Physiological Temperatures Reduce the Rate of Vesicle Pool Depletion and Short-Term Depression via an Acceleration of Vesicle Recruitment

Abstract

The timing and strength of synaptic transmission is profoundly dependent on temperature. However, the temperature dependence of the multiple mechanisms that contribute to short-term synaptic plasticity is poorly understood. Here, we use voltage-clamp recordings to quantify the temperature dependence of exocytosis at the calyx of Held synapse. EPSC and miniature EPSC amplitudes were larger at physiological temperature, but quantal content during low-frequency (0.05 Hz) stimulation was constant after temperature jumps from 22-24°C to 35-37°C. The initial degree of EPSC depression during 100 Hz stimuli trains was unchanged with temperature, as were estimates of release probability and vesicle pool size. In contrast, physiological temperatures dramatically relieved depression measured after 40 stimuli at 100 Hz by increasing twofold the rate of recovery from depression. Presynaptic calyx recordings revealed that physiological temperature increased capacitance jumps resulting from 0.5 and 1 ms depolarizations by increasing Ca 2ϩ influx. When Ca 2ϩ entry was equalized at the two temperatures, exocytosis exhibited little temperature dependence for brief depolarizations. However, in response to longer depolarizations, raising temperature increased a slow phase of exocytosis, without affecting overall Ca 2ϩ entry or the size of the readily releasable pool of vesicles. Higher temperatures also increased the rate of presynaptic Ca 2ϩ current inactivation; nevertheless, the degree of steady-state EPSC depression was greatly reduced. Our results thus suggest that changes in steady-state EPSCs during stimulus trains at physiological temperature reflect larger quantal amplitudes and faster refilling of synaptic vesicle pools, leading to reduced short-term depression during prolonged high-frequency firing.

Actin Filaments Regulate Exocytosis at the Hair Cell Ribbon Synapse

“…However, phalloidin itself does not alter the calcium-triggered exocytosis, suggesting that the actin network does not act in a dynamic fashion on secretion. Although actin filaments populate the hair cell cytoplasm (our study and Furness et al, 2005), synapsin is absent in hair cells (Layton et al, 2005;McLean et al, 2009;Uthaiah and Hudspeth, 2010). Synapsin is a synaptic protein known to interact with actin to cluster and mobilize a reserve pool of vesicles upon dephosphorylation and phosphorylation cycling, respectively (Greengard et al, 1993).…”

“…Therefore, the actin network might provide an efficient means for hair cells to operate vesicle replenishment at a high rate (Moser and Beutner, 2000;Spassova et al, 2004;. In addition, our recordings at room temperature most probably underestimate the relevance of actin in vesicle trafficking because actin depolymerization, synaptic replenishment, and hair cell exocytosis are all temperature dependent (Wendel and Dancker, 1986;Kushmerick et al, 2006;Nouvian, 2007). Conversely, calcium channels themselves might undergo a higher mobility after the actin network disruption, as has been shown in cone and rod photoreceptors (Mercer et al, 2011).…”

Synaptic vesicle dynamics in mouse rod bipolar cells

“…However, both membrane retrieval and pool refilling rates have been reported to be temperature-sensitive (Pyott & Rosenmund 2002;Kushmerick et al, 2006;Rendon & von Gersdorff 2007). Thus, it is conceivable that at physiological temperature, both membrane recovery and pool refilling in the mouse rod bipolar cell may be even faster than reported here.…”

Calmodulin enhances ribbon replenishment and shapes filtering of synaptic transmission by cone photoreceptors

“…Furthermore, model 2 predicts that inhibiting Ca 2+ /CaM effects on vesicle attachment would slow replenishment slightly faster in mammalian RBCs, where  fast = 400 ms and  slow = 5.9 s, measured at room temperature (Singer and Diamond, 2006). Recovery is likely to be faster in vivo because the rate of vesicle recruitment at the calyx of Held synapse is enhanced at physiological temperatures (Kushmerick et al, 2006). Physiological temperatures can influence the timing of Ca 2+ entry, quickening I Ca activation and enhancing inactivation (Kushmerick et al, 2006).…”