Hatta K, Ankri N, Faber D S, Korn H
Biologie Cellulaire et Moléculaire du Neurone, INSERM U261, Institut Pasteur, 25, rue du Dr Roux, 75724 Cedex 15, Paris, France.
Neuroscience. 2001;103(2):561-79. doi: 10.1016/s0306-4522(00)00570-4.
In vivo recordings from Mauthner cells in adult zebrafish (Danio rerio) and goldfish (Carassius auratus) preparations with potassium chloride filled electrodes revealed a new class of long-lasting synaptic events in these cells. Their decay time constant ranged from 20 to 80ms, which is about 20 times longer than that of previously identified fast glycinergic inhibitory postsynaptic potentials in this neuron. The average time to peak of these slow events ranged from 1 to 6ms. We demonstrated that they are also inhibitory since (i) they were resistant to antagonists of the excitatory glutamatergic receptors; (ii) their amplitude was increased following chloride loading of the Mauthner cell; (iii) their reversal potential was the same as that of fast, glycinergic inhibitory postsynaptic potentials; and (iv) they produced an inhibitory shunt of the cell's membrane resistance. Furthermore, as with the fast inhibitory postsynaptic potentials, the decay time of the slow events is voltage dependent, increasing when the Mauthner cell is depolarized. However, these inhibitory postsynaptic potentials had a different pharmacological profile to the fast glycinergic ones. That is, they persisted in the presence of strychnine at doses that abolished the fast ones and they were more sensitive to bicuculline. These data are compatible with the notion that these inhibitory postsynaptic potentials are mediated by activation of a different inhibitory receptor type, and may be GABAergic. In addition, the decay time constant of the fast inhibitory postsynaptic current was shorter than the first of the two components that contribute to the bi-exponential decay reported previously for miniature inhibitory postsynaptic currents in Mauthner cells of larval zebrafish. This suggests developmental modifications and/or a switch in the assembly of glycine receptor subtypes. While amplitude distributions of the fast miniature inhibitory postsynaptic potentials recorded in the presence of tetrodotoxin generally could fit with a single Gaussian function, the amplitude histograms of slow miniature events were skewed, often with multiple nearly equally spaced peaks, consistent with the synchronous release of several quantal units. These previously undescribed slow unitary inhibitory postsynaptic potentials contribute to inhibitory synaptic noise recorded in the Mauthner cells. Specifically, autocorrelation analysis revealed gamma-like rhythms (30-80Hz) in each of two phases, characterized as "noisy" and "quiet", and dominated by the fast and slow inhibitory postsynaptic potentials, respectively. The major frequencies of these two states were significantly different (i.e. around 90 and 40Hz, respectively), suggesting that the fast and slow inhibitory postsynaptic potentials are derived from different inhibitory networks. Chloride-filled Mauthner cells gradually hyperpolarized in the presence of tetrodotoxin, reflecting the effect of ongoing activity in the interneurons that produce the slow events. We conclude that this new class of inhibitory postsynaptic potentials contributes to the tonic inhibition which controls the Mauthner cell's excitability. In physiological conditions, this regulatory influence is expressed as a continuous shunt of this neuron's input resistance and responsiveness to sensory inputs.
使用填充有氯化钾的电极，对成年斑马鱼（Danio rerio）和金鱼（Carassius auratus）标本中的Mauthner细胞进行的体内记录揭示了这些细胞中一类新的持久突触事件。它们的衰减时间常数在20至80毫秒之间，这比该神经元中先前鉴定的快速甘氨酸能抑制性突触后电位的衰减时间常数长约20倍。这些缓慢事件的平均峰值时间在1至6毫秒之间。我们证明它们也是抑制性的，因为：（i）它们对兴奋性谷氨酸能受体拮抗剂有抗性；（ii）Mauthner细胞氯化物加载后其幅度增加；（iii）它们的反转电位与快速甘氨酸能抑制性突触后电位的反转电位相同；（iv）它们产生细胞膜电阻的抑制性分流。此外，与快速抑制性突触后电位一样，缓慢事件的衰减时间也依赖于电压，当Mauthner细胞去极化时增加。然而，这些抑制性突触后电位与快速甘氨酸能突触后电位具有不同的药理学特征。也就是说，在能消除快速抑制性突触后电位的士的宁剂量下，它们仍然存在，并且它们对荷包牡丹碱更敏感。这些数据与这些抑制性突触后电位由不同类型的抑制性受体激活介导且可能是GABA能的观点一致。此外，快速抑制性突触后电流的衰减时间常数比先前报道的斑马鱼幼体Mauthner细胞微小抑制性突触后电流双指数衰减的两个成分中的第一个成分的衰减时间常数短。这表明甘氨酸受体亚型的组装存在发育修饰和/或转换。虽然在河豚毒素存在下记录的快速微小抑制性突触后电位的幅度分布通常可以拟合单个高斯函数，但缓慢微小事件的幅度直方图是倾斜的，通常有多个几乎等距的峰值，这与几个量子单位的同步释放一致。这些先前未描述的缓慢单位抑制性突触后电位有助于Mauthner细胞中记录的抑制性突触噪声。具体而言，自相关分析在两个阶段中的每个阶段都揭示了类似γ的节律（30 - 80Hz），分别被表征为“嘈杂”和“安静”阶段，并且分别由快速和缓慢抑制性突触后电位主导。这两种状态的主要频率有显著差异（即分别约为90Hz和40Hz），表明快速和缓慢抑制性突触后电位来自不同的抑制性网络。在河豚毒素存在下，填充氯化物的Mauthner细胞逐渐超极化，这反映了产生缓慢事件的中间神经元中持续活动的影响。我们得出结论，这类新的抑制性突触后电位有助于控制Mauthner细胞兴奋性的强直抑制。在生理条件下，这种调节影响表现为该神经元输入电阻的持续分流以及对感觉输入的反应性。
