A model of gamma‐frequency network oscillations induced in the rat CA3 region by carbachol in vitro

TLDR

Carbachol and kainate induce sustained ~40 Hz gamma oscillations in the rat CA3 region that depend on GABA A, AMPA receptors, and gap junctions, with interneurons firing 5–20 Hz tightly locked to field potentials while pyramidal cells fire sparsely at ~2 Hz. The study used a detailed multicompartmental network of 3072 pyramidal cells and 384 interneurons to simulate the conditions under which such experimentally observed gamma oscillations could arise. The model incorporates a sparse plexus of pyramidal axons coupled by gap junctions, glutamatergic excitation onto interneurons, inhibitory synapses onto pyramidal axons and somata, and a high spontaneous firing rate in pyramidal axons. Simulations showed that robust gamma oscillations emerge when pyramidal axons are gap‑junction coupled, that somatic firing is unnecessary, that the model reproduces the dependence on GABA A, AMPA, and gap junctions, and predicts that many pyramidal action potentials during sustained gamma originate in axons.

Abstract

Abstract Carbachol (> 20 μ m ) and kainate (100 n m ) induce, in the in vitro CA3 region, synchronized neuronal population oscillations at ≈ 40 Hz having distinctive features: (i) the oscillations persist for hours; (ii) interneurons in kainate fire at 5–20 Hz and their firing is tightly locked to field potential maxima (recorded in s. radiatum); (iii) in contrast, pyramidal cells, in both carbachol and kainate, fire at frequencies as low as 2 Hz, and their firing is less tightly locked to field potentials; (iv) the oscillations require GABA A receptors, AMPA receptors and gap junctions. Using a network of 3072 pyramidal cells and 384 interneurons (each multicompartmental and containing a segment of unmyelinated axon), we employed computer simulations to examine conditions under which network oscillations might occur with the experimentally determined properties. We found that such network oscillations could be generated, robustly, when gap junctions were located between pyramidal cell axons, as suggested to occur based on studies of spontaneous high‐frequency (> 100 Hz) network oscillations in the in vitro hippocampus. In the model, pyramidal cell somatic firing was not essential for the oscillations. Critical components of the model are (i) the plexus of pyramidal cell axons, randomly and sparsely interconnected by gap junctions; (ii) glutamate synapses onto interneurons; (iii) synaptic inhibition between interneurons and onto pyramidal cell axons and somata; (iv) a sufficiently high rate of spontaneous action potentials generated in pyramidal cell axons. This model explains the dependence of network oscillations on GABA A and AMPA receptors, as well as on gap junctions. Besides the existence of axon–axon gap junctions, the model predicts that many of the pyramidal cell action potentials, during sustained gamma oscillations, are initiated in axons.