Observations Nicola Allen Neuroscience has a new star

Where did your interest in science begin?

ALLEN: Growing up in the UK, we used to do these experiments in our science classes, like tossing a grid out on the grass and counting all the different kinds of plants we could find. They were simple, but they made me curious about the world around me. My biology teachers were also really excellent and very encouraging while I applied for university.

For a while, I thought I might become a veterinarian because I loved animals, so I started taking courses in anatomical sciences. But I quickly realized I wasn’t as interested in applying treatments as I was in figuring out the mechanisms behind them. I wanted to get to the root of the problem and make a difference by developing something new, rather than implementing what we already had. So that drew me toward a career in research.

What led you to neuroscience, and eventually astrocytes?

ALLEN: As an undergrad, the two things I found most interesting were neuroscience and immunology, probably because they’re the two major systems we knew the least about. I actually wrote my undergraduate thesis on how the immune system might interact with the brain, but this was long before we thought of neuroimmunology as its own discipline.

I did my PhD in London, studying how neurons are affected during stroke. I was using classic neurophysiology techniques to measure the neurons’ electrical activity. It’s amazing, really, to record what the brain is doing in real time. But there was also this recent explosion of new tools in molecular biology, so my advisor sent me to New York for a three-week course in molecular neuroscience at Cold Spring Harbor Laboratory.

That’s when I saw Ben Barres give a completely mind-blowing talk that changed everything for me.

Ben went up in front of this room of neuroscientists and showed us that when you isolate neurons from the rest of the brain and grow them in a dish, they don’t form any connections with each other. They don’t communicate. But if you add these other cells—astrocytes—then there are now tons of synaptic connections and tons of electrical activity moving through the neuronal circuit.

It was this amazing finding that really changed how I thought about brain development and what all these different cell types do. I immediately thought, I need to do my postdoc with this person. And that’s when I moved to Stanford University.

What was the perception of astrocytes at the time?

ALLEN: Astrocytes are a type of non-neuronal brain cell called glia. Glia were first thought to exist as a sort of structural scaffolding for the neurons to grow on. Then, we learned that astrocytes support the neurons in some more specialized ways, like bringing nutrients from the blood vessels to help fuel the neuron’s activity. So, they were important, but not considered to play an active role in how our brain communicates or processes information.

Once we had better tools to study these cells, all of that changed. But it took a long time for the rest of the field to appreciate our findings.

How do astrocytes contribute to Alzheimer’s disease?

ALLEN: Most Alzheimer’s research has focused on the amyloid plaques that can form between neurons. What’s interesting is that these plaques are surrounded by astrocytes and other glia. But we’re just starting to investigate what these cells are doing there.

We also have data showing that Alzheimer’s patients have far more genetic changes in their glial cells than in their neurons. That’s made a lot of people start paying attention to these other cell types.

What’s especially interesting to me is how astrocytes could be contributing to even earlier stages of the disease. My lab has now identified the specific proteins that astrocytes secrete to promote synapse formation and stabilization. In Alzheimer’s models, astrocytes seem to produce less of these signals, sometimes even before any symptoms arise. That’s key, because synapse loss is a major driver of cognitive decline. We’re now testing whether restoring these signals could be enough to rescue some of the synapse loss or delay it long enough to preserve cognitive function.

How does this work relate to Salk’s new Neuroimmunology Initiative

ALLEN: The Neuroimmunology Initiative brings together researchers from neuroscience, immunology, aging, and cancer to understand how the immune and nervous systems impact each other in both health and disease.

For example, my lab recently found that as we age, astrocytes start activating immune genes. These are brain cells expressing immune signals that are typically used to fight off infections or cancer. That raised a lot of questions: What’s triggering this? Is it helpful or harmful? How does it affect neuronal function, memory, and behavior?

To answer these kinds of questions, I’m collaborating with Professors Susan Kaech, Diana Hargreaves, Axel Nimmerjahn, and other experts here at Salk. Together, we’re unpacking the role of glial-immune interactions in aging, Alzheimer’s, cancer, chronic pain, and more.

I think it’s possible that at the end of this, we could have a drug that dampens down the chronic neuroinflammation that contributes to all of these disorders.

What project are you most excited about right now?

ALLEN: I’m really excited that we’re finally at a place where we can start to use what we’ve learned about astrocytes to modify the state of the brain.

Now that we’ve identified the proteins that astrocytes use to trigger synapse formation, we’re developing tools to deliver them as needed: adding or blocking these signals when you want to create, repair, or remodel the connections between neurons. It’s a totally different way of treating the brain—not by altering neurons directly, but by tuning the environment around them.

I think 20 years ago, people would’ve thought it wasn’t possible, or that you should focus on making drugs that target neurons. But neurons are very precious, so if we can do an intervention that doesn’t mess with the neurons directly, but instead uses these environmental cues to guide their activity toward a healthier state, to me, that’s a better way.