Synaptic depression related to presynaptic axon conduction block.

Abstract

SUMMARY1. The depression of synaptic transmission, which occurs during prolonged repetitive activation, was examined in the opener muscle of the crayfish walking leg.2. Excitatory post-synaptic potentials (e.p.s.p.s) initially facilitated but then declined to low amplitudes after about 4000 stimulus pulses had been delivered; this depression is presynaptic in origin.3. Axon conduction blocks occurred at points of bifurcation along the entire length of the presynaptic nerve. This resulted in failure of the nerve impulse to invade some branches of the terminal arborization.4. Nerve terminal invasion failure caused either intermittent or complete inactivation of some synaptic release sites; this was associated with depression of the post-synaptic response.5. The statistics of transmitter release during prolonged repetitive stimulation were examined by focal extracellular recording methods. Transmitter release could be described by binomial statistics, and depression involved a drop in m, n and p.6. The rate of spontaneous quantal release did not decrease, however, arguing against transmitter depletion.7. It is concluded that repetitivestimulationeventuallyleads to depolarization of the axon membrane. This causes impulse propagation failure which reduces the number of synaptic release sites that are activated and mimics a drop in the effective stimulation rate; both effects cause synaptic depression.

Calcium released by photolysis of DM‐nitrophen triggers transmitter release at the crayfish neuromuscular junction.

“…This could be due to an oversimplified formulation of the relation between calcium and transmitter release, to a progressive activation of calcium-dependent potassium current and consequent spike reduction, or to synaptic depression. Even though depression at this synapse is uncommon (Hatt & Smith, 1976), we are increasing, in some cases, MEJP frequency to a range equivalent to 50-100 action potentials per second. Despite these complications, we observe a non-linear relation between EJP amplitude and MEJP frequency during the early rising and subsequent falling phases of the responses to illumination.…”

“…However, at the squid giant synapse MEPSP frequency is not measurable, due to the high input conductance of the postsynaptic axon, so a relationship between intracellular calcium and asynchronous transmitter release could not be studied. The crayfish NMJ is better suited for observing miniature excitatory junctional potential (MEJP) frequency and evoked release to a spike, with little or no depression of transmitter release occurring at high frequency stimulation (Hatt & Smith, 1976). We chose to raise intracellular calcium in the crayfish presynaptic boutons using the caged calcium compound DM-nitrophen and record MEJP frequency and evoked release, relating their frequency and amplitude changes respectively to a non-linear summation model with a high degree of calcium co-operativity.…”

Information processing in the axon

“…Extra activity-dependent delays might have important consequences for synaptic transmission. For instance, the synaptic delay was extended by 1-2 ms during repetitive stimulation of crayfish motor neurons 64 . Monosynaptic connections to motor neurons show an increase in synaptic latency concomitant with the synaptic depression that is induced by repetitive stimulation at 5-10 Hz and that induced near-propagation failures 65 .…”

“…When the action potential fails to propagate along the axon, no signal can reach the output of the cell. Conduction failure filters communication with postsynaptic neurons, and has been observed experimentally in various axons including vertebrate spinal axons 68,69 , spiny lobster or crayfish motor neurons 33,64,70,71 , leech mechanosensory neurons [72][73][74][75][76] , thalamocortical axons 77 , rabbit nodose ganglion neurons 78 , rat dorsal root ganglion neurons 63,79 , neurohypophysial axons 17,80 and hippocampal pyramidal cells 39,66,81 . Several factors determine whether propagation along axons fails or succeeds.…”

Modification of motor nerve terminal excitability by alkanols and volatile anaesthetics

“…It therefore seems reasonable to conclude, tentatively, that accommodation represents inactivation of the sodium current system (Hodgkin & Huxley, 1952a), and at relatively low levels ofdepolarization this process is enhanced by propanol, enflurane, and, to varying extents, by other alkanols and volatile anaesthetics. A shift in the hyperpolarizing direction of the inactivation curve for gNa has been demonstrated with alkanols and volatile anaesthetics in crayfish and squid giant axon (Oxford & Swenson, 1979;Haydon & Urban, 1983a,b), and (with diethylether) at the frog node of Ranvier (Kendig et al, 1979 (Hatt & Smith, 1976;Grossman et al, 1979;Grossman & Kendig, 1982). However, the same shift at the sites ofneuronal initiation ofaction potentials might have a substantial effect on cell firing in response to excitatory synaptic input.…”