Seminar One: Mapping the Mouse Brain-An Investigation of Dopamine Circuitry

Date and Location

Date: April 8, 2019 at 5 p.m. in the La Plata Multipurpose Room

Speaker: Justin Buck

Background

In this experiment, researchers looked at the dopamine circuitry in a mouse brain, as its connections can cause development of projections (in the prefrontal cortex), sex differences, and are an important part of neural development. They also found that in females, the presence of dopamine regulates maternal and pair bonding behavior. In terms of psychiatry, researchers wanted to look at the dopamine pathways in the mouse brain, and how deficiencies in different regions and sections of the brain can affect the body as a whole. Therefore, through experimentation they were able to construct a “brain mapping pipeline” for dopamine circuitry in mice using serial thin tissue sectioning methods (thin slices allow light to shine through the sections of the brain).

Observations

Slicing the brain into thin sections for imaging can distort each slice and cause the loss of information with each piece, so researchers made the tissue sections clear by removing lipids and replacing them with a protein-like solution that allows light to travel through it more easily, allowing for deeper imaging. Through taking hundreds of thousands of images of each section and using light microscopy methods, the researchers were able to stitch together a three-dimensional model of the brain. One of the most interesting things they found was that this model could be used to observe cell counts (which directly corresponds to increased or decreased activity) in different regions of the brain in response to different stimuli.

The speaker chose to research this mainly due to his own broad research interests in human disease models. He was most interested in specific diseases like schizophrenia, which can be studied further by creating other clinically relevant maps, like serotonin circuitry, in the same manner.

Map constructed from X-Clarity Imaging Techniques

Reflection and Questions

Overall, I really enjoyed this seminar. I thought the speaker was well versed in his area of research, and I could tell that he held a lot of passion for the subject and for the future of his own research experience. The content was relatively easy to understand in terms of terminology that was used, and the imaging techniques and concepts were kept simple for ease of comprehension. In all, it was a great seminar experience, especially for someone who doesn’t know much about the mapping of signaling pathways in model organisms, and how they can affect human disease models.

Questions:

  1. How long did it take for the separate images of each brain slice to be stitched together into one comprehensive map?
  2. How exactly can the model organism be used to learn more about human diseases associated with dopamine levels, like schizophrenia?
  3. How do you feel about the future of using 3D modeling techniques to further understand the inner workings of the brain?

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