Randy Bruno: Studying rodent whiskers uncovers how our brains process sensory input

Understanding sensory processing – by a whisker

Randy Bruno, Ph.D., currently Assistant Professor of Neuroscience at Columbia University, was once a computer scientist struggling with artificial intelligence problems. He realized the answers he sought could only be found in living brains.

“As a student in computer science,” says Dr. Bruno, “I asked, ‘How can I even begin to replicate human intelligence until I can understand how human intelligence works?’ That’s when I started looking at neuroscience.”

Dr. Bruno is interested in sensory processing – how it is that one can touch a surface or look across the room or hear something and instantly make sense of it. Also, how it is that one can think about that stimulus, learn and remember things about it, and contextualize it among the constant storm of stimuli people are pelted with daily. This is the domain of the neocortex, a six-layer part of the mammalian brain that is involved in higher functions such as sensory perception, cognition, and language.

The neocortex receives information from the thalamus, which receives information from sensory organs interacting with the outside world. What Dr. Bruno wants to discover, to use his words, is “How does the neocortex do the magical stuff that it does?”

Axons from the rat thalamus (lower right) innervate separate barrel columns in the cortex (upper left), as seen by GFP (green fluorescent protein) labeling

 

Rolling out the barrels

To study this complex area, Dr. Bruno has focused his research on what is known as the rodent whisker barrel system. In 1970, researchers discovered that the array of whiskers in many rodents corresponds neatly to that of barrel-shaped areas in the fourth layer of the neocortex; further, it was found that there is a one-to-one correlation between a given whisker and its matching barrel within the neocortex, so that if the whisker is moved, signals from the thalamus cause a neuron within the corresponding barrel to fire.

“There are a number of advantages involved in studying sensory processing through this focus,” says Dr. Bruno. “For one, the different layers of the rodent neocortex connect to the same other brain regions as ours, so we can get useful information out of our experiments. Also, whiskers are easy to excite and the barrel cortex is superficially located so we can easily perform in vivo investigations.”

Rodents use their whiskers in much the same way that people would use their fingertips to get information about something in front of them. A person feels something smooth and cool and is able to make a determination about it, just as if it were pointy or hot. We know this happens but we don’t know how – yet.

“Through in vivo experiments, we can flick a whisker and see the action potential from the neurons firing,” says Dr. Bruno. “We know from past research that individual neurons are very weak and that the thalamus therefore uses a massive convergence of many signals at once to get the target neurons to do something. One of the things my lab is studying is the timing code: how the pattern and timing of information-encoded signals works in different layers of the neocortex.”

Recording nerve activity in real time

 

Two brains in one

As mentioned before, the barrels are located in cortical layer IV. Dr. Bruno’s research has found that neurons in other layers but in the same general region as the barrels are unaffected by these signals. This means that the different layers of the neocortex are functionally independent of each other – they keep doing their jobs at the same time, which, according to Dr. Bruno, “turns generations of science on its head. It shows that there are separate pathways by which sensory experiences get transmitted to the brain.”

In fact, his experiments are showing that the once-monolithic neocortex is actually more like two cortexes in one, which may prove a fruitful new avenue for research.

“We’re finding that the neocortex can be analyzed in terms of having an upper layer and a lower layer,” he says. “Cells in the upper layers have a different way of coding information than those in the lower layers. They have different channels, different morphologies. Our results, therefore, show that while information is being sent to both layers, they are interpreted differently in each. The question is, why? Do they control different aspects of perception or behaviors or learning? We still don’t know for sure.”

What we do know is that the excitation of rodent whiskers causes observable and measurable signals to be spread to specific areas of the neocortex, just as other forms of excitation spread from layer to layer, and area to area. According to Dr. Bruno, this information can be important in identifying ways to address certain neurological disorders.

“A lot of disorders are diseases of propagating excitation,” he says. “Epilepsy and Parkinson’s, for example, are the result of signals that lead to uncontrolled movements. One of the reasons why we think our research is useful is if the neocortical layers are independent of one another, we should be able to design drugs for different disorders, based on the different layers of the brain and the biophysical properties of the affected neurons. For example, we know that seizures in certain models start in deep layers of the cerebral cortex; knowing what excites them will tell us how to control, target, or stop the excitation.

“Also,” Dr. Bruno continues, “if we can understand the basis of a circuit problem, we can find the underlying cause of the disorder and other problems that we think are secondary to the disorder but that may actually precede it. I’m excited by our progress to date, and also by where it might lead.”

In vivo imaging of the cortex

 

To learn more about Dr. Bruno and his work, visit his Member Profile