2P or not 2P: The Question of Seizure Initiation. Issue 5 (September 2020)

• Record Type: Journal Article
• Authors: Somarowthu, Ala; Goldberg, Ethan M.
• Is Part Of: Epilepsy currents. Volume 20:Issue 5(2020)
• Page Start: 291
• Page End: 293
• Publication Date: 2020-09
• Subjects: Epilepsy -- Periodicals; 616.853005
• DOI: 10.1177/1535759720941023
• Languages: English
• ISSNs: 1535-7597

Abstract

Layer- and Cell-Specific Recruitment Dynamics During Epileptic Seizures In Vivo Aeed F, Shnitzer T, Talmon R, Schiller Y. Ann Neurol. 2020;87(1):97-115. doi:10.1002/ana.25628 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.