Shift from phasic to tonic GABAergic transmission following laser-lesions in the rat visual cortex
Shift from phasic to tonic GABAergic transmission following laser-lesions in the rat visual cortex
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DOI：
10.1007/s00424-012-1191-y
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发表时间：
2013-06-01
影响因子：
4.5
通讯作者：
Mittmann, Thomas
中科院分区：
文献类型：
--
作者：
Imbrosci, Barbara;Neubacher, Ute;Mittmann, Thomas
GABA能神经传递强度的降低经常被报道在脑损伤后。这种减弱的抑制被认为影响脑损伤后的神经缺陷、神经元过度兴奋和功能恢复。因此，揭示抑制作用改变的机制至关重要。在本研究中，我们使用了离体-体外模型的激光损伤在大鼠视觉皮层的特点的细胞相关的变化，在损伤附近的组织中的GABA能传递。在损伤后第一周，VGAT阳性GABA能末梢的数量以及GABA合成酶GAD 67和GAD 65的表达水平保持不变。然而，降低频率的微型抑制性突触后电流（mIPSC），以及增加的成对脉冲比（PPR）诱发IPSC建议功能减少的阶段性GABA释放。同时，我们发现GABA（A）受体介导的紧张性抑制增强。在这些发现的基础上，我们提出，皮质病变引起GABA能传递的转变，减少相位和加强紧张成分。因此，我们认为，它不是，传统上认为，整体抑制强度主要是由皮质病变，而是GABA能突触信号的时间准确性受到损害。
Reduction in the strength of GABAergic neurotransmission has often been reported following brain lesions. This weakened inhibition is believed to influence neurological deficits, neuronal hyperexcitability and functional recovery after brain injuries. Uncovering the mechanisms underlying the altered inhibition is therefore crucial. In the present study we used an ex vivo-in vitro model of laser lesions in the rat visual cortex to characterize the cellular correlates of changes in GABAergic transmission in the tissue adjacent to the injury. In the first week post-injury the number of VGAT positive GABAergic terminals as well as the expression level of the GABA synthesizing enzymes GAD67 and GAD65 remained unaltered. However, a reduced frequency of miniature inhibitory postsynaptic currents (mIPSCs) together with an increased paired-pulse ratio (PPR) of evoked IPSCs suggested a functional reduction of phasic GABA release. In parallel, we found an enhancement in the GABA(A) receptor-mediated tonic inhibition. On the basis of these findings, we propose that cortical lesions provoke a shift in GABAergic transmission, decreasing the phasic and reinforcing the tonic component. We therefore suggest that it is not, as traditionally assumed, the overall inhibitory strength to be primarily compromised by a cortical lesion but rather the temporal accuracy of the GABAergic synaptic signaling.