Presynaptic long-term facilitation at the crayfish neuromuscular junction: voltage-dependent and ion-dependent phases

Abstract

Long-term facilitation (LTF) of synaptic transmission was investigated in the crayfish opener muscle to determine the factors necessary for its induction and expression. LTF was induced without action potentials by intracellular depolarization of presynaptic nerve terminals. Following induction, the synaptic transmission was enhanced by about 80% for a period of several hours. Intracellular recordings from pre- and postsynaptic cells, combined with ionic and pharmacological tests, permitted dissection of LTF into 2 phases: an initial tetanic phase that depended on the presence of both sodium and calcium ions and a subsequent long-lasting phase. This latter long-lasting enhancement of synaptic transmission was induced by repeated depolarizations of synaptic terminals but did not depend on the influx of sodium or calcium ions or on intracellular release of calcium ions. Both tetanic and long-lasting phases of LTF are attributable to activity of a single neuron, i.e., they are homosynaptic phenomena. Furthermore, LTF is associated with an increase of quantal release, whereas the size of quanta remains unchanged. During the long-lasting phase of LTF, the nerve terminal releases more transmitter for a given depolarization than before induction of LTF. Thus, the locus of LTF is presynaptic. Our findings suggest the presence of a voltage-dependent mechanism in the presynaptic membrane different from voltage-gating of Na or Ca channels. Such a mechanism may be important in the establishment of long-lasting synaptic changes at the crayfish neuromuscular junction and perhaps in other neural systems.

Posttetanic potentiation at the crayfish neuromuscular junction is dependent on both intracellular calcium and sodium ion accumulation

“…Additional support for PTP being sodium dependent is given by experiments in crayfish in which sodium influx is blocked by TTX and trains of depolarizing pulses equivalent to action potentials in releasing transmitter were delivered through an intracellular electrode. These experiments revealed reduced PTP under conditions where sodium accumulation was prevented (Wojtowicz and Atwood, 1988).…”

“…Therefore, it is difficult to ensure that calcium influx did not occur during stimulation in a calcium-free solution unless direct measurements of [Ca"], can be made. Experiments by Wojtowicz and Atwood (1988) in the crayfish showed that PTP (or the tetanic phase of LTF, as they refer to it) does not occur when high-frequency stimulation is given in solutions effective in blocking calcium influx. Since PTP is not observed under these conditions (Wotjowicz and Atwood, 1988), this suggests that sodium alone has no direct effect on transmitter release.…”

“…A longer, more robust stimulation, that is, 20-33 Hz for 5-10 min, will produce two different kinds of long-term enhancement: posttetanic potentiation (PTP), which decays in minutes, and longterm facilitation (LTF), which lasts for tens of minutes to hours. PTP has been linked to the entry and accumulation of calcium and/or sodium ions into the presynaptic terminals during neural activity (Wojtowicz and Atwood, 1988). A direct measurement of [Ca2+], following a PTP-inducing train at the crayfish NMJ, using the fluorescent indicator fura-2, has shown that [Ca*+], decays at the same rate as PTP (Delaney et al, 1989) suggesting that [Ca2+], is important for this process.…”

Long‐lasting Potentiation of a Direct Central Connection between Identified Motor Neurons in the Locust

“…In the crayfish, a presynaptic voltage-dependent component that is independent of voltage-dependent scdium or calcium channels contributes to long-lasting facilitation at the neuromuscular junction (Wojtowicz and Atwood, 1988). However, in the locust, the potentiation caused by injection of depolarizing current into the soma of PFFl was not as large or as consistent as that caused by FETi stimulation, the potentiation occumng in 50% of the experiments, as opposed to 75% following FETi stimulation.…”

Increased Ca2+ influx through Na+/Ca2+ exchanger during long‐term facilitation at crayfish neuromuscular junctions

“…Crustacean neuromuscular junctions display numerous forms of synaptic plasticity in which transmission is strengthened following previous activity. Long‐term facilitation is one such form of synaptic enhancement that is prominent at crayfish tonic limb NMJs, whereby extensive motor neuron activity results in increased release of transmitter evoked by subsequent action potentials by activating previously ‘silent’ synapses (Wojtowicz & Atwood, 1985, 1986, 1988; Wojtowicz et al 1988, 1994). LTF results from an accumulation of Na + ions during intense presynaptic activity, whose extrusion by an electrogenic Na + /K + pump results in a post‐tetanic hyperpolarization that activates presynaptic hyperpolarization and cyclic nucleotide‐activated (HCN) channels; these act in concert with the actin cytoskeleton and [Ca 2+ ] i elevated by conditioning activity through a calcineurin‐sensitive kinase cascade to synthesize proteins that awaken synapses (Beaumont et al 2001, 2002; Zhong & Zucker, 2004).…”