Overstreet-Wadiche Linda S, Bromberg Daniel A, Bensen Aesoon L, Westbrook Gary L
Vollum Institute, L474, Oregon Health and Science University, Portland, Oregon 97239, USA.
J Neurosci. 2006 Apr 12;26(15):4095-103. doi: 10.1523/JNEUROSCI.5508-05.2006.
In humans and experimental animals, structural and functional changes in neural circuits can accompany the development of epilepsy. In the dentate gyrus, seizures enhance adult neurogenesis, but it is unclear to what extent newborn granule cells participate in seizure-induced synaptic reorganization. During the first weeks of their existence, mouse newborn granule cells labeled with enhanced green fluorescent protein have only short dendrites that lack excitatory input. We report that pilocarpine-induced seizures accelerated the morphological development of labeled granule cells, causing their dendrites to extend through the molecular layer. In whole-cell recordings 5-16 d after seizure induction, perforant-path stimulation now evoked glutamatergic input to newborn granule cells. These synaptic responses were mediated by monosynaptic as well as recurrent polysynaptic input. Thus, seizures facilitated functional integration of adult-generated granule cells. One month later, subsequent generations of newborn cells also showed alterations in dendrite morphology, suggesting persistent effects of seizures on granule cell maturation. The sensitivity of newborn granule cells to seizures could contribute to hyperexcitability during the latent period.
在人类和实验动物中，神经回路的结构和功能变化可能伴随癫痫的发展。在齿状回中，癫痫发作会增强成体神经发生，但尚不清楚新生颗粒细胞在多大程度上参与癫痫诱导的突触重组。在其存在的最初几周内，用增强型绿色荧光蛋白标记的小鼠新生颗粒细胞只有短的树突，且缺乏兴奋性输入。我们报告，毛果芸香碱诱导的癫痫发作加速了标记颗粒细胞的形态发育，使其树突延伸穿过分子层。在癫痫发作诱导后5 - 16天的全细胞记录中，穿通通路刺激现在可诱发对新生颗粒细胞的谷氨酸能输入。这些突触反应由单突触以及反复的多突触输入介导。因此，癫痫发作促进了成体产生的颗粒细胞的功能整合。一个月后，后代新生细胞的树突形态也出现改变，表明癫痫发作对颗粒细胞成熟有持续影响。新生颗粒细胞对癫痫发作的敏感性可能导致潜伏期的过度兴奋。
