Stochastic and deterministic dynamics of intrinsically irregular firing in cortical inhibitory interneurons

Neurons send information to other neurons in the brain by generating fast electrical pulses called action potentials (or spikes). When stimulated by input signals of a constant size, neurons generally respond with regular patterns of spiking leading to rhythmical brain activity. However, neurons known as irregular spiking interneurons are unique: the relationship between the input they receive and whether or not they produce a spike appears to be random. The molecular mechanism behind this phenomenon is not clear. Mendonca et al. set out to investigate whether irregular spiking is truly random, or whether there is some degree of predictability. The experiments used genetically modified mice in which irregular spiking interneurons were specifically labeled with a fluorescent protein, which made them easier to find to record their electrical activity. Sophisticated statistical analyses showed that these neurons are not firing at random. Instead, there is a pattern to the timings of the spikes they produce. It was previously known that electrical spikes in neurons are generated by sodium ions and potassium ions moving across the membrane that surrounds each cell. Proteins called ion channels provide routes for these ions to pass through the membrane. Mendonca et al. show that compared to other neurons, irregular spiking interneurons have larger numbers of a specific type of potassium ion channel. Mimicking the effect of increasing the number of these potassium ion channels in the interneurons made the firing pattern of these neurons more irregular, while decreasing the number of these channels made the firing patterns more regular and predictable. A computer model of an irregular spiking interneuron showed that the activity of these potassium ion channels and a type of sodium ion channel plays a key role in producing irregular electrical spiking. Further analysis showed that irregular spiking interneurons can synchronize their activity with fast, but not slow, rhythms in brain activity. The findings of Mendonca et al. suggest that irregular spiking interneurons can disrupt slow regular electrical activity in the brain. Rhythms in brain activity vary depending on whether we are awake or asleep, and are altered in diseases such as epilepsy and schizophrenia. Now that we have a better understanding of how irregular spiking interneurons work, it should be possible to find out how they coordinate their activity with each other, and what effect they have on animal behavior.