Department of Physiology and Barshop Institute of Longevity and Aging Studies, University of Texas Health Sciences Center at San Antonio, San Antonio, Texas 78229.
J Neurosci. 2014 Feb 5;34(6):2111-9. doi: 10.1523/JNEUROSCI.3556-13.2014.
Homeostatic plasticity functions within the nervous system to maintain normal neural functions, such as neurotransmission, within predefined optimal ranges. The defined output of these neuronal processes is referred to as the set point, which is the value that the homeostatic system defends against fluctuations. Currently, it is unknown how stable homeostatic set points are within the nervous system. In the present study we used the CM9 neuromuscular junctions (NMJs) in the adult Drosophila to investigate the stability of the set point of synaptic homeostasis across the lifespan of the fly. At the fly NMJ, it is believed that the depolarization of the muscle by neurotransmitter during an action potential, represented by the EPSP, is a homeostatic set point that is precisely maintained via changes in synaptic vesicle release. We find that the amplitude of the EPSP abruptly increases during middle age and that this enhanced EPSP is maintained into late life, consistent with an age-dependent change to the homeostatic set point of the synapse during middle age. In support of this, comparison of the homeostatic response at the young versus the old synapse shows that the magnitude of the homeostatic response at the older synapse is significantly larger than the response at the young NMJ, appropriate for a synapse at which the set point has been increased. Our data demonstrate that the amplitude of the EPSP at the Drosophila NMJ increases during aging and that the homeostatic signaling system adjusts its response to accommodate the new set point.
体内平衡可塑性在神经系统中发挥作用，以维持正常的神经功能，如神经递质在预定义的最佳范围内的传递。这些神经元过程的定义输出被称为设定点，即体内平衡系统抵御波动的防御值。目前，尚不清楚神经系统内的体内平衡设定点有多稳定。在本研究中，我们使用成年果蝇的 CM9 神经肌肉接点 (NMJ) 来研究突触体内平衡设定点在果蝇寿命内的稳定性。在果蝇 NMJ 中，人们认为神经递质在动作电位期间使肌肉去极化，这由 EPSP 表示，是一个通过改变突触小泡释放来精确维持的体内平衡设定点。我们发现，EPSP 的幅度在中年时突然增加，并且这种增强的 EPSP 一直持续到老年，与突触的体内平衡设定点在中年发生年龄依赖性变化一致。为了支持这一点，对年轻和老年突触的体内平衡反应进行比较表明，老年突触的体内平衡反应幅度明显大于年轻 NMJ 的反应幅度，适合设定点已经增加的突触。我们的数据表明，果蝇 NMJ 的 EPSP 幅度在衰老过程中增加，并且体内平衡信号系统调整其反应以适应新的设定点。
