Department of Neurobiology, Kavli Institute for Neuroscience, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
J Neurosci. 2011 Dec 14;31(50):18289-302. doi: 10.1523/JNEUROSCI.4417-11.2011.
Inhibitory interneurons of the dorsal lateral geniculate nucleus of the thalamus modulate the activity of thalamocortical cells in response to excitatory input through the release of inhibitory neurotransmitter from both axons and dendrites. The exact mechanisms by which release can occur from dendrites are, however, not well understood. Recent experiments using calcium imaging have suggested that Na/K-based action potentials can evoke calcium transients in dendrites via local active conductances, making the backpropagating action potential a candidate for dendritic neurotransmitter release. In this study, we used high temporal and spatial resolution voltage-sensitive dye imaging to assess the characteristics of dendritic voltage deflections in response to Na/K action potentials in interneurons of the mouse dorsal lateral geniculate nucleus. We found that trains or single action potentials elicited by somatic current injection or local synaptic stimulation rapidly and actively backpropagated throughout the entire dendritic arbor and into the fine filiform dendritic appendages known to release GABAergic vesicles. Action potentials always appeared first in the soma or proximal dendrite in response to somatic current injection or local synaptic stimulation, and the rapid backpropagation into the dendritic arbor depended upon voltage-gated sodium and tetraethylammonium chloride-sensitive potassium channels. Our results indicate that thalamic interneuron dendrites integrate synaptic inputs that initiate action potentials, most likely in the axon initial segment, that then backpropagate with high fidelity into the dendrites, resulting in a nearly synchronous release of GABA from both axonal and dendritic compartments.
丘脑背外侧膝状体核的抑制性中间神经元通过从轴突和树突释放抑制性神经递质来调节丘脑皮质细胞对兴奋性输入的活动。然而,树突释放的确切机制还不是很清楚。最近使用钙成像的实验表明,基于 Na/K 的动作电位可以通过局部主动电导在树突中引发钙瞬变,使逆行动作电位成为树突神经递质释放的候选者。在这项研究中,我们使用高时间和空间分辨率的电压敏感染料成像来评估小鼠背外侧膝状体核中间神经元中对 Na/K 动作电位的树突电压偏移的特征。我们发现,通过体电流注射或局部突触刺激引发的动作电位串或单个动作电位迅速而主动地逆行传播到整个树突树突和细丝状树突末梢,这些末梢已知释放 GABA 能囊泡。动作电位总是首先出现在体部或近端树突中,无论是对体电流注射还是局部突触刺激的反应,而逆行到树突树突中的快速传播依赖于电压门控钠和四乙基氯化铵敏感钾通道。我们的结果表明,丘脑中间神经元的树突整合引发动作电位的突触输入,这些动作电位很可能发生在轴突起始段,然后以高保真度逆行传播到树突中,导致 GABA 从轴突和树突区室几乎同步释放。