Spatiotemporal patterns of γ frequency oscillations tetanically induced in the rat hippocampal slice

Abstract

We used transverse and longitudinal rat hippocampal slices to study the synchronization of γ frequency (> 20 Hz) oscillations, across distances of up to 4.5 mm. γ oscillations were evoked in the CA1 region by tetanic stimulation at one or two sites simultaneously, and were associated with population spikes. Tetanic stimuli that were strong enough to induce oscillations were associated with depolarization of both pyramidal cells and interneurones, largely produced by activation of metabotropic glutamate receptors. Computer simulations of γ oscillations were also performed in a model with pyramidal cells and interneurones, arranged in a chain of five cell groups. This model had suggested previously that interneurone networks alone could generate synchronous γ oscillations locally, but that pyramidal cell firing, by inducing spike doublets in interneurones, was necessary for the occurrence of highly correlated oscillations with small phase lag (< 2.5 ms), in a distributed network possessing long axon conduction delays. In both experiment and model, pyramidal cell spikes occurred in phase with local population spikes, as did the first spike of the interneurone doublet. The conductance of the interneurone α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionic acid (AMPA) receptor‐mediated conductance was manipulated in the model, while the relation between oscillations at opposite ends of the chain was examined. When the conductance was large enough for doublet firing to be synaptically induced in interneurones, oscillation phase lags were < 2.25 ms across the chain. As predicted, experimental blockade of AMPA receptors resulted in increased phase lags between two sites oscillating simultaneously, compared with control conditions. Both in model and in experiment, when stimuli to the two ends of the network were slightly different, cross‐network synchronization occurred with a shorter phase lag at high frequencies than at lower frequencies. These data suggest that, while interneurone networks alone can generate locally synchronized γ oscillations, firing of pyramidal cells, and the synaptically induced doublet firing in interneurones, contribute to the stability and tight synchrony of the oscillations in distributed networks.

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

“…Fast oscillations in limbic and extra-limbic structures can be reproduced in vitro by electrical tetanic stimulation (Whittington et al, 1997;Bracci et al, 1999;Vreugdenhil et al, 2005) as well as by the application of carbachol, high-K + solutions, kainic acid, or metabotropic agonists (Whittington et al, 1995;Fisahn et al, 1998;van der Linden et al, 1999;Dickson et al, 2000). Several findings support the view that these cortical activities reflect the synchronization of inhibitory GABAergic networks (see Traub et al, 1999;Whittington and Traub, 2003;Mann and Paulsen, 2007), with or without the contribution of excitatory glutamatergic networks (Bartos et al, 2007).…”

Genetically altered AMPA-type glutamate receptor kinetics in interneurons disrupt long-range synchrony of gamma oscillation

“…Pyramidal axon conduction velocity was 0.5 m͞s, giving a 3.84-ms conduction delay across the array. Gamma oscillations were induced in the network by tonic excitatory conductances (reversal potential 60 mV positive to rest), developing in the dendrites of pyramidal neurons (55-60 nS) and of interneurons (5.0-5.2 nS) (6).…”

“…Transverse dorsal hippocampal slices (400 m thick) were prepared from brains of male mice after decapitation following cervical dislocation, and maintained as described previously (6). Brief tetanic stimuli (100 Hz, 200 ms, 8-30 V, 50-s duration) at threshold for evoking gamma oscillations were delivered simultaneously to the stratum radiatum proximal to the cell body layer at two recording sites at either end of the CA1 region (separation 0.7-1.1 mm) every 4 min throughout each experiment.…”

“…Network simulations (containing model pyramidal cells, interneurons, and axon conduction delays) predict that tight synchrony between distant sites could arise as an emergent property-without a central pacemaker-when interneurons fire in doublets (4)(5)(6)(7). Precise timing of the doublet intervaldetermined in part by ␣-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-receptor mediated excitation from pyramidal cells, especially cells at a distance from the postsynaptic interneuron-provides a signal encoding phase lags between separated neurons; this signal would provide feedback to nearby pyramidal cells, in the form of synaptic inhibition, which would tend to correct for phase differences (ref.…”

Differential Expression of Group I Metabotropic Glutamate Receptors in Functionally Distinct Hippocampal Interneurons

“…Because of the large divergence of the output of individual interneurons onto large numbers of principal neurons (Buhl et al, 1994;Sik et al, 1995, Miles et al, 1996, the activity of an individual interneuron can have great impact on the excitability of the local neuronal network (Cobb et al, 1995;Katona et al, 1999). Networks of interconnected interneurons are able to generate synchronous oscillations (Buzsaki and Chrobak, 1995;Whittington et al, 1997). These oscillations are thought to be an electrophysiological substrate for temporal and spatial information processing within and between brain regions during specific behavioral states (Singer, 1993).…”