To facilitate the characterization of cortical neuronal function, the responses of cells in cat area 17 to intracellular injection of current pulses were quantitatively analyzed. A variety of response variables were used to separate the cells into subtypes using cluster analysis. Four main classes of neurons could be clearly distinguished: regular spiking (RS), fast spiking (FS), intrinsic bursting (IB), and chattering (CH). Each of these contained significant subclasses. RS neurons were characterized by trains of action potentials that exhibited spike frequency adaptation. Morphologically, these cells were spiny stellate cells in layer 4 and pyramidal cells in layers 2, 3, 5, and 6. FS neurons had short-duration action potentials (<0.5 ms at half height), little or no spike frequency adaptation, and a steep relationship between injected current intensity and spike discharge frequency. Morphologically, these cells were sparsely spiny or aspiny nonpyramidal cells. IB neurons typically generated a low frequency (<425 Hz) burst of spikes at the beginning of a depolarizing current pulse followed by a tonic train of action potentials for the remainder of the pulse. These cells were observed in all cortical layers, but were most abundant in layer 5. Finally, CH neurons generated repetitive, high-frequency (350-700 Hz) bursts of short-duration (<0.55 ms) action potentials. Morphologically, these cells were layer 2-4 (mainly layer 3) pyramidal or spiny stellate neurons. These results indicate that firing properties do not form a continuum and that cortical neurons are members of distinct electrophysiological classes and subclasses.

Cortical neurons are sensitive to the timing of their synaptic inputs. They can synchronize their firing on a millisecond time scale and follow rapid stimulus fluctuations with high temporal precision. These findings suggest that cortical neurons have an enhanced sensitivity to synchronous synaptic inputs that lead to rapid rates of depolarization. The voltage-gated currents underlying action potential generation may provide one mechanism to amplify rapid depolarizations. We have tested this hypothesis by analyzing the relations between membrane potential fluctuations and spike threshold in cat visual cortical neurons recorded intracellularly in vivo. We find that visual stimuli evoke broad variations in spike threshold that are caused in large part by an inverse relation between spike threshold and the rate of membrane depolarization preceding a spike. We also find that spike threshold is inversely related to the rate of rise of the action potential upstroke, suggesting that increases in spike threshold result from a decrease in the availability of Na ؉ channels. By using a simple neuronal model, we show that voltage-gated Na ؉ and K ؉ conductances endow cortical neurons with an enhanced sensitivity to rapid depolarizations that arise from synchronous excitatory synaptic inputs. Thus, the basic mechanism responsible for action potential generation also enhances the sensitivity of cortical neurons to coincident synaptic inputs. C ortical neurons process information by transforming a continuously varying spatiotemporal pattern of synaptic input into a train of action potentials. Although the cellular mechanisms underlying this process are not fully understood, one common view treats the cortical neuron as a leaky integration device. In this scheme, irregular synaptic input evokes changes in membrane potential (V m ) that accumulate over a membrane time constant until firing threshold is reached and spikes are generated (1-9). The spike output of such a neuron is proportional to its V m , and the membrane time constant constrains the cell's sensitivity to the timing of synaptic input. Neurons obeying these simple principles are thought to transmit information in their mean firing rates, and little or no information is thought to be conveyed in the timing of action potentials (refs. 9-10; see also ref. 11).Although it is generally not disputed that cortical neurons integrate their synaptic input and fire action potentials at rates proportional to V m , this does not exclude a possible sensitivity to the timing of synaptic inputs (11-15). Evidence from crosscorrelation studies (16-18) and recent demonstrations that cortical neurons can fire spike trains with high temporal fidelity (19-22) support this view. Thus, we can say with some confidence that cortical neurons are sensitive to the timing of their inputs, but how this temporal sensitivity is achieved at the cellular level is not fully understood.One important component of the temporal sensitivity of cortical neurons may stem from the voltage-gated conductances ...

Cortical neurons recorded in vivo exhibit 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 cortex in vivo and examined the relationships between spontaneous activity and visually evoked responses. Activity was assessed on a trial-by-trial basis by measuring the membrane potential (Vm) 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 in Vm relative to baseline, was linearly correlated with the preceding spontaneous Vm. 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 spontaneous Vm. Spike-triggered averaging of Vm revealed that visually evoked action potentials arise from transient depolarizations having a rise time of approximately 10 msec. Consistent with this, evoked spike count was found to be linearly correlated with the magnitude of Vm fluctuations in the gamma (20-70 Hz) frequency band. We also found that the threshold of visually evoked action potentials varied over a range of approximately 10 mV. Examination of simultaneously recorded intracellular and extracellular activity revealed a correlation between Vm depolarization 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.

Several theories have proposed a functional role for response synchronization in sensory perception. Critics of these theories have argued that selective synchronization is physiologically implausible when cortical networks operate at high levels of activity. Using intracellular recordings from visual cortex in vivo, in combination with numerical simulations, we find dynamic changes in spike threshold that reduce cellular sensitivity to slow depolarizations and concurrently increase the relative sensitivity to rapid depolarizations. Consistent with this, we find that spike activity and high-frequency fluctuations in membrane potential are closely correlated and that both are more tightly tuned for stimulus orientation than the mean membrane potential. These findings suggest that under high-input conditions the spike-generating mechanism adaptively enhances the sensitivity to synchronous inputs while simultaneously decreasing the sensitivity to temporally uncorrelated inputs.

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