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

Abstract

Carbachol (> 20 microM) and kainate (100 nM) induce, in the in vitro CA3 region, synchronized neuronal population oscillations at approximately 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 GABAA 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.

GABAergic synchronization in the limbic system and its role in the generation of epileptiform activity

“…Moreover, one component of the oscillation cycle shows a reversal potential close to the GABA A -mediated reversal (around −60 mV). In keeping with this evidence, computer modeling supports the hypothesis that gamma oscillations reflect the interactions within interneuron networks (Wang and Buzsáki, 1996;White et al, 1998;Traub, 2000;Bartos et al, 2001). …”

Highly Energized Inhibitory Interneurons are a Central Element for Information Processing in Cortical Networks

“…This notion has been underlined by elegant in vivo studies in mice showing that selective genetic modification of glutamate receptor subtypes in fast-spiking, PV þ interneurons strongly affects power and synchrony of gamma oscillations, together with impaired hippocampus-dependent cognitive functions. 50,51 56,86,98,112 This finding underlines the general principle of sparse coding by pyramidal cells, which has been suggested to provide an optimal trade-off between information processing and energy efficacy. 113,114 However, pyramidal cells comprise B85% of all neurons in the hippocampus proper, and even with sparse coding they are able to encode multiple representations of spatial and episodic memories.…”

Inhibitory interneurons and network oscillations

“…Previous work in vivo has demonstrated that hippocampal GABAergic interneuron types exhibit differentiable firing patterns in relation to network oscillations, indicating that they have specialized roles in controlling various oscillations in the brain (7). Similarly, previous work in vitro has demonstrated that both interneuroninterneuron and pyramidal cellinterneuron interactions can generate the gamma rhythm in the hippocampus, a result predicted by modeling work (8)(9)(10)(11)(12). The important finding of Middleton et al's study is the demonstration that certain interneurons have a specialized role in generating an oscillation at a certain frequency band.…”