Hilar mossy cell circuitry controlling dentate granule cell excitability.
Hilar mossy cell circuitry controlling dentate granule cell excitability.
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DOI：
10.3389/fncir.2013.00014
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发表时间：
2013
影响因子：
3.5
通讯作者：
Nakazawa K
中科院分区：
文献类型：
--
作者：
Jinde S;Zsiros V;Nakazawa K
谷氨酸能门苔藓细胞的齿状回可以兴奋或抑制远处的颗粒细胞，这取决于他们是否直接兴奋性预测颗粒细胞或他们的预测本地抑制性中间神经元占主导地位。然而，苔藓细胞损失的净效应是颗粒细胞兴奋还是抑制仍然存在争议。澄清这一争议与颞叶癫痫特别相关，颞叶癫痫的特征是齿状颗粒细胞过度兴奋和齿状门苔藓细胞的广泛丢失。两个截然相反的假说已经提出来解释这种颗粒细胞的过度兴奋性-“休眠篮状细胞”和“易激苔藓细胞”假说。“休眠篮状细胞”假说认为苔藓细胞在正常情况下对颗粒细胞产生净抑制作用，因此苔藓细胞的缺失导致齿状颗粒细胞过度兴奋。“易激苔藓细胞”假说则持相反观点，认为苔藓细胞通常会激发颗粒细胞，而癫痫中存活的苔藓细胞会增加它们的活性，导致颗粒细胞兴奋。由于不能选择性地消除苔藓细胞，因此很难检验这两种相反的假设。为此，我们开发了一种转基因毒素介导的苔藓细胞消融小鼠系。使用这些突变体，我们证明了广泛消除门苔藓细胞导致颗粒细胞过度兴奋，虽然观察到的苔藓细胞损失似乎不足以引起临床癫痫。在这篇综述中，我们专注于这一主题，并提出不同的中间神经元群体可能介导苔藓细胞诱导的translamellar侧抑制和intralamellar复发抑制。这些独特的局部电路在齿状门区可能集中参与齿状回的功能组织。
Glutamatergic hilar mossy cells of the dentate gyrus can either excite or inhibit distant granule cells, depending on whether their direct excitatory projections to granule cells or their projections to local inhibitory interneurons dominate. However, it remains controversial whether the net effect of mossy cell loss is granule cell excitation or inhibition. Clarifying this controversy has particular relevance to temporal lobe epilepsy, which is marked by dentate granule cell hyperexcitability and extensive loss of dentate hilar mossy cells. Two diametrically opposed hypotheses have been advanced to explain this granule cell hyperexcitability—the “dormant basket cell” and the “irritable mossy cell” hypotheses. The “dormant basket cell” hypothesis proposes that mossy cells normally exert a net inhibitory effect on granule cells and therefore their loss causes dentate granule cell hyperexcitability. The “irritable mossy cell” hypothesis takes the opposite view that mossy cells normally excite granule cells and that the surviving mossy cells in epilepsy increase their activity, causing granule cell excitation. The inability to eliminate mossy cells selectively has made it difficult to test these two opposing hypotheses. To this end, we developed a transgenic toxin-mediated, mossy cell-ablation mouse line. Using these mutants, we demonstrated that the extensive elimination of hilar mossy cells causes granule cell hyperexcitability, although the mossy cell loss observed appeared insufficient to cause clinical epilepsy. In this review, we focus on this topic and also suggest that different interneuron populations may mediate mossy cell-induced translamellar lateral inhibition and intralamellar recurrent inhibition. These unique local circuits in the dentate hilar region may be centrally involved in the functional organization of the dentate gyrus.
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影响因子：
2.2
作者：
Bernard, C;Esclapez, M;Bernard, C
通讯作者：
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影响因子：
3.5
作者：
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通讯作者：
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2.5
作者：
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通讯作者：
Sloviter, Robert S.