Reyes-Haro Daniel, Hernández-Santos José Antonio, Miledi Ricardo, Martínez-Torres Ataúlfo
Departamento de Neurobiología Celular y Molecular, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Campus Juriquilla, Boulevard Juriquilla 3001, Juriquilla, Querétaro CP76230, Mexico.
Departamento de Neurobiología Celular y Molecular, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Campus Juriquilla, Boulevard Juriquilla 3001, Juriquilla, Querétaro CP76230, Mexico.
Neuropharmacology. 2017 Feb;113(Pt A):407-415. doi: 10.1016/j.neuropharm.2016.10.024. Epub 2016 Oct 25.
The neostriatum plays a central role in motor coordination where nerve cells operate neuronal inhibition through GABAergic transmission. The neostriatum expresses a wide range of GABA-A subunits, including GABAρ1 and ρ2 which are restricted to a fraction of GABAergic interneurons and astrocytes. Spontaneous postsynaptic currents (sPSCs) evoked by 4-aminopyridine (4-AP) were recorded from neurones of the dorsal neostriatum, and their frequency was reduced > 50% by the selective GABAρ antagonist (1,2,5,6-Tetrahydropyridine-4-yl) methylphosphinic acid (TPMPA). Additionally, we recorded GABA evoked currents from astrocytes in vitro and in situ. Astrocytes in vitro showed modulation by pentobarbital and desensitization upon consecutive applications of GABA. However, modulation by pentobarbital was absent and no significant desensitization was detected from astrocytes in situ. Moreover, TPMPA-sensitive GABA-currents that were insensitive to bicuculline were also recorded from astrocytes in situ, consistent with our previous study where GABAρ expression was demonstrated. Finally, we assessed the mRNA expression of GABAρ3, through different stages of postnatal development; double immunofluorescence disclosed GABAρ3 expression in calretinin-positive interneurons as well as in astrocytes (>70%). These results add new information about the participation of GABAρ subunits in neostriatal interneurons and astrocytes.
新纹状体在运动协调中起核心作用，其中神经细胞通过GABA能传递发挥神经元抑制作用。新纹状体表达多种GABA - A亚基，包括GABAρ1和ρ2，它们仅存在于一部分GABA能中间神经元和星形胶质细胞中。从背侧新纹状体神经元记录了由4 - 氨基吡啶（4 - AP）诱发的自发性突触后电流（sPSC），其频率被选择性GABAρ拮抗剂（1,2,5,6 - 四氢吡啶 - 4 - 基）甲基次膦酸（TPMPA）降低了>50%。此外，我们在体外和原位记录了星形胶质细胞中GABA诱发的电流。体外培养的星形胶质细胞表现出戊巴比妥的调节作用以及连续应用GABA后的脱敏现象。然而，原位星形胶质细胞不存在戊巴比妥的调节作用，也未检测到明显的脱敏现象。此外，从原位星形胶质细胞中还记录到了对荷包牡丹碱不敏感但对TPMPA敏感的GABA电流，这与我们之前证明GABAρ表达的研究一致。最后，我们评估了出生后不同发育阶段GABAρ3的mRNA表达；双重免疫荧光显示GABAρ3在钙视网膜蛋白阳性中间神经元以及星形胶质细胞中表达（>70%）。这些结果为GABAρ亚基在新纹状体中间神经元和星形胶质细胞中的参与作用增添了新信息。
