Scientists use zebrafish to understand how the brain makes decisions!

Dr. Hannah Shoenhard was the lead author on this study. Hannah hopes to one day run a lab that connects the “small picture“ (molecules, genes, and proteins) to the “big picture“ (circuits and behaviors) in neuroscience. After earning her PhD in the Granato lab using zebrafish as a model system to study decision making, she moved to do a postdoc in the Sehgal lab studying sleep and memory in fruit flies.

or technically,

The calcium-sensing receptor (CaSR) regulates zebrafish sensorimotor decision making via a genetically defined cluster of hindbrain neurons

[See Original Abstract on Pubmed]

Authors of the study: Hannah Shoenhard, Roshan A. Jain, Michael Granato

How we make decisions is a question that scientists and philosophers have considered for ages. But did you know that there are different types of decision making? The type that we are most familiar with involves decisions that we make in our everyday lives: Should I walk to school or take the bus? Should I have pasta or salad for dinner? But the brain is actually responsible for lots of different kinds of decisions - some of which we don’t even think about! One type of decision making that is commonly studied in the field of neuroscience is called sensorimotor decision making. In this form of decision making, the brain takes in sensory information from the world, processes the information while considering past experiences, and then produces a behavioral response. 

Figure 1:

Image of a zebrafish used in scientific research. 

Source: https://news.mit.edu/2022/smarter-zebrafish-study-1118

To understand more about this type of decision making, Dr. Hannah Shoenhard, a recent Penn Neuroscience PhD graduate, and her lab used zebrafish, a common animal model that is used in neuroscience research. Her lab had previously found that when fish are presented with a sudden quiet sound, they respond with a “reorientation” response - the fish slowly turn their bodies. But if the fish are presented with a sudden loud sound, they respond with an “escape” response - the fish rapidly turn their bodies. Having learned about this fascinating behavioral phenomenon, Hannah was interested in how different proteins may be involved in this sensorimotor decision making process. Through whole-genome sequencing (a fancy way of scanning for important genes) in the zebrafish, the lab identified a protein named CaSR that is essential for sensorimotor decision. When the lab removed CaSR from the zebrafish, they found that they would produce the wrong response to a loud sound by reorienting instead of trying to escape.

Given that CaSR is important for normal sensorimotor decision making, Hannah next wanted to know which part of the zebrafish brain uses CaSR to perform this behavior. She first looked at the neurons that drive the escape response. When she reintroduced CaSR into these escape neurons, she found that it did not restore the correct escaping response. This meant that CaSR had to be acting elsewhere.

To find the location where CaSR is acting, Hannah developed a novel experimental strategy. This approach combined behavior and brain imaging. Hannah expressed CaSR in random sets of neurons in zebrafish that didn’t have any CaSR of their own. Some of these fish displayed normal decision-making, meaning CaSR had been expressed in the “correct” neurons, and some displayed impaired decision-making, meaning the “correct” neurons had been missed. Hannah then compared which neurons had CaSR in zebrafish that displayed normal decision-making or abnormal decision-making. Using this novel strategy, Hannah found a brain region in the zebrafish called DCR6, which is located in the hindbrain, near both the escape and reorientation neurons. The hindbrain controls many reflexive behaviors in both fish and humans. To validate her findings and test if this region is actually involved in sensorimotor decision making, she drove extra CaSR expression in the DCR6 and found that this was sufficient to drive escape responses in zebrafish exposed to quiet noises – in other words, the opposite of what happens when CaSR is missing.  Additionally, she used the original zebrafish strain that lacked CaSR and specifically restored CaSR only in DCR6 neurons. Hannah found that these fish performed reorientations in response to quiet sounds and escapes in response to loud sounds - just as we expect healthy zebrafish to do! 

Thus far, Hannah’s experiments have pointed to two major findings: 1) CaSR is important for normal sensorimotor decision making and 2) CaSR acts locally in DCR6 neurons, but not reorientation or escape neurons, to enable normal sensorimotor decision making. Given these findings, Hannah asked an important follow-up question - are there connections between DCR6 and reorientation or escape neurons? To answer this, she used a unique zebrafish strain that labels DCR6 neurons and escape neurons. Hannah found that DCR6 neurons do connect to escape neurons but found no connections with reorientation neurons. Nevertheless, Hannah and her colleagues were excited to find this result. 

Hannah’s amazing work in the zebrafish underscores that it is important to examine the brain both at a large scale (i.e., behavior and decision making) as well as a small scale (i.e., individual neurons and proteins, like CaSR) in order to more fully understand how it works. Secondly, her work tells us that decisions are the result of distinct parts of the brain working together to perform a behavior. When you decide to have a salad for dinner, there is one part of your brain that controls your muscles and allows you to eat the salad. There is a different part of your brain that helps in deciding to eat the salad in the first place! In the example of the zebrafish, reorientation/escape neurons allow the fish to perform the actions, but the decision making site is elsewhere - namely, in a brain region known as DCR6. On a final note, Hannah’s research reminds us of the incredible value and insight that animal models, like the zebrafish, bring to us. They allow us to study behaviors that are very seemingly very human (like decision making) in very deliberate and precise ways!

About the brief writer: Jafar Bhatti

Jafar is a PhD Candidate in Maria Geffen’s lab. He is broadly interested in brain networks involved in auditory processing and decision-making.

Want to learn more about how these researchers study decision making in zebrafish? You can find Hannah’s paper here!

How brain waves might help us see

Dr. Adeeti Aggarwal was the lead author on this study. Her ultimate career goal is to become an academic ophthalmologist whose clinical insights motivate her research in visual processing, and whose research also translates back to patient care. She is fascinated by how cortical networks transform visual sensory information into perception and how defects in sensory processing may alter or abolish perception such as in hallucinations or blindness. This interest has driven her research in graduate school and she hopes to continue studying how visual processing pathways participate in perceptual experience as her career progresses. 

or technically,

Visual evoked feedforward-feedback traveling waves organize neural activity across the cortical hierarchy in mice

[See Original Abstract on Pubmed]

Authors of the study: Adeeti Aggarwal, Connor Brennan, Jennifer Luo, Helen Chung, Diego Contreras, Max B. Kelz, Alex Proekt

Modern cameras do an amazing job of turning the photons of light in the world into pixels on our phone or laptop screen that faithfully capture that moment in time. The fact that we all walk around with the technology to do this sitting in our pockets is the result of decades of innovation and technological advancement. But even with everything that your smartphone’s camera can capture, we have an even more elegant piece of machinery doing all that and more sitting between our ears all day: our brains.

How is our ability to see different than a camera? To start, there’s the obvious difference in materials. Cameras are made of hard, man-made materials, whereas your brain is filled with comparatively squishier biological material. But even more importantly, a camera and your brain are trying to accomplish two different things. The goal of a camera is to recreate the world exactly as it is. The goal of your visual system is to use what you see to interact with the world. Unlike cameras, you need to do things like pay attention to one thing over another, predict what’s coming next, or change your behavior according to what you see.

We can think of the brain as needing to accomplish two things: 1) build up a representation of what is in the world, and 2) integrate that into our current understanding of the world and intended actions to accomplish something. One popular idea, or hypothesis, is that the brain accomplishes the first goal of building up a representation of the world by sending neural signals through several brain regions moving from the back of your head toward the front, termed feedforward communication. The second goal is then accomplished by integrating those signals with neural activity in other brain regions and then passing a signal backwards through the same regions from front to back, which is called feedback. These “traveling waves” of brain activity could coordinate brain activity across different parts of the brain and integrate the two goals of the visual system.

Figure 1

Illustration of the hypothesized direction of the flow of brain activity for feedforward waves (yellow) and feedback waves (blue). Figure made with biorender.com.

Testing this hypothesis has been difficult, because it requires the ability to look at brain activity across large portions of the brain as it changes very quickly and the tools to do this were only recently developed. Until recently, several scientists had used what tools were available to study feedforward and feedback activity, but they could only look for small snapshots of evidence of feedforward and feedback waves. However, last year a team of researchers at the University of Pennsylvania led by Dr. Adeeti Aggarwal, a former PhD student in the Neuroscience Graduate Group, used new technology to visualize these waves of activity across the mouse brain for the first time.

To do this, Dr. Aggarwal and her team recorded brain activity across several areas of the mouse brain while they flashed a green light in front of the mouse’s eye. By using a special kind of analysis that allowed them to get a cleaner look at the data, they were able to see the two kinds of brain waves that the hypothesis predicted. The first feedforward wave fluctuated quickly and moved from the back to the front of the brain, while the second feedback wave fluctuated more slowly and moved from the front to the back of the brain. Importantly, the team found that both waves of activity spread equally far across the brain, despite the feedforward wave fluctuating faster than the feedback wave. Through this and other observations the team concluded that the two waves of brain activity interact and integrate to form a cohesive wave of brain activity that could be combining the information about what the mouse is seeing with other brain signals.

This was exciting evidence that the kinds of feedforward and feedback waves that neuroscientists thought could coordinate visual information are actually present in the brain, but how might they help a mouse to see?  Your brain cells, called neurons, communicate with each other by sending a kind of signal called an action potential, or spike. Whether and how a neuron produces spikes is what ultimately influences what you see and how you behave. To demonstrate that these waves of brain activity could shape these important brain signals, Dr. Aggarwal and her team looked at whether the waves of brain activity had an impact on whether and how neurons produced spikes.  They found that neurons were more likely to produce spikes at the peaks of the slow oscillation than at the lower points. This links the waves of brain activity that they observed directly to spikes, which suggests that these waves are capable of coordinating brain information about what the mouse is seeing with other kinds of signals.

Dr. Aggarwal and her team’s paper provides exciting new evidence for how different parts of the brain can be coordinated through waves of activity, and future work will continue to determine how these waves can be linked to behavior and whether they can be seen in human brains as well. Understanding how the brain coordinates activity across brain regions to turn sight into action could be helpful in many ways. For one, this information could help to engineer better visual prosthetics for people who are blind. If these waves are necessary to coordinate brain activity across parts of the brain, it may be necessary for visual prosthetics to produce signals that work in the same way. Beyond direct human applications, incorporating similar principles into the design of robotic systems that need to coordinate information about the world with a set of goals or actions could produce robots that can better interact with the world to accomplish their goals. As with all scientific advancements, Dr. Aggarwal’s study is one exciting piece in many bigger puzzles.

About the brief writer: Catrina Hacker

Catrina Hacker is a PhD candidate working in Dr. Nicole Rust’s Lab. She is broadly interested in the neural correlates of cognitive processes and is currently studying how we remember what we see. She also co-directs PennNeuroKnow.

Interested in learning more about Adeeti’s work? Check out the full paper here!

Shedding light on migraines: Signals from the eye make people with migraine more sensitive to light

or technically,

Selective amplification of ipRGC signals accounts for interictal photophobia in migraine

[See Original Abstract on Pubmed]

Authors of the study: Harrison McAdams, Eric A Kaiser, Aleksandra Igdalova, Edda B Haggerty, Brett Cucchiara, David H Brainard, Geoffrey K Aguirre

Have you ever stepped outside and had to squint or shield your eyes from the sun? Bright light can be uncomfortable for anyone, but it can be especially painful to those who experience migraines. While headaches are often associated with migraines, another common symptom is photophobia, or sensitivity to light. Harrison McAdams, a neuroscience student in Dr. Geoffrey Aguirre‘s lab at Penn, wanted to find out what part of the eye or brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. might be responsible for the symptom of photophobia in migraines.

In order to discover how photophobia might arise, we need to understand how our eyes allow us to see our surroundings. The first step in vision is when light hits the retina, a sheet of cells that covers the back of the eye. The retina is made of three layers of neuronsA nerve cell that uses electrical and chemical signals to send information to other cells including other neurons and muscles with specific functions. Some of these neuronsA nerve cell that uses electrical and chemical signals to send information to other cells including other neurons and muscles can detect light: these are the rods and cones, and they become excited by photons, the particles that make up light. Rods work in dim light, while cones work in bright light and can sense red, green, or blue light. This is how we’re able to see in color! Rods and cones talk to other neuronsA nerve cell that uses electrical and chemical signals to send information to other cells including other neurons and muscles in the retina like RGCs (retinal ganglion cells), which then send signals out of the eye and to many different areas of the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals..

Figure 1: Anatomy of the eye and retina (adapted from webvision.med.utah.edu)

Most RGCs just listen to the rods and cones that talk to them; however, there are special RGCs that are “intrinsically photosensitive” (ipRGCs), which means they can detect light just like rods and cones do. These ipRGCs actually don’t help you see images. Instead, they are responsible for your sense of a day/night cycle and for helping your pupils adjust to the light or dark. There is also evidence that ipRGCs connect to the thalamus, an area of the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. which can sense pain. Harrison thought this connection could explain why light can be especially painful to people with migraine.

60 people participated in this study: 40 experienced photophobia from migraines and 20 did not have migraines for comparison. Pulses of different colored light were flashed in one eye to either activate the cones, the ipRGCs, or both. They rated how painful each flash of light was on a scale from 0 to 10, 10 being the most painful. People with photophobia tended to rate the “cone” light as more painful compared to those without, and their rating increased as the light got brighter. Since we know that they’re sensitive to bright light and that cones work in bright light, this makes sense. Interestingly, they also gave higher pain ratings to light which only activated the ipRGCs.

From this test, Harrison knew that ipRGC activity could cause pain. After recording pupil size while the light was flashing, he found no difference in people with or without migraine. This means that not all ipRGC functions are affected: It’s a specific strengthening of the signal from the retina to the pain-sensing area of the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals..

Why would our eyes be wired like this? Just like touching a hot stove can damage your hand, staring at the sun or shining a flashlight in your eyes can damage your retinas. And once those neuronsA nerve cell that uses electrical and chemical signals to send information to other cells including other neurons and muscles are gone, they’re gone for good--so take care of them! Although this signal can be helpful, warning us that what we’re doing is harmful, it seems like when the signal becomes too strong, people can develop migraines. Identifying the root of the problem is the first step in developing treatments to help people who live with this condition.

About the brief writer: Sierra Foshe

Sierra is a PhD student in Josh Dunaief's lab. She is interested in the mechanisms of retinal inflammation and degeneration.

Want to learn more about the role of ipRGCs in photophobia? You can find Harrison’s full paper here!

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.

It’s all about balance. How a reduction in inhibitory signals in the developing brain could contribute to cognitive deficits in ASD.

or technically,

Exploring the relationship between cortical GABA concentrations, auditory gamma-band responses and development in ASD: Evidence for an altered maturational trajectory in ASD.

[See Original Abstract on Pubmed]

Authors of the study: Russell G. Port, William Gaetz, Luke Bloy, Dah-Jyuu Wang, Lisa Blaskey, Emily S. Kuschner, Susan E. Levy, Edward S. Brodkin, and Timothy P.L. Roberts

Autism spectrum disorder (ASD) is a developmental disorder characterized by difficulty with social communication and repetitive behaviors.¹ ASD persists for one’s entire life, with an estimated 1-2% of children currently diagnosed.¹ This is a twenty- to thirty-fold increase from the prevalence recorded in the late 1960s, when ASD was first characterized.¹ Experts believe that this sharp increase is mainly due to the fact that doctors and parents are more aware of ASD and what the symptoms look like.² Despite the fact that people who have ASD are born with the disorder, ASD is hard to diagnose in babies and is often unnoticed until the child begins falling short of social or academic benchmarks.¹ The ability to detect autism earlier in young children could make a big difference in how much doctors are able to do to improve the lives of those patients. Russ Port and his graduate advisor Timothy Roberts designed this study to learn more about what makes the brainsThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. of people with ASD different from those of people who do not have ASD. The results of this study show promise for improving our ability to detect ASD earlier than is currently possible.

Russ knew that researchers in the field believed that ASD may be related to differences in how cells in the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. communicate with one another. The brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. is made up of specialized cells called neuronsA nerve cell that uses electrical and chemical signals to send information to other cells including other neurons and muscles that can send information to one another via electrical and chemical signals. In order for the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. to function normally, it must maintain a very careful balance between so-called ‘excitatory’ and ‘inhibitory’ chemical signals. Excitatory signals cause information to move from one neuronA nerve cell that uses electrical and chemical signals to send information to other cells including other neurons and muscles to the next, while inhibitory signals stop information from moving on to the next neuronA nerve cell that uses electrical and chemical signals to send information to other cells including other neurons and muscles (think red/green lights in traffic signals). You need both kinds of signals to make sure that information ends up reaching its proper destination. The most important inhibitory chemical signal is called GABA. Scientists have found that people with ASD have less GABA in their brainsThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. than people who do not have ASD. This leads to an imbalance between those excitatory and inhibitory signals in these people.

The electrical signals made by neuronsA nerve cell that uses electrical and chemical signals to send information to other cells including other neurons and muscles sending information to one another can be measured from the scalp using electroencephalography. When a large group of neuronsA nerve cell that uses electrical and chemical signals to send information to other cells including other neurons and muscles is working together at the same time, they create waves of electrical signals called brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. waves. One kind of brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. wave, gamma-band brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. waves (Gamma) are relatively fast, compared to the others. To get a better sense of what that means, see figure 1 below. You have the most Gamma in your brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. when you are really alert: for example, during learning or sensory input (smell, taste, touch, etc.). The creation of Gamma is dependent upon proper levels of GABA during brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. development. Since GABA is so important for the creation of Gamma, it may not surprise you to learn that Gamma, like GABA, are also reduced in people with ASD.

Figure 1. Brain waves (waveforms adapted from www.themusiciansbrain.com)

Russ wanted to look at this relationship between GABA and Gamma in his patients with ASD. He confirmed that participants who had ASD had lower levels of both GABA and Gamma than participants who did not have ASD. Interestingly, he also noticed that, in participants without ASD, those with more GABA also had more Gamma, and those with less GABA had less Gamma. In participants with ASD, no such relationship existed.

Excited about this unexpected result, Russ wondered why this relationship between levels of GABA and Gamma was absent in participants with ASD. He thought that it might have something to do with the way the brainsThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. of people with ASD develop. Therefore, in the next part of the study, he decided to study young people and adults separately. He hypothesized that he would find age-related differences in the relationship between Gamma and GABA that would shed more light on the developmental differences between people with and without ASD. In this part of the study, he found that there was no difference in the levels of Gamma between young people with and without ASD. However, the young people with ASD had lower levels of GABA than those without ASD. We know that GABA is important for the development of Gamma in the brainsThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. of young people. We also know that adults with ASD do have lower levels of Gamma than adults without ASD. The finding that there is a lower level of GABA in young people with ASD but not a lower level of Gamma is an important finding because it suggests that something happens during brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. development that causes levels of Gamma in adults with ASD to be lower than what is seen in adults without ASD.

Russ also found that, in young people without ASD, the older a participant was, the more GABA and Gamma they had. This relationship was not present in young people with ASD. In this group, there was no correlation between levels of GABA or Gamma and age. So, in young people with ASD, there isn’t the same increase in both GABA and Gamma as the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. develops that is seen in young people without ASD. Furthermore, Russ found that there was no relationship between levels of GABA and Gamma with age in either adult group. This suggests that once the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. is finished developing, the levels of GABA and Gamma stop increasing. With low GABA to begin with, young people with ASD are not able to create enough Gamma to match the levels of people without ASD before the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. stops developing. These lower levels of Gamma become permanent in adulthood.

Broadly speaking, these data are a great case study for the importance of balance between inhibitory and excitatory signals in the developing brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals.. Specifically, Russ’s work highlights the importance of the inhibitory signal GABA during early brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. development. This work also suggests that monitoring the levels of GABA and Gamma in young children could be used as a possible screening tool to detect ASD earlier. Earlier detection could help doctors develop more effective interventions or strategies for children with ASD and their families.

About the brief writer: Brenna Shortal

Brenna is a third year student in Alex Proekt’s lab. She is studying the similarities and differences between sleep and anesthesia with the goal of understanding how we wake up.

Citations:

1. Autism and Developmental Disabilities Monitoring Network Surveillance Year 2010 Principal Investigators. “Prevalence of Autism Spectrum Disorder Among Children Aged 8 Years — Autism and Developmental Disabilities Monitoring Network, 11 Sites, United States, 2010.” Morbidity and Mortality Weekly Report: Surveillance Summaries, vol. 63, no. 2, 2014, pp. 1–21. 

2. Stephen J. Blumberg, Matthew D. Bramlett, Michael D. Kogan, Laura A. Schieve, Jessica R. Jones, Michael C. Lu. “Changes in Prevalence of Parent-Reported Autism Spectrum Disorder in School-Aged U.S. Children: 2007 to 2011-2012. National Center for Health Statistics Reports.” National Center for Health Statistics, number 65, 2013.

Do you want to learn more about ASD and development? You can read Russ’s whole 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.