ELEMENTAL AND STRUCTURAL ORGANIZATION OF NEURONS AND GLIA

这个项目研究的是 在神经元活动中的钙调节， 强调中枢神经系统的树突和树突棘 系统神经元以前，钙成像和分析研究 海马脑片培养的CA 3神经元树突 特征为内质网（ER）的一个子集作为主要的 在15秒到15秒的时间内， 在传入突触活动后10分钟。与此相反， 线粒体钙摄取与内质网平行 仅在突触活动后的第一分钟内隔离。 一项新的研究揭示了一种不同的钙螯合模式， 交感神经元在这些神经元中，总Ca （X射线微量分析）与游离胞质溶质的记录平行 Ca 2+瞬变（fura- 2），在去极化后， 定义的Ca 2+瞬变，为持续（升高） 至5分钟）和线粒体内的强钙螯合， 而ER Ca变化不大。这种线粒体Ca 蓄积量大，呈时间依赖性（总量超过10 mmol/kg 45秒去极化后的Ca浓度），可逆和 对破坏线粒体转运途径的药物敏感。 以前我们已经证明雌二醇使树突棘加倍 海马神经元密度通过其对抑制 海马中间神经元这些结果提供了一个有吸引力的 解释雌激素影响认知的观察， 在成年生物体中的可塑性。海马的新研究 培养的神经元显示脑源性神经营养因子 （BDNF），其涉及GABA能神经递质的调节。 神经元，下调了40%，雌二醇治疗后。 这反过来又增加了这些神经元的兴奋性，导致 刺增加了两倍这些观察揭示了一种功能性的 雌二醇和BDNF之间的联系（作为GABA能的调节剂） 中间神经元）在树突活性依赖性增强中的作用 刺

This project studies the physiology and development of calcium regulation during neuronal activity, with special emphasis on the dendrites and dendritic spines of central nervous system neurons. Previously, Ca imaging and analytical studies on dendrites of CA3 neurons in hippocampal slice cultures had characterized a subset of endoplasmic reticulum (ER) as the major calcium-sequestering organelle in the time frame of seconds to 15 minutes following afferent synaptic activity. In contrast, mitochondrial calcium uptake operates in parallel with ER sequestration only over the first minute following synaptic activity. A new study reveals a different mode of Ca sequestration in sympathetic neurons. In these neurons, measurements of total Ca (x-ray microanalysis) in parallel with recordings of free cytosolic Ca2+ transients (fura- 2), following depolarizations that evoke defined Ca2+ transients, provide direct evidence for sustained (up to 5 min) and robust calcium sequestration within mitochondria, while ER Ca was little changed. This mitochondrial Ca accumulation is large, time dependent (more than 10 mmol/kg total Ca concentration after a 45 sec depolarization), reversible and sensitive to agents that disrupt mitochondrial transport pathways. Previously we had shown that estradiol doubles dendritic spine density of hippocampal neurons via its effect on inhibitory hippocampal interneurons. These results provided an attractive explanation for the observation that estrogen affects cognition and plasticity in adult organisms. New studies with hippocampal neurons in culture reveal that brain-derived neurotrophic factor (BDNF), which has been implicated in the regulation of GABAergic neurons, is downregulated by 40% following estradiol treatment. This, in turn, increases excitatory tone in these neurons, leading to a twofold increase in spines. These observations reveal a functional link between estradiol and BDNF (as a regulator of GABAergic interneurons) in the activity-dependent enhancement of dendritic spines.