Cellular mechanisms contributing to response variability of cortical neurons in vivo

Cortical neurons recorded in vivo exhibit highly variable responses to the repeated presentation of the same stimulus. To further understand the cellu lar mechanisms underlying this phenomenon, we performed intracellular recor dings from neurons in cat striate cortex in vivo and examined the relations hips between spontaneous activity and visually evoked responses. Activity w as assessed on a trial-by-trial basis by measuring the membrane potential ( V-m) fluctuations and spike activity during brief epochs immediately before and after the onset of an evoked response. We found that the response magn itude, expressed as a change in V-m relative to baseline, was linearly corr elated with the preceding spontaneous V-m. This correlation was enhanced wh en the cells were hyperpolarized to reduce the activation of voltage-gated conductances. The output of the cells, expressed as spike counts and latenc ies, was only moderately correlated with fluctuations in the preceding spon taneous V-m. Spike-triggered averaging of V-m revealed that visually evoked action potentials arise from transient depolarizations having a rise time of similar to 10 msec. Consistent with this, evoked spike count was found t o be linearly correlated with the magnitude of V-m fluctuations in the gamm a (20-70 Hz) frequency band. We also found that the threshold of visually e voked action potentials varied over a range of similar to 10 mV. Examinatio n of simultaneously recorded intracellular and extracellular activity revea led a correlation between V-m depolarization and spike discharges in adjace nt cells. Together these results demonstrate that response variability is a ttributable largely to coherent fluctuations in cortical activity preceding the onset of a stimulus, but also to variations in action potential thresh old and the magnitude of high-frequency fluctuations evoked by the stimulus .