Kerr Jason N D, Plenz Dietmar
Unit of Neural Network Physiology, Laboratory of Systems Neuroscience, National Institute of Mental Health, Bethesda, Maryland 20892, USA.
J Neurosci. 2004 Jan 28;24(4):877-85. doi: 10.1523/JNEUROSCI.4475-03.2004.
Up-states represent a key feature of synaptic integration in cortex and striatum that involves activation of many synaptic inputs. In the striatum, the sparse firing and tight control of action potential timing is in contrast to the large intracellular membrane potential depolarizations observed during the up-state. One hallmark of striatal spiny projection neurons is the delay to action potential generation in both up-states and suprathreshold depolarization by somatic current injection. By studying somatic and dendritic intracellular calcium ([Ca2+]i) transients during spontaneous up-states in cortex-striatum-substantia nigra organotypic cultures, we show that the delay between up-state onset and action potential generation determines dendritic peak [Ca2+]i. Peak [Ca2+]i from single action potentials reached maximum values when action potentials were close to up-state onset and sharply decayed to near subthreshold up-state [Ca2+] levels as a function of time (tau = 47 +/- 26 msec for tertiary dendrite). Similarly, a precisely timed action potential elicited during subthreshold up-states through somatic current injection established that the delay between up-state onset and action potential generation is the critical variable that controls peak [Ca2+]i. Blocking NMDA channels internally with high intracellular Mg2+ ([Mg2+]i) (10 mm) abolished the dependency of peak [Ca2+]i on action potential timing during spontaneous up-states. Finally, high [Mg2+]i specifically blocked [Ca2+]i transients that resulted from local NMDA application in conjunction with backpropagating action potentials. We conclude that precisely timed, single action potentials during striatal up-states control peak dendritic calcium levels. We suggest that this mechanism might play an important role in synaptic plasticity of the corticostriatal pathway.
上状态代表了皮质和纹状体中突触整合的一个关键特征，涉及许多突触输入的激活。在纹状体中，稀疏放电和对动作电位时间的严格控制与在上状态期间观察到的大的细胞内膜电位去极化形成对比。纹状体棘状投射神经元的一个标志是在上状态和通过体细胞电流注入产生的阈上 depolarization 期间动作电位产生的延迟。通过研究皮质 - 纹状体 - 黑质器官型培养物中自发上状态期间的体细胞和树突状细胞内钙（[Ca2+]i）瞬变，我们表明上状态开始和动作电位产生之间的延迟决定了树突状峰值[Ca2+]i。当动作电位接近上状态开始时，单个动作电位的峰值[Ca2+]i 达到最大值，并随着时间的推移急剧衰减至接近阈下上状态[Ca2+]水平（三级树突的 tau = 47 +/- 26 毫秒）。同样，通过体细胞电流注入在阈下上状态期间引发的精确计时动作电位确定，上状态开始和动作电位产生之间的延迟是控制峰值[Ca2+]i 的关键变量。用高细胞内镁（[Mg2+]i）（10 毫米）在内部阻断 NMDA 通道消除了自发上状态期间峰值[Ca2+]i 对动作电位时间的依赖性。最后，高[Mg2+]i 特异性阻断了由局部 NMDA 应用与反向传播动作电位共同导致的[Ca2+]i 瞬变。我们得出结论，纹状体上状态期间精确计时的单个动作电位控制树突状钙水平峰值。我们认为这种机制可能在皮质纹状体通路的突触可塑性中起重要作用。
