Cerebellum
Two decades of research, perseverance, and the pursuit of understanding the brain's most neuron-dense region
Where It All Started
I started doing cerebellar research in 2003. That year I had just received my PhD and was doing a postdoc at a medical center in Boston. My advisor, Dr. Harrison, asked me to take on a project no one else wanted to do — using electrophysiology to record the firing patterns of cerebellar Purkinje cells. At that time, everyone was working on the hippocampus and prefrontal cortex; the cerebellum was considered to only control movement, and few people paid attention to it.
Our lab only had three people back then. Me, a technician Jenny, and another postdoc Mike. The equipment was old — the electrophysiology recorder was a product from the 1990s, and the data acquisition card frequently crashed. I arrived at the lab at 7 AM every day and left at 11 PM. For the first six months, we didn't publish anything.
In 2005, I received my first R01 grant — a total of 1.2 million dollars, distributed over five years. This funding allowed me to establish my own lab at Johns Hopkins. I recruited two graduate students, bought new equipment, and began systematically studying the role of the cerebellum in motor learning.
Building the Lab
During those years, we published several papers. In 2007, we published an article on cerebellar long-term depression in the Journal of Neuroscience, which has been cited approximately 400 times. In 2009, we discovered a new cerebellar circuit connecting the dentate nucleus to the motor cortex, published in Neuron.
When Things Started to Fall Apart
Problems started in 2015.
NIH funding rates dropped from 30% to 10%. One of my R01s didn't get renewed. A postdoc got his own faculty position and left, taking the entire project he was responsible for with him. I started laying people off. First a technician, then a graduate student transferred to another lab.
We could only use the old single-photon confocal for experiments, with much lower data quality. Several submissions were criticized by reviewers for insufficient imaging resolution; I couldn't explain why. In 2019, I almost shut down the lab. I sat in my office doing the math — without new funding, we could only survive until June 2020. I started contacting other labs for my graduate students.
My wife said I couldn't just give up like this. I had been in this field for 16 years. The students needed to finish their dissertations.
A New Beginning
In February 2020, we received a new R01 to study the role of the cerebellum in autism. The reviewers gave very high scores. The funding was 1.9 million dollars, distributed over four years.
This required me to make some decisions.
Our lab is very small now. 2 postdocs, 1 technician, and I often do experiments myself. This is about the same as when I first started in 2005.
We collaborated with clinicians and recruited 47 autism patients for brain imaging. We found that their cerebellar gray matter volume was 8% to 12% smaller than normal, primarily concentrated in cerebellar posterior lobe lobules VI and VII. This finding is currently being written into a paper.
What Remains to Be Done
I don't know how long the lab can continue. The R01 will end in 2024, and I'll be 60 then. If it doesn't get renewed, I'll probably retire.
There are still a few things I want to do.
The cerebellum contains 80% of the brain's total neurons.
After all these years, we still understand very little.
This is the work I do.