Balancing Act in the Brain: Excitatory and Inhibitory Activity

By Kathryn Ippolito, MPFI Postbac 2019-20

We constantly receive input from the world around us—sights, sounds, feelings—some of which demand our attention immediately, while others fade in and out of notice. Neurons are the cells in our brain that hold information about these inputs and trigger a response. To do so, they form networks with each other, from microcircuits consisting of just a few cells to those that coordinate multiple processes in different areas. By efficiently connecting various pieces of information, these networks make it possible for us to build a nuanced, and fairly accurate, representation of the world in our heads.

Neurons communicate through electrical currents called action potentials, which are either excitatory or inhibitory. Excitatory currents are those that prompt one neuron to share information with the next through an action potential, while inhibitory currents reduce the probability that such a transfer will take place. It typically takes more than one excitatory connection to generate an action potential, but as you might expect, hundreds of electrical signals are constantly converging on any given neuron.

The measured effect of all excitatory and inhibitory currents received by one cell is known as global excitatory/inhibitory (E/I) balance. Although there are many more excitatory neurons in the cortex, inhibitory neurons are a diverse and influential group that regulate the activity of their excitatory counterparts. They are considered balanced when the ratio between E/I activity remains approximately constant, even under a wide range of conditions. Neuroscientists are interested in E/I balance because it is essential for stable brain function—in particular, our brain’s ability to faithfully capture information about the world and integrate it with our existing knowledge. To that end, most studies of E/I balance are done in the cortex and the hippocampus, two areas of the brain associated with high-level cognition and memory. E/I balance can also be examined in a particular time frame, from milliseconds to half a second or more. This is known as temporal E/I balance and it gives scientists insight into how different patterns of action potentials are used to represent different elements of a stimulus.

Many questions remain about how E/I balance is established, maintained, and useful for different activities of the brain from sleep to identifying features. To answer these questions, E/I balance is studied through an array of electrophysiological, molecular, computational, and optogenetic techniques. One long-standing method is intracellular recording, which measures the voltage or current in a cell by isolating part of it in the tip of a hollow glass needle containing an electrode. Experiments with intracellular recording can show patterns of electrical activity during different brain states or how inhibitory and excitatory currents can pair up within milliseconds. Computational modeling, alternatively, can predict how E/I balance affects circuits throughout the brain, strengthening connections between certain cells that share unique, important information and inhibiting redundant connections. Moving forward, researchers are attempting to replicate those theoretical findings with an emphasis on disrupted circuits and how unbalanced E/I activity can contribute to neurological disorders like Alzheimer’s.

At MPFI, several labs are studying how E/I balance affects different aspects of brain function. Check out the Wang Lab to learn more about how some inhibitory neurons play a role in establishing coordinated patterns of activity across multiple brain regions or the Taniguchi Lab to see how a different kind of inhibitory neuron affects cortex development at birth. Feel free to visit our techniques page to learn more about the methods mentioned above.