Genetic enhancement of thalamocortical network activity by elevating alpha 1g-mediated low-voltage-activated calcium current induces pure absence epilepsy.
J Neurosci
; 29(6): 1615-25, 2009 Feb 11.
Article
em En
| MEDLINE
| ID: mdl-19211869
ABSTRACT
Absence seizures are a leading form of childhood epilepsy. Human and mouse P/Q-type calcium channel gene mutations initiate a complex absence epilepsy and ataxia phenotype, and in mice, secondarily elevate neuronal low-voltage-activated T-type calcium currents. These currents influence thalamocortical network activity and contribute to the generation of cortical spike-wave discharges (SWDs) associated with absence seizures. To address whether enhanced thalamocortical T-type currents suffice to induce an epileptic phenotype, two BAC transgenic mouse lines overexpressing the Cacna1g gene for alpha1G T-type calcium channels were generated with low and high transgene copy numbers that exhibit elevated alpha1G expression and showed increased functional T-type currents measured in thalamic neurons. Both lines exhibit frequent bilateral cortical SWDs associated with behavioral arrest but lack other overt neurological abnormalities. These models provide the first evidence that primary elevation of brain T-type currents are causally related to pure absence epilepsy, and selectively identify Cacna1g, one of the three T-type calcium channel genes, as a key component of a genetically complex epileptogenic pathway.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Tálamo
/
Córtex Cerebral
/
Epilepsia Tipo Ausência
/
Canais de Cálcio Tipo T
/
Rede Nervosa
Tipo de estudo:
Etiology_studies
Limite:
Animals
Idioma:
En
Revista:
J Neurosci
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Estados Unidos