Cellular Mechanisms Contributing to Response Variability of Cortical NeuronsIn Vivo

Abstract

Cortical neurons recordedin vivoexhibit highly variable responses to the repeated presentation of the same stimulus. To further understand the cellular mechanisms underlying this phenomenon, we performed intracellular recordings from neurons in cat striate cortexin vivoand examined the relationships between spontaneous activity and visually evoked responses. Activity was 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 magnitude, expressed as a change inV_mrelative to baseline, was linearly correlated with the preceding spontaneousV_m. This correlation was enhanced when the cells were hyperpolarized to reduce the activation of voltage-gated conductances. The output of the cells, expressed as spike counts and latencies, was only moderately correlated with fluctuations in the preceding spontaneousV_m. Spike-triggered averaging ofV_mrevealed that visually evoked action potentials arise from transient depolarizations having a rise time of ∼10 msec. Consistent with this, evoked spike count was found to be linearly correlated with the magnitude ofV_mfluctuations in the γ (20–70 Hz) frequency band. We also found that the threshold of visually evoked action potentials varied over a range of ∼10 mV. Examination of simultaneously recorded intracellular and extracellular activity revealed a correlation betweenV_mdepolarization and spike discharges in adjacent cells. Together these results demonstrate that response variability is attributable largely to coherent fluctuations in cortical activity preceding the onset of a stimulus, but also to variations in action potential threshold and the magnitude of high-frequency fluctuations evoked by the stimulus.