TY - JOUR
T1 - Calcium-channel number critically influences synaptic strength and plasticity at the active zone
AU - Sheng, Jiansong
AU - He, Liming
AU - Zheng, Hongwei
AU - Xue, Lei
AU - Luo, Fujun
AU - Shin, Wonchul
AU - Sun, Tao
AU - Kuner, Thomas
AU - Yue, David T.
AU - Wu, Ling Gang
N1 - Funding Information:
We thank K. Sätzler and J. Lübke for providing the electron microscopy data for analysis, and J. Diamond, J. Xu and M. Baydyuk for comments on the manuscript. This work was supported by the US National Institute of Neurological Disorders and Stroke Intramural Research Program.
PY - 2012/7
Y1 - 2012/7
N2 - How synaptic-vesicle release is controlled at the basic release structure, the active zone, is poorly understood. By performing cell-attached current and capacitance recordings predominantly at single active zones in rat calyces, we found that single active zones contained 5-218 (mean, 42) calcium channels and 1-10 (mean, 5) readily releasable vesicles (RRVs) and released 0-5 vesicles during a 2-ms depolarization. Large variation in the number of calcium channels caused wide variation in release strength (measured during a 2-ms depolarization) by regulating the RRV release probability (P RRV) and the RRV number. Consequently, an action potential opened-1/41-35 (mean,-1/47) channels, resulting in different release probabilities at different active zones. As the number of calcium-channels determined P RRV, it critically influenced whether subsequent release would be facilitated or depressed. Regulating calcium channel density at active zones may thus be a major mechanism to yield synapses with different release properties and plasticity. These findings may explain large differences reported at synapses regarding release strength (release of 0, 1 or multiple vesicles), P RRV, short-term plasticity, calcium transients and the requisite calcium-channel number for triggering release.
AB - How synaptic-vesicle release is controlled at the basic release structure, the active zone, is poorly understood. By performing cell-attached current and capacitance recordings predominantly at single active zones in rat calyces, we found that single active zones contained 5-218 (mean, 42) calcium channels and 1-10 (mean, 5) readily releasable vesicles (RRVs) and released 0-5 vesicles during a 2-ms depolarization. Large variation in the number of calcium channels caused wide variation in release strength (measured during a 2-ms depolarization) by regulating the RRV release probability (P RRV) and the RRV number. Consequently, an action potential opened-1/41-35 (mean,-1/47) channels, resulting in different release probabilities at different active zones. As the number of calcium-channels determined P RRV, it critically influenced whether subsequent release would be facilitated or depressed. Regulating calcium channel density at active zones may thus be a major mechanism to yield synapses with different release properties and plasticity. These findings may explain large differences reported at synapses regarding release strength (release of 0, 1 or multiple vesicles), P RRV, short-term plasticity, calcium transients and the requisite calcium-channel number for triggering release.
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U2 - 10.1038/nn.3129
DO - 10.1038/nn.3129
M3 - Article
C2 - 22683682
AN - SCOPUS:84862845536
SN - 1097-6256
VL - 15
SP - 998
EP - 1006
JO - Nature neuroscience
JF - Nature neuroscience
IS - 7
ER -