Altered hippocampal interneuron activity precedes ictal onset

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

doi:10.1101/064956

Cited by 20 publications

(40 citation statements)

References 65 publications

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“…7F). 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 2018).…”

Section: Discussionsupporting

confidence: 93%

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: Discussionsupporting

confidence: 93%

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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“…22,31 They also reported different recruitment dynamics of PNs compared to PV-and SOM-expressing INs during the preictal and ictal phases during propagation of magnesium free induced seizures in brain slices in vitro, and the preictal and ictal phases of pilocarpine-and pentylenetetrazol-induced hippocampal seizures in vivo. 31 Importantly, these studies concentrated on the dynamics over longer time windows (seconds), whereas we concentrated on much shorter time windows (<1 second) at the onset of spikes and seizures. induced by a cholinergic nicotinic blocker, spikes originated in layer 2/3, whereas slow waves were generated in the deeper neocortical layer.…”

Section: Discussionmentioning

confidence: 98%

Layer‐ and Cell‐Specific Recruitment Dynamics during Epileptic Seizures In Vivo

Aeed

Shnitzer

Talmon

et al. 2019

Annals of Neurology

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Objective To investigate the network dynamics mechanisms underlying differential initiation of epileptic interictal spikes and seizures. Methods We performed combined in vivo 2‐photon calcium imaging from different targeted neuronal subpopulations and extracellular electrophysiological recordings during 4‐aminopyridine–induced neocortical spikes and seizures. Results Both spikes and seizures were associated with intense synchronized activation of excitatory layer 2/3 pyramidal neurons (PNs) and to a lesser degree layer 4 neurons, as well as inhibitory parvalbumin‐expressing interneurons (INs). In sharp contrast, layer 5 PNs and somatostatin‐expressing INs were gradually and asynchronously recruited into the ictal activity during the course of seizures. Within layer 2/3, the main difference between onset of spikes and seizures lay in the relative recruitment dynamics of excitatory PNs compared to parvalbumin‐ and somatostatin‐expressing inhibitory INs. Whereas spikes exhibited balanced recruitment of PNs and parvalbumin‐expressing INs, during seizures IN responses were reduced and less synchronized than in layer 2/3 PNs. Similar imbalance was not observed in layers 4 or 5 of the neocortex. Machine learning–based algorithms we developed were able to distinguish spikes from seizures based solely on activation dynamics of layer 2/3 PNs at discharge onset. Interpretation During onset of seizures, the recruitment dynamics markedly differed between neuronal subpopulations, with rapid synchronous recruitment of layer 2/3 PNs, layer 4 neurons, and parvalbumin‐expressing INs and gradual asynchronous recruitment of layer 5 PNs and somatostatin‐expressing INs. Seizures initiated in layer 2/3 due to a dynamic mismatch between local PNs and inhibitory INs, and only later spread to layer 5 by gradually and asynchronously recruiting PNs in this layer. ANN NEUROL 2020;87:97–115

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“…In primate cortex there are only limited possibilities to target cell types based on molecular markers. Primate studies have therefore analyzed action potential waveforms and firing statistics to distinguish between fast-spiking interneurons and excitatory cells, which generally yields high overlap with genetic and morphological markers of cell classes (McCormick et al, 1985;Senzai et al, 2019;Miri et al, 2018;Gentet et al, 2012;Cardin et al, 2009;Vinck et al, 2013a;Ardid et al, 2015;Mitchell et al, 2007;Perrenoud et al, 2016;Hasenstaub et al, 2005;Nowak et al, 2003;Trainito et al, 2019). Furthermore, the differentiation between distinct excitatory cell types depends at present primarily on firing characteristics (Nowak et al, 2003;Bartho et al, 2004).…”

Section: E-i Interactions Arementioning

confidence: 99%

“…Previous studies have distinguished between fast-spiking interneurons and excitatory cells based on the peak-to-trough duration of the AP waveform. This approach is motivated by several considerations: 1) The percentage of inhibitory (GABAergic) interneurons in cortex is small (Hendry et al, 1987;Rudy et al, 2011) 2) Inhibitory interneurons, especially fast-spiking interneurons, typically have narrow-waveform APs (Vinck and Bosman, 2016;Gentet et al, 2012;Senzai et al, 2019;Csicsvari et al, 2003;Miri et al, 2018;Perrenoud et al, 2016;Sirota et al, 2008;McCormick et al, 1985). 3) By contrast, most excitatory neurons have broad-waveform APs (Senzai et al, 2019;Gentet et al, 2012;Hasenstaub et al, 2005;Perrenoud et al, 2016;McCormick et al, 1985).…”

Section: Classification and Characterization Of Neuron Typesmentioning

confidence: 99%

“…3) By contrast, most excitatory neurons have broad-waveform APs (Senzai et al, 2019;Gentet et al, 2012;Hasenstaub et al, 2005;Perrenoud et al, 2016;McCormick et al, 1985). 4) In most systems, the percentages of narrow-waveform neurons and inhibitory interneurons are comparable (Senzai et al, 2019;Ardid et al, 2015;Miri et al, 2018;Csicsvari et al, 2003;Sirota et al, 2008). Various techniques, including optogenetics, have been used to validate the identification of neuron types based on AP waveform (Senzai et al, 2019;Miri et al, 2018;Gentet et al, 2012;Bartho et al, 2004).…”

Section: Classification and Characterization Of Neuron Typesmentioning

confidence: 99%

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A distinct class of bursting neurons with strong gamma synchronization and stimulus selectivity in monkey V1

Onorato

Neuenschwander

Hoy

et al. 2019

Preprint

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Cortical computation depends on interactions between excitatory and inhibitory neurons. The contributions of distinct neuron-types to sensory processing and network synchronization in primate visual-cortex remain largely undetermined. We show that in awake monkey V1, there exists a distinct cell-type (≈30% of neurons) that has narrow-waveform action-potentials, high spontaneous discharge-rates, and fires in high-frequency bursts. These neurons are more stimulus-selective and phase-locked to gamma (30-80Hz) oscillations as compared to other neuron types. Unlike the other neuron-types, their gamma phase-locking is highly predictive of their orientation tuning. We find evidence for strong rhythmic inhibition in these neurons, suggesting that they interact with interneurons to act as excitatory pacemakers for the V1 gamma rhythm. These neurons have not been observed in other primate cortical areas and we find that they are not present in rodent V1. However, they resemble the excitatory "chattering" neurons previously identified by intracellular recordings in cat V1. Given its properties, this neuron type should be pivotal for the encoding and transmission of V1 stimulus information.

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Altered hippocampal interneuron activity precedes ictal onset

Cited by 20 publications

References 65 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

Layer‐ and Cell‐Specific Recruitment Dynamics during Epileptic Seizures In Vivo

A distinct class of bursting neurons with strong gamma synchronization and stimulus selectivity in monkey V1

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