Connectivity and Neuronal Synchrony during Seizures.
J Neurosci
; 41(36): 7623-7635, 2021 09 08.
Article
em En
| MEDLINE
| ID: mdl-34326143
ABSTRACT
There is uncertainty regarding when and which groups of neurons fire synchronously during seizures. While several studies found heterogeneous firing during seizures, others suggested synchronous neuronal firing in the seizure core. We tested whether neuronal activity during seizures is orderly in the direction of the excitatory neuronal connections in the circuit. There are strong excitatory connections laterally within the septotemporally organized lamella and inhibitory trans-lamellar connections in the hippocampus, which allow testing of the connectivity hypothesis. We further tested whether epileptogenesis enhances synchrony and antiseizure drug administration disrupts it. We recorded local field potentials from CA1 pyramidal neurons using a small microelectrode array and kindled rats by a rapid, recurrent hippocampal stimulation protocol. We compared cross-correlation, theta phase synchronization, entropy, and event synchronization. These analyses revealed that the firing pattern was correlated along the lamellar, but not the septotemporal, axis during evoked seizures. During kindling, neuronal synchrony increased along the lamellar axis, while synchrony along the septotemporal axis remained relatively low. Additionally, the theta phase distribution demonstrated that CA1 pyramidal cell firing became preferential for theta oscillation negative peak as kindling progressed in the lamellar direction but not in the trans-lamellar direction. Last, event synchronization demonstrated that neuronal firings along the lamellar axis were more synchronized than those along the septotemporal axis. There was a marked decrease in synchronization and phase preference after treatment with phenytoin and levetiracetam. The synchrony structure of CA1 pyramidal neurons during seizures and epileptogenesis depends on anatomic connectivity and plasticity.SIGNIFICANCE STATEMENT We could improve the efficacy of brain stimulation to treat seizures by understanding the structure of synchrony. Electrical stimulation may disrupt seizures by desynchronizing neurons, but there is an uncertainty on which groups of neurons fire synchronously or chaotically during seizures. Here, we demonstrate that neurons linked by excitatory connections fire synchronously during seizures, and this synchrony is modulated by epileptogenesis and antiseizure drugs. Closed-loop brain stimulation carefully targeted to disrupt synchrony may improve the treatment of seizures.
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Base de dados:
MEDLINE
Assunto principal:
Convulsões
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Potenciais de Ação
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Hipocampo
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Rede Nervosa
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Neurônios
Tipo de estudo:
Guideline
Limite:
Animals
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article