Wilcox K S, Dichter M A
Department of Physiology, University of Pennsylvania, School of Medicine, Philadelphia 19104.
J Neurosci. 1994 Mar;14(3 Pt 2):1775-88. doi: 10.1523/JNEUROSCI.14-03-01775.1994.
Most rapid synaptic inhibition in the vertebrate forebrain is mediated by GABA acting via GABAA and GABAB postsynaptic receptors. GABAergic neurotransmission exhibits frequency-dependent modulation; sequential inhibitory post-synaptic currents (IPSCs) evoked with interstimulus intervals between 25 msec and 4 sec routinely result in the attenuation of the amplitude of the second IPSC. This form of synaptic plasticity is known as paired pulse depression (PPD). The mechanism of PPD is presently unknown and the experiments performed in this study were designed to determine directly the location of the mechanism of PPD in hippocampal neurons maintained in low-density tissue culture. Evoked IPSCs were recorded between pairs of cultured neurons grown in relative isolation that were simultaneously being recorded with the whole-cell, patch-clamp technique. It was therefore possible to measure miniature IPSCs (mIPSCs) originating from the same synapses that were being stimulated to evoke release. PPD occurred routinely in this system, but the amplitudes of mIPSCs following IPSCs were unchanged. These results indicate that a presynaptic mechanism mediates PPD. The inability of GABAB receptor antagonists to block PPD revealed that this form of presynaptic plasticity was not due to autoinhibition of transmitter release via activation of presynaptic GABAB receptors. However, manipulations that significantly lowered the probability of release of neurotransmitter during the first action potential of a trial (e.g., lower calcium or baclofen) prevented the development of PPD. These results indicate that, under baseline conditions, the quantal content for IPSCs is relatively large for a single action potential, but the quantal content rapidly decreases, such that subsequent action potentials consistently result in much smaller IPSCs for periods as long as 4 sec.
脊椎动物前脑中最快的突触抑制是由γ-氨基丁酸（GABA）通过GABAA和GABAB突触后受体介导的。GABA能神经传递表现出频率依赖性调制；在25毫秒至4秒的刺激间隔下诱发的连续抑制性突触后电流（IPSCs）通常会导致第二个IPSC的幅度衰减。这种突触可塑性形式被称为双脉冲抑制（PPD）。PPD的机制目前尚不清楚，本研究中进行的实验旨在直接确定PPD机制在低密度组织培养中维持的海马神经元中的位置。在相对孤立生长的成对培养神经元之间记录诱发的IPSCs，同时用全细胞膜片钳技术进行记录。因此，可以测量源自被刺激以诱发释放的相同突触的微小IPSCs（mIPSCs）。在该系统中PPD通常会发生，但IPSCs之后的mIPSCs幅度没有变化。这些结果表明，一种突触前机制介导了PPD。GABAB受体拮抗剂无法阻断PPD，这表明这种形式的突触前可塑性不是由于通过激活突触前GABAB受体对递质释放的自身抑制。然而，在试验的第一个动作电位期间显著降低神经递质释放概率的操作（例如，降低钙或巴氯芬）可防止PPD的发生。这些结果表明，在基线条件下，对于单个动作电位，IPSCs的量子含量相对较大，但量子含量会迅速下降，以至于随后的动作电位在长达4秒的时间内持续导致小得多的IPSCs。
