Understanding how brains compute by looking into a fly’s eye

The neurons in our brain perform intricate computations to process information and generate behavior. Their activity can often be described mathematically: neural circuits can add, subtract, divide, and multiply, as well as perform a host of more complex computations. However, we still only poorly understand how individual neurons contribute to the complex operations in real neural circuits. Dr. Damon Clark, Assistant Professor of Molecular, Cellular, and Developmental Biology at Yale University, believes that we must understand the principles and mechanisms by which small neural circuits compute, and that understanding will be central to the more complex computations associated with human brain function.

To investigate these principles, Dr. Clark has focused on understanding the interactions of neurons in the tiny brain of the fruit fly. His lab measures behavior in the fly (see video of the fly walking on the ball), which allows them to test hypotheses quickly and iteratively. Advanced microscopes in lab allow researchers to measure the activity of individual neurons within the brain, while the fly watches movies and behaves. In addition to these experimental tools, the lab also creates and tests mathematical models of circuits within the fly’s brain. Some of the projects Dr. Clark’s lab is researching are:

  • Dr. Clark’s research focuses on the small network of visual neurons in the eye of the fruit fly in order to understand how individual neurons contribute to broader algorithms within neural circuits. The fly’s visual circuits offer several advantages for answering computational questions: a relatively small number of neurons are involved; the neurons are accessible and it is possible to measure from identical neurons in many different flies; Dr. Clark’s team has fine control of the input to the network (by presenting flies with movies); and most importantly, the lab can use genetic tools to manipulate the network. This means they can essentially switch a neuron off and see how that changes how the fly brain functions. Interestingly, although the fly's eye and human eye are radically different anatomically, Dr. Clark’s work, and the work of others, has shown that the mathematics performed by these two different visual systems is often surprisingly similar.
  • The fruit fly’s visual-motor transformations serve as an ideal model in which Dr. Clark can hope to follow neural processing as the brain transforms a visual stimulus into a behavioral output. The main advantage of working with fruit flies is a whole suite of genetic tools that can manipulate a fly’s neural network, turning neurons on or off and changing the proteins expressed in individual neurons. For instance, the team can turn off one class of neurons in a fly, then put the fly into a virtual reality device and measure its responses to visual stimuli. By comparing these responses to those in non-modified flies, Dr. Clark’s team can learn how the fly’s perception of its world changes and how single neurons contribute to the fly’s behavior. By understanding the rules that govern how these small brains work, Dr. Clark hopes to gain insight into larger, more complex brains like our own.

Dr. Damon Clark enjoys problem solving and the thrill of discovery. He loves being the first person to find something brand new, and has occasionally delayed sharing exciting results, just to savor them.

Dr. Clark obtained an undergraduate degree in physics; as an undergraduate, he worked on a project analyzing mammalian brain architecture. After graduating he wasn’t certain he wanted to continue on in research; he grew up on a college campus, and by the end of college had never really lived off of one. He spent the year after graduation in Somaliland as a Princeton-in-Africa Fellow for the International Rescue Committee, working on grants, needs assessments, and map-making.  Eventually, because of his quantitative skills, he ended up working on a large U.N.-funded survey of refugees returning to Somaliland from Ethiopia -- even while working in Africa, he was drawn to quantitative research. This project made him realize that scientific research should, indeed, be his career.

As a graduate student in physics at Harvard, he worked in Aravinthan Samuel's lab on quantitative approaches to measuring C. elegans behavior and neural activity. He briefly returned to his home state of California to work as a postdoctoral fellow at Stanford in Tom Clandinin's lab, where he began studying visual motion processing in Drosophila. He's now happily tinkering away on various new fly projects in his lab at Yale. He credits his physics background for giving him quantitative tools to model neural systems, and also allowing him to engineer new equipment – leading to innovative experiments in his lab.

http://clarklab.commons.yale.edu

Alfred P. Sloan Fellowship in Neuroscience, 2015

Searle Scholar Award, 2014

Smith Family Award for Excellence in Biomedical Research, 2013

Jane Coffin Childs Postdoctoral Fellowship, 2008-2011

NSF Graduate Research Fellowship, 2002-2005