Layer- and Cell-Specific Recruitment Dynamics during Epileptic Seizures In Vivo.
Ann Neurol
; 87(1): 97-115, 2020 01.
Article
em En
| MEDLINE
| ID: mdl-31657482
ABSTRACT
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;8797-115.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Recrutamento Neurofisiológico
/
Convulsões
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Células Piramidais
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Interneurônios
Limite:
Animals
Idioma:
En
Revista:
Ann Neurol
Ano de publicação:
2020
Tipo de documento:
Article