How different levels of brain development help adolescent cognition - or don’t

Adam Pines was the lead author on this study. Adam is a postdoctoral fellow in the Stanford PanLab for Precision Psychiatry and Translational Neuroscience. He completed his Ph.D. in Neuroscience at UPenn in 2022. His other research interests include developmental neuroscience, brain-environment interactions, and adaptive plasticity in the brain.

or technically,

Dissociable multi-scale patterns of development in personalized brain networks

[See Original Abstract on Pubmed]

Authors of the study: Adam R. Pines, Bart Larsen, Zaixu Cui, Valerie J. Sydnor, Maxwell A. Bertolero, Azeez Adebimpe, Aaron F. Alexander-Bloch, Christos Davatzikos, Damien A. Fair, Ruben C. Gur, Raquel E. Gur, Hongming Li, Michael P. Milham, Tyler M. Moore, Kristin Murtha, Linden Parkes, Sharon L. Thompson-Schill, Sheila Shanmugan, Russell T. Shinohara, Sarah M. Weinstein, Danielle S. Bassett, Yong Fan & Theodore D. Satterthwaite

You don’t need to be a scientist to know that kids get smarter as they grow up - they get better at things like problem-solving, thinking flexibly, and remembering information. But what exactly is changing in the brain to make these cognitive skills, which researchers call “executive function” easier?

Like instruments in a band, different areas of the human brain have different roles and will perform together in different combinations to everything from processing what your eyes see, to controlling your muscles, to solving a crossword, to feeling emotions. A group of brain regions that work together is called a functional brain network. Some functional brain networks perform easier, or “lower-order”  tasks, like sensing pain when you get a cut. Others perform harder, more complex tasks, like solving physics equations or learning a language, which are considered “higher-order”. 

Dr. Adam Pines, who recently graduated from the Neuroscience Graduate Group, wanted to know how all these functional networks mature as kids age and how this pattern of development relates to kids’ improving executive function. To study this, Adam had two challenges. First, we don’t know how many functional networks there “really” are in the brain; you can divide the brain up into different numbers of chunks and still do a good job of grouping regions that activate together and separating those that don’t (Figure 1, Columns). Second, the layout of everyone’s functional networks is a tiny bit different: one network may take up a little more space in one person, for instance, or the parts of the brain that do a certain task on one person may be just a little bit more to the left on another (Figure 1, Rows). Therefore, Adam made personalized functional networks (PFNs), which are maps of a person’s unique functional network layout, for every subject in the study. He also tried grouping the brain into different numbers of networks to see whether this would change his results.

Figure 1: Illustration of personalized functional networks mapped for varying numbers of networks.

Adam mapped the unique functional networks of each person in the study (PFNs), as shown in the rows. He also divided the brain’s activity into different numbers of networks, with maps of 4, 7, and 13 networks pictured. Different colors show that the brain regions are part of different functional networks.

To make personalized functional networks (PFNs) for each subject (Figure 1, Rows), Adam and his colleagues mapped the layout of every functional network in the average person and mathematically tweaked the layout to fit each participant’s unique pattern of brain activation. Then, they repeated this step using different numbers of networks in their baseline map (Figure 1, Columns) and labeled whether each network did lower- or higher-order functions. In the end, they had 29 brain maps for each person (each dividing brain activity into 2 to 30 functional networks), that they could compare to each participant’s age and score on a test of executive function.

First, Adam compared PFNs across participants ages 8 through 23 and found that lower- and higher-order networks tended to develop differently. Lower-order networks (each of which does an easier task) became more interconnected over the course of adolescence, while higher-order networks (each of which does a harder task) became less interconnected. Next, he tested how these PFN patterns were related to kids’ executive function. Interestingly, he found executive function tends to be better when very low-order and very high-order networks are distinct, but networks that fall in the middle (ones that do medium-complexity tasks) are more interconnected. Dividing the brain into a greater number of PFNs, Adam saw this effect grow stronger, especially in lower-order networks.

Taken together, Adam’s results are surprising because, while aging makes higher-order networks more distinct (which is better for executive function), lower-order networks actually become more interconnected (which is worse for executive function)! This may mean that while increasingly distinct higher-order networks allow kids’ executive function to improve as they grow up, their brains’ lower-order networks are already starting to decline. These findings will be important for future scientists studying how kids’ executive function develops and may help uncover why some kids struggle with cognitive development.

About the brief writer: Margaret Gardner

Margaret is a PhD student in the Brain-Gene-Development Lab working with Dr. Aaron Alexander-Bloch. She is interested in studying how different biological and demographic factors influence people’s brain development and their risk for mental illnesses.

Want to read Adam’s work for yourself? You can find the full article (complete with equations and pretty brain pictures) here!

How do the brain’s structure and function develop together through adolescence?

or technically,

Development of structure-function coupling in human brain networks during youth

[See Original Abstract on Pubmed]

Authors of the study: Graham L. Baum, Zaixu Cui, David R. Roalf, Rastko Ciric, Richard F. Betzel, Bart Larsen, Matthew Cieslak, Philip A. Cook, Cedric H. Xia, Tyler M. Moore, Kosha Ruparel, Desmond J. Oathes, Aaron F. Alexander-Bloch, Russell T. Shinohara, Armin Raznahani, Raquel E. Gur, Ruben C. Gur, Danielle S. Bassett, and Theodore D. Satterthwaite

An important part of learning about the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. is not just understanding the way one individual brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. region works, but also how different brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. regions connect to each other. For example, our eyes receive visual information, but you only know what objects you are looking at because that visual information is also associated with your other senses and your memories. The connections between brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. regions are not completely set once a person is born, they develop as that person grows. There are several ways that these connections can develop. One way is structural, which is the physical connections between regions. These are the white matterA class of brain tissue made up of long and wire-like axons and tracts, acting as a highway of connections among the brain's cortical surface regions connections that stretch from region to region and the synapsesthe point of communication between neurons; the tiny gap between two neurons, where nerve impulses are relayed formed between cells in different regions. Another type of connection between regions is functional. This means that when one region is active and doing a task, the other region is active as well. When the structure between brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. regions also supports the functional connections between those regions, that is called structure-function coupling. Graham Baum, Neuroscience Graduate Group student and member of the Satterthwaite lab, wanted to know how structure-function coupling develops in youth.

BrainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. regions can be classified in groups based on what they process. If a brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. region only focuses on a single simple thing such as light, heat or taste, then it is called unimodal. If a brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. region associates multiple types of information that come from different brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. regions, that brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. region can be called transmodal. When children grow up, the senses are among the first parts of the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. to develop since they are more concrete; they require less abstract thought. The more evolved transmodal parts of the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. are the ones that develop later in life. It is also possible to measure how much a transmodal region is connected to other brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. regions, which is called the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. region’s participation coefficient. Graham’s study focused on the differences in development of unimodal and transmodal types of brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. regions.

To study structure-function coupling, Graham scanned people from ages 8 to 23 using MRI imaging. He made two maps for each person. The first map was a structural map, made with diffusion weighted imagingA method for imaging and measuring properties of white matter using magnetic resonance imaging.. This map showed the physical connections between regions of the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals.. The next map was a functional map. To make this map, each participant was scanned with a MRI machine while they were doing a task where they needed to remember a number of things and then repeat them back to the experimenter. That allowed Graham to make a map of the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. to see how each region of the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. communicated with every other region of the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. during this task. The last step was to correlate the structural connections with the functional connections. Each region in the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. then had a number to represent its structure-function coupling. This final value is what Graham measured and compared between participants.

The first thing Graham found was that regions that were unimodal had stronger structure-function coupling compared to transmodal areas. The more regions that one brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. region was communicating with, the weaker structure-function coupling it had. This was true across all ages. He next wanted to know how structure-function associations would change with age. To do this, he compared the structure-function coupling between younger participants and older participants. BrainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. regions that were unimodal did not change much with age. The regions that changed the most with age were the transmodal areas that support complex thought.

These age differences in structure-function coupling were exciting, but they were done across different people of different ages. Graham added to this by scanning a group of participants and then scanning those same participants about 2 years later. For most adolescents, 2 years can be a significant amount of time to change in terms of brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. development. When Graham scanned the same people twice, he confirmed that transmodal brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. regions within the same individuals developed stronger structure-function coupling over time.

The last thing Graham wanted to know is whether these structure-function connections would actually be related to behavior. He looked at how people actually did on the behavioral task that he used to make the functional maps. He found that higher structure-function coupling in a region called the rostrolateral prefrontal cortex (rlPFC) was associated with better performance on the task. The structure-function coupling of the rlPFC could also predict how two people of the same age would do on the task.

Graham’s work shows us something we didn’t know before, how the development of white matterA class of brain tissue made up of long and wire-like axons and tracts, acting as a highway of connections among the brain's cortical surface regions helps to support the way that the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. develops its cognitive abilities. This work gives us the ability to predict brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. function as humans age and develop. Additionally, this work can help us try to understand disorders that are defined by the disconnect between structural and functional development such as certain neuropsychiatric disorders.

About the brief writer: Rebecca Somach

Rebecca is a PhD Candidate in Akiva Cohen’s lab. She is interested in using electrophysiology to answer interesting and novel questions in neuroscience. Her current research focuses on how mild traumatic brain injury alters the neuronal circuitry of sleep.

Want to learn more about structure-function coupling, and how it changes as we develop? Check out Graham’s paper here.

Improving how we visualize brain changes from youth to adulthood

or technically,

Adam Pines was the lead author on this study. Adam is a PhD candidate in Ted Satterthwaite's Lab. He is interested in understanding how psychopathology emerges from neurocognitive development

Leveraging multi-shell diffusion for studies of brain development in youth and young adulthood

[See Original Abstract on Pubmed]

Authors of the study: Adam R. Pines, Matthew Cieslak, Bart Larsen, Graham L. Baum, Philip A. Cook, Azeez Adebimpe, Diego G. Dávila, Mark A. Elliott, Robert Jirsaraie, Kristin Murtha, Desmond J. Oathes, Kayla Piiwaa, Adon F.G. Rosen, Sage Rush, Russell T. Shinohara, Danielle S. Bassett, David R. Roalf, Theodore D. Satterthwaite

As people grow from childhood to adolescence, most changes are pretty clear: you might see a niece or nephew again after a couple years and find they have changed quite a bit, whether they are several inches taller or sporting new favorite phrases and hobbies. During this time of growing up, there are many complex changes happening in the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. that are less visible.

One of the things that changes across development is the strength of connections between brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. regions. Why does this matter? Well, different parts of your brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. communicate with each other to produce the thoughts and actions that guide our daily life. When a brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. region communicates more with a particular brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. region than another, that connection gets stronger. The changes in these connections usually follow a reliable pattern across development, with some individual differences based on our unique experiences. It is important to know what changes to expect in the connections between different brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. regions during development, so that we can learn to spot when things go awry. Adam Pines of the UPenn Neuroscience Graduate Group and member of the Satterthwaite lab was interested in finding the best ways to measure changes in these connections across development by comparing several methods for analysis.

To visualize the connections between brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. regions, scientists look at a type of tissue called white matterA class of brain tissue made up of long and wire-like axons and tracts, acting as a highway of connections among the brain's cortical surface regions. To understand what white matterA class of brain tissue made up of long and wire-like axons and tracts, acting as a highway of connections among the brain's cortical surface regions is and why it is important, we need to zoom in and start with the basic building block of the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals.: the neuronA nerve cell that uses electrical and chemical signals to send information to other cells including other neurons and muscles. NeuronsA nerve cell that uses electrical and chemical signals to send information to other cells including other neurons and muscles are a specialized kind of brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. cell. The communication between neuronsA nerve cell that uses electrical and chemical signals to send information to other cells including other neurons and muscles is what drives most everything we see, think, and do. The part of the neuronA nerve cell that uses electrical and chemical signals to send information to other cells including other neurons and muscles that makes up white matterA class of brain tissue made up of long and wire-like axons and tracts, acting as a highway of connections among the brain's cortical surface regions is often covered in an insulating coating called myelin. Myelin helps signals travel faster from one end of a neuronA nerve cell that uses electrical and chemical signals to send information to other cells including other neurons and muscles to the other. Collectively, these connections are called white matterA class of brain tissue made up of long and wire-like axons and tracts, acting as a highway of connections among the brain's cortical surface regions because the coating makes them appear white.

Techniques have been developed to image white matterA class of brain tissue made up of long and wire-like axons and tracts, acting as a highway of connections among the brain's cortical surface regions using an odd-sounding but effective principle: “follow the water.” You may not think of water when you think of the inner-workings of the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals., but 73% of the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. is actually water.¹ In areas of the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. without this myelin coating, water is going in all directions. However, myelin is resistant to water, so it essentially forms little water slides in the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals.. Only where there is white matterA class of brain tissue made up of long and wire-like axons and tracts, acting as a highway of connections among the brain's cortical surface regions is the water moving in one direction more than all others. Researchers take advantage of this and “follow the water” to measure 1) the direction of the water and 2) how fast it is going. This tells them the direction of the connection between brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. regions and the strength of those connections. This technique is called diffusion weighted imagingA method for imaging and measuring properties of white matter using magnetic resonance imaging.. With these basic principles, diffusion weighted imagingA method for imaging and measuring properties of white matter using magnetic resonance imaging. is able to map out where white matterA class of brain tissue made up of long and wire-like axons and tracts, acting as a highway of connections among the brain's cortical surface regions is and measure its properties.

Although it is a powerful tool, interpreting the results of diffusion weighted imagingA method for imaging and measuring properties of white matter using magnetic resonance imaging. requires a lot of complex modelling. Not all models are best suited for studying brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. development. The best model would be the one that showed changes in the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. with age and that was not affected too much by people moving while they were in the scanner (called in-scanner motion). Imaging of the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. has the same problem you do when taking a picture of anything moving - things get blurry. Lots of people can get fidgety in the scanner but especially kids, making finding a metric that isn’t affected by in-scanner motion extra important when studying brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. development. Adam wanted to figure out which diffusion weighted imagingA method for imaging and measuring properties of white matter using magnetic resonance imaging. measures researchers should be using to study brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. development.

Adam tested different methods by seeing how the output of each related to age and to in-scanner motion. Each method had a slightly different set of outputs or metrics that he looked at. He found that the metrics of each related to age and in-scanner motion differently. Some metrics were more affected by the age of the participant than others whereas other metrics were more affected by in-scanner motion. Remember, in order to study brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. development, the best metrics would be the ones that were most affected by age and least affected by in-scanner motion. Adam found that each metric varied quite a bit in how well it was associated with age. However, he found that one particular method, the Laplacian-regularized Mean Apparent Propagator (MAPL), was less affected by in-scanner motion than the other methods he tested. MAPL is a relatively new method and, before Adam’s study, no one was sure how well it would work for measuring brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. development.

Based on Adam’s work, other researchers now know what metrics are best to study white matterA class of brain tissue made up of long and wire-like axons and tracts, acting as a highway of connections among the brain's cortical surface regions to determine what is happening in the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. during development. This work is important because it allows future research on brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. development to be more reliable by leading researchers away from model metrics that would miss the effects they are most interested in. By looking at white matterA class of brain tissue made up of long and wire-like axons and tracts, acting as a highway of connections among the brain's cortical surface regions during development using previous methods, researchers have already discovered different pathways that are related to normal development, anxiety and depression, and more. Adam’s work will allow for many more future discoveries like these that help us better understand problems that occur during development!

About the brief writer: Sara Taylor

Sara Taylor is a PhD Candidate in Ted Brodkin’s lab. She is interested in understanding how behaviors associated with Autism Spectrum are related to each other as well as their genetic basis.

Citations:

1. Mitchell, H. H., Hamilton, T. S., Steggerda, F. R., & Bean, H. W. (1945). The chemical composition of the adult human body and its bearing on the biochemistry of growth. Journal of Biological Chemistry, 158(3), 625-637.

   
   You can find the paper here.

Want to learn more about how these methods for studying brain development work? You can find Adam Pines’ full paper here!

Are teens uniquely susceptible to long-term effects of stress?

or technically,

Adolescent Chronic Unpredictable Stress Exposure Is a Sensitive Window for Long-Term Changes in Adult Behavior in Mice.

[See Original Abstract on Pubmed]

Authors of the study: Nicole L Yohn & Julie A Blendy

Stress happens. Whether it’s a dead car battery or a looming work deadline, stress is a fact of life. However, the types of stressors we experience and how they might affect us are constantly changing. Adolescence is one stage of life where these changes are particularly apparent. Most of us can appreciate how the nature of stressors change during adolescence (school pressures, dating and friendships, availability of drugs/sex/alcohol, huge physical and emotional developments, etc.), but less appreciated are the ways in which teens may be uniquely susceptible to the long-term and detrimental effects of these stressors.

This question of if and why adolescents are especially sensitive to stress shaped Nicole Yohn’s research at the University of Pennsylvania in the laboratory of Dr. Julie Blendy. Previous research has shown that human brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. development is not fully completed until about the age of 25. In this sense, our brainsThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. are still undergoing tremendous remodeling during our teenage years. Nicole wondered if exposure to stress during this period of continuing brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. development may contribute to the increase in mental disorders, like anxiety, depression, and drug abuse, which often emerge during these years. This was an important question-- even though there’s plenty of research linking stress to mental disorders, there are very few studies looking at how the two are connected. Nicole set out to bridge that gap.

One of the most important (and most frustrating) aspects of stress is that it’s both chronic and unpredictable. In order to best model these aspects of stress in the lab, Nicole created a mouse model and designed her experiment such that each mouse was exposed to three different types of stressors a day for twelve consecutive days. These stressors consisted of things like food restriction, exposure to cold temperatures, isolation, and other unpleasant situations. To ask whether exposure to stress during adolescence is more damaging than exposure to stress during adulthood, Nicole compared two groups of mice-- one that faced these chronic and unpredictable stressors during puberty and one that experienced the stressors during adulthood. Both groups of mice were tested for behaviors associated with anxiety and depression, the most prevalent stress-related disorders.

So, does stress during particular stages of development alter susceptibility to mental illness? Nicole found that it seems to depend on exactly which mental illness we’re talking about. For example, Nicole observed depression-like behaviors in all mice exposed to stress, regardless of whether they experienced that stress during puberty or adulthood. In contrast, anxiety behaviors only appeared if stress occurred during adolescence, not adulthood. The sex of the mice also seemed to be an important factor in effects of stress on behavior. In one behavioral assessment, female mice showed more anxiety than males. This might mean that how we respond to stress may have something to do with sex-specific hormonesA substance produced in the body that controls or regulates the activity of certain cells or organs. Many hormones are produced by special glands and travel through the blood to reach the location in the body where they act..

Speaking of hormonesA substance produced in the body that controls or regulates the activity of certain cells or organs. Many hormones are produced by special glands and travel through the blood to reach the location in the body where they act. and chemicals, Nicole wanted to look for a chemical that might underlie the different effects stress has on adolescents versus adults. One chemical she chose to investigate was corticotropin releasing factor (Crf) -- a hormoneA substance produced in the body that controls or regulates the activity of certain cells or organs. Many hormones are produced by special glands and travel through the blood to reach the location in the body where they act. that’s released in the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. when we feel stressed. Crf is responsible for the extra alertness or the feeling of butterflies in our stomachs we might notice before doing something important, like giving a presentation. While a short-term boost of Crf might be helpful in focusing our attention on the task at hand, too much Crf can be a bad thing. When looking at Crf levels in the brainsThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. of her mice, Nicole found increases only in mice that were exposed to stress during adolescence. Interesting, right? It seems like this increase in Crf could be what’s causing the development of anxiety in adolescent but not adult animals.

What do we know for sure? Nicole’s work suggests that mice are especially susceptible to stress during adolescence. She also showed that being female might make you even more susceptible to the long-lasting effects of stress. While more research is needed to determine whether these findings hold true for humans, Nicole has established a good model for future studies to look into how stress affects us throughout our lives, and how we might be able to prevent or lessen the damage it causes.

About the brief writer: Kara McGaughey

Fascinated by the long-standing linguistic connection between the gut and the brain ("gutsy," "gut feeling," "gut instinct," etc.), Kara is using her second year in NGG to examine the interplay between microbiota and brain development.

My back hurts, my hand hurts: is pain different in different parts of the body?

or technically,

Sparse genetic tracing reveals regionally specific functional organization of mammalian nociceptors.

[See Original Abstract on Pubmed]

Authors of the study: William Olson, Ishmail Abdus-Saboor, Lian Cui, Justin Burdge, Tobias Raabe, Minghong Ma, Wenqin Luo

Have you ever wondered why you can feel the details of an object with your fingertips, but not with your elbow? Your body detects sensations including touch and pain using specialized nerves that detect information in your environment and transmit it to your brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals.. Together, these nerves are called the “sensory system.” As you may have noticed, however, this system does not treat all body regions the same. This is why your fingertips are much more sensitive to touch stimuli than other parts of your body (imagine trying to feel Braille with the back of your hand). Our fingertips are very sensitive to touch mainly because they contain more ‘touch-sensitive’ nerve endings than other body regions.

Pain perception relies on ‘pain-sensitive’ nerve endings that are distinct from our ‘touch-sensitive’ nerve endings. But just like for touch, certain regions of our body, like our fingertips, are more sensitive to pain than others. Interestingly, unlike for touch, this is not because we have more ‘pain-sensitive’ nerve endings in pain-sensitive areas. In fact, we have relatively few ‘pain-sensitive’ nerve endings in our fingertips -- even though they are extremely sensitive to pain! This observation surprised Will Olson, a neuroscience graduate student in Wenqin Luo’s lab. He wondered how certain parts of the body are more sensitive to pain than others.

To figure this out, he carefully studied the shape and size of pain nerve endings in mice. These nerves are like wires that run all the way from your skin into your spinal cord. This means there are two endings of these nerves: one in the skin and one in the spinal cord. Will took a good look at both ends. He saw that, in general, ‘pain-sensitive’ nerves come in different shapes and sizes depending on where in the body they are found. Interestingly, he found that pain nerve endings have a low density in the mouse paw, just like in the human hand! The pain nerve endings in the paw also looked very similar to pain nerve endings in other parts of the mouse. This surprised Will because he knew that mice have very high pain sensitivity in their paws. He wondered, if the density and the shape of the pain nerves in the paw skin is the same as in other parts of the body, then why are paws so sensitive to pain?! The answer became clear when Will looked at these nerves in the spinal cord -- in the spinal cord, paw pain nerves look completely different from pain nerves that come from other parts of the mouse. Will hypothesized that the special shape of these paw pain nerves could enhance pain sensation in the paw. And in fact, Will found that these paw pain nerves are better at sending information to the spinal cord than pain nerves that come from other parts of the mouse.

While these findings are interesting and could even help some of us decide on the least painful place to get a tattoo, this study might also help people with chronic pain. Chronic pain occurs when people feel pain for weeks, months or even years. Based on this study, we may be able to identify specific causes of chronic pain in different parts of the body. For example, chronic back pain might be very different from chronic joint pain. Our current pain medications are not effective as treatments for many forms of chronic pain. The lack of good treatments has contributed to the increase in opioid prescriptions that led to opioid addiction crisis. Identifying more specific causes of chronic pain could give researchers ideas for better ways to treat it.

About the brief writer: Patti Murphy

Patti is a PhD Candidate in Michael Granato's lab. Patti is interested in understanding and developing therapeutics for functional nerve regeneration, particularly to restore voluntary motor control after spinal cord injury.

Do you want to learn more about how we feel pain? You can read Will’s entire paper here.

Highway to the brain: cells responsible for touch need a support system to grow really long distances during development

or technically,

Roof Plate-Derived Radial Glial-like Cells Support Developmental Growth of Rapidly Adapting Mechanoreceptor Ascending Axons

[See Original Abstract on Pubmed]

Authors of the study: Kim Kridsada, Jingwen Niu, Zhiping Wang,Parthiv Haldipur, Long Ding, Jian J. Li, Anne G. Lindgren, Eloisa Herrera, Gareth M. Thomas, Victor V. Chizhikov, Kathleen J. Millen, and Wenqin Luo

Have you ever thought about going on a cross-country road trip, perhaps from Washington D.C to San Francisco? To make traveling such a long distance easier, you may need road signs telling you where to go and highways to make your journey more direct. In the same way that we need directions and fuel for a long trip, the neuronsA nerve cell that uses electrical and chemical signals to send information to other cells including other neurons and muscles that mediate our sense of touch (also known as mechanoreceptorA type of neuron (nerve cell) that senses mechanical stimuli like touch cells) need a way to get their axonsA specialized part of a neuron that sends electrical and chemical signals to other cells. Axons are typically long and thin like a wire. from the periphery of your body (e.g., hands, toes, and legs) to their final destination, the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals.! During nervous system development, it’s really important for these cells to reach the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. in order to provide us with a proper sense of touch; these cells help you feel the carpet under your feet as you get out of bed, the fork in your hand as you eat your lunch, and even that light tap on your shoulder when somebody is trying to get your attention. So how exactly do these touch neuronA nerve cell that uses electrical and chemical signals to send information to other cells including other neurons and muscles axonsA specialized part of a neuron that sends electrical and chemical signals to other cells. Axons are typically long and thin like a wire. travel so far to ultimately reach the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals.? Kim Kridsada, a neuroscience graduate student in Wenqin Luo’s lab, sought to figure this out.

Kim noticed that during development, the mechanoreceptorA type of neuron (nerve cell) that senses mechanical stimuli like touch (“touch”) cell axonsA specialized part of a neuron that sends electrical and chemical signals to other cells. Axons are typically long and thin like a wire. that had to travel the farthest (e.g. from hands and feet to the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals.) also seemed to grow closer to a group of specialized cells in the spinal cord compared to cells that didn’t have as far to go. She thought that maybe these specialized cells could be guiding cells (aka acting as a highway) and also sending signals (aka “road signs”) out to the touch cell axonsA specialized part of a neuron that sends electrical and chemical signals to other cells. Axons are typically long and thin like a wire. that helped them grow through the spinal cord to eventually reach the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals.. Kim found that these support cells indeed sent out signals, in the form of specific growth-promoting proteinsAn essential molecule found in all cells. DNA contains the recipes the cell uses to make proteins. Examples of proteins include receptors, enzymes, and antibodies., that could be used by the touch neuronsA nerve cell that uses electrical and chemical signals to send information to other cells including other neurons and muscles to grow in the correct directions. The support cells that Kim found surrounding these touch cells were part of a particular class of cells known as radial glial-like cells (RGLCs), which are cells that can help with growth and development of neuronal cells. Kim wondered how important these RGLCs were for the touch cells - did the touch cells need them to grow along this highway to reach the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals.? She hypothesized that without this RGLC highway, the touch cells wouldn't grow as far. To test whether RGLCs are truly needed in the body for touch cells to grow long distances, Kim studied mice that did not have any RGLCs but still had touch cells that were capable of growing. Interestingly, she found that in mice that had no RGLCs, their touch cells axonsA specialized part of a neuron that sends electrical and chemical signals to other cells. Axons are typically long and thin like a wire. were much shorter and 40% of their touch cells did not grow long enough to reach their correct destination in the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals.! Taken together, these findings suggest that RGLCs are really important in the body for helping touch cells axonsA specialized part of a neuron that sends electrical and chemical signals to other cells. Axons are typically long and thin like a wire. eventually make their way to the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals..

Overall, Kim discovered a previously unknown group of support cells (RGLCs) in the spinal cord that help touch cell axonsA specialized part of a neuron that sends electrical and chemical signals to other cells. Axons are typically long and thin like a wire. make connections over long distances, from the periphery of the body to eventually the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals.. These findings are really important not only for our understanding of how we develop a very important sense (touch), but could also be used to improve regeneration in people who have suffered injuries and have, as a result, lost their sense of touch. Thanks to Kim’s work, we now know that these spinal cord cells help certain touch cells grow long distances, so we could try to develop drugs or therapies that target them so that growth of touch cells during regeneration happens more easily.

About the brief writer: Elelbin Ortiz

Elelbin is a PhD Candidate in Michael Granato’s lab. She is interested in understanding how animals set behavioral thresholds, or ways to decide whether information from the environment requires a response or not. She is interested in understanding how an animal's genes (DNA) influence how these behavioral thresholds are set.

Do you want to learn more about touch, RGLCs, and development? You can read Kim’s whole paper here.