying persistent gamma oscillations has been suggested to involve gap-junctional communication between axons of principal neurons, but the precise relationship between this neuronal activity and the gamma oscillation has remained elusive. Here we demonstrate that gamma oscillations coexist with high-frequency oscillations (>90 Hz). High-frequency oscillations can be generated in the axonal plexus even when it is physically isolated from pyramidal cell bodies. They were enhanced in networks by nonsomatic γ-aminobutyric acid type A (GABA A ) receptor activation, were modulated by perisomatic GABA A receptor-mediated synaptic input to principal cells, and provided the phasic input to interneurons required to generate persistent gamma-frequency oscillations. The data suggest that high-frequency oscillations occurred as a consequence of random activity within the axonal plexus. Interneurons provide a mechanism by which this random activity is both amplified and organized into a coherent network rhythm.