Statistical analysis of amplitude fluctuations in EPSCs evoked in rat CA1 pyramidal neurones in vitro.

Abstract

1. EPSCs were evoked in CA1 pyramidal neurones of young rats in vitro by extracellular stimulation of axons in a restricted stratum radiatum field, and were recorded using the whole‐cell technique. 2. Quantal fluctuations in EPSC amplitude could be demonstrated for nineteen of fifty EPSCs analysed. Quantal currents (at the soma) ranged from 2.6 to 9.5 pA (after correction for the access resistance) with a mean of 4.0 +/‐ 2.0 pA. 3. Quantal variance was negligible for the majority (13/19) of the EPSCs. However, a large quantal variance (with a coefficient of variation > 0.4) is one possible reason why a large number of the EPSCs (29/50) could not be shown to have quantal fluctuations. 4. The statistical pattern of fluctuations in the amplitude of the majority of the quantal EPSCs (18/19) could not be described by conventional models of transmitter release. 5. The time course of the EPSC and a compartmental model of CA1 pyramidal neurones were used to calculate synaptic location. The quantal current (at the soma) was independent of the electrotonic location of the synapse at which it was evoked. The peak quantal conductance generating each quantal current ranged from 0.5 to 6.8 nS (mean 1.3 +/‐ 1.4 nS), its magnitude increasing with distance from the soma. The mean peak conductance is likely to be generated by the opening of at least 60‐160 AMPA channels.

The high variance of AMPA receptor- and NMDA receptor-mediated responses at single hippocampal synapses: Evidence for multiquantal release

“…A previous investigation of the responses evoked by minimal stimulation has noted that multiquantal release does not obey binomial statistics (5). This discovery is also evident in our results, which are as follows: if the average number of vesicles released is 4 in the experiment of Fig.…”

“…The largest responses were up to 10 times larger than the smallest response, implying a wide dynamic range for multiquantal transmission. In the case where we were able to study the AMPAmediated response, the maximal response was 40 pA, much larger than quantal size (5)(6)(7)(8)(9)(10)(11). This large maximal current is in line with recent experiments showing that direct application of glutamate to synapses in culture (23,32) and in brain slices (33) can produce currents up Ϸ100 pA.…”

“…Our finding of a high CV at single identified spines therefore argues that release is multiquantal. An additional finding is that the maximum AMPA-mediated response can be very large (Ͼ40 pA), much larger than measurements of quantal size (5)(6)(7)(8)(9)(10)(11) or the average mEPSCs generated by synapses with a comparable distance from the soma (Ϸ5 pA; ref. 11).…”

“…A minimal stimulation method has been extensively used to study the ''unitary'' responses generated by single axonal inputs. There are now reports from seven independent laboratories indicating that the amplitude distribution of the excitatory postsynaptic potential (EPSP) can have evenly spaced peaks (5)(6)(7)(8)(9)(10)(11)(12), the signature of quantal transmission. Statistical analysis shows that the peaks cannot be attributed to sampling artifacts.…”

A Review of Glutamate Receptors I: Current Understanding of Their Biology

“…One form of hippocampal LTP involves the activation of the NMDA receptors and a rise in postsynaptic Ca ++ in the CA1 region but there is still considerable debate as to the site at which the increase in synaptic strength is expressed [304][305][306][307] . Presynaptic mechanisms, which can be measured at excitatory synapses on cultured hippocampal neurons by analysis of the progressive block of NMDA receptormediated synaptic currents by the irreversible open channel blocker, dizocilpine ((+) MK-801), should be reflected in a change in release probability 398 .…”