Sun Hua Yu, Lyons Susan A, Dobrunz Lynn E
Department of Neurobiology and Civitan International Research Center, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
J Physiol. 2005 Nov 1;568(Pt 3):815-40. doi: 10.1113/jphysiol.2005.093948. Epub 2005 Aug 18.
Although it is presynaptic, short-term plasticity has been shown at some synapses to depend upon the postsynaptic cell type. Previous studies have reported conflicting results as to whether Schaffer collateral axons have target-cell specific short-term plasticity. Here we investigate in detail the short-term dynamics of Schaffer collateral excitatory synapses onto CA1 stratum radiatum interneurones versus pyramidal cells in acute hippocampal slices from juvenile rats. In response to three stimulus protocols that invoke different forms of short-term plasticity, we find differences in some but not all forms of presynaptic short-term plasticity, and heterogeneity in the short term plasticity of synapses onto interneurones. Excitatory synapses onto the majority of interneurones had less paired-pulse facilitation than synapses onto pyramidal cells across a range of interpulse intervals (20-200 ms). Unlike synapses onto pyramidal cells, synapses onto most interneurones had very little facilitation in response to short high-frequency trains of five pulses at 5, 10 and 20 Hz, and depressed during trains at 50 Hz. However, the amount of high-frequency depression was not different between synapses onto pyramidal cells versus the majority of interneurones at steady state during 2-10 Hz trains. In addition, a small subset of interneurones (approximately 15%) had paired-pulse depression rather than paired-pulse facilitation, showed only depression in response to the high-frequency five pulse trains, and had more steady-state high-frequency depression than synapses onto pyramidal cells or the majority of interneurones. To investigate possible mechanisms for these differences in short-term plasticity, we developed a mechanistic mathematical model of neurotransmitter release that explicitly explores the contributions to different forms of short-term plasticity of the readily releasable vesicle pool size, release probability per vesicle, calcium-dependent facilitation, synapse inactivation following release, and calcium-dependent recovery from inactivation. Our model fits the responses of each of the three cell groups to the three different stimulus protocols with only two parameters that differ with cell group. The model predicts that the differences in short-term plasticity between synapses onto CA1 pyramidal cells and stratum radiatum interneurones are due to a higher initial release probability per vesicle and larger readily releasable vesicle pool size at synapses onto interneurones, resulting in a higher initial release probability. By measuring the rate of block of NMDA receptors by the open channel blocker MK-801, we confirmed that the initial release probability is greater at synapses onto interneurones versus pyramidal cells. This provides a mechanism by which both the initial strength and the short-term dynamics of Schaffer collateral excitatory synapses are regulated by their postsynaptic target cell.
虽然短期可塑性是突触前的，但在某些突触中已表明它取决于突触后细胞类型。关于施affer侧支轴突是否具有靶细胞特异性短期可塑性，先前的研究报告了相互矛盾的结果。在这里，我们详细研究了幼年大鼠急性海马切片中，施affer侧支兴奋性突触到CA1辐射层中间神经元与锥体细胞上的短期动力学。针对三种引发不同形式短期可塑性的刺激方案，我们发现了一些但并非所有形式的突触前短期可塑性存在差异，并且突触到中间神经元上的短期可塑性存在异质性。在一系列脉冲间隔（20 - 200毫秒）内，大多数中间神经元上的兴奋性突触比锥体细胞上的突触具有更少的双脉冲易化。与锥体细胞上的突触不同，大多数中间神经元上的突触对5、10和20赫兹的五个脉冲的短高频串刺激反应时，几乎没有易化，而在50赫兹串刺激时则出现抑制。然而，在2 - 10赫兹串刺激的稳态下，锥体细胞上的突触与大多数中间神经元上的突触之间的高频抑制量没有差异。此外，一小部分中间神经元（约15%）具有双脉冲抑制而非双脉冲易化，对高频五个脉冲串刺激仅表现出抑制，并且比锥体细胞或大多数中间神经元上的突触具有更多的稳态高频抑制。为了研究这些短期可塑性差异的可能机制，我们开发了一个神经递质释放的机制性数学模型，该模型明确探讨了可快速释放囊泡池大小、每个囊泡的释放概率、钙依赖性易化、释放后突触失活以及钙依赖性失活恢复对不同形式短期可塑性的贡献。我们的模型仅用两个因细胞组而异的参数，就拟合了三个细胞组对三种不同刺激方案的反应。该模型预测，CA1锥体细胞和辐射层中间神经元上的突触之间短期可塑性的差异，是由于中间神经元上的突触每个囊泡的初始释放概率更高以及可快速释放囊泡池更大，从而导致更高的初始释放概率。通过测量开放通道阻滞剂MK - 801对NMDA受体的阻断率，我们证实中间神经元上的突触相对于锥体细胞上的突触，初始释放概率更高。这提供了一种机制，通过该机制施affer侧支兴奋性突触的初始强度和短期动力学均受其突触后靶细胞调节。
