Kasyanov A M, Maximov V V, Byzov A L, Berretta N, Sokolov M V, Gasparini S, Cherubini E, Reymann K G, Voronin L L
Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, 117865, Moscow, Russia.
Neuroscience. 2000;101(2):323-36. doi: 10.1016/s0306-4522(00)00366-3.
Computer simulations and electrophysiological experiments have been performed to test the hypothesis on the existence of an ephaptic interaction in purely chemical synapses. According to this hypothesis, the excitatory postsynaptic current would depolarize the presynaptic release site and further increase transmitter release, thus creating an intrasynaptic positive feedback. For synapses with the ephaptic feedback, computer simulations predicted non-linear amplitude-voltage relations and voltage dependence of paired-pulse facilitation. The deviation from linearity depended on the strength of the feedback determined by the value of the synaptic cleft resistance. The simulations showed that, in the presence of the intrasynaptic feedback, recruitment of imperfectly clamped synapses and synapses with linear amplitude-voltage relations tended to reduce the non-linearity and voltage dependence of paired-pulse facilitation. Therefore, the simulations predicted that the intrasynaptic feedback would particularly affect small excitatory postsynaptic currents induced by activation of electrotonically close synapses with long synaptic clefts. In electrophysiological experiments performed on hippocampal slices, the whole-cell configuration of the patch-clamp technique was used to record excitatory postsynaptic currents evoked in CA3 pyramidal cells by activation of large mossy fibre synapses. In accordance with the simulation results, minimal excitatory postsynaptic currents exhibited "supralinear" amplitude-voltage relations at hyperpolarized membrane potentials, decreases in the failure rate and voltage-dependent paired-pulse facilitation. Composite excitatory postsynaptic currents evoked by activation of a large amount of presynaptic fibres typically bear linear amplitude-voltage relationships and voltage-independent paired-pulse facilitation. These data are consistent with the hypothesis on a strong ephaptic feedback in large mossy fibre synapses. The feedback would provide a mechanism whereby signals from large synapses would be amplified. The ephaptic feedback would be more effective on synapses activated in isolation or together with electrotonically remote inputs. During synchronous activation of a large number of neighbouring inputs, suppression of the positive intrasynaptic feedback would prevent abnormal boosting of potent signals.
已进行计算机模拟和电生理实验，以检验关于纯化学突触中存在电突触相互作用这一假说。根据该假说，兴奋性突触后电流会使突触前释放位点去极化，并进一步增加递质释放，从而形成突触内正反馈。对于具有电突触反馈的突触，计算机模拟预测了非线性幅度 - 电压关系以及双脉冲易化的电压依赖性。与线性的偏差取决于由突触间隙电阻值决定的反馈强度。模拟结果表明，在存在突触内反馈的情况下，不完全钳制突触和具有线性幅度 - 电压关系的突触的募集倾向于降低双脉冲易化的非线性和电压依赖性。因此，模拟预测突触内反馈将特别影响由具有长突触间隙的电紧张性紧密突触激活所诱导的小兴奋性突触后电流。在对海马切片进行的电生理实验中，采用膜片钳技术的全细胞配置来记录通过激活大型苔藓纤维突触在CA3锥体细胞中诱发的兴奋性突触后电流。与模拟结果一致，最小兴奋性突触后电流在超极化膜电位下表现出“超线性”幅度 - 电压关系、失败率降低以及电压依赖性双脉冲易化。由大量突触前纤维激活诱发的复合兴奋性突触后电流通常具有线性幅度 - 电压关系和电压非依赖性双脉冲易化。这些数据与大型苔藓纤维突触中存在强电突触反馈的假说一致。该反馈将提供一种机制，通过该机制来自大型突触的信号将被放大。电突触反馈在单独激活或与电紧张性远距离输入一起激活的突触上会更有效。在大量相邻输入同步激活期间，抑制突触内正反馈将防止强信号的异常增强。
