콘텐츠로 건너뛰기
Merck
  • Properties of the epileptiform activity in the cingulate cortex of a mouse model of LIS1 dysfunction.

Properties of the epileptiform activity in the cingulate cortex of a mouse model of LIS1 dysfunction.

Brain structure & function (2022-02-02)
E Domínguez-Sala, A Andreu-Cervera, P Martín-Climent, R Murcia-Ramón, S Martínez, Emilio Geijo-Barrientos
초록

Dysfunction of the LIS1 gene causes lissencephaly, a drastic neurological disorder characterized by a deep disruption of the cortical structure. We aim to uncover alterations of the cortical neuronal networks related with the propagation of epileptiform activity in the Lis1/sLis1 mouse, a model lacking the LisH domain in heterozygosis. We did extracellular field-potential and intracellular recordings in brain slices of the anterior cingulate cortex (ACC) or the retrosplenial cortex (RSC) to study epileptiform activity evoked in the presence of bicuculline (10 µM), a blocker of GABAA receptors. The sensitivity to bicuculline of the generation of epileptiform discharges was similar in wild type (WT) and Lis1/sLis1 cortex (EC50 1.99 and 2.24 µM, respectively). In the Lis1/sLis1 cortex, we observed a decreased frequency of the oscillatory post-discharges of the epileptiform events; also, the propagation of epileptiform events along layer 2/3 was slower in the Lis1/sLis1 cortex (WT 47.69 ± 2.16 mm/s, n = 25; Lis1/sLis1 37.34 ± 2.43 mm/s, n = 15; p = 0.004). The intrinsic electrophysiological properties of layer 2/3 pyramidal neurons were similar in WT and Lis1/sLis1 cortex, but the frequency of the spontaneous EPSCs was lower and their peak amplitude higher in Lis1/sLis1 pyramidal neurons. Finally, the propagation of epileptiform activity was differently affected by AMPA receptor blockers: CNQX had a larger effect in both ACC and RSC while GYKI53655 had a larger effect only in the ACC in the WT and Lis1/sLis1 cortex. All these changes indicate that the dysfunction of the LIS1 gene causes abnormalities in the properties of epileptiform discharges and in their propagation along the layer 2/3 in the anterior cingulate cortex and in the restrosplenial cortex.

MATERIALS
제품 번호
브랜드
제품 설명

Sigma-Aldrich
Anti-Chicken IgY (IgG) (whole molecule)−FITC antibody produced in rabbit, affinity isolated antibody, buffered aqueous solution