Exploring the Neural Maps of Memory and Space: A Conversation with Assistant Professor Andy Alexander

Since joining UC Santa Barbara’s Department of Psychological & Brain Sciences in 2023, Dr. Andy Alexander has been building a research program that probes one of neuroscience’s most fundamental questions—how the brain constructs our sense of space and memory. A systems neuroscientist by training, Dr. Alexander combines large-scale electrophysiology, neural circuit manipulations, and ethologically inspired behavioral tasks to reveal how the neocortex, thalamus, and hippocampal networks give rise to spatial cognition and prediction. In this interview, he reflects on his scientific journey from his first hippocampal recordings at UC San Diego to his current work leading the Alexander Lab at UCSB, where cutting-edge tools meet deeply naturalistic approaches to understanding how brains navigate and remember.

Andy, tell us about your journey. What first sparked your interest in spatial cognition and memory, and how did your undergraduate and graduate experiences at UC San Diego shape the research questions you pursue today?

I began college at UC San Diego feeling unfocused. After struggling through my first few quarters, I unexpectedly found inspiration in a lower-division neurobiology course. That class sparked a deep interest in neuroscience and led me to the pre-med track. I soon began volunteering in Dr. Andrea Chiba’s behavioral neuroscience lab, where I had the opportunity to assist with in vivo electrophysiology recordings in the hippocampus.

In this study, we implanted electrodes intracranially to record the activity of single neurons as rats performed an object recognition task. I was especially fascinated by hippocampal place cells—neurons that fire bursts of action potentials when the animal enters specific locations in the recording arena. To assess the quality of our recordings and verify electrode placement, we monitored real-time voltage changes by running the signal through a speaker during the experiments.

The first time I heard those action potentials and could predict the animal’s location based on the firing patterns, I was completely hooked. It was thrilling to listen to brain activity in real time. That experience changed everything for me. I decided to leave the medical track and commit fully to pursuing neuroscience research.

In your graduate and postdoctoral work, you explored how retrosplenial cortex and other cortical circuits process spatial relationships. Could you describe one of your most illuminating findings from this period, and how it informs the directions you’re now taking at UCSB?

One of the most significant discoveries I’ve been involved in was identifying a novel, functionally defined cell type that we named the egocentric boundary vector cell. These neurons become active whenever the animal occupies a position and orientation such that environmental features—like objects or boundaries—appear at a specific distance and angle relative to its body. For example, a given egocentric boundary vector cell might consistently fire when a wall is located 10 centimeters away at a 30-degree angle clockwise from the animal’s current heading.

Across the full population, these neurons collectively represent all directions around the animal, suggesting they play a crucial role in our sense of where objects are located relative to ourselves as we move through the world. It was an exciting time, as several research groups simultaneously discovered similar spatially tuned cells in different brain areas, highlighting a broader principle of spatial encoding. A major focus of my current lab is to understand how these receptive fields emerge from incoming sensory inputs and to explore how these neurons interact across areas to support egocentric spatial representation.

Your new lab at UCSB focuses on interactions between the neocortex, thalamus, and the extended hippocampal formation. Why are these circuits particularly critical to understanding spatial cognition and mnemonic processes, and what cutting-edge techniques are you using to study them?

We are particularly interested in the direct and indirect processing loops connecting the anterior thalamus, retrosplenial cortex, and extended hippocampal formation. Our focus on this circuitry in relation to spatial cognition and episodic memory stems from several key observations. First, these regions are densely interconnected through reciprocal projections, suggesting the potential for specialized functional integration. Second, disruption of any of these areas—through inactivation, lesion, or other forms of perturbation—leads to impairments in both spatial navigation and episodic memory. Third, neurons within each of these regions exhibit spatially tuned receptive fields, and disorientation is a common symptom in individuals with memory disorders such as Alzheimer’s disease. Taken together, these findings point to a strong overlap between the neural circuits supporting spatial cognition and those underlying episodic memory.

This connection feels intuitive to me—it's difficult to recall a personal experience without also remembering where it occurred. Our goal is to characterize and manipulate neural activity and interregional interactions during tasks that rely on spatial memory. By doing so, we aim to uncover fundamental computational principles that govern how these interconnected brain regions support spatial and memory functions.

To achieve this, we use a range of state-of-the-art techniques to observe and manipulate neural activity in freely moving rodents. Our primary method is high-density in vivo electrophysiology, which allows us to record the electrical signals of hundreds of neurons across multiple brain areas simultaneously—while animals navigate and remember. In addition, we employ targeted techniques to selectively disrupt specific connections between brain regions, leaving other circuits intact. This enables us to make more precise causal inferences about the role of specific neural pathways in behavior.

You mention using “ethologically inspired” behavioral tasks in your research. How do you design these tasks to capture naturalistic behaviors in mice and rats, and why is it important that they mirror real-world settings?

A central focus of our lab is investigating the neural circuitry that supports predictive behavior. Prediction—the ability to use prior experience to guide future decisions—is a hallmark of intelligent behavior. We believe that neocortical circuits evolved, at least in part, to support predictive processing, and we find it incredibly compelling to study this function at the level of neural populations.

To explore predictive behavior in rodents, we developed a novel "target chasing" task in which mice and rats pursue a moving visual stimulus for reward. Through repeated experience, the animals learn the movement patterns of the target and begin to take navigational shortcuts to intercept it more efficiently. These shortcuts serve as a behavioral readout of prediction, and we're excited to investigate the neural dynamics that unfold during the lead-up to and execution of this behavior.

We describe our pursuit task as ethologically inspired, since chasing behavior is common in natural rodent settings—whether during social interaction, courtship, aggression, or hunting. While the task itself isn’t exactly natural—animals run freely in a dark arena where the floor acts as a projector screen displaying moving visual targets—the underlying sensorimotor and predictive demands closely mirror those found in real-world contexts. We believe this design allows us to gain more accurate insights into how the brain predicts and responds to dynamic stimuli in complex environments.

Understanding spatial cognition can have broad implications. Could you share how your research might eventually translate to real-world applications?

Several aspects of our work have the potential to translate beyond the lab. As mentioned earlier, impairments in spatial cognition are often early indicators of broader cognitive decline. By advancing our understanding of how the brain processes spatial information, we hope to shed light on how these same circuits deteriorate in neurodegenerative diseases. Additionally, our research on egocentric spatial processing may one day contribute to the development of assistive technologies for individuals with sensory impairments, such as blindness. Beyond applications in human health, insights into the brain’s spatial algorithms could also inform computational strategies in fields like robotics and autonomous navigation.

Collaboration is often key in science. Are there any interdisciplinary or cross-departmental collaborations at UCSB you’re particularly excited to pursue? How might working with colleagues in other fields enrich your research?

One of the many reasons I’m excited to be at UCSB is the strong potential for collaboration. There’s a vibrant community of neuroscientists on campus with overlapping research interests, particularly in systems neuroscience and neurotechnology. My lab uses several forms of in vivo neuroimaging to measure calcium activity in neural circuits, and UCSB has a particularly strong group of researchers developing tools in this area, including Spencer Smith, Ikuko Smith, Sung Soo Kim, and Michael Goard.

I’ve already had the opportunity to collaborate closely with Prof. Michael Goard on several projects related to our shared interest in navigation, and we will be co-mentoring an incoming graduate student! I also see great potential for collaboration with Prof. Michael Beyeler, particularly around computational modeling of predictive behaviors. Additionally, I’m a big fan of Prof. Mary Hegarty’s work in spatial cognition, and I would love to design navigation experiments that could be tested in both rodents and humans.

You joined the department in 2023 and have already begun teaching and mentoring students. What’s one key piece of advice you share with your trainees about approaching neuroscience research?

I emphasize to students in the lab the importance of maintaining a healthy work–life balance. It’s easy to fall into the habit of working constantly as a graduate student, but I don’t think that’s always productive—or sustainable. I’ve certainly experienced periods of burnout during both graduate school and my postdoctoral training. In some ways, it’s difficult to avoid given the nature of our experiments—when the animals are behaving well and the recordings are going smoothly, it can feel necessary to push hard and make the most of it. But it’s equally important to recognize when to step back. There are times when the best thing you can do—for your science and your well-being—is to pause, take a breath, and recharge.

On a personal note, you describe yourself as someone who loves the outdoors—running, cycling, golfing, or even skateboarding. How do these hobbies recharge you, and do they ever spark new perspectives on your scientific work?

I’ve definitely come up with some of my best experimental ideas while running. There’s something about the meditative rhythm of it that helps me think clearly and gain perspective. Skateboarding and golf are a bit different—they’re mentally demanding in a way that fully absorbs my attention. I don’t think much about work while doing them, which makes them a valuable way to disconnect and take a real mental break.

Finally, looking ahead, what are you most eager to explore in the next few years of your research program at UCSB? Are there big questions you hope to answer about how the brain constructs and recalls spatial representations?

All of the students in the lab are working on amazing projects, and I’m genuinely excited to watch both their scientific growth and the development of their research unfold. I believe we’re in a strong position to investigate the neural mechanisms underlying predictive behaviors using our pursuit paradigm, and I’m particularly looking forward to integrating our experimental findings with computational modeling to better understand how optimal behavior emerges in more naturalistic contexts.

I’m also very enthusiastic about our ongoing work on the retrosplenial cortex—exploring its roles in spatial cognition, learning, memory, and its involvement in disease states. It’s an exciting time for the lab, and I’m eager to see where this work takes us.