Plasticity and function of backpropagating Action Potential mediated calcium signals in dendritic spines

神经元阈值以上激活后的动作电位(AP)传回树突树。反向传播动作电位(BaP)介导的树突段和相邻棘细胞的去极化导致电压门控钙通道介导的内流进入树突和棘细胞。与局部突触介导的钙信号相比，这些全局钙信号激活的脊椎数量要多得多，但人们对它们的功能知之甚少。在内侧嗅觉皮质II层星状细胞中，我们将进一步研究这些(BaP)介导的钙瞬变(BAPCaTs)是影响突触传递的自我调节的可塑性事件的可能性。我们将研究bAPCaTs活性依赖增强的诱导和表达机制，以及它们对突触传递和电路功能的功能影响。研究将结合使用全细胞膜片钳记录和带有低亲和力钙指示剂的双光子钙成像(荧光素4FF)。这一指标的缓冲能力较低，这将使我们能够在监测bAPCats的同时研究它们的生物学效应。将Alexa 594添加到记录南部，来自单独红色通道的形态数据允许将功能数据与脊柱形态测量相结合。我们将利用双光子谷氨酸去化技术来研究bAPCaTs与单棘突触传递之间的相互作用。

Action potentials (APs) following suprathreshold activation of neurons propagate back into the dendritic tree. Backpropagating Action Potential (bAP)-mediated depolarization of dendritic segments and adjacent spines results in voltage-gated calcium channel mediated influx into dendrites and spines. These global calcium signals activate a much larger number of spines than local synaptically mediated calcium transients, but their function is poorly understood. In medial entorhinal cortex layer II stellate cells, we will further examine the possibility that these (bAP)-mediated calcium transients (bAPCaTs) are self-regulatory, plastic events with an impact on synaptic transmission. Mechanisms underlying induction and expression of activity-dependent boosting of bAPCaTs as well as their functional implications for synaptic transmission and circuit function will be studied. Investigations will be performed using combined whole-cell patch clamp recordings and two-photon calcium imaging with low affinity calcium indicators (fluo4FF). The low buffer capacity of this indicator will enable us to study biological effects of bAPCaTs while monitoring them. Adding Alexa 594 to the recording soution, morphological data from a separate red channel permits combination of functional data with spine morphometry. Two-photon glutamate uncaging will be applied to study the interaction of bAPCaTs and synaptic transmission in single spines.