Effects of 4-aminopyridine on sharp wave-ripples in rat hippocampal slices

Richter, Johannes P.; Behrens, Christoph; Chakrabarty, Arnab; Heinemann, Uwe

doi:10.1097/wnr.0b013e3282f79c61

Cited by 5 publications

(2 citation statements)

References 24 publications

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“…Similarly, when excitation or inhibition is altered without a concomitant change of the other factor in this balance, a disturbance in the activity of SWRs may occur. For instance, relatively small to moderate enhancement of basal neuronal excitability following blockade/loss of potassium channels (Richter et al, 2008;Simeone et al, 2013;Trompoukis et al, 2020;Contreras et al, 2023) or elevation of extracellular potassium concentration (Papatheodoropoulos and Kostopoulos, 2002b), can greatly affect the pattern of SWRs' generation.…”

Section: Fxs-associated Effects On Normal Spontaneous Activitiesmentioning

confidence: 99%

Rescue of sharp wave-ripples and prevention of network hyperexcitability in the ventral but not the dorsal hippocampus of a rat model of fragile X syndrome

Leontiadis,

Trompoukis,

Tsotsokou

et al. 2023

Front. Cell. Neurosci.

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Fragile X syndrome (FXS) is a genetic neurodevelopmental disorder characterized by intellectual disability and is related to autism. FXS is caused by mutations of the fragile X messenger ribonucleoprotein 1 gene (Fmr1) and is associated with alterations in neuronal network excitability in several brain areas including hippocampus. The loss of fragile X protein affects brain oscillations, however, the effects of FXS on hippocampal sharp wave-ripples (SWRs), an endogenous hippocampal pattern contributing to memory consolidation have not been sufficiently clarified. In addition, it is still not known whether dorsal and ventral hippocampus are similarly affected by FXS. We used a Fmr1 knock-out (KO) rat model of FXS and electrophysiological recordings from the CA1 area of adult rat hippocampal slices to assess spontaneous and evoked neural activity. We find that SWRs and associated multiunit activity are affected in the dorsal but not the ventral KO hippocampus, while complex spike bursts remain normal in both segments of the KO hippocampus. Local network excitability increases in the dorsal KO hippocampus. Furthermore, specifically in the ventral hippocampus of KO rats we found an increased effectiveness of inhibition in suppressing excitation and an upregulation of α1GABAA receptor subtype. These changes in the ventral KO hippocampus are accompanied by a striking reduction in its susceptibility to induced epileptiform activity. We propose that the neuronal network specifically in the ventral segment of the hippocampus is reorganized in adult Fmr1-KO rats by means of balanced changes between excitability and inhibition to ensure normal generation of SWRs and preventing at the same time derailment of the neural activity toward hyperexcitability.

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Section: Fxs-associated Effects On Normal Spontaneous Activitiesmentioning

confidence: 99%

Rescue of sharp wave-ripples and prevention of network hyperexcitability in the ventral but not the dorsal hippocampus of a rat model of fragile X syndrome

Leontiadis,

Trompoukis,

Tsotsokou

et al. 2023

Front. Cell. Neurosci.

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“…Transient fast ripple oscillations observed in local field potential recordings are thought to represent population spikes from clusters of abnormally bursting neurons (Bragin et al, 2000). While many factors, including ephaptic interactions (Bikson et al, 2003), gap junctions (Draguhn et al, 1998;Traub et al, 1999;Middleton et al, 2008), and several forms of channelopathies (Richter et al, 2008), can be implicated in the generation of different forms of high-frequency oscillations, here we do not attempt to model these several mechanisms for the case of fast ripples. Instead, we focus on the spectral properties of fast ripples resulting from in-phase and out-of-phase neuronal firing during population discharges.…”

Section: Methodsmentioning

confidence: 99%

Emergent Dynamics of Fast Ripples in the Epileptic Hippocampus

Ibarz¹,

Foffani²,

Cid³

et al. 2010

J. Neurosci.

162

206

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Fast ripples are a type of transient high-frequency oscillations recorded from the epileptogenic regions of the hippocampus and the temporal cortex of epileptic humans and rodents. These events presumably reflect hypersynchronous bursting of pyramidal cells. However, the oscillatory spectral content of fast ripples varies from 250 to 800 Hz, well above the maximal firing frequency of most hippocampal pyramidal neurons. How such high-frequency oscillations are generated is therefore unclear. Here, we combine computational simulations of fast ripples with multisite and juxtacellular recordings in vivo to examine the underlying mechanisms in the hippocampus of epileptic rats. We show that populations of bursting cells firing individually at 100 -400 Hz can create fast ripples according to two main firing regimes: (1) in-phase synchronous firing resulting in "pure" fast ripples characterized by single spectral peaks that reflect single-cell behavior and (2) out-of-phase firing that results in "emergent" fast ripples. Using simulations, we found that fast ripples generated under these two different regimes can be quantitatively separated by their spectral characteristics, and we took advantage of this separability to examine their dynamics in vivo. We found that in-phase firing can reach frequencies up to 300 Hz in the CA1 and up to 400 Hz in the dentate gyrus. The organization of out-of-phase firing is determined by firing delays between cells discharging at low frequencies. The two firing regimes compete dynamically, alternating randomly from one fast ripple event to the next, and they reflect the functional dynamic organization of the different regions of the hippocampus.

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