External Drive to Inhibitory Cells Induces Alternating Episodes of High- and Low-Amplitude Oscillations

Electrical oscillations in neuronal network activity are ubiquitous in the brain and have been associated with cognition and behavior. Intriguingly, the amplitude of ongoing oscillations, such as measured in EEG recordings, fluctuates irregularly, with episodes of high amplitude alternating with episodes of low amplitude. Despite the widespread occurrence of amplitude fluctuations in many frequency bands and brain regions, the mechanisms by which they are generated are poorly understood. Here, we show that irregular transitions between sub-second episodes of high- and low-amplitude oscillations in the alpha/beta frequency band occur in a generic neuronal network model consisting of interconnected inhibitory and excitatory cells that are externally driven by sustained cholinergic input and trains of action potentials that activate excitatory synapses. In the model, we identify the action potential drive onto inhibitory cells, which represents input from other brain areas and is shown to desynchronize network activity, to be crucial for the emergence of amplitude fluctuations. We show that the duration distributions of high-amplitude episodes in the model match those observed in rat prefrontal cortex for oscillations induced by the cholinergic agonist carbachol. Furthermore, the mean duration of high-amplitude episodes varies in a bell-shaped manner with carbachol concentration, just as in mouse hippocampus. Our results suggest that amplitude fluctuations are a general property of oscillatory neuronal networks that can arise through background input from areas external to the network. Rhythmic changes in electrical activity are observed throughout the brain, and arise as a result of reciprocal interactions between excitatory and inhibitory neurons. Synchronized activity of a large number of neurons gives rise to macroscopic oscillations in electrical activity, which can be measured in EEG recordings and are thought to have a key role in learning and memory. Interestingly, the amplitude of ongoing oscillations fluctuates irregularly, with high-amplitude episodes alternating with low-amplitude episodes. Although these amplitude fluctuations occur in many brain regions, the mechanisms by which they are generated are still poorly known. To get insight into potential mechanisms, we investigated whether such fluctuations occur in a computational model of a neuronal network. We show that the model generates amplitude fluctuations that are similar to those observed in experimental data and that external input from other brain areas to the inhibitory cells of the network is essential for their generation. This input can disrupt the synchrony of activity, causing transitions between episodes of high synchrony (high oscillation amplitudes) and episodes of low synchrony (low oscillation amplitudes). Episodes of high synchrony are relevant for brain function because they provide favorable conditions for learning.