New Jobs for Dendrites

Dendrites, Microscopes and a Whole New Way to Look at the Brain
October 10, 2014

The way neurologists think about how our brains operate may soon change. That is according UNC School of Medicine cell biologist Spencer Smith, who studies the brain as part of President Obama’s BRAIN initiative. In his most recent study, published in the journal Nature, Smith discovered that brain cells have extra functions that nobody ever knew about.

Smith discovered that the parts of our nerve cells known as dendrites can manufacture their own electrical signals. He was able to see this using a two-photon microscope he designed himself. Neuron DiagramAll that jargon masks how cool and how big this study really is. But to get around that, we need a little background, starting with what Smith’s team found.

Dendrites, shown as number 1 in the picture, are pretty boring as far as brain activity goes. Dendrites pick up the signal and pass it to the soma (number 6), which sends it down the axon (number 2) to the axon terminals (number 4). The axon terminals send the signal over a synapse to the dendrites of the next neuron and so the process repeats.

That has been the doctrine in neurology for decades, but Smith discovered that is not the whole story. Brain signals come in the form of electrical impulses, and Smith saw individual dendrites were actually able to make their own impulses, on top of passing along the ones they pick up.

Smith was examining the visual cortex (the part of the brain that processes vison) of mice. He found that dendrites only made their own signals when the mice saw certain things. What this suggests is that the dendrite signals were actually helping the mice process what they were seeing by adding extra signals to certain stimuli.

Think of a neuron as your television. Dendrites are like the cable inputs. They pick up the signal from the cable box and pass it along. The internal circuitry that reads the signal is the soma and the screen is the axon terminals. Smith’s discovery would be like your cable input deciding by itself to boost your signal from standard definition to HD. Further, the fact that dendrites seem to choose what signals get amplified is like the cable inputs selectively making Downton Abbey and shark week HD while leaving golf and C-SPAN in standard definition.

This is huge news in the neuroscience world because scientists thought the dendrites just conducted signals, but Smith’s research shows that dendrites might also help the brain process information. If they actually do aid in processing information, that could alter the way we think about how we process information.

This study did focus solely on the visual cortex, a relatively small part of the brain, but Smith says he thinks dendrites probably make their own signals in other parts of the brain as well.

“Mother Nature tends to use variations on a theme quite often, rather than reinventing the wheel,” Smith said via email.

Two-Photon MicroscopeNow onto the second reason why this study is so cool. In order to make this discovery, Smith needed to clearly see individual dendrites. This is a huge challenge because dendrites are mere thousandths of a millimeter thick and they are packed so closely together that getting a high-resolution image is extremely difficult.

The basic principle behind most microscopic scanning technologies is the scanner puts radiation in and the tissue changes it somehow before sending it back. Based on the reflections and what the tissue sends back, a computer can put together an image. For example a CT scan bombards part of the body with X-Rays, which bounce off onto detectors placed around the body. An MRI magnetizes part of the body then sends a radio signal in to knock the magnetized tissue off balance. The machine picks up how long it takes the chemical bonds in the tissue to right themselves and makes an image based on that. The trouble is the dendrites are packed so closely that both techniques give muddy images on that scale.

So Smith adapted an imager called a two-photon microscope to help isolate individual dendrites, where a functional MRI has to average signals from billions of dendrites.

“If one needs high-resolution imaging of mammalian brains,” Smith said. “Two-photon imaging is the only game in town.”

The two-photon microscope works off the same principle as other scans: light goes in, light comes out. The main difference is how the light goes in and comes out. The goal of the two-photon system is for a tissue to absorb two low-energy photons at the same time and release one higher-energy photon in their place.

Dendritic SpikeThat phenomenon is difficult to achieve, which works in Smith’s favor. In order to get a two-photon absorption, you have to fire a lot of photons into a very small area very quickly, which means focusing the beam to a very small area. What this allows Smith to do is pinpoint exactly what he wants to see and bombard it, while the surrounding area and other stuff in the picture won’t get enough photons quickly enough to do a two-photon absorption. Smith, therefore, only sees what he wants to.

This can be a little tricky to visualize but think of it like driving on a foggy night. If you put your high beams on to try to see all of your surroundings you can see a little of everything but you also get a lot of fog. With your more focused low-beams, you don’t get as much of your surroundings but you at least have a clear view of the lane lines.

With the high resolution of his two-photon microscope, Smith could look into a mouse’s brain with such clarity that he could see individual dendrites, but not much of the surrounding material. This allowed him to attach electrodes to those dendrites and monitor when they made their own signals and when they just passed the signals they were given.

Despite his recent breakthrough, Smith is not yet sure how these signal-making dendrites affect how our brains work. He says the next step is determining where else these signal-makers show up. To that end, he is developing a new two-photon microscope that can image larger parts of the brain with the same resolution as the one he developed for this study.

-Daniel Lane

Daniel Lane covers science, engineering, medicine and the environment in North Carolina.