Altered hippocampal interneuron activity precedes ictal onset

Miri, Mitra L; Vinck, Martin; Pant, Rima; Cardin, Jessica A.

doi:10.7554/elife.40750

Cited by 65 publications

(44 citation statements)

References 94 publications

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“…This is further supported by our cell‐attached recordings, and is consistent with a recent report of an acceleration of PV activation ahead of SST and pyramidal cell activation, in two acute, pharmacological in vivo models (Miri et al . ).…”

Section: Discussionmentioning

confidence: 97%

Feedforward inhibition ahead of ictal wavefronts is provided by both parvalbumin‐ and somatostatin‐expressing interneurons

Parrish

Codadu

Scott

et al. 2019

The Journal of Physiology

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Key points There is a rapid interneuronal response to focal activity in cortex, which restrains laterally propagating activity, including spreading epileptiform activity. The interneuronal response involves intense activation of both parvalbumin‐ and somatostatin‐expressing interneurons. Interneuronal bursting is time‐locked to glutamatergic barrages in the pre‐ictal period. Ca 2+ imaging using conditional expression of GCaMP6f provides an accurate readout of the evolving firing patterns in both types of interneuron. The activation profiles of the two interneuronal classes are temporally offset, with the parvalbumin population being activated first, and typically, at higher rates. Abstract Previous work has described powerful restraints on laterally spreading activity in cortical networks, arising from a rapid feedforward interneuronal response to focal activity. This response is particularly prominent ahead of an ictal wavefront. Parvalbumin‐positive interneurons are considered to be critically involved in this feedforward inhibition, but it is not known what role, if any, is provided by somatostatin‐expressing interneurons, which target the distal dendrites of pyramidal cells. We used a combination of electrophysiology and cell class‐specific Ca 2+ imaging in mouse brain slices bathed in 0 Mg 2+ medium to characterize the activity profiles of pyramidal cells and parvalbumin‐ and somatostatin‐expressing interneurons during epileptiform activation. The GCaMP6f signal strongly correlates with the level of activity for both interneuronal classes. Both interneuronal classes participate in the feedfoward inhibition. This contrasts starkly with the pattern of pyramidal recruitment, which is greatly delayed. During these barrages, both sets of interneurons show intense bursting, at rates up to 300Hz, which is time‐locked to the glutamatergic barrages. The activity of parvalbumin‐expressing interneurons appears to peak early in the pre‐ictal period, and can display depolarizing block during the ictal event. In contrast, somatostatin‐expressing interneuronal activity peaks significantly later, and firing persists throughout the ictal events. Interictal events appear to be very similar to the pre‐ictal period, albeit with slightly lower firing rates. Thus, the inhibitory restraint arises from a coordinated pattern of activity in the two main classes of cortical interneurons.

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Section: Discussionmentioning

confidence: 97%

Feedforward inhibition ahead of ictal wavefronts is provided by both parvalbumin‐ and somatostatin‐expressing interneurons

Parrish

Codadu

Scott

et al. 2019

The Journal of Physiology

View full text Add to dashboard Cite

show abstract

“…However, the seemingly paradoxical role of interneurons in seizure must be taken into account when interpreting these findings. While interneurons serve a clear role in restraining seizure propagation, there is also evidence that interneurons are complicit in seizure initiation, potentially serving a causal role 38,43,44,[105][106][107][108] . One hypothesized pathway through which interneuron hyperactivity may contribute to seizure is through the accumulation of chloride in these circuits which can make GABAergic signalling excitatory instead of inhibitory 37,109 , www.nature.com/scientificreports/ a behavior not implemented in our model to preserve mathematical tractability.…”

Section: Discussionmentioning

confidence: 99%

Neurostimulation stabilizes spiking neural networks by disrupting seizure-like oscillatory transitions

Rich

Hutt

Skinner

et al. 2020

Sci Rep

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An improved understanding of the mechanisms underlying neuromodulatory approaches to mitigate seizure onset is needed to identify clinical targets for the treatment of epilepsy. Using a Wilson–Cowan-motivated network of inhibitory and excitatory populations, we examined the role played by intrinsic and extrinsic stimuli on the network’s predisposition to sudden transitions into oscillatory dynamics, similar to the transition to the seizure state. Our joint computational and mathematical analyses revealed that such stimuli, be they noisy or periodic in nature, exert a stabilizing influence on network responses, disrupting the development of such oscillations. Based on a combination of numerical simulations and mean-field analyses, our results suggest that high variance and/or high frequency stimulation waveforms can prevent multi-stability, a mathematical harbinger of sudden changes in network dynamics. By tuning the neurons’ responses to input, stimuli stabilize network dynamics away from these transitions. Furthermore, our research shows that such stabilization of neural activity occurs through a selective recruitment of inhibitory cells, providing a theoretical undergird for the known key role these cells play in both the healthy and diseased brain. Taken together, these findings provide new vistas on neuromodulatory approaches to stabilize neural microcircuit activity.

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“…By replicating results from the animal literature in which destructive, pharmacological, or optogenetic manipulations have been performed. Previous studies in animal models have shown that neuronal firing is less precise when feed-forward inhibition is altered (Foffani et al, 2007;Ibarz et al, 2010;Miri et al, 2018;Trevelyan, 2009). This lack of action potential timing reliability has been related to several cellular processes.…”

Section: Discussionmentioning

confidence: 99%

Dual mechanisms of ictal high frequency oscillations in human rhythmic onset seizures

Smith

Merricks

Liou

et al. 2020

Preprint

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High frequency oscillations (HFOs) recorded from intracranial electrodes during epileptiform discharges are a proposed biomarker of epileptic brain tissue and may also be useful for seizure forecasting, with mixed results. Despite such potential for HFOs, there is limited investigation into the spatial context of HFOs and their relationship to simultaneously recorded neuronal activity. We sought to further understand the biophysical underpinnings of ictal HFOs using unit recordings in the human neocortex and mesial temporal lobe during rhythmic onset seizures. We compare features of ictal discharges in both the seizure core and penumbra (spatial seizure domains defined by multiunit activity patterns). We report differences in spectral features, unit-local field potential coupling, and information theoretic characteristics of HFOs before and after local seizure invasion. Furthermore, we tie these timing-related differences to spatial domains of seizures, showing that penumbral discharges are widely distributed and less useful for seizure localization.

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Altered hippocampal interneuron activity precedes ictal onset

Cited by 65 publications

References 94 publications

Feedforward inhibition ahead of ictal wavefronts is provided by both parvalbumin‐ and somatostatin‐expressing interneurons

Feedforward inhibition ahead of ictal wavefronts is provided by both parvalbumin‐ and somatostatin‐expressing interneurons

Neurostimulation stabilizes spiking neural networks by disrupting seizure-like oscillatory transitions

Dual mechanisms of ictal high frequency oscillations in human rhythmic onset seizures

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