This week for The Bridge, I was thinking about the complex branching structure in Purkinje cell dendrites. Purkinje cells look very different from other cells because of their enormous dendrites. Neurons are often classified by their shape. I want to use this week’s post to emphasize how a Purkinje cell’s shape stands out from other cell types. I sent Richelle some photos of other types of cells, and I’d like to share those photos here with you.
For reference, let’s start with a Purkinje cell. Here’s the latest Purkinje portrait from my experiments last week. Look at all those dendrites!
In this photo, you can see the Purkinje cell’s cell body (round part at the bottom) and the large dendrites extending up from it like a tree. You can even see some of the dendritic spines (little dots on the branches). Dendritic spines are the molecular sites where learning and memory happen.
The next cell type of cell I want to show you is called a glial cell (singular = glial cell, plural = glia / glial cells). There are many types of glial cells. Glial cells are not neurons; rather, their purpose is to nourish and support neurons, and make electrical impulses travel faster through neurons. Glia are found all over the nervous system, both inside and outside the brain. Here are some glial cells that I photographed as an undergraduate researcher at Boston University back in 2010.
In this image, you can see the outline of the glial cell in green. This cell was stained with green fluorescent protein (GFP). The blue part (stained with DAPI) is the nucleus, which is where the cell’s DNA resides.
Here’s another glial cell. As you can see, glia come in all shapes and sizes. The shapes of the glial cells in these photos vary a lot because these cells were not photographed while in brain slices. These cells lived in petri dishes and on small cover slips, where neurons and glia were cultured together, and then placed onto slides for viewing.
In the next photo, you can see both glial cells and neurons from a part of the brain called the hippocampus. The hippocampus is generally responsible for memory, and it’s a hotspot for research on Alzheimer’s disease.
There’s a lot going on in this photo. The spread-out glial cells from the previous two photos were from the edge of the culture in the petri dish. In contrast, this photo came from the middle of the petri dish where things are more crowded. The blue dots (kind of look like grapes) surrounded by green are a crowd of glial cells. Above those, you can see hippocampal neurons called pyramidal neurons. Pyramidal neurons have smaller nuclei than these glia, and they have green extensions that are marked with red dots. The red dots are from a stain that allows us to see which of the green extensions are dendrites, and which one is the axon. Since the red marks dendrites, it will not be present on the axon. In a brain slice, it’s easier to know which extensions are dendrites and which is the axon; however, in a cell culture in a petri dish, all the extensions from the cells go in every direction and get all mixed together. We use special stains to tell them apart.
Now that you know how to recognize Purkinje cells, pyramidal cells, and glia, I want to show you one more image to emphasize the differences between photographing a neuron in a brain slice vs. a petri dish. In the previous photos, the pyramidal cells’ extensions go in any direction they want because the neural circuit they came from is disconnected. This next neuron is also a pyramidal cell, however, the photo was taken in a slice (and using completely different experimental techniques). In the slice, the pyramidal cell grows its dendrites and axon in the right direction, toward the other brain structures with which it communicates. The photo below shows a pyramidal neuron in a slice. The neuron is stained with a dye, which clearly shows the cell body (middle dark spot) and begins to travel down the axon and dendrites. This neuron beautifully shows the characteristic triangular shape of a pyramidal cell in the brain (not a petri dish), and was photographed by Heather Titley, a Postdoctoral Scholar at The University of Chicago. Heather and I work together in the Hansel Lab.
This image was taken by Heather Titley, a Postdoctoral Scholar at The University of Chicago. The picture shows a pyramidal neuron (See the characteristic triangle shape?) from a frontal region of the brain called somatosensory cortex.
Neurons (and all cells) come in many different, beautiful, and fascinating shapes and sizes. If you want to see more types of cells, look up “starburst amacrine cells” and “menorah cells” on Google images. These days, neuroscientists are using neuronal morphology to classify neurons. Neurons are typically classified in many ways, but there’s no reigning consensus on whether it’s best to classify by shape, size, location, what neurotransmitters they use, or something else. Regardless of how you prefer to classify neurons, I believe we can all appreciate the art that results from imaging different types of neurons around the brain.
This week I created some illustrations in response to a text question/answer written by Dana. I am experimenting with styles right now. I created several sketches to brainstorm content and now I am rearranging this material to create experimental graphics.
Compiling images of the brain/mouse maze, thought bubbles, human brain, mouse brain, light bulb. New ideas come to light by researching mice to understand our humanity.
Question + Artwork Below…
Why do scientists use mice to study diseases?
In research, it is increasingly common to use mice to model diseases. Today, mice can show symptoms of autism, Alzheimer’s, Parkinson’s, Schizophrenia, ataxia, cancers, and almost any other disease and disorder you can think of. Using mouse models of diseases and disorders enables researchers to learn about how the condition hurts the brain, and attempt to devise treatment strategies. The overarching goal with translational rodent research is to see what went wrong in the brain, and try to fix it with therapies that could potentially alleviate suffering for people who have these diseases and disorders.
Most researchers would prefer to use a model of the brain and stop bugging all these mice. However, creating a model brain assumes that we already know everything about how the brain works. In order to create a useful model, researchers would truly have to understand how every part of the brain functions and connects to other parts. Despite huge advances in neuroscience, we’re quite a long way from knowing this much about the brain. Until we have such a deep knowledge, we must rely on mice or other model organisms to model diseases for us.
Historically, there have been cases where research animals were obtained inappropriately, and their well-being was ignored. Today, special regulations and committees are in place at research institutions to advocate for the safety and comfort of research animals. These committees include experts in the field, veterinarians, and non-scientists from the community. Scientists are prohibited from performing experiments until they have the committee’s approval. When deciding if it is appropriate to use animals in research, this committee considers ways to minimize stress and discomfort for the animals, as well as the importance of the research. In all research, these committee members and the scientists conducting the studies take care to demonstrate respect for research animals.
Artwork 1: Why do scientists use mice to study diseases?