An itch we can't scratch ... yet

or technically,

TRPC3 Is Dispensable for β-Alanine Triggered Acute Itch.

[See Original Abstract on Pubmed]

Authors of the study: Peter Dong, Changxiong Guo, Shengxiang Huang, Minghong Ma, Qin Liu & Wenqin Luo

You’re sitting peacefully on your couch and all of a sudden your nose itches. Annoying, right? Why does this happen? More importantly, how can our bodies sense this itch in the first place? This “itch” sensation, also known as pruritoception, has evolved in humans and other animals as an important alarm system for possible threats. These include anything from small microbes to poisons/toxins that can come from plants, food, and even some medications. Although we know that this sensation exists, neuroscientists don’t know much about how the cells in our brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. (neuronsA nerve cell that uses electrical and chemical signals to send information to other cells including other neurons and muscles) sense itch in the first place.

The skin is the largest organ of the human body, and within it lie many different sensors for detecting stimuli from the outside world. One class of these sensors - called nociceptors - send information to the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. about pain, temperature, and, you guessed it, itch. One important nociceptor for itch is called the “Mas-related G-proteinAn essential molecule found in all cells. DNA contains the recipes the cell uses to make proteins. Examples of proteins include receptors, enzymes, and antibodies. coupled receptorReceives an input some stimulus and transmits a the information to other cells or neurons. member D” (yikes!), we’ll call that the MRGPRD receptorReceives an input some stimulus and transmits a the information to other cells or neurons. from now on. The reason it’s important for itch is because it detects the itch-inducing chemical, 𝛽-alanine. MRGPRD is broadly expressed, which just means scientists find a lot of this receptorReceives an input some stimulus and transmits a the information to other cells or neurons. in certain parts of the spinal cord. The spinal cord is an organ that is really important for touch and itch because it allows the body to communicate with the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals.. However, in order for information from organs such as the skin to reach the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals., it needs specific “decoder 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 will convert this initial information at the level of the spinal cord into a format the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. will understand. You can think of these decoder 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. as being analogous to Google Translate. If you’re visiting a foreign country and need to translate a word you’ve read, you can use your Google Translate app to translate it into English, a language you understand. However, scientists don’t really know which 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. are functioning as decoders to convert the information the MRGPRD detects to the kind of information that the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. can understand. Peter Dong, a neuroscience graduate student working with Dr. Wenqin Luo at UPenn, set out to try to address this question in his research.

One family of “decoder 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 have been shown to play a role in the detection of many senses such as temperature, pressure, and pain is known as the “transient receptorReceives an input some stimulus and transmits a the information to other cells or neurons. potential” (TRP, pronounced “trip”) family. However, the exact role of TRP 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. in decoding itch sensations remains uncertain. Peter chose to test one proteinAn essential molecule found in all cells. DNA contains the recipes the cell uses to make proteins. Examples of proteins include receptors, enzymes, and antibodies. in this family, called TRPC3, to determine whether or not it was the “translator” of information being detected by MRGPRD. Why TRPC3? Well, TRPC3 has been shown to respond to touch sensation, and in Peter’s study, the data showed that TRPC3 is present in the same neuronsA nerve cell that uses electrical and chemical signals to send information to other cells including other neurons and muscles that contain MRGPRD. The next question Peter wanted to ask was whether MRGPRD-containing cells needed TRPC3 in the spinal cord in order to properly translate their messages for the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals.. So he studied a mouse that did not have any TRPC3 proteinAn essential molecule found in all cells. DNA contains the recipes the cell uses to make proteins. Examples of proteins include receptors, enzymes, and antibodies. anywhere in its body, including the spinal cord. We’ll call this the TRPC3 “knockout” mouse. Peter found that even in mice without TRPC3, MRGPRD was still present. This suggests that TRPC3 is not needed for normal MRGPRD presence and functioning.

So what does this mean? Is TRPC3 the proteinAn essential molecule found in all cells. DNA contains the recipes the cell uses to make proteins. Examples of proteins include receptors, enzymes, and antibodies. converting itch signals from MRGPRD to the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. or not? Peter and his colleagues addressed this question by doing behavioral studies on their TRPC3 knockout mice. They injected 𝛽-alanine (the itch-inducing chemical) into the back or cheek of mice lacking TRPC3 proteinAn essential molecule found in all cells. DNA contains the recipes the cell uses to make proteins. Examples of proteins include receptors, enzymes, and antibodies., and then measured how much they scratched to test if TRPC3 is required for itch sensation. They found that normal mice and TRPC3 knockout mice both still scratched a lot. This suggests that TRPC3 alone is not needed for itch, because the mice lacking TRPC3 were still very itchy.

Though Peter wanted to scratch his itch of knowing which proteinAn essential molecule found in all cells. DNA contains the recipes the cell uses to make proteins. Examples of proteins include receptors, enzymes, and antibodies. translates sensory information from MRGPRD to the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals., TRPC3 is not it. Although he was a little disappointed, this is actually a really good thing to know! This finding will give insight to researchers that can try to study other types of 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. in the TRP family as well as additional groups of proteinAn essential molecule found in all cells. DNA contains the recipes the cell uses to make proteins. Examples of proteins include receptors, enzymes, and antibodies. families! This research not only helps us understand why and how humans evolved to detect itch, but it also provides a stepping stone for the development of treatments for patients who suffer chronic itch as a symptom of diseases such as multiple sclerosis, neuropathy or shingles. Currently there are no good medications to relieve chronic itch, therefore, knowing more about how we detect itch at a molecular level will help scientists develop medications to improve the quality of life of these patients.

About the brief writer: Solymar Rolon

Solymar is a PhD Candidate in Maria Geffen’s lab. She is studying the role of amygdala-thalamic projections in auditory behavior.

Want to learn more about what TRPC3 does in itch modulation? Check out Peter’s full 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.