An evaluation of causes for unreliability of synaptic transmission.

Abstract

Transmission at individual synaptic contacts on CAI hippocampal pyramidal neurons has been found to be very unreliable, with greater than half of the arriving presynaptic nerve impulses failing to evoke a postsynaptlc response. This conclusion has been reached using the method of minimal stimulation of chafer collaterals and whole cell recording in hippocampal slices; with mimal stimulation only one or a few synapses are activated on the target neuron and the behavior of individual synapses can be examined. Four sources for the unreliability of synaptic t ssin have been investigated: (J) the fluctuation of axon thresholds at the site of stimulation causing the failure to generate a nerve impulse in the appropriate Schaffer collaterals, (it) the failure of nerve impulses generated at the site of stimulation to arrive at the synapse because of conduction failures at axon branch points, (aT) an artifactual synaptic unreliability due to performing experiments in vitro at temperatures well below the normal mammalian body temperature, and (iv) transmission failures due to probabilistic release at synapses with a very low capacity to release transmitter. We eliminate the first three causes as sinfcat contributions and conclude that probabilistic release mehanisms at low capacity synapses are the main cause of unreliability of synaptic transmission.Several recent studies have documented the unreliability of central nervous system synapses: typically, a postsynaptic response is produced less than half of the time when a presynaptic nerve impulse arrives at a synapse (1-3). Synaptic unreliability, defined as the fraction of presynaptic impulses that fail to cause a postsynaptic response, has been thought to result from the statistical nature of neurotransmitter release (1-3). But other sources for the unreliability, described below, have not been excluded.Four alternative causes for synaptic unreliability need to be considered: (i) Threshold fluctuations. If the threshold of axons being stimulated happened to fluctuate randomly from stimulus to stimulus (4, 5) and if the stimulating current is near threshold, the apparent failures in transmission might reflect those trials on which the stimulus failed to reach threshold. According to this mechanism, synaptic transmission would appear to fail simply because no METHODSWe have used standard methods as described by Stevens and Wang (7). Briefly, transverse hippocampal slices were prepared from Harlan-Sprague-Dawley rats between 2 and 4 weeks old. After an hour of stabilization in an incubation chamber, slices were mounted submerged in the recording chamber and superfused with a 95% 02/5%(C02 solution containing 120 mM NaCl, 3.5 mM KCl, 1.25 mM NaH2PO4, 26 mM NaHCO3, 1.3 mM MgCl2, and 2.5 mM CaCl2; Mg and Ca concentrations were modified in some experiments as specified in the text. Whole cell voltage clamp recordings were obtained from CA1 (or CA3 as specified in the text) pyramidal cells using 3-to 5-Mfl pipettes filled with a solution containing 130 mM cesium gluc...

Limit on the Role of Activity in Controlling the Release-Ready Supply of Synaptic Vesicles

“…By carefully adjusting the stimulation strength, we found a narrow range of settings in which a fraction of the stimuli would fail to trigger a regenerative current. This threshold window allowed the quantification of very small changes in axonal excitability over the course of the experiment [Allen and Stevens (1994) and references therein]. Figure 1 B shows that the average probability of firing did not change substantially during the experiment.…”

“…The experiment summarized in Figure 1 B provides a good test for whether a stimulating device introduces unanticipated errors into the sorts of experiments detailed here. Because small changes in stimulus intensity can lead to large changes in the number of axons stimulated (Allen and Stevens, 1994), we stress that it is not adequate to instead monitor only changes in the size of the electrical artifact associated with each stimulus.…”

Instability of Attractors in Auto-associative Networks with Bio-inspired Fast Synaptic Noise

“…It is likely that the reported short-time synaptic noise determines the transmission of information in the brain [1,2,3,4]. By means of a modified attractor neural network, we shall illustrate here that fast synaptic noise may result in a nonequilibrium condition [6] consistent with short-time depression [5].…”

Neuronal Encoding of Visual Motion in Real-Time

“…This uncertainty can have several causes such as the stochastic opening and closing of ion channels (White et al 2000), or probabilistic transmitter release at chemical synapses (e.g. Allen and Stevens 1994). Moreover, even the sensory input itself may be noisy, as is the case for the visual system due to the stochastic nature of light.…”