Schwaller B, Tetko I V, Tandon P, Silveira D C, Vreugdenhil M, Henzi T, Potier M-C, Celio M R, Villa A E P
Department of Medicine, University of Fribourg, CH-1700 Fribourg, Switzerland.
Mol Cell Neurosci. 2004 Apr;25(4):650-63. doi: 10.1016/j.mcn.2003.12.006.
Networks of GABAergic interneurons are of utmost importance in generating and promoting synchronous activity and are involved in producing coherent oscillations. These neurons are characterized by their fast-spiking rate and by the expression of the Ca(2+)-binding protein parvalbumin (PV). Alteration of their inhibitory activity has been proposed as a major mechanism leading to epileptic seizures and thus the role of PV in maintaining the stability of neuronal networks was assessed in knockout (PV-/-) mice. Pentylenetetrazole induced generalized tonic-clonic seizures in all genotypes, but the severity of seizures was significantly greater in PV-/- than in PV+/+ animals. Extracellular single-unit activity recorded from over 1000 neurons in vivo in the temporal cortex revealed an increase of units firing regularly and a decrease of cells firing in bursts. In the hippocampus, PV deficiency facilitated the GABA(A)ergic current reversal induced by high-frequency stimulation, a mechanism implied in the generation of epileptic activity. We postulate that PV plays a key role in the regulation of local inhibitory effects exerted by GABAergic interneurons on pyramidal neurons. Through an increase in inhibition, the absence of PV facilitates synchronous activity in the cortex and facilitates hypersynchrony through the depolarizing action of GABA in the hippocampus.
γ-氨基丁酸能中间神经元网络在产生和促进同步活动方面至关重要，并参与产生连贯的振荡。这些神经元的特征在于其快速放电率以及钙结合蛋白小白蛋白（PV）的表达。其抑制活性的改变被认为是导致癫痫发作的主要机制，因此在基因敲除（PV-/-）小鼠中评估了PV在维持神经元网络稳定性中的作用。戊四氮在所有基因型中均诱发全身性强直阵挛性发作，但PV-/-小鼠的发作严重程度明显高于PV+/+动物。从颞叶皮质超过1000个神经元体内记录的细胞外单单位活动显示，规则放电的单位增加，而爆发式放电的细胞减少。在海马体中，PV缺乏促进了高频刺激诱导的GABA（A）能电流反转，这是癫痫活动产生中所涉及的一种机制。我们推测，PV在调节γ-氨基丁酸能中间神经元对锥体神经元施加的局部抑制作用中起关键作用。通过增加抑制作用，PV的缺失促进了皮质中的同步活动，并通过海马体中GABA的去极化作用促进了超同步化。
