The high-conductance state of neocortical neurons in vivo

Neocortical neurons in vivo are subjected to intense synaptic bombardment, leading to a 'high-conductance state' that differs markedly from the conditions measured in cortical slices in vitro.During barbiturate anaesthesia, as well as in slices, neuronal activity is greatly reduced compared with states of activated or desynchronized electroencephalogram (EEG) activity, such as in awake animals. During EEG-activated states, intracellular recordings show a depolarized and fluctuating membrane potential, a low input resistance and high levels of spontaneous firing. In slices, cells have a high input resistance, are hyperpolarized and show little spontaneous activity.Active dendritic properties such as the ability to generate and propagate action potentials have important implications for the integration of synaptic inputs. Computational models have been used to investigate these implications for in vivo processing.These models predict the following 'computational principles' for high-conductance states: enhanced responsiveness and gain modulation; equalization of synaptic efficacies; increased temporal resolution; and probabilistic and irregular behaviour. By virtue of these principles, cortical neurons would be tuned to optimally track fine temporal variations in their synaptic inputs despite their stochastic nature.In dynamic-clamp experiments, in vitro electrophysiology is combined with computational modelling to 'recreate' the characteristics of high-conductance states in cortical slices, allowing the effects of the high-conductance state on neuronal responsiveness to be measured directly.Such experiments confirm that synaptic noise enhances neuronal responsiveness and modulates the gain of neurons. They could also be used to test the predictions that it equalizes synaptic efficacies, increases temporal resolution and induces probabilistic behaviour.