Physiological sharp wave-ripples and interictal events in vitro: what’s the difference?

Abstract

Sharp wave-ripples and interictal events are physiological and pathological forms of transient high activity in the hippocampus with similar features. Sharp wave-ripples have been shown to be essential in memory consolidation, whereas epileptiform (interictal) events are thought to be damaging. It is essential to grasp the difference between physiological sharp wave-ripples and pathological interictal events to understand the failure of control mechanisms in the latter case. We investigated the dynamics of activity generated intrinsically in the Cornu Ammonis region 3 of the mouse hippocampus in vitro, using four different types of intervention to induce epileptiform activity. As a result, sharp wave-ripples spontaneously occurring in Cornu Ammonis region 3 disappeared, and following an asynchronous transitory phase, activity reorganized into a new form of pathological synchrony. During epileptiform events, all neurons increased their firing rate compared to sharp wave-ripples. Different cell types showed complementary firing: parvalbumin-positive basket cells and some axo-axonic cells stopped firing as a result of a depolarization block at the climax of the events in high potassium, 4-aminopyridine and zero magnesium models, but not in the gabazine model. In contrast, pyramidal cells began firing maximally at this stage. To understand the underlying mechanism we measured changes of intrinsic neuronal and transmission parameters in the high potassium model. We found that the cellular excitability increased and excitatory transmission was enhanced, whereas inhibitory transmission was compromised. We observed a strong short-term depression in parvalbumin-positive basket cell to pyramidal cell transmission. Thus, the collapse of pyramidal cell perisomatic inhibition appears to be a crucial factor in the emergence of epileptiform events.

Excitation and Inhibition Compete to Control Spiking during Hippocampal Ripples: Intracellular Study in Behaving Mice

“…First, the ripple-coherent fast oscillation of Vm is likely a reflection of the rhythmic, basket interneuron firing-induced IPSPs (Buzsáki et al, 1992;Ylinen et al, 1995;Csicsvari et al, 1999a, b;Klausberger et al, 2003;Klausberger and Somogyi, 2008;Rácz et al, 2009;Bähner et al, 2011;Varga et al, 2012;Hájos et al, 2013;Karló cai et al, 2014). Second, spike threshold was elevated during ripples.…”

“…This model is primarily supported by in vitro slice experiments, including the demonstration of antidromic spikes recorded intracellularly in pyramidal cells during ripples in vitro (Papatheodoropoulos, 2008;Bähner et al, 2011), and the observation that gap junction blockers abolish ripples in vitro (Draguhn et al, 1998;Schmitz et al, 2001; and in vivo (Ylinen et al, 1995). Competing models require inhibition and interactions between excitation and inhibition (Buzsáki et al, 1992;Whittington et al, 1995;Ylinen et al, 1995;Traub et al, 1996;Brunel and Wang, 2003;Geisler et al, 2005;Rácz et al, 2009;Taxidis et al, 2012;Varga et al, 2012;Hájos et al, 2013;Chiovini et al, 2014;Karló cai et al, 2014). Interpretation of in vitro studies is constrained because the exact activity in vitro may depend on a variety of experimenter-set conditions.…”

Extracellular Calcium Controls the Expression of Two Different Forms of Ripple-Like Hippocampal Oscillations

“…Physiological ripples are thought to mostly represent inhibitory potentials elicited from perisomatic innervating interneurons onto pyramidal cells (Ylinen et al, 1995;Csicsvari et al, 1999). In contrast, pathological fast ripples reflect PSs from clusters of glutamatergic neurons (Ibarz et al, 2010;Bragin et al, 2011). Data suggest that firing synchronization fundamentally differs between normal and pathological HFOs, with ϳ10% pyramidal cells firing sparsely during ripples (Csicsvari et al, 2000) and larger pool of neurons tightly contributing to fast ripples (Ibarz et al, 2010).…”

Intracranial neuronal ensemble recordings and analysis in epilepsy

“…This phenomenon was validated using various experimental models including acute and subacute slice and whole brain preparations (de Curtis and Avanzini, 2001;Steriade and Amzica, 1999), (de Curtis et al, 2012;Matsumoto and Ajmone-Marsan, 1964), (de Curtis and Avanzini, 2001;Karlócai et al, 2014).…”

“…The authors of these studies postulated a dynamic change in the network behavior during the transition from normal to epileptic states (Karlócai et al, 2014). In this hypothesis, increasing excitation in the hippocampus results in increasing activity in inhibitory circuitry, leading to acute and selective breakdown of the parvalbuminergic perisomatic inhibition.…”