Beyond the Paper: A Conversation with Parley Belsey and Eric Yttri

Interviewed by Rosalind S.E. Carney, DPhil

To make full use of optogenetic and molecular techniques in the study of motor control, rich behavioral paradigms for rodents must rise to the same level of sophistication and applicability as human or non-human primates. In their Open Source Tools and Methods paper, Belsey and colleagues describe the layout, construction, use, and data analysis from joystick-based reaching in a head-fixed mouse (shown in Video 1 below; https://github.com/YttriLab/Joystick). The step-by-step guide to building the joystick is designed for both experienced rodent motor labs and new groups looking to enter into this research space. Using the joystick, mice learn to consistently perform large, easily quantifiable reaches, including during a two-armed bandit probabilistic learning task. The metrics of performance (reach trajectory, amplitude, speed, duration, and inter-reach interval) can be used to quantify behavior or trigger stimulation in a closed loop with behavior. The authors provide a highly customizable, low cost, and reproducible open-source solution for studying motor control, decision making and reaching reaction time. The development of this tool enables behavioral work to complement recent advances in rodents while remaining accessible to smaller institutions and labs, thus providing a high-throughput method to study unexplored features of action selection, motivation, and value-based decisions.

(Left) Parley Belsey, Research Associate, Carnegie Mellon University, Pittsburgh, PA 
(Right) Eric Yttri, Assistant Professor, Carnegie Mellon University, Pittsburgh, PA

RC: How did you become interested in developing this open-source tool?

Parley: “I started in the lab as an undergraduate researcher. My background was in art and education, which included teaching basic science to children and their parents. When I joined Eric’s lab, I was given the opportunity to build a system that would enable our lab to perform reaching tasks in rodents. From the start, we wanted to create an open-source tool that other researchers could easily access and modify to suit their needs.”

Eric: “We develop tools when we need to—in response to specific research questions. I have studied the neural substrates of reaching for essentially my whole research career, first in monkeys and then in mice. It has always struck me that those of us who study reaching in humans or monkeys spend a lot of time looking at how a reach is performed in terms of distance, direction, and speed. For decades, studies that involved reaching in mice typically just examined whether a lever is pressed or not. Spatiotemporal control aspects of reaching in rodents are not generally considered. Our previous publication (Yttri & Dudman, 2016) was the direct forerunner to this joystick because in that study, knowing the real-time kinematics unlocked the results that we found. Specifically, we discovered that direct and indirect pathway projections from the basal ganglia are not pro- or anti-movement, but instead learn how to perform movement—something we could never examine without the real-time kinematics.”

How did you develop this open-source tool?

Parley: “ I approached the project as a design problem focused on modularity and cost. I looked around the lab for various scientific materials that could be repurposed as components of the tool. For example, I found that a cut Falcon tube functioned well as a stand, and a pen cap filled with glue supported a handle. The build manual was written as instructions that I would have wanted to follow if I had to build it from scratch with no experience. I included step-by-step pictures and links for purchasing materials. The video is a diptych that shows a mouse using the joystick to reach out in any direction for a sugar-water reward, alongside a visualization of the task and data being collected through the Arduino. It showcases the hardware, software, and application of the joystick system.”

Eric: “I think that the concept of open-source tools centers around the creative use of incorporating whatever materials you can into a low-cost solution to address a research question. Parley was extremely creative in her approach, manipulating materials already at hand in the lab to see if they could stably function as components of the tool. Another member of the lab, Mark Nicholas, who is a co-author on thispublication, developed the acquisition and analysis software for the joystick.”

“ I approached the project as a design problem focused on modularity and cost. I looked around the lab for various scientific materials that could be repurposed as components of the tool. ”

Parley Belsey

What was your motivation to develop this open-source tool?

Eric: “We have previously developed tools based on our research needs, but there is potential for broader use by many labs, especially given the joystick’s modularity. I want to help level the playing field for scientific pursuit. I believe that less established, smaller labs or labs with less funding should have the same doors open to them as other labs.”

Why is this tool an important contribution to the field?

Parley: “ Using the joystick, we can conduct behavior tasks normally only possible in experiments using primates, in mice. The joystick system is deliberately built in a way that you can remove or add components quickly to change its utilization. For example, to add a light stimulus, we just had to attach a light to the platform and make minor coding changes for the light to be switched on during the experiment. Therefore, there is crossover potential for different types of tasks to be combined with various stimuli.”

Eric: “Mouse reaches are quite complex. Parley did an admirable job showing that many aspects of reaching that we typically consider to be exclusively primate can be also examined with the joystick. Therefore, more research doors open, especially in combination with genetic or viral targeting in mice, such as optogenetics. The potential use of the joystick expands beyond motor control. It could be used for decision making, motivation, and addiction studies—pretty much any experiment in which a mouse presses a lever. A lever typically is used to inform whether a press occurs or not in behavioral tasks. However, the joystick has the potential to provide a much richer data set. The speed can be used to assess confidence while reaction time can gauge attentiveness. Alternatively, each forelimb can control an independent joystick, opening the door to more complex control and decision-making paradigms.”

Do you have any recommendations for other researchers who wish to create and distribute an open-source tool?

Parley: “ When constructing a tool, I recommend taking time to optimize components as much as possible. It is crucial to thoroughly document, photograph, and annotate the building process with comments on what worked and what didn’t. Version control of documentation is also important, as it is easier to make additions or fix mistakes when there is documented history of why something was designed or built the way it was originally. In terms of publishing an open-source tool, we wrote the paper in the sequential steps of building the joystick, using the joystick, and quantifying the kinematic behavior that the joystick captures. Therefore, the readers are guided through the process of purchasing tool components, construction of the tool, and its implementation.”

Eric: “This type of creative project is probably best suited for a technician or an undergraduate student who can take on more risky goals than students in a masters or doctoral program. However, the developed tool can still be fundamental to other projects in the lab. Parley was well suited to take on this challenge because of her visual and structural background in art. Ideally, open-source tools should be written as a one-stop-shop guide to building and using a tool.”

How was your experience publishing an open-source tool with eNeuro?

Eric: “eNeuro Editor-in-Chief Christophe Bernard wrote an editorial on the new open-source tools and methods paper category that really resonated with me. Access and discoverability for a broad readership were key, and eNeuro provides a great forum for publishing open-source tools and methods. We originally posted the tool on bioRxiv and Github, but as my lab is new, there was no guarantee that many researchers would see it. In terms of the review process, we received the reviewers’ comments quickly. The simplified consensus review made it easy for us to address the comments.”

Parley: “ This was my first experience publishing a paper. I found the review process to be organized and fair.”

“Parley was well suited to take on this challenge because of her visual and structural background in art. Ideally, open-source tools should be written as a one-stop-shop guide to building and using a tool.“

Eric Yttri, PhD

How would you describe the mentoring philosophies in the lab?

Parley: “ I really enjoy working with Eric because he sets up his trainees for success. Eric has an open-door policy in and out of the lab to ask questions. I appreciate being given the space to figure things out on my own yet feel comfortable to ask for guidance when needed. Eric does a great job at creating a lab environment that encourages us to share knowledge and ask questions during lab meetings.”

Eric: “To me, mentorship is about capturing someone’s passion; science is already difficult enough. I believe that when people come into the lab, they should be looking forward to what they are doing. I approach mentorship as determining how each person can fit the lab in a way that gives them space to grow and learn. One of my mentors, Larry Snyder, told me that learning takes failure—“if you don’t break something now and then, you are not trying hard enough.” On my part, this requires having patience and avoiding micromanagement. Instead, I help to guide the trainees along their journey of scientific research and education.”

What are your future research goals?

Parley: “ I have continued working in Eric’s lab since graduating to determine if I want to pursue research as a career. I am currently working with Mark on a project that uses the joystick to examine how lesions in the motor cortex affect various aspects of reaching in mice.”

Eric: “In general, research in the lab focusses on understanding in a broad sense how we transform thoughts into actions. We are looking to pair the joystick with another open-source tool that we developed called B-SOID (An Open Source Unsupervised Algorithm for Discovery of Spontaneous Behaviors; Hsu and Yttri, 2020; Github video link). From video recordings of a mouse within its home cage, B-SOID extracts which behaviors are being performed without bias, e.g., locomotor, grooming, and other behaviors. Therefore, we can analyze both reductionist learned behaviors and well as spontaneous naturalistic behaviors.

Movie 1. Supplementary joystick performance and readout. Video of mouse performance and online reach-position readout, including task state, threshold, time, and number of trials performed.

References:

1. Hsu AI, Yttri EA. B-SOiD: An Open Source Unsupervised Algorithm for Discovery of Spontaneous Behaviors.bioRxiv.2020 Mar 7;770271.
2. Yttri EA, Dudman JT. Opponent and bidirectional control of movement velocity in the basal ganglia.Nature.2016 May;533(7603):402–6.

Read the full article:

Open-Source Joystick Manipulandum for Decision-Making, Reaching, and Motor Control Studies in Mice
Parley P. Belsey, Mark A. Nicholas, and Eric A. Yttri