Liang R, Pang Z-P, Deng P, Xu Z C
Institute of Neuroscience and the 2nd Affiliated Hospital of Guangzhou Medical College, Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province, the Ministry of Education of China, Guangzhou, China.
Neuroscience. 2009 May 5;160(2):412-8. doi: 10.1016/j.neuroscience.2009.02.046. Epub 2009 Mar 1.
Pyramidal neurons in hippocampal CA1 regions are highly sensitive to cerebral ischemia. Alterations of excitatory and inhibitory synaptic transmission may contribute to the ischemia-induced neuronal degeneration. However, little is known about the changes of GABAergic synaptic transmission in the hippocampus following reperfusion. We examined the GABA(A) receptor-mediated inhibitory postsynaptic currents (IPSCs) in CA1 pyramidal neurons 12 and 24 h after transient forebrain ischemia in rats. The amplitudes of evoked inhibitory postsynaptic currents (eIPSCs) were increased significantly 12 h after ischemia and returned to control levels 24 h following reperfusion. The potentiation of eIPSCs was accompanied by an increase of miniature inhibitory postsynaptic current (mIPSC) amplitude, and an enhanced response to exogenous application of GABA, indicating the involvement of postsynaptic mechanisms. Furthermore, there was no obvious change of the paired-pulse ratio (PPR) of eIPSCs and the frequency of mIPSCs, suggesting that the potentiation of eIPSCs might not be due to the increased presynaptic release. Blockade of adenosine A1 receptors led to a decrease of eIPSCs amplitude in post-ischemic neurons but not in control neurons, without affecting the frequency of mIPSCs and the PPR of eIPSCs. Thus, tonic activation of adenosine A1 receptors might, at least in part, contribute to the enhancement of inhibitory synaptic transmission in CA1 neurons after forebrain ischemia. The transient enhancement of inhibitory neurotransmission might temporarily protect CA1 pyramidal neurons, and delay the process of neuronal death after cerebral ischemia.
海马体CA1区的锥体神经元对脑缺血高度敏感。兴奋性和抑制性突触传递的改变可能导致缺血诱导的神经元变性。然而，关于再灌注后海马体中γ-氨基丁酸能（GABAergic）突触传递的变化知之甚少。我们检测了大鼠短暂性前脑缺血后12小时和24小时时，CA1锥体神经元中GABA(A)受体介导的抑制性突触后电流（IPSCs）。缺血后12小时，诱发的抑制性突触后电流（eIPSCs）幅度显著增加，再灌注后24小时恢复到对照水平。eIPSCs的增强伴随着微小抑制性突触后电流（mIPSC）幅度的增加，以及对外源性GABA应用的反应增强，表明突触后机制参与其中。此外，eIPSCs的配对脉冲比率（PPR）和mIPSCs的频率没有明显变化，这表明eIPSCs的增强可能不是由于突触前释放增加所致。阻断腺苷A1受体导致缺血后神经元中eIPSCs幅度降低，但对照神经元中未出现这种情况，且不影响mIPSCs的频率和eIPSCs的PPR。因此，腺苷A1受体的紧张性激活可能至少部分地促成了前脑缺血后CA1神经元中抑制性突触传递的增强。抑制性神经传递的短暂增强可能会暂时保护CA1锥体神经元，并延迟脑缺血后神经元死亡的进程。
