Staff Nathan P, Spruston Nelson
Department of Neurobiology and Physiology, Institute for Neuroscience, Northwestern University, Evanston, Illinois 60208, USA.
Hippocampus. 2003;13(7):801-5. doi: 10.1002/hipo.10129.
The hippocampus has been used extensively as a model to study plastic changes in the brain's neural circuitry. Immediately after high-frequency stimulation to hippocampal Schaffer collateral axons, a dramatic change occurs in the relationship between the presynaptic CA3 and the postsynaptic CA1 pyramidal neurons. For a fixed excitatory postsynaptic potential (EPSP), there arises an increased likelihood of action potential generation in the CA1 pyramidal neuron. This phenomenon is called EPSP-spike (E-S) potentiation. We explored E-S potentiation, using patch-clamp techniques in the hippocampal slice preparation. A specific protocol was developed to measure the action potential probability for a given synaptic strength, which allowed us to quantify the amount of E-S potentiation for a single neuron. E-S potentiation was greatest when gamma-aminobutyric acid (GABA)ergic inhibition was intact, suggesting that modulation of inhibition is a major aspect of E-S potentiation. Expression of E-S potentiation also correlated with a reduced action-potential threshold, which was greatest when GABAergic inhibition was intact. Conditioning stimuli produced a smaller threshold reduction when inhibition was blocked, but some reduction also occurred in the absence of a conditioning stimulus. Together, these results suggest that E-S potentiation is caused primarily through a reduction of GABAergic inhibition, leading to larger EPSPs and reduced action potential threshold. Our findings do not rule out, however, the possibility that modulation of voltage-gated conductances also contributes to E-S potentiation.
海马体已被广泛用作研究大脑神经回路可塑性变化的模型。在对海马体的谢弗侧支轴突进行高频刺激后，突触前CA3和突触后CA1锥体神经元之间的关系会发生显著变化。对于固定的兴奋性突触后电位（EPSP），CA1锥体神经元产生动作电位的可能性增加。这种现象被称为EPSP-锋电位（E-S）增强。我们在海马体脑片标本中使用膜片钳技术探索了E-S增强。我们制定了一个特定的方案来测量给定突触强度下的动作电位概率，这使我们能够量化单个神经元的E-S增强量。当γ-氨基丁酸（GABA）能抑制完整时，E-S增强最大，这表明抑制的调节是E-S增强的一个主要方面。E-S增强的表达也与动作电位阈值的降低相关，当GABA能抑制完整时，这种降低最为明显。当抑制被阻断时，条件刺激产生的阈值降低较小，但在没有条件刺激的情况下也会出现一些降低。总之，这些结果表明，E-S增强主要是通过GABA能抑制的减少引起的，导致更大的EPSP和降低的动作电位阈值。然而，我们的发现并不排除电压门控电导的调节也有助于E-S增强的可能性。
