Inositol-1,4,5-trisphosphate receptor-mediated Ca mobilization is not required for cerebellar long-term depression in reduced preparations
Inositol-1,4,5-trisphosphate receptor-mediated Ca mobilization is not required for cerebellar long-term depression in reduced preparations
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DOI：
10.1152/jn.1998.80.6.2963
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发表时间：
1998-12-01
影响因子：
2.5
通讯作者：
Linden, DJ
中科院分区：
文献类型：
--
作者：
Narasimhan, K;Pessah, IN;Linden, DJ
小脑长时程抑制（LTD）是一种信息储存的细胞模型系统，其中浦肯野神经元（PN）的平行纤维和攀爬纤维同时激活引起平行纤维-PN突触强度的持续衰减。爬升纤维和平行纤维输入可以分别由PN和外源性谷氨酸脉冲的直接去极化代替。平行纤维-PN突触具有高密度的mGluR 1受体，其与磷酸肌醇周转偶联。几条证据表明，通过平行纤维刺激激活mGluR 1是诱导小脑LTD所必需的。由于磷酸肌醇水解有两种初始产物，1，2-二酰基甘油和肌醇-1，4，5-三磷酸（IP 3），我们希望确定是否通过IP 3受体的IP 3信号传导和随后的Ca动员是诱导小脑LTD所必需的。首先，对急性分离的和培养的PN进行游离胞质Ca的比率成像。确定谷氨酸脉冲促进LTD诱导的阈值低于产生Ca瞬变的阈值。此外，单独去极化和谷氨酸加去极化产生的钙瞬变没有显着差异。其次，没有发现有效的和选择性的IP 3受体通道阻滞剂xestospongin C影响LTD的诱导，无论是急性解离或培养的PN在浓度足以阻止mGluR 1诱发的钙动员。第三，在LTD诱导方案中用外源合成二酰基甘油替代mGluR活化是成功的。两者合计，这些结果表明，IP 3信号级联的激活是不需要诱导小脑LTD在减少的准备。
Cerebellar longterm depression (LTD) is a cellular model system of information storage in which coincident parallel fiber and climbing fiber activation of a Purkinje neuron (PN) gives rise to a sustained attenuation of parallel fiber-PN synaptic strength. Climbing fiber and parallel fiber inputs may be replaced by direct depolarization of the PN and exogenous glutamate pulses, respectively. The parallel fiber-PN synapse has a high-density of mGluR1 receptors that are coupled to phosphoinositide turnover. Several lines of evidence indicated that activation of mGluR1 by parallel fiber stimulation is necessary for the induction of cerebellar LTD. Because phosphoinositide hydrolysis has two initial products, 1,2-diacylglycerol and inositol-1,4,5-trisphosphate (IP3), we wished to determine whether IP3 signaling via IP3 receptors and consequent Ca mobilization were necessary for the induction of cerebellar LTD. First, ratiometric imaging of free cytosolic Ca was performed on both acutely dissociated and cultured PNs. It was determined that the threshold for glutamate pulses to contribute to LTD induction was below the threshold for producing a Ca transient. Furthermore, the Ca transients produced by depolarization alone and glutamate plus depolarization were not significantly different. Second, the potent and selective IP3 receptor channel blocker xestospongin C was not found to affect the induction of LTD in either acutely dissociated or cultured PNs at a concentration that was sufficient to block mGluR1-evoked Ca mobilization. Third, replacement of mGluR activation by exogenous synthetic diacylglycerol in an LTD induction protocol was successful. Taken together, these results suggest that activation of an IP3 signaling cascade is not required for induction of cerebellar LTD in reduced preparations.