Kreitzer A C, Regehr W G
Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
Neuron. 2001 Mar;29(3):717-27. doi: 10.1016/s0896-6273(01)00246-x.
Brief depolarization of cerebellar Purkinje cells was found to inhibit parallel fiber and climbing fiber EPSCs for tens of seconds. This depolarization-induced suppression of excitation (DSE) is accompanied by altered paired-pulse plasticity, suggesting a presynaptic locus. Fluorometric imaging revealed that postsynaptic depolarization also reduces presynaptic calcium influx. The inhibition of both presynaptic calcium influx and EPSCs is eliminated by buffering postsynaptic calcium with BAPTA. The cannabinoid CB1 receptor antagonist AM251 prevents DSE, and the agonist WIN 55,212-2 occludes DSE. These findings suggest that Purkinje cells release endogenous cannabinoids in response to elevated calcium, thereby inhibiting presynaptic calcium entry and suppressing transmitter release. DSE may provide a way for cells to use their firing rate to dynamically regulate synaptic inputs. Together with previous studies, these findings suggest a widespread role for endogenous cannabinoids in retrograde synaptic inhibition.
研究发现，小脑浦肯野细胞的短暂去极化会抑制平行纤维和攀缘纤维的兴奋性突触后电流（EPSCs）达数十秒之久。这种去极化诱导的兴奋抑制（DSE）伴随着配对脉冲可塑性的改变，提示其作用位点在突触前。荧光成像显示，突触后去极化也会减少突触前钙内流。用BAPTA缓冲突触后钙可消除对突触前钙内流和EPSCs的抑制。大麻素CB1受体拮抗剂AM251可阻止DSE，而激动剂WIN 55,212-2则可阻断DSE。这些发现表明，浦肯野细胞会在钙升高时释放内源性大麻素，从而抑制突触前钙内流并抑制递质释放。DSE可能为细胞利用其放电频率动态调节突触输入提供了一种方式。与之前的研究一起，这些发现提示内源性大麻素在逆行性突触抑制中具有广泛作用。
