Endocannabinoids mediate rapid retrograde signaling at interneuron right-arrow pyramidal neuron synapses of the neocortex.
Endocannabinoids mediate rapid retrograde signaling at interneuron right-arrow pyramidal neuron synapses of the neocortex.
复制标题
内源性大麻素介导新皮质中间神经元右箭头锥体神经元突触的快速逆行信号传导。
DOI：
10.1152/jn.01037.2002
复制
发表时间：
2003
影响因子：
2.5
通讯作者：
Levine,EricS
中科院分区：
文献类型：
--
作者：
Trettel,Joseph;Levine,EricS
在新皮质中，抑制性中间神经元严格调节锥体神经元 (PN) 的放电模式和整合特性。新皮质的内源性大麻素系统可能在 PN 接收的抑制性（即 GABA 能）输入的活动依赖性调节中发挥重要作用。在本研究中，利用小鼠感觉皮层切片中 2/3 PN 层的全细胞记录，我们确定了 PN 衍生的内源性大麻素在控制传入抑制强度中的作用。将诱发的抑制电流与突触后去极化的重复时期配对，会导致暂时的抑制抑制，这种抑制是由突触后 Ca2+ 的增加引起的，并表现为突触前 GABA 释放的减少。 1 型大麻素受体的拮抗剂 (AM251) 阻断去极化诱导的诱发抑制性突触后电流 (eIPSC) 的抑制，大麻素 WIN55,212-2 降低 eIPSC 幅度和闭塞抑制。 WIN55,212-2 介导的 eIPSC 抑制程度与去极化诱导的 eIPSC 抑制程度密切相关，表明 WIN 敏感传入神经受到 PN 去极化的抑制。此外，用 AM404 阻断内源性大麻素的摄取可以强烈调节 eIPSC 抑制的动力学和程度。我们的结论是，PN 中内源性大麻素的释放可以实现对突触前抑制的突触后控制，并且可能对新皮质 PN 的整合特性产生深远的影响。
In the neocortex, inhibitory interneurons tightly regulate the firing patterns and integrative properties of pyramidal neurons (PNs). The endocannabinoid system of the neocortex may play an important role in the activity-dependent regulation of inhibitory (i.e., GABAergic) inputs received by PNs. In the present study, using whole cell recordings from layer 2/3 PNs in slices of mouse sensory cortex, we have identified a role for PN-derived endocannabinoids in the control of afferent inhibitory strength. Pairing evoked inhibitory currents with repeated epochs of postsynaptic depolarization led to a transient suppression of inhibition that was induced by a rise in postsynaptic Ca2+and was expressed as a reduction in presynaptic GABA release. An antagonist (AM251) of the type-1 cannabinoid receptor blocked the depolarization-induced suppression of evoked inhibitory postsynaptic currents (eIPSCs), and the cannabinoid WIN55,212-2 reduced eIPSC amplitude and occluded suppression. The degree of WIN55,212-2-mediated inhibition of eIPSCs was strongly correlated with the magnitude of depolarization-induced suppression of the eIPSCs, suggesting that the WIN-sensitive afferents are suppressed by PN depolarization. Moreover, blocking endocannabinoid uptake with AM404 strongly modulated the kinetics and magnitude of eIPSC suppression. We conclude that the release of endocannabinoids from PNs allows for the postsynaptic control of presynaptic inhibition and could have profound consequences for the integrative properties of neocortical PNs.