Generation of Sharp Wave-Ripple Events by Disinhibition

Abstract

Sharp wave-ripple complexes (SWRs) are hippocampal network phenomena involved in memory consolidation. To date, the mechanisms underlying their occurrence remain obscure. Here, we show how the interactions between pyramidal cells, parvalbumin-positive (PV +) basket cells, and an unidentified class of anti-SWR interneurons can contribute to the initiation and termination of SWRs. Using a biophysically constrained model of a network of spiking neurons and a rate-model approximation, we demonstrate that SWRs emerge as a result of the competition between two interneuron populations and the resulting disinhibition of pyramidal cells. Our models explain how the activation of pyramidal cells or PV + cells can trigger SWRs, as shown in vitro, and suggests that PV + cell-mediated short-term synaptic depression influences the experimentally reported dynamics of SWR events. Furthermore, we predict that the silencing of anti-SWR interneurons can trigger SWRs. These results broaden our understanding of the microcircuits supporting the generation of memory-related network dynamics. Significance Statement The hippocampus is a part of the mammalian brain that is crucial for episodic memories. During periods of sleep and inactive waking, the extracellular activity of the hippocampus is dominated by sharp wave-ripple events (SWRs), which have been shown to be important for memory consolidation. The mechanisms regulating the emergence of these events are still unclear. We developed a computational model to study the emergence of SWRs and to explain the roles of different cell types in regulating them. The model accounts for several previously unexplained features of SWRs and thus advances the understanding of memory-related dynamics.

Inhibition is the hallmark of CA3 intracellular dynamics around awake ripples

“…w(a ac ) r ca3 the result of disinhibition, however our data does not offer clear evidence for widespread disinhibition in CA3 preceding the population burst (Evangelista et al, 2020). Importantly, ripple generation by disinhibition does not account for the lack of ripples in the DOWN state, despite the elevated neuronal activity in CA3.…”

Prenatal alcohol exposure disrupts hippocampal sharp-wave ripple-associated spike dynamics

“…Instead, these changes may be due to deficits in local CA1 pyramidal cell-interneuron interactions as evident by a decrease in pyramidal cell population activity highlighted in Fig4. It is likely that this difference in excitation and inhibition throughout the CA1 network would disrupt underlying SPW-R spiking, as SPW-Rs generation and underlying spiking dynamics are supported by precise pyramidal cell-interneuron interactions (5,39,(42)(43)(44)(45)(46)(47)(48).…”

“…Because of the decreased pyramidal cell and interneuron recruitment into SPW-R events, we next sought to characterize the roles of excitation and inhibition in local circuits during SPW-Rs through the quantification of pyramidal and interneuron population activity. Because SPW-Rs are supported by precise pyramidal cell-interneuron or excitation-inhibition dynamics (5,39,(42)(43)(44)(45)(46)(47)(48), we hypothesized that the relative contribution of putative pyramidal cells and putative interneurons during SPW-Rs will be altered in moderate PAE.…”

A computational study of suppression of sharp wave ripple complexes by controlling calcium and gap junctions in pyramidal cells

“…Conductance densities of somato-dendrites were taken from the basic model [ 31 ] excluding the fast sodium in lower areas of the soma (0.070 S/cm 2 ) to ensure that only a small number of spikes turn into soma spikes [ 33 , 34 ]. The densities of the ionic conductances were the same in all axonal compartments of the main axon, collaterals, and the axonal initial segment (AIS): Na (Fast) 0.3 S/cm 2 and potassium delayed-rectifier 0.4S/cm 2 ( Table 1 ).…”