The Number of Components of Enhancement Contributing to Short-Term Synaptic Plasticity at the Neuromuscular Synapse during Patterned Nerve Stimulation Progressively Decreases As Basal Release Probability Is Increased from Low to Normal Levels by Changing Extracellular Ca²⁺

Abstract

Presynaptic short-term plasticity (STP) dynamically modulates synaptic strength in a reversible manner on a timescale of milliseconds to minutes. For low basal vesicular release probability (prob 0 ), four components of enhancement, F1 and F2 facilitation, augmentation (A), and potentiation (P), increase synaptic strength during repetitive nerve activity. For release rates that exceed the rate of replenishment of the readily releasable pool (RRP) of synaptic vesicles, depression of synaptic strength, observed as a rundown of postsynaptic potential amplitudes, can also develop. To understand the relationship between enhancement and depression at the frog (Rana pipiens) neuromuscular synapse, data obtained over a wide range of prob 0 using patterned stimulation are analyzed with a hybrid model to reveal the components of STP. We find that F1, F2, A, P, and depletion of the RRP all contribute to STP during repetitive nerve activity at low prob 0 . As prob 0 is increased by raising Ca o 2ϩ (extracellular Ca 2ϩ ), specific components of enhancement no longer contribute, with first P, then A, and then F2 becoming undetectable, even though F1 continues to enhance release. For levels of prob 0 that lead to appreciable depression, only F1 and depletion of the RRP contribute to STP during rundown, and for low stimulation rates, F2 can also contribute. These observations place prob 0 -dependent limitations on which components of enhancement contribute to STP and suggest some fundamental mechanistic differences among the components. The presented model can serve as a tool to readily characterize the components of STP over wide ranges of prob 0 .

New insights into short-term synaptic facilitation at the frog neuromuscular junction

“…Such a PPF increase under low external Ca 2ϩ concentration was observed in earlier studies using experimental and computational methods (Holohean and Magleby 2011;Magleby and Zengel 1982). Fundamentally, this is due to a dramatic decrease in initial vesicle fusion under low Ca 2ϩ conditions during the first stimulus, and correspondingly enhanced release during the second and subsequent pulses due to the effects of residual Ca 2ϩ .…”

Effect of adenosine on short-term synaptic plasticity in mouse piriform cortex in vitro: adenosine acts as a high-pass filter

“…Short‐term synaptic plasticity rests on multiple mechanisms characterized by different time courses (e.g., Curtis and Eccles ; Richards ; Zucker and Regehr ; Fioravante and Regehr ; Holohean and Magleby ; Hennig ; de Jong and Fioravante ). Thus, on the basis of their dynamics, up to three distinct STF mechanisms have been distinguished: facilitation proper, with a time course in the hundreds of msec range, and two mechanisms whose influences persist for seconds to minutes: augmentation and post‐tetanic potentiation.…”

Adenosine A1 and A2A receptor‐mediated modulation of acetylcholine release in the mice neuromuscular junction

“…This is not surprising as NMJs are not usually facilitating synapses in basal conditions. They are more probably depressing synapses (Zucker & Regehr, ; Holohean & Magleby, ). In NMJs there is a high probability that a synaptic vesicle from the readily releasable pool will release its contents after a nerve impulse under resting conditions, particularly when this probability is not reduced in μ‐CgTx‐GIIIB media.…”