Posts tagged sensory cells
Articles and news from the latest research reports.
Sensing Gravity with Acid: Scientists Discover a Role for Protons in Neurotransmission
While probing how organisms sense gravity and acceleration, scientists at the Marine Biological Laboratory (MBL) and the University of Utah uncovered evidence that acid (proton concentration) plays a key role in communication between neurons. The surprising discovery is reported this week in Proceedings of the National Academy of Sciences.
The team, led by the late MBL senior scientist Stephen M. Highstein, discovered that sensory cells in the inner ear continuously transmit information on orientation of the head relative to gravity and low-frequency motion to the brain using protons as the key synaptic signaling molecule. (The synapse is the structure that allows one neuron to communicate with another by passing a chemical or electrical signal between them.)
“This addresses how we sense gravity and other low-frequency inertial stimuli, like acceleration of an automobile or roll of an airplane,” says co-author Richard Rabbitt, a professor at University of Utah and adjunct faculty member in the MBL’s Program in Sensory Physiology and Behavior. “These are very long-lasting signals requiring a a synapse that does not fatigue or lose sensitivity over time. Use of protons to acidify the space between cells and transmit information from one cell to another could explain how the inner ear is able to sense tonic signals, such as gravity, in a robust and energy efficient way.”
The team found that this novel mode of neurotransmission between the sensory cells (type 1 vestibular hair cells) and their target afferent neurons (calyx nerve terminals), which send signals to the brain, is continuous or nonquantal. This nonquantal transmission is unusual and, for low-frequency stimuli like gravity, is more energy efficient than traditional synapses in which chemical neurotransmitters are packaged in vesicles and released quantally.
The calyx nerve terminal has a ball-in-socket shape that envelopes the sensory hair cell and helps to capture protons exiting the cell. “The inner-ear vestibular system is the only place where this particular type of synapse is present,” Rabbitt says. “But the fact that protons are playing a key role here suggests they are likely to act as important signaling molecules in other synapses as well.”
Previously, Erik Jorgensen of University of Utah (who recently received a Lillie Research Innovation Award from the MBL and the University of Chicago) and colleagues discovered that protons act as signaling molecules between muscle cells in the worm C. elegans and play an important role in muscle contraction. The present paper is the first to demonstrate that protons also act directly as a nonquantal chemical neurotransmitter in concert with classical neurotransmission mechanisms. The discovery suggests that similar intercellular proton signaling mechanisms might be at play in the central nervous system.
A team of NIH-supported researchers is the first to show, in mice, an unexpected two-step process that happens during the growth and regeneration of inner ear tip links. Tip links are extracellular tethers that link stereocilia, the tiny sensory projections on inner ear hair cells that convert sound into electrical signals, and play a key role in hearing. The discovery offers a possible mechanism for potential interventions that could preserve hearing in people whose hearing loss is caused by genetic disorders related to tip link dysfunction. The work was supported by the National Institute on Deafness and Other Communication Disorders (NIDCD), a component of the National Institutes of Health.
The findings appear in the June 11, 2013 online edition of PLoS
Biology. The senior author of this study is Gregory I. Frolenkov, an associate professor in the College of Medicine at the University of Kentucky, Lexington, and his fellow, Artur A. Indzhykulian, Ph.D., is the lead author.
Stereocilia are bundles of bristly projections that extend from the tops of sensory cells, called hair cells, in the inner ear. Each stereocilia bundle is arranged in three neat rows that rise from lowest to highest like stair steps. Tip links are tiny thread-like strands that link the tip of a shorter stereocilium to the side of the taller one behind it. When sound vibrations enter the inner ear, the stereocilia, connected by the tip links, all lean to the same side and open special channels, called mechanotransduction channels. These pore-like openings allow potassium and calcium ions to enter the hair cell and kick off an electrical signal that eventually travels to the brain, where it is interpreted as sound.
The findings build on a number of recent discoveries in laboratories at the NIDCD and elsewhere that have carefully plotted the structure and function of tip links and the proteins that comprise them. Earlier studies had shown that tip links are made up of two proteins—cadherin-23 (CDH23) and protocadherin-15 (PCDH15)—that join to make the link, with PCDH15 at the bottom of the tip link at the site of the mechanotransduction channel, and CDH23 on the upper end. Scientists assumed that the assembly was static and stable once the two proteins bonded.
Tip links break easily with exposure to noise. But unlike hair cells, which can’t regenerate in humans, tip links repair themselves, mostly within a matter of hours. The breaking of tip links, and their regeneration, has been known for many years, and is seen as one of the causes of the temporary hearing loss you might experience after a loud blast of sound (or a loud concert). Once the tip links regenerate, hair cell function returns, usually to normal levels. What scientists didn’t know was how the tip link reassembled.
To study tip link assembly, the researchers treated young, postnatal (5-7 days) mouse sensory hair cells with BAPTA—a substance that, like loud noise, damages and disrupts tip links. To image the proteins, the group pioneered an improved scanning electron microscopy (SEM) technique of immunogold labeling that uses antibodies bound to gold particles that attach to the proteins. Then, using SEM, they imaged the cells at high resolution to determine the positions of the proteins before, during, and after BAPTA treatment.
What the researchers found was that after a tip link is chemically disrupted, a new tip link forms, but instead of the normal combination of CDH23 and PCDH15, the link is made up of PCDH15 proteins at both ends. Over the next 24 hours, the PCDH15 protein at the upper end is replaced by CDH23 and the tip link is back to normal.
Why tip links regenerate using a two-step instead of a neat one-step process is not known. For reasons that are still unclear, CDH23 disappears from stereocilia after noise damage while PDCH15 stays around. Looking to regenerate quickly, the lower PDCH15 latches onto another PDCH15, forming a shorter and functionally slightly weaker tip link. Later, at some time during the 36 hours after the damage, when CDH23 returns, PDCH15 gives up its provisional partner and latches onto its much stronger mate in CDH23. In other words, PDCH15 prefers to be with CDH23, but in a pinch it will bond weakly with another bit of PDCH15 until CDH23 shows up.
The researchers coupled the SEM observations with electrophysiology studies to show how the functional properties of the tip links changed throughout this two-step process. The temporary PCDH15/PCDH15 tip link has a slightly different functional response than the permanent PDCH15/CDH23 combination. Researchers were able to correlate the differences in function with the protein combinations that make up the tip link.
Additional experiments revealed that when hair cells develop, the tip links use the same two-step process.
Previous research has shown that both CDH23 and PCDH15 are required for normal hearing and vision. In fact, NIDCD scientists in earlier studies have shown that mutations in either of these genes can cause the hearing loss or deaf-blindness found in Usher Syndrome types 1D and 1F.
“In the case of deaf individuals who are unable to make functional CDH23, knowledge of this new temporary alliance of PCDH15 proteins to form a weaker, but still functional, tip link could inform treatments that would encourage the double PCDH15 bond to become permanent and maintain at least limited hearing,” said Tom Friedman, Ph.D., chief of the Laboratory of Molecular Genetics at the NIDCD, where the research began.
When our noses pick up a scent, whether the aroma of a sweet rose or the sweat of a stranger at the gym, two types of sensory neurons are at work in sensing that odor or pheromone. These sensory neurons are particularly interesting because they are the only neurons in our bodies that regenerate throughout adult life—as some of our olfactory neurons die, they are soon replaced by newborns. Just where those neurons come from in the first place has long perplexed developmental biologists.
Previous hypotheses about the origin of these olfactory nerve cells have given credit to embryonic cells that develop into skin or the central nervous system, where ear and eye sensory neurons, respectively, are thought to originate. But biologists at the California Institute of Technology (Caltech) have now found that neural-crest stem cells—multipotent, migratory cells unique to vertebrates that give rise to many structures in the body such as facial bones and smooth muscle—also play a key role in building olfactory sensory neurons in the nose.
"Olfactory neurons have long been thought to be solely derived from a thickened portion of the ectoderm; our results directly refute that concept," says Marianne Bronner, the Albert Billings Ruddock Professor of Biology at Caltech and corresponding author of a paper published in the journal eLIFE on March 19 that outlines the findings.
The two main types of sensory neurons in the olfactory system are ciliated neurons, which detect volatile scents, and microvillous neurons, which usually sense pheromones. Both of these types are found in the tissue lining the inside of the nasal cavity and transmit sensory information to the central nervous system for processing.
In the new study, the researchers showed that during embryonic development, neural-crest stem cells differentiate into the microvillous neurons, which had long been assumed to arise from the same source as the odor-sensing ciliated neurons. Moreover, they demonstrated that different factors are necessary for the development of these two types of neurons. By eliminating a gene called Sox10, they were able to show that formation of microvillous neurons is blocked whereas ciliated neurons are unaffected.
They made this discovery by studying the development of the olfactory system in zebrafish—a useful model organism for developmental biology studies due to the optical clarity of the free-swimming embryo. Understanding the origins of olfactory neurons and the process of neuron formation is important for developing therapeutic applications for conditions like anosmia, or the inability to smell, says Bronner.
"A key question in developmental biology—the extent of neural-crest stem cell contribution to the olfactory system—has been addressed in our paper by multiple lines of experimentation," says Ankur Saxena, a postdoctoral scholar in Bronner’s laboratory and lead author of the study. "Olfactory neurons are unique in their renewal capacity across species, so by learning how they form, we may gain insights into how neurons in general can be induced to differentiate or regenerate. That knowledge, in turn, may provide new avenues for pursuing treatment of neurological disorders or injury in humans."
Next, the researchers will examine what other genes, in addition to Sox10, play a role in the process by which neural-crest stem cells differentiate into microvillous neurons. They also plan to look at whether or not neural-crest cells give rise to new microvillous neurons during olfactory regeneration that happens after the embryonic stage of development.
Monell scientists identify elusive taste stem cells
Scientists at the Monell Center have identified the location and certain genetic characteristics of taste stem cells on the tongue. The findings will facilitate techniques to grow and manipulate new functional taste cells for both clinical and research purposes.
"Cancer patients who have taste loss following radiation to the head and neck and elderly individuals with diminished taste function are just two populations who could benefit from the ability to activate adult taste stem cells," said Robert Margolskee, M.D., Ph.D., a molecular neurobiologist at Monell who is one of the study’s authors.
Taste cells are located in clusters called taste buds, which in turn are found in papillae, the raised bumps visible on the tongue’s surface.
Two types of taste cells contain chemical receptors that initiate perception of sweet, bitter, umami, salty, and sour taste qualities. A third type appears to serve as a supporting cell.
A remarkable characteristic of these sensory cells is that they regularly regenerate. All three taste cell types undergo frequent turnover, with an average lifespan of 10-16 days. As such, new taste cells must constantly be regenerated to replace cells that have died.
For decades, taste scientists have attempted to identify the stem or progenitor cells that spawn the different taste receptor cells. The elusive challenge also sought to establish whether one or several progenitors are involved and where they are located, whether in or near the taste bud.
Drawing on the strong physiological relationship between oral taste cells and endocrine (hormone producing) cells in the intestine, the Monell team used a marker for intestinal stem cells to probe for stem cells in taste tissue on the tongue.
Stains for the stem cell marker, known as Lgr5 (leucine-rich repeat-containing G-protein-coupled receptor 5), showed two patterns of expression in taste tissue. The first was a strong signal underlying taste papillae at the back of the tongue and the second was a weaker signal immediately underneath taste buds in those papillae.
The Monell scientists hypothesize that the two levels of expression could indicate two different populations of cells. The cells that more strongly express Lgr5 could be true taste stem cells, whereas those with weaker expression could represent those stem cells that have begun the transformation into functional taste cells.
Additional studies revealed that the Lgr5-expressing cells were capable of becoming any one of the three major taste cell types.
The findings are published online in the journal Stem Cells.
"This is just the tip of the iceberg," said senior author Peihua Jiang, Ph.D., also a Monell molecular neurobiologist. "Identification of these cells opens up a whole new area for studying taste cell renewal, and contributes to stem cell biology in general."
Future studies will focus on identifying the factors that program the Lgr5-expressing cells to differentiate into the different taste cell types, and explore how to grow these cells in culture, thus providing a renewable source of taste receptor cells for research and perhaps even clinical use.
(Image: Getty)
Super-sensory hearing?
The discovery of a previously unidentified hearing organ in the South American bushcrickets’ ear could pave the way for technological advancements in bio-inspired acoustic sensors research, including medical imaging and hearing aid development.
Researchers from the University of Bristol and University of Lincoln discovered the missing piece of the jigsaw in the understanding of the process of energy transformation in the ‘unconventional’ ears of the bushcrickets (or katydids).
Bushcrickets have four tympana (or ear drums) – two on each foreleg; but until now it has been unknown how the various organs connect in order for the insect to hear. As the tympana (a membrane which vibrates in reaction to sound) does not directly connect with the mechanoreceptors (sensory receptors), it was a mystery how sound was transmitted from air to the mechano-sensory cells.
Sponsored by the Human Frontiers Science Program (HFSP), the research was developed in the lab of Professor Daniel Robert, a Royal Society Fellow at the University of Bristol. Dr Fernando Montealegre-Z, who is now at the University of Lincoln’s School of Life Sciences, discovered a newly identified organ while carrying out research into how the bushcricket tubing system in the ear transports sound. The research focussed on the bushcricket Copiphora gorgonensis, a neotropical species from the National Park Gorgona in Colombia, an island in the Pacific. Results suggest that the bushcricket ear operates in a manner analogous to that of mammals. A paper detailing this remarkable new breakthrough is published in the journal, Science.