GGR Newsletter
July 2025
GGR Newsletter
July 2025
Mary D. Cundiff, Ph.D.
July 2025
We know surprisingly, or maybe not so surprisingly, little about the brain. While we have developed countless techniques to study the organs of the body, the brain remains stubbornly opaque. Known for its complexity, it is also uniquely inaccessible, constantly changing, and responsible for the very act of studying itself.
The Complexity of the Brain
The human brain is a marvel of complexity, both structurally and functionally. Composed of ~86 billion neurons, each capable of forming thousands of synapses, it creates a dense, high-dimensional network of interactions. And it’s not just which neurons interact, but how, when, and where; factors influenced by timing, receptor types, neurotransmitters, and whether signals are excitatory or inhibitory. These characteristics provide the framework for a seemingly infinite number of possibilities and patterns. Sound overwhelming? We’re just getting started.
Perhaps the most elusive property of the brain is “plasticity”, the ability to rewire in response to learning, experience, and injury. Patterns that might seem stable one moment can shift the next. And while we often speak about the neurons, they’re just one part of the picture. The brain also includes glia, immune cells, and vascular structures, all of which play vital roles but are largely left out of mainstream narratives.
Think about thinking…
What makes the brain truly different from other organs is that it produces “emergent properties”: consciousness, memory, emotions, and perception. These are not the result of individual neurons but of complex, dynamic networks. This makes the brain qualitatively different from the kidney for instance, whose function can be more directly traced to biochemistry and physiology. Consciousness in particular, presents a deep philosophical and scientific challenge. What does it mean to “think”? Some argue that advanced AI may now “think,” but thinking is not necessarily the same as experiencing. Philosopher Thomas Nagel once posed the question: “What is it like to be a bat?” His point was that consciousness is defined not by function, but by what it’s like to exist as a conscious being. An organism is said to be conscious if there is “something that it is like to be that organism - something that it is like for the organism”. It’s not something like a functional state because a robot can act like a human, even though it “experienced” nothing. Are you spiraling yet from thinking about how the brain is thinking? Welcome to neuroscience.
The Problem of Access
The brain is wildly complex and has an infinite number of patterns and possibilities to try and make sense of, but probably the biggest barrier to being able to study the brain is that it’s difficult to access directly and safely. Unlike a liver or a tumor, you can't just biopsy a healthy, functioning human brain. In the rare cases that we do get a sample, it is done on unhealthy tissue, making it problematic for studying normal brain structure. In a recent groundbreaking study, a small biopsy was obtained to access an underlying lesion. Google scientists were able to reconstruct a petavoxel of human cerebral cortex at a nanoscale resolution.
The tools available to us have advanced rapidly over the years but they are still slow and the outputs are generally noisy. Non-invasive tools like fMRI and EEG offer glimpses into brain activity, but they’re indirect. For example, fMRI tracks changed blood flow, where increased blood flow to a brain region suggests increased activity, but this is not technically signaling. And while invasive studies are more common in animal models, like mice, these experiments are limited by species differences, variability, and interpretation challenges. After all, you can’t exactly ask a mouse how it feels.
Even something as simple as color perception reveals how tricky this is: how do you know that the “red” you see is the same red I see? We might agree on the label, but the internal experience could be wildly different. This is the heart of one of neuroscience’s “impossible” questions and remains an active area of research.
Brains Studying Brains: A Paradox in Progress
To begin understanding the brain, you must ask focused, specific questions. Neuroscience is a vast field, and depending on the question, researchers draw from different subdisciplines:
Molecular and Cellular Neuroscience
What genes and proteins correspond to the different cellular mechanisms and functions? How are neurons sending signals in a specific context? Neurons send signals both electrically and chemically (neurotransmitters), again increasing the number of possible outcomes.
Circuit and Systems Neuroscience
How do different brain regions talk to each other and coordinate entire network signaling? What happens when they rewire (plasticity)? Your brain not only processes how you experience the world cognitively, but also physically. How are sensory signals processed?
Developmental and Computational Neuroscience
How does the brain wire itself in embryos and then change and rewire through experience? Can we build algorithms that simulate brain circuitry and how it changes?
Side Quest: During your first couple years of life, your ~86 billion neurons are building TONS of connections; far more than are needed in a mature brain. This process is sometimes referred to as “synaptic blooming”. The formation and strength of these connections are experience-dependent. Children will then also go through what is called “synaptic pruning” (Figure 1), a process first discovered in cats in the 1960s. The brain will actually eliminate or “prune” unnecessary and weak neural connections. It is a process meant to make circuits more refined and efficient, peaking during childhood and adolescence.
Figure 1. Synaptic pruning and neuroevelopmental disorders
From Faust et al. 2021
Cognitive Neuroscience
What brain regions support attention, language, or decision-making? How do we form and retrieve memories? How does someone study consciousness?
Clinical and Translational Neuroscience
How does the brian change in disease and how do drugs affect brain function? Remember, the brain sends signals electrically as well as chemically. How can we use electrical stimulation for treatment? Deep brain stimulation is a well accepted treatment for diseases such as Parkinson’s disease, in which the stimulation is meant to compensate for the loss of signal resulting from a loss of dopamine.
A Thought Experiment
One of the most useful exercises I did during my PhD was to ask: If I had unlimited tools and funding, how would I test this hypothesis?
Let’s say you want to study movement disorders. You begin by identifying a brain region (call it Group B) active during walking. Where is Group B getting input from (Group A)? What types of cells are in Group A? Where does Group B send its output (Group C)? Can you isolate specific cell types in Group C and measure their activity only during walking?
Now imagine all of this again but in a disease model. How do these connections change? Can you precisely measure that change? Can you modify it?
Each layer adds more complexity. The gap between the question and the tools needed to answer it often spans years of trial and error, model building, and data wrangling. That’s why PhDs in neuroscience often take 5–7 years. You need caffeine, patience, and a bit of delusion.
Next-Generation tools for studying the brain
Thankfully, the field is evolving. Two recent breakthroughs are paving the way for a new era of brain research:
The Armamentarium by the Allen Institute
This massive collaboration brought together researchers from 29 institutions to create a toolbox of enhancer AAV vectors. AAVs, or Adeno-associated viruses, utilize the harmless “deliver DNA to a cell” engineering of a virus as a way to deliver targeted gene tools or therapies. AAVs aren’t new, but these are optimized for specificity, enabling researchers to modulate cells contributing to disease without affecting neighboring ones. It’s like upgrading from a sledgehammer to a scalpel.
Krakencoder: A Universal Translator for Brain Maps
A 2025 study introduced Krakencoder, a tool that converts between different types of brain connectome maps, linking structure, function, and individualized patient data. It bridges the gap between how a brain is built and how it behaves, with significant implications for personalized medicine.
Studying the brain is like trying to reverse-engineer a supercomputer, with no instruction manual, faulty wiring that changes over time, and a mysterious core function (consciousness) that can’t be directly measured. And yet, every year, we inch closer to understanding how the brain works; not through one magic tool or theory, but through a mosaic of approaches, insights, and innovations.
To study the organ that named itself, we have to balance precision with imagination, data with philosophy, and theory with trial and error. The tools are finally catching up to the questions. And that’s what makes this moment in neuroscience so thrilling.