TY - JOUR T1 - Competition between Phasic and Asynchronous Release for Recovered Synaptic Vesicles at Developing Hippocampal Autaptic Synapses JF - The Journal of Neuroscience JO - J. Neurosci. SP - 420 LP - 433 DO - 10.1523/JNEUROSCI.4452-03.2004 VL - 24 IS - 2 AU - Yo Otsu AU - Vahid Shahrezaei AU - Bo Li AU - Lynn A. Raymond AU - Kerry R. Delaney AU - Timothy H. Murphy Y1 - 2004/01/14 UR - http://www.jneurosci.org/content/24/2/420.abstract N2 - Developing hippocampal neurons in microisland culture undergo rapid and extensive transmitter release-dependent depression of evoked (phasic) excitatory synaptic activity in response to 1 sec trains of 20 Hz stimulation. Although evoked phasic release was attenuated by repeated stimuli, asynchronous (miniature like) release continued at a high rate equivalent to ∼2.8 readily releasable pools (RRPs) of quanta/sec. Asynchronous release reflected the recovery and immediate release of quanta because it was resistant to sucrose-induced depletion of the RRP. Asynchronous and phasic release appeared to compete for a common limited supply of release-ready quanta because agents that block asynchronous release, such as EGTA-AM, led to enhanced steady-state phasic release, whereas prolongation of the asynchronous release time course by LiCl delayed recovery of phasic release from depression. Modeling suggested that the resistance of asynchronous release to depression was associated with its ability to out-compete phasic release for recovered quanta attributable to its relatively low release rate (up to 0.04/msec per vesicle) stimulated by bulk intracellular Ca2+ concentration ([Ca2+]i) that could function over prolonged intervals between successive stimuli. Although phasic release was associated with a considerably higher peak rate of release (0.4/msec per vesicle), the [Ca2+]i microdomains that trigger it are brief (1 msec), and with asynchronous release present, relatively few quanta can accumulate within the RRP to be available for phasic release. We conclude that despite depression of phasic release during train stimulation, transmission can be maintained at a near-maximal rate by switching to an asynchronous mode that takes advantage of a bulk presynaptic [Ca2+]i. ER -