This Postdoc Is Tapping Into the Symphony of the Brain

In a recent paper, Jesús E. Pérez-Ortega, a postdoc in the lab of Professor Rafael Yuste, examined how neurons in mouse brains respond to visual stimuli, and found that it's just as important for some neurons to be activated as it is for other neurons to be inhibited. Together, those neuronal states create the harmonious "symphony" that constitutes the mouse's field of vision. What led Pérez-Ortega to an interest in that topic, and to a postdoc at Columbia? Columbia News sat down with him to find out.  

What first got you interested in neuroscience and the brain?

My interest in neuroscience started to take shape when I was taking biomedical engineering courses in my final semesters as an undergraduate at the National Autonomous University of Mexico (UNAM). I studied mechatronics—which sits at the intersection of mechanics, electronics, and software—in the engineering college there.

One course I took specifically explored cutting-edge developments in neuroscience and their integration with mechatronics, which really intrigued me. I was particularly inspired by the work of Miguel Nicolelis, who was working on advancing brain-machine interfaces. With a background in building robots and mechatronic systems, I became fascinated by the prospect of controlling these technologies using neuronal signals. In other words, how we can build a system that allows our neuron signals from our brain to control robots and other physical technologies. It’s a huge, growing field, and one example of the important uses for it is building new limbs that people with paralysis can control simply through thought.

Under the guidance of Serafín Castañeda, a professor at the Engineering School, as part of my undergraduate thesis, I developed and implemented a virtual instrumentation system for recording the activity of several neurons simultaneously.

Later, Professor José Bargas encouraged me to deepen my exploration of neuronal ensembles and their significance in brain function by pursuing a PhD in neuroscience. During that period I improved the instrumentation system I started, known now as Im-Patch®. Im-Patch is a user-friendly software that allows scientists to record single neuron’s electrical activity using the patch-clamp technique, while simultaneously capturing images of hundreds of neurons to measure their activity through fluorescence, known as calcium imaging. This advanced tool has helped researchers from different laboratories and has been cited in many international journals providing valuable insights into brain function.

What made you choose Columbia for your postdoc?

Columbia is renowned for its neuroscience research, with influential figures like Nobel laureates Eric Kandel and Richard Axel, who have shaped the field. My advisor, Rafael Yuste, is also well-known for his work on neuronal ensembles, and was a major draw for me to come here. Luis Carrillo-Reid, who was a PhD student at UNAM, came to Columbia as a postdoc, and conducted impressive research in Yuste’s lab, utilizing cutting-edge technologies like two-photon microscopy and optogenetics. His work and achievements inspired me to apply. Since he knew me and my work, he recommended Yuste to hire me. Columbia’s location in New York City, one of the greatest cities in the world, was also an appealing factor.

Can you describe your recent Nature Communications paper? What’s the takeaway for those of us who aren’t in the field?

Our paper “Stimulus encoding by specific inactivation of cortical neurons” in Nature Communications explores how groups of neurons in the visual cortex of mice respond to visual stimuli. Using advanced imaging techniques, we discovered that neurons use a trinary coding system—they can be activated, inhibited (offsembles), or neither. While it’s well-known that neurons activate in response to stimuli, our research highlights the crucial role of inhibited neurons, or offsembles. This combination of activation and inhibition enhances the brain’s ability to process visual information accurately and reliably.

The brain uses a combination of activation and inhibition of neurons to create a more precise and reliable way of processing visual information.

Imagine your brain is like a symphony orchestra, with each musician (neuron) playing a specific part. Some musicians are actively playing their instruments (activated neurons), while others remain intentionally silent, waiting for their turn (inhibited neurons). Together, they create a harmonious symphony, much like how your brain processes visual information with precision and complexity.

Is there a big open question that this paper is helping to answer?

This paper challenges the conventional understanding of how our brain encodes perception and memories by showing that neuronal inhibition is as important as activation. It is the first to demonstrate selective inhibition of specific neurons (offsembles) in encoding stimuli. The finding raises important new questions, such as whether similar mechanisms exist in other parts of the brain, both cortical and subcortical. It also prompts inquiries into the stability of offsembles over time and how their plasticity compares to that of activated neurons (onsembles). These questions are crucial for advancing our understanding of brain function and cognitive processes.

What are your plans after your postdoc?

I am currently working on the final project of my postdoc. Looking ahead, my goal is to secure a position as a principal investigator in Mexico next year, leveraging the experience I’ve gained during my postdoctoral research.

How do you like living in New York? Do you have any favorite activities in your neighborhood or around the city?

I love living in New York City. It is a fantastic place to connect with people from diverse backgrounds and to share languages, food, and traditions. I’ve made friends from all over the world in various settings like work, parties, and social gatherings, which has been incredible. One hidden gem I enjoy is Ellington in the Park, inside Riverside Park near the river. It’s perfect for picnics, gathering with friends, enjoying a beer, playing ping pong, and catching stunning sunsets, especially in the summer—it is truly a special spot.