Reliability of spike encoding in neocortical neurons

The spontaneous and driven activity of cortical neurons have a high degree of irregularity ( I ) , yet it is not known whether this variability carries information or simply reflects intrinsic noise. We have assessed reliability in the generation of spike trains, using intracellular recording and current injection in vitro, and found that when the identical fluctuating current stimulus was repeatedly injected, the evoked spike pattern was highly consistent, with the precision depending strongly on characteristics of the stimulus. These results indicate that action potential generation in neocortex is a highly reliable process which may enable neurons to faithfully encode incoming information into preciselytimed spike sequences. It is central to our understanding of cortical function that neurons respond selectively to certain features of the environment with a change in their firing rate (2). It has also been widely observed that such responses are marked by a high degree of irregularity in the temporal patterning of action potentials ( I ) , yet the significance of this variability is poorly understood. On one hand, variability of spike timing could arise from the noise inherent in the biophysical processes involved in the generation (3) and transmission of neural signals (4). Alternatively, spike patterns may contain information about the environment above and beyond that conveyed by the mean rate (5). Spike variability would then be attributed to unobserved changes in stimuli or internal state rather than simply to intrinsic noise. To test whether cortical information processing could plausibly rely on coding within the fine temporal structure of spike trains, we performed experiments on an in vitro cortical slice preparation chosen so that the state of a single neuron and its input could be well-controlled experimentally. Reliability was assessed with a simple paradigm: a given stimulus was repeatedly presented and the consistency of the sequence of spikes was evaluated. In order to isolate the process of spike-generation from those of synaptic transmission and dendritic integration, somatic whole-cell recordings were made in the current-clamp configuration ( 6 ) , and spike trains were elicited using current injected through the recording electrode, near the presumed site of action potential generation (7). First, simple current pulses (0-0.5 nA, 0.9 sec) were used to evoke trains of action potentials. The variability of spike count was small, and variability of interspike interval (ISI; compared across trials for each interval from 1 to n and then averaged across intervals) was low. However, the variance of ISIs rendered the time of occurrence of spikes increasingly desynchronized through the course of the pulse (Fig. 1A). Hence, the timing of the first spike of each train was tightly locked to the onset of the current pulse, while the timing of the last spike in the train was highly variable. Thus, responses to pulse stimuli indicate reliability of spike rate (as measured by total count or reciprocal ISI) but lack of reliability in timing (as measured relative to stimulus onset). Naturally-occurring input is likely to differ considerably from the current pulse stimuli. In vivo, synaptic activity typically results in hyperpolarizing and depolarizing transients (8). Accordingly, signals with random dynamic modulation were generated by computer to approximate the summation of many synaptic currents as seen at the soma (9). When the identical input sequence (same random seed) was repeatedly injected, patterns of spikes with precise and stable timing were elicited (Fig. 1B). As with pulse stimuli, both spike count and ISIs showed little variability. In contrast to pulse stimuli, however, variability of spike timing was also extremely low. While variance of ISIs did not lead to desynchronization, a more discrete form of variability 0.0 Time (s) 1.0 0.0 Time (s) 1.0