Mainen and Sejnowski (1995) have previously shown that the timing of spikes produced by cortical neurons in response to somatic current injection can be highly reliable. The currents they injected were obtained by passing a Gaussian signal through a low-pass filter representing the time course of an EPSC, and adding a constant offset. Although such a Gaussian current is obtained in the limit as the number of inputs becomes large, Mainen and Sejnowski (1995) did not explicitly relate the current they injected to the underlying synaptic drive.
Fig. 1A shows a typical experiment in which the same current was injected into the soma of a pyramidal neuron in layer II/III of a slice of rat neocortex, and the response on 20 consecutive trials was recorded. In the experiment shown, a single 1024 msec waveform was generated according to eq. (2) and then stored; this precise waveform was injected on 20 trials. Fig. 1A shows that most of the spikes are aligned with a ``jitter'' of 1 msec or less, although a few ``stray'' or ``displaced'' spikes are also seen. In agreement with the observations of Mainen and Sejnowski (1995), these results show that cortical neurons can generate precisely repeated outputs in response to precisely repeated inputs, even when the driving current corresponds to a synthetic synaptic current generated by an ensemble of independent inputs. The small remaining output variability seen in Fig. 1A is due to some combination of experimental instability and the intrinsic imprecision of spike generator. Experiments in which precisely the same current is injected establish a limit on the output precision of which these neurons are capable. The output variability increases as other sources of variability, such as synaptic ``noise'', are considered.
Synaptic failures occurring at even a relatively low rate dramatically increase the output variability. Fig. 1B shows the response of the same neuron to injected current (as in Fig. 1A, generated according to the synaptic model described in eq. (2) ), but assuming that synapses failed to elicit a postsynaptic response on average 3 out of every 10 spikes (). The response to 20 consecutive trials was recorded. Thus in contrast to Fig. 1A--in which precisely the same current was injected on each trial--for this experiment a somewhat different waveform, corresponding to the random removal of 3/10 spikes from the input ensemble, was injected on every trial. Fig. 1B shows that spikes are no longer well aligned, indicating that under these conditions synaptic failures are the dominant source of output variability.