Descending projections from the substantia nigra pars reticulata differentially control seizures.
Proc Natl Acad Sci U S A
; 116(52): 27084-27094, 2019 Dec 26.
Article
em En
| MEDLINE
| ID: mdl-31843937
ABSTRACT
Three decades of studies have shown that inhibition of the substantia nigra pars reticulata (SNpr) attenuates seizures, yet the circuits mediating this effect remain obscure. SNpr projects to the deep and intermediate layers of the superior colliculus (DLSC) and the pedunculopontine nucleus (PPN), but the contributions of these projections are unknown. To address this gap, we optogenetically silenced cell bodies within SNpr, nigrotectal terminals within DLSC, and nigrotegmental terminals within PPN. Inhibition of cell bodies in SNpr suppressed generalized seizures evoked by pentylenetetrazole (PTZ), partial seizures evoked from the forebrain, absence seizures evoked by gamma-butyrolactone (GBL), and audiogenic seizures in genetically epilepsy-prone rats. Strikingly, these effects were fully recapitulated by silencing nigrotectal projections. By contrast, silencing nigrotegmental terminals reduced only absence seizures and exacerbated seizures evoked by PTZ. These data underscore the broad-spectrum anticonvulsant efficacy of this circuit, and demonstrate that specific efferent projection pathways differentially control different seizure types.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article