How the brain interprets electrical impulses sent by neurons

University of California, San Diego neurobiologists have uncovered evidence that sheds light on the long-standing mystery of how the brain makes sense of the information contained in electrical impulses sent to it by millions of neurons from the body.

In a paper published this week in the early on-line version of the journal Nature, a UCSD team led by Massimo Scanziani explains how neurons, or nerve cells, in the brain sort out information before deciding how to respond. The paper will appear in a forthcoming print issue of Nature.

Light, sound and odors, for example, are transformed by our sensory organs into a code made of series of electrical impulses that travel along neurons from the body to the brain. Information about the onset and the intensity of a stimulus is thought to be sent to the brain by the timing and frequency of these electrical impulses. How information is sorted by the brain has been an open question. The group discovered that different neurons in the brain are dedicated to respond to specific portions of the information.

“Our work shows that deciphering the enormous amount of information that is conveyed to the brain at any time-point is a matter of division of labor between specialized neurons,” explains Scanziani, an assistant professor of biology. “Each neuron literally ’picks’ the type information it is supposed to process, that it is competent for. Very much like each musician in an orchestra only reads that part of the score of a symphony that was written for his or her own instrument.”

Because they needed to see and record electrical impulses from individual nerve cells, the researchers used slices of rat brain, which when bathed in an appropriate solution can be kept alive under a microscope. To mimic incoming information, the first author on the paper, Frédéric Pouille, a postdoctoral fellow in Scanziani’s laboratory, provided an electrical stimulus—analogous to the score in Scanziani’s analogy—and then monitored which nerve cell read which part of the information. Pouille and Scanziani found some nerve cells that were only responsive to the first impulse that arrived, while other nerve cells only responded to multiple electrical impulses arriving at certain frequencies.

“While some neurons only responded to the onset of each package of information, which, in other words, means: Hey, something just arrived, other neurons actually looked into the package and played the notes,” says Scanziani.

Each of these specialized brain neurons has a highly branched structure where many neurons carrying sensory information can form connections. At any moment, each of these specialized brain neurons might be receiving multiple messages from multiple sources, but is only selectively responding to certain information about the timing or frequency of the impulses it is receiving.

Why is the timing of information so important? Visual, tactile and auditory information needs to be synchronized. If it were not, then one might, for example, perceive someone’s lips move before hearing the words being spoken—like a badly dubbed foreign film.

The brain also needs to know how intense a stimulus is because intensity will influence what action needs to be taken. For example, an uncomfortable shoe will become more and more difficult to ignore as your foot develops a blister. As the blister develops, the interval between subsequent electrical impulses arriving at the brain would decrease; in other words, their frequency would increase. Scanziani speculates that there might even be an “alarm neuron” in the brain that responds to high frequency electrical impulses by triggering the appropriate muscle response to escape the stimulus.

“This study advances our understanding of how the brain reads a code made of identical electrical impulses, in order to produce a coherent perception of the world,” he says. “Deciphering the language of the brain will help us understand the neuronal basis for sensation and cognition and their associated disorders.”

In their paper, the UCSD researchers also determine a chain of physiological mechanisms working in concert to allow these brain neurons to selectively respond to a specific pattern of incoming electrical impulses. Communication across the connections between neurons is usually chemical rather than electrical. The researchers found that the differences in the way the individual brain neurons released and responded to these chemicals could explain their differing responses to incoming information.

Scanziani and Pouille’s experiments focused on the hippocampus—a region of the brain known to be important in learning in memory. But they believe that other regions of the brain may also use the same principles to sort information. However, the researchers point out that brain slices are a simplified system, and more research is needed before they will understand the finer details of this sorting.

“This is only part of the picture,” cautions Scanziani. “We are not looking at the whole orchestra, maybe only the violins and the oboes. But down the line we plan to look at further classes of nerve cells.”

The research study was initiated when Scanziani was an assistant professor at the Brain Research Institute of the University of Zurich. The work was supported by the National Institutes of Health and the Swiss National Science Foundation.