Cannabinoid modulation of backpropagating action potential-induced calcium transients in layer 2/3 pyramidal neurons.
Cannabinoid modulation of backpropagating action potential-induced calcium transients in layer 2/3 pyramidal neurons.
复制标题
大麻素对 2/3 层锥体神经元反向传播动作电位诱导的钙瞬变的调节。
DOI：
10.1093/cercor/bhs168
复制
发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Levine,EricS
中科院分区：
文献类型：
--
作者：
Hsieh,LawrenceS;Levine,EricS
内源性大麻素（eCB）在调节整个大脑的突触信号传递方面发挥着重要作用。在新皮层的2/3层中，eCB介导的GABA释放抑制导致锥体神经元（PN）的兴奋性增强。eCB系统还参与依赖于反向传播动作电位（bAP）的尖峰时间依赖性可塑性。树突反向传播在神经元功能的许多方面起着重要作用，并且可以通过固有树突电导以及突触输入来调节。本研究探讨了eCB系统在PN树突中调制反向传播的作用。使用树突状钙成像和体细胞膜片钳记录从小鼠体感皮层切片，我们发现，1型大麻素受体的激活增强bAP诱导的钙瞬变在第2/3层，但不是第5层PN的顶端树突。这种作用是通过抑制GABA能传递介导的，因为它被GABA A受体拮抗剂阻止，并且与大麻素抑制抑制性突触活性相关。最后，我们发现，在去极化诱导的抑制过程中，活性依赖性的eCB释放增强了bAP诱导的树突状钙瞬变。两者合计，这些结果指出了一个潜在的重要作用的eCB系统在调节树突状细胞的反向传播层2/3 PN。
Endocannabinoids (eCBs) play a prominent role in regulating synaptic signaling throughout the brain. In layer 2/3 of the neocortex, eCB-mediated suppression of GABA release results in an enhanced excitability of pyramidal neurons (PNs). The eCB system is also involved in spike timing-dependent plasticity that is dependent on backpropagating action potentials (bAPs). Dendritic backpropagation plays an important role in many aspects of neuronal function, and can be modulated by intrinsic dendritic conductances as well as by synaptic inputs. The present studies explored a role for the eCB system in modulating backpropagation in PN dendrites. Using dendritic calcium imaging and somatic patch clamp recordings from mouse somatosensory cortical slices, we found that activation of type 1 cannabinoid receptors potentiated bAP-induced calcium transients in apical dendrites of layer 2/3 but not layer 5 PNs. This effect was mediated by suppression of GABAergic transmission, because it was prevented by a GABAAreceptor antagonist and was correlated with cannabinoid suppression of inhibitory synaptic activity. Finally, we found that activity-dependent eCB release during depolarization-induced suppression of inhibition enhanced bAP-induced dendritic calcium transients. Taken together, these results point to a potentially important role for the eCB system in regulating dendritic backpropagation in layer 2/3 PNs.