Fast Synaptic Vesicle Reuse Slows the Rate of Synaptic Depression in the CA1 Region of Hippocampus

Abstract

During short-term synaptic depression, neurotransmission rapidly decreases in response to repetitive action potential firing. Here, by blocking the vacuolar ATPase, alkalinizing the extracellular pH, or exposing hippocampal slices to pH buffers, we impaired neurotransmitter refilling, and electrophysiologically tested the role of vesicle reuse in synaptic depression. Under all conditions, synapses onto hippocampal CA1 pyramidal cells showed faster depression with increasing stimulation frequencies. At 20 Hz, compromising neurotransmitter refilling increased depression within 300 ms reaching completion within 2 s, suggesting a minimal contribution of reserve vesicles to neurotransmission. In contrast, at 1 Hz, depression emerged gradually and became significant within 100 s. Moreover, the depression induced by pH buffers was reversible with a similar frequency dependence, suggesting that the frequency-dependent increase in depression was caused by impairment of rapid synaptic vesicle reuse. These results indicate that synaptic vesicle trafficking impacts the kinetics of short-term synaptic plasticity at an extremely rapid time scale.

Dynamin and Activity Regulate Synaptic Vesicle Recycling in Sympathetic Neurons

“…In hippocampal or neocortical neurons, rapidly recycled SVs in the RRP are capable of rapid reuse (45) and slow the rate of synaptic depression (46). Our study shows that synaptic transmission in cultured SCG neurons also decreases rapidly in response to repetitive action potential firing (Fig.…”

Ca2+Influx Slows Single Synaptic Vesicle Endocytosis

“…To investigate the properties of single synaptic vesicle exocytosis and endocytosis, we expressed the pHluorin-tagged version of the vesicular glutamate transporter (vGlut-pHluorin) in dissociated hippocampal cultures (Voglmaier et al, 2006) using a lentiviral expression system (Ertunc et al, 2007). Earlier work has shown that vGlut-pHluorin expression results in low levels of surface fluorescence, enabling reliable detection of single vesicle fusion events (Balaji and Ryan, 2007).…”

Strain Differences in Presynaptic Function

“…Furthermore, we found increased short term depression that occurred at lower stimulus frequencies in DBA mice. Impairment of fast vesicle recycling may result in a frequency-dependent increase in short term depression in hippocampal CA1 synapses, which may emerge in early phases (300 ms at 20 Hz) of stimulation (36). Taken together, these observations suggest differences in replenishment of the readily releasable pool in DBA mice.…”