Probing the Brain’s Chemistry

Our brains are constantly awash in chemicals that serve as messengers, transporting signals from one neuron to another.  It’s a really nifty system, although scientists still aren’t clear on how, exactly, those chemical messages end up being converted into behaviors like kicking a ball or doing really complicated mathematical computations. If scientists could get a clear picture of how that conversion works, it would further our understanding of brain function, and open up a host of new treatments for diseases like Parkinson’s or diabetes.

So how do we figure out which chemicals are in the brain and what they’re doing in real time?

Chemist Leslie Sombers and her graduate student Leyda Lugo-Morales use an elegant approach that allows for real-time measurement of chemical fluctuations in the brain.  They use voltammetry, which sounds really cool and Frankenstein-y, but is basically a method of electrochemical scanning where voltage is applied to, and current is collected from, a carbon fiber microelectrode that is about 10 times smaller than a human hair.  The resulting data is in the shape of a graph called a voltammogram.  The size of the graph indicates how much of a particular chemical is present and the shape tells the researchers which chemical it is. So they can “see” and measure specific chemicals accurately, without worrying about interference from all of the other chemicals in our inundated brains.

Some of the chemicals Sombers is interested in measuring – like glucose, for instance –are normally invisible to electrochemical measuring techniques like voltammetry.  So to make it work, Sombers attaches an enzyme to the electrode that reacts with glucose. The glucose molecule reacts with the enzyme and produces hydrogen peroxide, which oxidizes as an electrical potential is applied to the electrode. The resulting current gets measured, and that data is captured in the voltammogram. When the scientists see the hydrogen peroxide in their voltammogram, they know they’ve found glucose.

The most commonly used method of electrochemical scanning takes about 10 to 20 seconds per scan, but Sombers and Lugo-Morales can make 10 full scans per second, which gives them information about chemical fluctuations in the brain in real time.

“Speed is the key,” Sombers says. “We use carbon for our electrode, which is a great material because it’s biologically friendly and inexpensive, but it isn’t really a catalyst. By ramping the voltage up and down at 400 volts per second, we build an oxygen layer on the surface of the electrode. The oxygen acts as a catalyst to help oxidize the hydrogen peroxide generated by the enzyme attached to the probe, and we can measure the molecules we are looking for and how they fluctuate in real time.”

Lugo-Morales has already used the probe to make real-time measurements of glucose fluctuations at different locations in a rodent brain. She found that the amounts differed depending upon where the probe was located and that they fluctuated quite a bit over very short times –subseconds – which is how quickly our neurons work. This suggests that our brains depend on some pretty precise regulation of glucose in order to function. Other tests for other chemicals will surely follow.

“A lot of people want to understand glucose dynamics in the brain,” Sombers says. “Sixty  to 70 percent of diabetics show neuronal dysfunction, plus glucose has been linked to diseases like schizophrenia and Alzheimer’s.  If we can understand how glucose is used by the brain we can create better treatments for these diseases.”