Our society is hampered with sensory information. Reach out and touch an object around you it might be hot, cold, sharp soft, rough or smooth, and you will know that your brain is processing a dizzying array of information in this simple action. We know that our brain has layers of complexity that we have in our environment, but deciphering that intricacy at a cell level is a huge task. How do our genes, cells, and electrical impulses come together to decode the world around us?
Jerry Chen, an adjunct professor of biology at Boston University, is attempting to break this code. Chen has published new research in Science that demonstrates how the mouse brain processes the sense of touch at a cellular level using a technology called Comprehensive Readout of Activity and Cell Type Markers. Chen''s findings may have significant implications for our ability to provide therapies for disorders where sensory processing is disrupted, e.g. autism spectrum disorder.
In this conversation, we talk to Chen about his research objectives, findings, and implications.
What did you wish to do with your research? What made you want to look into this topic?
Jerry Chen (JC): Our neurobiologists are interested in discovering the neural basis for perception and cognition. The brain is the most complex organ in the body. This complexity is partly reflected by the fact that billions of neurons in the brain are not all the same. We must deconstruct the brain down to its individual components and then begin by asking how these components interact during behavior.
Is it possible to explain the first-of-its-kind neuron catalog technique that helped with this study, and its implications?
Our colleagues from theAllen Institute for Brain Sciencehad a goal of generating a neuron catalog by completing a census of all of the types of cells in the brain. This is part of a collective effort by several institutions.
The catalog does not specify the molecular composition of the neurons, nor does it indicate the function of the neurons or how they perform. This new information from the catalog is then used by our research team to consolidate our information, which is the activity patterns of the cells. This is why we recommend using the CRACK technology to better understand and process the function of the neurons in the catalog. This is why we hope that the catalog 2.0 will open the door to future generations.
How did you use this technology in your research?
JC: We used the CRACK platform to investigate a specific part of the cortex involved in our perception of touch. We looked at how different neurons from the catalog process information and talk to other neurons when an animal touches objects in their environment. We also looked at how neurons adapt when the environment changes.
How important is the advent of spatial transcriptomics to enhance our brain''s understanding?
JC: Spatial transcriptomics is a powerful tool to investigate not only the brain, but any tissue or organ in the body. Five to ten years ago, we were limited in being able to see how a few genes were expressed in the brain at a time. Today, with the latest spatial transcriptomic technologies, we were able to see how hundreds or even thousands of genes are expressed in a single sample. This demonstrates new connections in how patterns of genes in neurons were previously unknown.
What were the conclusions?
JC: When you see the world around you, your brain does a process of processing the stimuli that create the scene, but it also tries to fill information based on what you''ve learned in the past. Occasionally, you feel something, like a sharp edge, that really jumps out and tells you that youve found your keys. We essentially discover that there is a dedicated circuit that is called hub cells. These cells provide the brain with an insight that needs to be investigated.
In the current study, you examined 11 different cell types. How long will it take to profile all cortexs cell types?
JC: The 11 cell types that we examined have already been identified as atlas. This way, you may consider the cities that are part of continents. I believe this is fair to say that our understanding of cell types has historically been on the continent level, sometimes zooming to countries. However, we now have the capacity to look at cities and we can look at many different locations at the same time. The benefit of this approach is that the rate at which we can profile all of these cells.
What was the most surprising conclusion?
JC: When your environment changes, hub cells, identified as important for feature detection, respond in interesting ways. There are a number of genes that are known to be crucial for learning and adaptability, which can go up or down depending on changing environments. These genes are always on in hub cells, which goes against some current guidelines. This could be a way for the circuit to remember or not forget how to process information in the old environment.
How are hub cells that are experience-agnostic and how do they depict the vast array of sensory experiences in our planet?
JC: Were looking at these hub cells in adult animals. There are some evidence that the hub cells might have accumulated sensory experiences early during development as the animal was experiencing the world for the first time. Potentially other cell types are responding to fresher experiences, but these hub cells may be there to not forget those early life experiences.
How unpredictable are these findings to the human brain?
JC: A recent study examined some of the mouse cell types with those discovered in humans. It appears that these differences in several of the cell types we looked at, however, that humans have continued to evolve and diversify. What this means is that our genomes can have a significant influence on how the circuits in the brain are organized, which might result in specific functions described in our study.
What is the significance of these findings?
JC: Our findings have implications for a wide range of neurological disorders such as stroke, to neuropsychiatric disorders such as Autism Spectrum Disorder, where an individual sense of perception may be altered. Instead of envisioning the brain as a homogenous piece of tissue, understanding which cell types are the most appropriate will help us develop highly targeted therapies. This allows us to make significant advances toward directly treating the underlying cause of specific symptoms while also potentially avoiding undesirable side effects from other therapies and interventions.
What are you looking for next?
JC: Using new technology and insights, we were beginning to see specialized neural plasticity composed of specific cell types in the catalog or the surprise finding in our study. This is one area that we were following up on, and we were examining potentially similar kinds of circuits in other parts of the brain, both during learning and memory.