Putative Single Quantum and Single Fibre Excitatory Postsynaptic Currents Show Similar Amplitude Range and Variability in Rat Hippocampal Slices

Abstract

Transmission at excitatory synapses in the mammalian brain is thought to depend on the release of transmitter quanta through exocytosis of presynaptic vesicles (Katz, 1969). The number of vesicles released by a single presynaptic action potential is important for understanding the impact of a single synapse, and the variability in transmission from one impulse to the next. In addition, the number of vesicles released may be an important factor for synaptic regulation and plasticity, such as facilitation, post-tetanic potentiation and long-term potentiation (LTP). Three recent studies suggest that an increase in the number of transmitter quanta underlies hippocampal LTP (Malinow and Tsien, 1990; Bekkers and Stevens 1990; Malinow, 1991), whereas other reports suggest a postsynaptic mechanism (Kauer et al., 1988; Muller et al., 1988; Foster and McNaughton, 1989). We have used the whole-cell recording technique to compare putative quantal and single fibre responses at excitatory synapses in rat hippocampal slices, and find (i) a surprisingly large variability in single fibre excitatory postsynaptic currents (sfEPSCs); (ii) an equally large variability of putative quantal (pq) EPSCs elicited by hyperosmolar media or ruthenium red; (iii) the observed amplitude ranges for the sfEPSCs and the pqEPSCs overlap almost completely; and (iv) in neither case can the variability be attributed to a scatter in electrotonic distance from the soma of the engaged synapses. Thus, the data are compatible with the hypothesis that a presynaptic action potential usually releases only a single quantum. Other possibilities are also discussed.

An evaluation of causes for unreliability of synaptic transmission.

“…We find, in confirmation of what has been reported earlier (1)(2)(3), that unreliability, estimated as for the cell in Fig. 1 Neurobiology: Men and Stevens 10382 Neurobiology: Allen and Stevens using electrical stimulation of fiber pathways to initiate presynaptic nerve impulses, some portion of the observed unreliability probably is due to axon threshold fluctuations: those axons near threshold will produce nerve impulses with a probability less than unity and, thus, will contribute to the apparent synaptic unreliability.…”

“…Since the majority of impulse arrivals do not result in a postsynaptic response, hippocampal circuitry must be very redundant. The fact that the average synaptic current is only about 0.2 nA at peak (1,11) and the observation that synchronous activity of several dozen synapses is required to reach threshold (12) fit well with this notion of redundancy: no single synapse is very effective in determining a neuron's output, and many must cooperate to produce a spike train. If the estimates for the average number of synapses one neuron contributes to a target neuron are accurate (10,(13)(14)(15)(16), the cooperativity must be spread over rather large population ofcells.…”

“…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)(2)(3). But other sources for the unreliability, described below, have not been excluded.…”

“…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)(2)(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)(2)(3).…”

“…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 (1). The idea of minimal stimulation is to decrease the stimulation current until only a single axon (that projects to the neuron from which recordings are being made) is activated.…”