Hage Travis A, Khaliq Zayd M
Cellular Neurophysiology Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892.
Cellular Neurophysiology Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892
J Neurosci. 2015 Apr 8;35(14):5823-36. doi: 10.1523/JNEUROSCI.3904-14.2015.
Substantia nigra dopamine neurons fire tonically resulting in action potential backpropagation and dendritic Ca(2+) influx. Using Ca(2+) imaging in acute mouse brain slices, we find a surprisingly steep relationship between tonic firing rate and dendritic Ca(2+). Increasing the tonic rate from 1 to 6 Hz generated Ca(2+) signals up to fivefold greater than predicted by linear summation of single spike-evoked Ca(2+)-transients. This "Ca(2+) supralinearity" was produced largely by depolarization of the interspike voltage leading to activation of subthreshold Ca(2+) channels and was present throughout the proximal and distal dendrites. Two-photon glutamate uncaging experiments show somatic depolarization enhances NMDA receptor-mediated Ca(2+) signals >400 μm distal to the soma, due to unusually tight electrotonic coupling of the soma to distal dendrites. Consequently, we find that fast tonic firing intensifies synaptically driven burst firing output in dopamine neurons. These results show that modulation of background firing rate precisely tunes dendritic Ca(2+) signaling and provides a simple yet powerful mechanism to dynamically regulate the gain of synaptic input.
黑质多巴胺神经元持续放电，导致动作电位反向传播和树突状钙离子内流。利用急性小鼠脑片的钙离子成像技术，我们发现持续放电频率与树突状钙离子之间存在惊人的陡峭关系。将持续放电频率从1赫兹提高到6赫兹，所产生的钙离子信号比单峰诱发的钙离子瞬变线性总和预测值高出五倍之多。这种“钙离子超线性”主要是由峰间电压去极化导致阈下钙离子通道激活产生的，并且在近端和远端树突中均存在。双光子谷氨酸解笼实验表明，由于胞体与远端树突之间异常紧密的电紧张耦合，胞体去极化会增强胞体远端400微米以上由NMDA受体介导的钙离子信号。因此，我们发现快速持续放电会增强多巴胺神经元中突触驱动的爆发式放电输出。这些结果表明，背景放电频率的调节精确地调整了树突状钙离子信号传导，并提供了一种简单而强大的机制来动态调节突触输入增益。
