The average human is made up of 37.2 trillion cells! TRILLION! That’s 37,200,000,000,000 cells! And they are not all the same – far from it, and we are still uncovering all sorts of new types of cells too. I don’t know about you but I find this incredibly exciting and fascinating – probably why I have a cell biology background. But I wanted to celebrate this on my blog by restarting my ‘Cellfie’ of the month feature after 2 years!
If you were around in the Soph talks science world back in 2016 and 2017, you may remember that my ‘Cellfie’ of the month posts were about the stem cells I was using in my PhD and all sorts of different aspects of cell culture and growing cells in a lab. But you probably know by now that I am no longer working in the lab, so I have changed the format of these slightly. Each month I will invite a different researcher from around the world to share a gorgeous image of the cells they work with and a few words about what they are, how they are using them in their research and anything about the wonderful universe that is a cell.
So, for this month, I spotted the most stunning image on Twitter and I was thrilled when the wonderful Jennifer J agreed to share and write about it on Soph talks science. So, I’ll pass you over to learn some more about the amazing brain cells in this image.
This is an image of a mouse cerebellum. The cerebellum is a brain structure that lays at the back of the brain, nestled between the forebrain and the brain stem. The cerebellum is typically thought of as being a motor structure that is important for executing complex coordinated motions smoothly and with appropriate timing. More recently, scientists have been discovering non-motor functions for the cerebellum as well. For example, it seems as though the cerebellum is important for cognitive functions such as learned associations with fear.
Here, we can see the different cell types that make up the cerebellar cortex: Purkinje cells (white/magenta), molecular layer interneurons (cyan), and granule cells (blue). Together these cells comprise a local circuit.
Purkinje cells are the sole output of cerebellar cortex. Granule cells send up excitatory inputs onto the Purkinje cells with axons that run parallel to each other, hitting the Purkinje cell dendrites perpendicularly. These axonal projections are called parallel fibres. Purkinje cells also receive excitatory input from climbing fibres (not shown) which wrap around the Purkinje cell bodies and dendrites like ivy climbing up the cell. Finally, the Purkinje cells receive inhibitory inputs from the molecular layer interneurons (basket cells and stellate cells) which also innervate each other. Having so many different inputs into Purkinje cells allows for incredible modulation of firing patterns that the Purkinje cells then send out of the cerebellar cortex in order to instruct behaviour.
In order to be able to see these different cells, we can use a technique called immunohistochemistry to “stain” for different proteins using antibodies. Antibodies have sticky ends that bind to specific targets. We first apply a primary antibody which will stick to our protein of interest. We then apply a second antibody, which is bound to a fluorophore which is a tag that glows under the microscope, that has sticky ends that will bind to the first antibody. When we then image the brain section using a fluorescent microscope, the fluorophores will let us see where our protein of interest is.
Here I have done an immunohistochemistry experiment where I stained for several different proteins in order to visualise the components of the local circuit in cerebellar cortex. Parvalbumin shows up in Purkinje cells and molecular layer interneurons and allows me to see the different cells types of the upper cortical layers (the Purkinje cell layer and the molecular layer). Dystroglycan highlights the Purkinje cell dendrites and cell bodies where synapses are being made with other cells of the circuit. DAPI is a stain that shows up in the nucleus of every cell but is most striking in the granule cells in the granule cell layer due to their dense, tightly packed arrangement.
For my research, I use genetically manipulated mice to delete or mutate dystroglycan; a brain protein important for proper cell migration during early development. Using immunohistochemistry in both normal and mutated brain tissue, I can see how the mutation or loss of dystroglycan affects other proteins in the brain across development.
The cerebellum is a useful model for studying issues in cellular migration and synapses between brain cells because it is a fairly isolated circuit of brain cells. Recall that of all of the cell types in the cerebellum that I have mentioned, Purkinje cells are the only cells that send information out of the cerebellum. Otherwise, all cerebellar cells communicate only within the cerebellum. Furthermore, the connections between cerebellar cell types are very well known, making it easy to interpret data relating the communication between brain cells and how that communication might be perturbed in mutant mouse models. The cerebellum is also a useful system for studying dystroglycan because Purkinje cells are the only cells in the cerebellum that express dystroglycan. Elsewhere in the brain, there are multiple cell types that express dystroglycan, making it complicated to see how the protein operates in a cell-specific manner.
If you want to learn more about these brain cells, the brain itself or any of the techniques or proteins mentioned by Jennifer, please ask your questions below in the comments. And remember there is no such thing as a stupid question!
What cells would you like to learn more about next?
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