Disinhibition-Mediated LTP in the Hippocampus is Synapse Specific
Disinhibition-Mediated LTP in the Hippocampus is Synapse Specific
复制标题
海马体中去抑制介导的 LTP 是突触特异性的
DOI：
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发表时间：
2011
影响因子：
5.3
通讯作者：
M. Woodin
中科院分区：
文献类型：
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作者：
Jake Ormond;M. Woodin
海马区CA1区成对的突触前和突触后活动诱导GABA能突触的长期抑制性突触可塑性。这种配对诱导的GABA能可塑性减弱了突触抑制，这是由于GABA受体介导的电流的反转电位通过神经元特异性K+-CL−共转运体KCC2功能的降低而去极化。当配对诱导的GABA能可塑性在CA1的前馈抑制性突触被诱导时，抑制作用的降低导致锥体神经元Schaffer侧支介导的突触后电位的幅度增加。这种形式的抑制性突触可塑性被称为去抑制介导的长时程增强(LTP)。在本研究中，我们研究了去抑制介导的LTP是否是突触特异性的。我们在成年SD大鼠的海马片上进行了这些实验。我们发现，EGABA潜在的去极化并不局限于配对的通路，而是在未配对的控制通路上以同样的程度表达。然而，GABA能传递的总体强度通过GABA能电导的异构性增加维持在未配对的途径上。在成对和未成对的通路上，EGABA的配对诱导的去极化需要通过L电压门控钙通道和N-甲基-d-天冬氨酸受体的钙内流。然而，非配对通路的电导增加只需要通过L类通道的钙内流。由于GABA能电导的增加，去抑制介导的LTP仍然局限于成对的通路，因此是突触特异性的，这表明它可能是海马依赖学习和记忆的一种新机制。
Paired pre- and postsynaptic activity in area CA1 of the hippocampus induces long-term inhibitory synaptic plasticity at GABAergic synapses. This pairing-induced GABAergic plasticity weakens synaptic inhibition due to a depolarization of the reversal potential for GABAA receptor-mediated currents (EGABA) through a decrease in the function of the neuron-specific K+–Cl− cotransporter KCC2. When pairing-induced GABAergic plasticity is induced at feed-forward inhibitory synapses in the CA1, the decrease in inhibition produces an increase in the amplitude of Schaffer collateral-mediated postsynaptic potentials in pyramidal neurons. This form of inhibitory synaptic plasticity is termed disinhibition-mediated long-term potentiation (LTP). In the present study, we investigated whether disinhibition-mediated LTP is synapse specific. We performed these experiments in hippocampal slices prepared from adult Sprague Dawley rats. We found that the underlying depolarization of EGABA is not restricted to the paired pathway, but rather is expressed to the same extent at unpaired control pathways. However, the overall strength of GABAergic transmission is maintained at the unpaired pathway by a heterosynaptic increase in GABAergic conductance. The pairing-induced depolarization of EGABA at the paired and unpaired pathways required Ca2+-influx through both the L-type voltage-gated Ca2+ channels and N-methyl-d-aspartic acid receptors. However, only Ca2+-influx through L-type channels was required for the increased conductance at the unpaired pathway. As a result of this increased GABAergic conductance, disinhibition-mediated LTP remains confined to the paired pathway and thus is synapse specific, suggesting it may be a novel mechanism for hippocampal-dependent learning and memory.