Wang Yong, Manis Paul B
Department of Otolaryngology/Head and Neck Surgery, University of North Carolina, Chapel Hill, North Carolina, USA.
J Neurophysiol. 2008 Sep;100(3):1255-64. doi: 10.1152/jn.90715.2008. Epub 2008 Jul 16.
The endbulb of Held synapses between the auditory nerve fibers (ANF) and cochlear nucleus bushy neurons convey fine temporal information embedded in the incoming acoustic signal. The dynamics of synaptic depression and recovery is a key in regulating synaptic transmission at the endbulb synapse. We studied short-term synaptic depression and recovery in mature (P22-38) CBA mice with stimulation rates that were comparable to sound-driven activities recorded in vivo. Synaptic depression in mature mice is less severe ( approximately 40% at 100 Hz) than reported for immature animals and the depression is predominately due to depletion of releasable vesicles. Recovery from depression depends on the rate of activity and accumulation of intracellular Ca2+ at the presynaptic terminal. With a regular stimulus train at 100 Hz in 2 mM external [Ca2+], the recovery from depletion was slow (tauslow, approximately 2 s). In contrast, a fast (taufast, approximately 25 ms), Ca2+-dependent recovery followed by a slower recovery (tauslow, approximately 2 s) was seen when stimulus rates or external [Ca2+] increased. In normal [Ca2+], recovery from a 100-Hz Poisson-like train is rapid, suggesting that Poisson-like trains produce a higher internal [Ca2+] than regular trains. Moreover, the fast recovery was slowed by approximately twofold in the presence of calmidazolium, a Ca2+/calmodulin inhibitor. Our results suggest that endbulb synapses from high spontaneous firing rate auditory nerve fibers normally operate in a depressed state. The accelerated synaptic recovery during high rates of activity is likely to ensure that reliable synaptic transmission can be achieved at the endbulb synapse.
听觉神经纤维（ANF）与蜗神经核簇状神经元之间的 Held 终球突触传递着嵌入传入声信号中的精细时间信息。突触抑制和恢复的动力学是调节 Held 终球突触处突触传递的关键。我们研究了成熟（P22 - 38）CBA 小鼠的短期突触抑制和恢复情况，刺激频率与体内记录的声音驱动活动相当。成熟小鼠中的突触抑制不如未成熟动物严重（100 Hz 时约为 40%），且这种抑制主要是由于可释放囊泡的耗竭。从抑制中恢复取决于活动速率和突触前终末细胞内 Ca2+的积累。在 2 mM 细胞外[Ca2+]条件下，以 100 Hz 的规则刺激序列刺激时，从耗竭状态恢复较慢（慢时间常数 tauslow，约 2 s）。相比之下，当刺激频率或细胞外[Ca2+]增加时，会出现快速（快时间常数 taufast，约 25 ms）的 Ca2+依赖性恢复，随后是较慢的恢复（慢时间常数 tauslow，约 2 s）。在正常[Ca2+]条件下，从 100 - Hz 泊松样序列刺激中恢复很快，这表明泊松样序列刺激产生的细胞内[Ca2+]比规则序列刺激更高。此外，在 Ca2+/钙调蛋白抑制剂 calmidazolium 存在的情况下，快速恢复减慢了约两倍。我们的结果表明，来自高自发放电率听觉神经纤维的 Held 终球突触通常在抑制状态下运作。高活动率期间加速的突触恢复可能确保在 Held 终球突触处实现可靠的突触传递。
