Author Archives: Catherine Yao

The neurobiological mechanisms of the visual system involves the primary visual cortex (V1) transmitting retinal input to multiple higher visual areas (HVAs) such as the posteromedial (PM) area. Each V1 or HVA neuron has a unique receptive field, or region of sensory space that affects the neuron’s firing rate in response to incoming stimuli. When the stimulus enlarges to a certain size, the average firing rate of individual neurons will drastically decrease; however, it is unclear why this pattern, or surround suppression, is not as radical in PM neurons. We hypothesize that V1 axonal inputs converge, or overlap, more to PM than those to alternative HVAs. We inject fluorescent tags, tdTomato, in-vivo in mouse V1 and wait for the tags to express in V1 to HVAs axons. The brains are then sliced, and tdTomato is imaged in-vitro under a microscope. MatLab is then used to analyze the width of the fluorescent tdTomato area, or the width of axon spread for each HVA. We expect PM’s axon spread width will be larger than the other HVAs, suggesting higher convergence of V1 to PM input. These findings will ultimately benefit our neurobiological understanding of the visual circuits that lead to perception.

A few days ago, I had a chat with Dr. Lindsey Glickfeld to learn a little more about her and her journey to the Glickfeld Lab. As she was talking, I heard a lot of insightful and comforting words that I hope to share with the blog today. (I also hope you readers appreciate the title because the Glickfeld Lab focuses on perception!)

1. Be Proactive about your Passion

For her undergraduate studies, Dr. Glickfeld attended Stanford University, and like most college students, she didn’t know what she wanted to study. She was always fond towards science and the natural world and followed the path of a Bachelor’s degree in biology. I asked her where her interest in neurobiology began if she had majored in solely biology. She explained that she didn’t know that neurobiology was a thing or a specific field, and it was a little bit of luck that opened the doors. As a freshman, she was sifting through research job listings and saw an opening from a graduate student looking for a research technician. Dr. Glickfeld thought that the opportunities that came with this job looked appealing; she joined this neurobiology lab and stayed for the rest of her time at Stanford!

She graduated from Stanford with a B.S. in biological sciences and attended the University of California at San Diego for her Ph.D., studying inhibitory interneurons in cortical circuits. Her passion in neurobiology continued to flourish during her postdoctoral fellowship at Harvard University. Now, she is an Assistant Professor in the Department of Neurobiology at Duke University, and the principal investigator of the Glickfeld Lab!

2. Some Lessons Learned

“Learn to code.” As an undergraduate, Dr. Glickfeld was not sure whether to take an introductory computer science class or another biological sciences class. When she turned to a graduate student in her lab, the second opinion told her not to waste her time with the computer science class. The graduate student’s justification was that the programs and code functions in the comp-sci class could be found online. It wasn’t until Dr. Glickfeld was a postdoc that she first learned how to code and encourages others to learn how to code early.

“When the research is working . . . make hay.” As an experienced researcher, Dr. Glickfeld tries to extract different types of data from the same experiment to save time and money. She covers all the bases and passes down this tip to lab members. In fact, the project I am working on now was kicked off by past data that was reanalyzed in MatLab; so when experiments are working, “make hay because it always comes in handy.”

3. Silly Moments in Science

When Dr. Glickfeld first arrived to Duke to start up the Glickfeld Lab, she came with Dr. Court Hull, who is our next door neighbor in the Bryan Research Building. They were setting up some new equipment and finished getting the 2-photon microscope ready. Everyone in both labs were super excited and ready to image a mouse brain under the scope. Because the 2-photon microscope fires lasers that may damage eyesight, everyone gathered around the scope with safety goggles. Dr. Glickfeld remembers how silly they all looked, squished around in a circle, waiting for something to show up on the microscope. After spending all that time setting up the equipment, no data showed up; they saw nothing. She laughed recalling this moment and apologized for not telling a science related memory. Yet, I appreciated that her favorite memory in lab was non-scientific, and I wanted to share this memory to show the community that has been built between these two labs.

I’ve become more and more comfortable being here at the Glickfeld Lab knowing that I have a kind and supportive mentor ready to help. I hope anyone reading gets a better feel on what the environment at the Glickfeld Lab is like, and I am enthusiastic for what’s to come!

When I first sat down with Lindsey Glickfeld, she explained every unknown neurobiology term with a diagram, which I will try to emulate throughout this blog post. I think trying to explain the Glickfeld Lab’s focus on the synaptic organization of the mouse visual cortex with words might be a bit tiring on the eyes. I want to give a little background on the mouse visual cortex since the Glickfeld Lab uses the mouse model; I hope the diagram and its caption below is more appealing than a big blob of words!

(A) Follow the right side of the flow chart . . . Visual processing begins in retina, then to the dorsal lateral geniculate nucleus (dLGN) in the thalamus. From dLGN, the visual information moves to the primary visual cortex (V1) and then to the higher visual areas (HVAs). (B) A zoomed in diagram of V1 and different HVAs. Please ignore the red . . . most of this blog’s focus is on V1 to LM, AM, and PM.

Before I dive a little deeper into my project, I want to define some neurobiology jargon that is essential to understand this research at the Glickfeld Lab. Surround suppression can be defined as the “neuron’s initial increase in firing is followed by a decrease in firing as the stimulus become progressively larger,” and visual receptive fields can be defined as “a portion of sensory space that can elicit neuronal responses when stimulated.” But, maybe this diagram of surround suppression on one specific neuron might make a little more sense; the receptive field is drawn as the red and green figures and the stimulus as the white and black gratings.

Surround suppression is shown through the initial direct relationship between firing rate and stimulus size following an inverse relationship between the same variables.

Now that the background is out of the way, I’ll start to explain what I plan to research this summer. I am working under Jenny Li, my mentor, who is focused on the pathway from the primary visual cortex (V1) to higher visual areas (HVAs). Past research has looked at V1 and three HVAs that receive the strongest direct input from V1: lateromedial (LM), anterolateral (AM), and posteromedial (PM). However, there was one HVA that caught researchers’ eyes: PM. Unlike the other two HVAs, PM had significantly less surround suppression and bigger receptive fields (see below for yet another diagram!). Jenny is interested in these differences between higher visual areas.

To discover and eliminate variables that may play into this phenomenon, I will be measuring the width of axon spread from V1 to HVAs. I will accomplish this by performing burr hole surgeries for viral injections, perfusions, brain slicing, and finally imaging. If there are differing widths of axon spread, it could be a possible anatomical explanation for why PM show less surround suppression and larger receptive fields than other prominent HVAs.

In the bigger picture, the mouse’s visual system is different from the primate’s  visual system: lower acuity, lack of trichromacy and fovea, and more. However, the similarities do outnumber the differences. Furthermore, it is much easier to monitor and manipulate specific cells types and circuits in mice, helping us advance towards to goal of understanding how vision works. By studying the mouse’s cortical circuits rather than its vision, researchers can discover fundamental principles of cortical processing that may be universal across species. 

Some coronal brain slices!

Mounted coronal slices!

I applied to BSURF in hopes of a hands-on research experience that would allow  me to explore the mechanisms of the brain. I sat at my desk and wrote about my fascinations in the subject. I typed away about neurons and different brain cortexes, or in other words, the very basics of neurobiology. My background in neurobiology was little to nothing, and to be honest, I was a little worried to enter the Glickfeld Lab.

However, I must thank Lindsey Glickfeld, the principal investigator, and Jenny Li, my mentor, as they provided me with informative papers and articles on both general and specific neurobiology discoveries. I was initially overwhelmed with the neurobiology jargon, trying to understand terms like LM vs PM, surround suppression, receptive fields, and more. I knew these words were familiar to the current members in this lab, but completely foreign to me. In my attempts to read each paper, I felt like an imposter, utterly confused on every other word. However, Lindsey and Jenny have sat down with me to discuss each article and have encouraged me to ask questions throughout this process. They draw helpful diagrams on the walls or on napkins, and it is not just them; other lab members come over to help me dissect through confusing data or puzzling procedures.

Although my level of neurobiology knowledge is nowhere near the level of my colleagues, I would argue that it has slowly been on the rise. Things have started to click . . . hence the title. I will admit that it does takes me a relatively long time to read each paper, but I have become more comfortable with the language and am developing a better grasp on neurobiology itself.

Here in the Glickfeld Lab, I am eager to learn from my mentors and lab members. I hope to get to know my colleagues better than the mutual hi in the hallway or the smile and nod in the elevators. I am excited to research something that falls under my interests without the lurking stress of academics. Furthermore, I know I will struggle (I already have!), and I know I will make mistakes. But, I will do my best to power through and learn from these obstacles. I expect to fail, but I also expect to stand back up with the help of my lab. I am grateful to have strong support in the Glickfeld Lab, and I cannot wait to spend my summer here learning under extremely bright minds.

Me in front of the Bryan Research Building!