Induced sharp wave‐ripple complexes in the absence of synaptic inhibition in mouse hippocampal slices

Abstract

The characteristic, behaviour-related network oscillations of the mammalian hippocampus (θ, γ and ripples) are accompanied by strongly phase-coupled action potentials in specific subsets of GABAergic interneurones. It has been suggested that the resulting phasic, repetitive inhibition shapes rhythmic coherent activity of the neuronal network. Here, we examined whether synaptic inhibition entrains ∼200 Hz network ripples by applying the GABA A receptor antagonist gabazine to CA1 minislices of mouse hippocampus. Gabazine blocked spontaneously occurring sharp wave-ripple (SPW-R) activity. However, local application of KCl to the dendritic layer elicited excitatory sharp waves on which ∼200 Hz ripple oscillations were superimposed with equal temporal properties of native SPW-R. The activity also persisted in the additional presence of blockers of glutamatergic synaptic transmission. In contrast, synchrony was largely abolished after addition of gap junction blockers. Thus, GABAergic transmission appears to be involved in the generation of sharp waves but phasic inhibition is no prerequisite for the precise synchronization of hippocampal neurones during high-frequency oscillations at ∼200 Hz. Gap junctions on the other hand seem to be necessary to orchestrate coordinated activity within the ripple frequency domain.

Quantitative prediction of intermittent high-frequency oscillations in neural networks with supralinear dendritic interactions

“…AMPA antagonists abolish the SPW/R activity in both CA1 and in CA3 (30). Although SPW/R events usually are initiated in CA3, they also are found in the functionally disconnected region CA1 (30,31). This data indicates that the recurrent excitatory connectivity is essential for their generation in both regions, as assumed in the model.…”

“…(i) They agree in the frequency of the highfrequency oscillations. Ripples in in vitro slice preparations (30,31,33) generally have a higher oscillation frequency than those detected in vivo (29,34). The model suggests that this higher oscillation frequency is caused by the reduction of longer-range connections during slice preparation and suggests a decrease in the oscillation frequency with increasing slice thickness (Fig.…”

“…S7). This, together with the broader delay distribution in networks with long-range connections, also might explain why there are only weak lower-frequency ripples (if any) in the globally connected region CA3 in vivo (22,29,34), whereas there are marked high-frequency ripples in thin-slice preparations of CA3 (30,31,33). (ii) The events in the model and SPW/Rs have similar shape (rate profile) and duration.…”

“…For hippocampal region CA1 (and for regions which are similar with respect to their singleneuron and network properties), the model predicts events of increased activity with high-frequency oscillations of ∼200 Hz (SI Text, Section B). Indeed, in CA1 and neighboring regions, SPW/ Rs, intermittent strong increases in network activity (sharp waves) with high-frequency oscillations (ripples) of ∼200 Hz, have been found (28)(29)(30)(31). Does the model provide a plausible explanation for SPW/Rs?…”

Mechanisms of physiological and epileptic HFO generation

“…In some studies loss of inhibition resulted in a transformation of sharp wave ripples, with HFO in the ripple band, to epileptiform discharges, with superimposed fast ripples, suggesting a role of inhibition in ripples and not fast ripples (Behrens et al, 2007). Evidence on roles for gap junctions in HFOs is both negative (D'Antuono et al, 2005) and positive (Nimmrich et al, 2005). A study of CA3 in elevated extracellular K + argues for a role for intrinsic burst firing characteristic of CA3 pyramidal cells (Dzhala and Staley, 2004).…”