A disinhibitory nigra-parafascicular pathway amplifies seizure in temporal lobe epilepsy.
Nat Commun
; 11(1): 923, 2020 02 17.
Article
em En
| MEDLINE
| ID: mdl-32066723
ABSTRACT
The precise circuit of the substantia nigra pars reticulata (SNr) involved in temporal lobe epilepsy (TLE) is still unclear. Here we found that optogenetic or chemogenetic activation of SNr parvalbumin+ (PV) GABAergic neurons amplifies seizure activities in kindling- and kainic acid-induced TLE models, whereas selective inhibition of these neurons alleviates seizure activities. The severity of seizures is bidirectionally regulated by optogenetic manipulation of SNr PV fibers projecting to the parafascicular nucleus (PF). Electrophysiology combined with rabies virus-assisted circuit mapping shows that SNr PV neurons directly project to and functionally inhibit posterior PF GABAergic neurons. Activity of these neurons also regulates seizure activity. Collectively, our results reveal that a long-range SNr-PF disinhibitory circuit participates in regulating seizure in TLE and inactivation of this circuit can alleviate severity of epileptic seizures. These findings provide a better understanding of pathological changes from a circuit perspective and suggest a possibility to precisely control epilepsy.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Substância Negra
/
Núcleos Intralaminares do Tálamo
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Epilepsia do Lobo Temporal
/
Vias Neurais
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Limite:
Animals
/
Humans
/
Male
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article