Neocortical Network Activity in Vivo is Generated Through a Dynamic Balance of Excitation and Inhibition

The recurrent excitatory and inhibitory connections between and within layers of the cerebral cortex are fundamental to the operation of local cortical circuits. Models of cortical function often assume that recurrent excitation and inhibition are balanced, and we recently demonstrated that spontaneous network activity in vitro contains a precise balance of excitation and inhibition; however, the existence of a balance between excitation and inhibition in the intact and spontaneously active cerebral cortex has not been directly tested. We examined this hypothesis in the prefrontal cortex in vivo, during the slow (<1 Hz) oscillation in ketamine-xylazine-anesthetized ferrets. We measured persistent network activity (Up states) with extracellular multiple unit and local field potential recording, while simultaneously recording synaptic currents in nearby cells. We determined the reversal potential and conductance change over time during Up states and found that the body of Up state activity exhibited a steady reversal potential (-37 mV on average) for hundreds of milliseconds, even during substantial (21 nS on average) changes in membrane conductance. Furthermore, we found that both the initial and final segments of the Up state were characterized by significantly more depolarized reversal potentials and concomitant increases in excitatory conductance, compared with the stable middle portions of Up states. This ongoing temporal evolution between excitation and inhibition, which exhibits remarkable proportionality within and across neurons in active local networks, may allow for rapid transitions between relatively stable network states, permitting the modulation of neuronal responsiveness in a behaviorally relevant manner.