Distinct roles for Cav2.1-2.3 in activity-dependent synaptic dynamics.
Distinct roles for Cav2.1-2.3 in activity-dependent synaptic dynamics.
复制标题
Cav2.1-2.3 在活动依赖性突触动力学中的独特作用。
DOI：
10.1152/jn.00335.2013
复制
发表时间：
2014
影响因子：
2.5
通讯作者：
Frerking,MatthewE
中科院分区：
文献类型：
--
作者：
Ricoy,UlisesM;Frerking,MatthewE
大部分中枢神经系统的突触传递高度依赖于通过电压门控钙通道Cav2.1-Cav2.3的突触前钙内流。除了引发胞吐外，这种钙流入还会增加短期突触的可塑性。在体内发生的突触前活动的复杂模式中，几种形式的可塑性结合起来产生动态的突触输出，其中给定的兴奋性突触后电位（EPSP）的大小响应于给定的峰值取决于突触前活动的短期历史。目前尚不清楚不同的Cav2通道是否在定义这些突触动力学中发挥不同的作用，如果是的话，在什么条件下不同的Cav2家族成员最有效地决定突触输出。我们通过测量钙通道选择性毒素对成年小鼠海马切片中Schaffer侧突触突触传递的影响来研究这些问题，这些影响分别来自低频刺激和体内记录的复杂刺激序列。阻断Cav2.1对刺激序列低频组分突触传递的抑制作用大于对刺激序列高频组分突触传递的抑制作用，说明Cav2.1对低频突触传递的贡献率大于高频。相对于Cav2.1, Cav2.2在> ~ 20hz频率下对突触传递的贡献不成比例地降低，而Cav2.3在> ~ 1hz频率下对突触传递的贡献不成比例地增加。不同Cav2家族成员的这些活性依赖效应塑造了gabab受体介导的突触前抑制的过滤特性。因此，不同的Cav2通道在不同频率范围内与突触传递的耦合不同，从而导致突触动力学和突触前神经调节的频率调谐。
Synaptic transmission throughout most of the CNS is steeply dependent on presynaptic calcium influx through the voltage-gated calcium channels Cav2.1–Cav2.3. In addition to triggering exocytosis, this calcium influx also recruits short-term synaptic plasticity. During the complex patterns of presynaptic activity that occur in vivo, several forms of plasticity combine to generate a synaptic output that is dynamic, in which the size of a given excitatory postsynaptic potential (EPSP) in response to a given spike depends on the short-term history of presynaptic activity. It remains unclear whether the different Cav2 channels play distinct roles in defining these synaptic dynamics and, if so, under what conditions different Cav2 family members most effectively determine synaptic output. We examined these questions by measuring the effects of calcium channel-selective toxins on synaptic transmission at the Schaffer collateral synapse in hippocampal slices from adult mice in response to both low-frequency stimulation and complex stimulus trains derived from in vivo recordings. Blockade of Cav2.1 had a greater inhibitory effect on synaptic transmission during low-frequency components of the stimulus train than on synaptic transmission during high-frequency components of the train, indicating that Cav2.1 had a greater fractional contribution to synaptic transmission at low frequencies than at high frequencies. Relative to Cav2.1, Cav2.2 had a disproportionately reduced contribution to synaptic transmission at frequencies >20 Hz, while Cav2.3 had a disproportionately increased contribution to synaptic transmission at frequencies >1 Hz. These activity-dependent effects of different Cav2 family members shape the filtering characteristics of GABABreceptor-mediated presynaptic inhibition. Thus different Cav2 channels vary in their coupling to synaptic transmission over different frequency ranges, with consequences for the frequency tuning of both synaptic dynamics and presynaptic neuromodulation.