Breaking News
May 3, 2019 - Vaping and Smoking May Signal Greater Motivation to Quit
May 3, 2019 - Dementia looks different in brains of Hispanics
May 3, 2019 - Short-Staffed Nursing Homes See Drop In Medicare Ratings
May 3, 2019 - Study of teens with eating disorders explores how substance users differ from non-substance users
May 3, 2019 - Scientists develop new video game that may help in the study of Alzheimer’s
May 3, 2019 - Arc Bio introduces Galileo Pathogen Solution product line at ASM Clinical Virology Symposium
May 3, 2019 - Cornell University study uncovers relationship between starch digestion gene and gut bacteria
May 3, 2019 - How to Safely Use Glucose Meters and Test Strips for Diabetes
May 3, 2019 - Anti-inflammatory drugs ineffective for prevention of Alzheimer’s disease
May 3, 2019 - Study tracks Pennsylvania’s oil and gas waste-disposal practices
May 3, 2019 - Creating a better radiation diagnostic test for astronauts
May 3, 2019 - Vegans are often deficient in these four nutrients
May 3, 2019 - PPDC announces seed grants to develop medical devices for children
May 3, 2019 - Study maps out the frequency and impact of water polo head injuries
May 3, 2019 - Research on Reddit identifies risks associated with unproven treatments for opioid addiction
May 3, 2019 - Good smells may help ease tobacco cravings
May 3, 2019 - Medical financial hardship found to be very common among people in the United States
May 3, 2019 - Researchers develop multimodal system for personalized post-stroke rehabilitation
May 3, 2019 - Study shows significant mortality benefit with CABG over percutaneous coronary intervention
May 3, 2019 - Will gene-editing of human embryos ever be justifiable?
May 3, 2019 - FDA Approves Dengvaxia (dengue vaccine) for the Prevention of Dengue Disease in Endemic Regions
May 3, 2019 - Why Tonsillitis Keeps Coming Back
May 3, 2019 - Fighting the opioid epidemic with data
May 3, 2019 - Maggot sausages may soon be a reality
May 3, 2019 - Deletion of ATDC gene prevents development of pancreatic cancer in mice
May 2, 2019 - Targeted Therapy Promising for Rare Hematologic Cancer
May 2, 2019 - Alzheimer’s disease is a ‘double-prion disorder,’ study shows
May 2, 2019 - Reservoir bugs: How one bacterial menace makes its home in the human stomach
May 2, 2019 - Clinical, Admin Staff From Cardiology Get Sneak Peek at Epic
May 2, 2019 - Depression increases hospital use and mortality in children
May 2, 2019 - Vicon and NOC support CURE International to create first gait lab in Ethiopia
May 2, 2019 - Researchers use 3D printer to make paper organs
May 2, 2019 - Viral infection in utero associated with behavioral abnormalities in offspring
May 2, 2019 - U.S. Teen Opioid Deaths Soaring
May 2, 2019 - Opioid distribution data should be public
May 2, 2019 - In the Spotlight: “I’m learning every single day”
May 2, 2019 - 2019 Schaefer Scholars Announced
May 2, 2019 - Podcast: KHN’s ‘What The Health?’ Bye-Bye, ACA, And Hello ‘Medicare-For-All’?
May 2, 2019 - Study describes new viral molecular evasion mechanism used by cytomegalovirus
May 2, 2019 - SLU study suggests a more equitable way for Medicare reimbursement
May 2, 2019 - Scientists discover first gene involved in lower urinary tract obstruction
May 2, 2019 - Researchers identify 34 genes associated with increased risk of ovarian cancer
May 2, 2019 - Many low-income infants receive formula in the first few days of life, finds study
May 2, 2019 - Global study finds high success rate for hip and knee replacements
May 2, 2019 - Taking depression seriously: What is it?
May 2, 2019 - With Head Injuries Mounting, Will Cities Put Their Feet Down On E-Scooters?
May 2, 2019 - Scientists develop small fluorophores for tracking metabolites in living cells
May 2, 2019 - Study casts new light into how mothers’ and babies’ genes influence birth weight
May 2, 2019 - Researchers uncover new brain mechanisms regulating body weight
May 2, 2019 - Organ-on-chip systems offered to Asia-Pacific regions by Sydney’s AXT
May 2, 2019 - Adoption of new rules drops readmission penalties against safety net hospitals
May 2, 2019 - Kids and teens who consume zero-calorie sweetened beverages do not save calories
May 2, 2019 - Improved procedure for cancer-related erectile dysfunction
May 2, 2019 - Hormone may improve social behavior in autism
May 2, 2019 - Alzheimer’s disease may be caused by infectious proteins called prions
May 2, 2019 - Even Doctors Can’t Navigate Our ‘Broken Health Care System’
May 2, 2019 - Study looks at the impact on criminal persistence of head injuries
May 2, 2019 - Honey ‘as high in sugars as table sugar’
May 2, 2019 - Innovations to U.S. food system could help consumers in choosing healthy foods
May 2, 2019 - FDA Approves Mavyret (glecaprevir and pibrentasvir) as First Treatment for All Genotypes of Hepatitis C in Pediatric Patients
May 2, 2019 - Women underreport prevalence and intensity of their own snoring
May 2, 2019 - Concussion summit focuses on science behind brain injury
May 2, 2019 - Booker’s Argument For Environmental Justice Stays Within The Lines
May 2, 2019 - Cornell research explains increased metastatic cancer risk in diabetics
May 2, 2019 - Mount Sinai study provides fresh insights into cellular pathways that cause cancer
May 2, 2019 - Researchers to study link between prenatal pesticide exposures and childhood ADHD
May 2, 2019 - CoGEN Congress 2019: Speakers’ overviews
May 2, 2019 - A new strategy for managing diabetic macular edema in people with good vision
May 2, 2019 - Sagent Pharmaceuticals Issues Voluntary Nationwide Recall of Ketorolac Tromethamine Injection, USP, 60mg/2mL (30mg per mL) Due to Lack of Sterility Assurance
May 2, 2019 - Screen time associated with behavioral problems in preschoolers
May 2, 2019 - Hormone reduces social impairment in kids with autism | News Center
May 2, 2019 - Researchers synthesize peroxidase-mimicking nanozyme with low cost and superior catalytic activity
May 2, 2019 - Study results of a potential drug to treat Type 2 diabetes in children announced
May 2, 2019 - Multigene test helps doctors to make effective treatment decisions for breast cancer patients
May 2, 2019 - UNC School of Medicine initiative providing unique care to dementia patients
May 2, 2019 - Nestlé Health Science and VHP join forces to launch innovative COPES program for cancer patients
May 2, 2019 - Study examines how our brain generates consciousness and loses it during anesthesia
May 2, 2019 - Transition Support Program May Aid Young Adults With Type 1 Diabetes
May 2, 2019 - Study shows how neutrophils exacerbate atherosclerosis by inducing smooth muscle-cell death
May 2, 2019 - Research reveals complexity of how we make decisions
Researchers create new light-activated tools for controlling neurons

Researchers create new light-activated tools for controlling neurons

By enabling super-fast remote control of specific cells, light-activated proteins allow researchers to study the function of individual neurons within a large network – even an entire brain. Now one of the pioneers of ‘optogenetics’ and colleagues have created two new tools – protein pores which when illuminated allow Ca2+ into cells or K+ out – for switching neurons on or off using light. Published in Frontiers in Neuroscience, their study shows that these synthetic ‘ion channels’ can be used to control specific neurons, even in live animals.

Controlling neurons with light

Georg Nagel’s research group at the University of Würzburg combines DNA from across the kingdoms of life – from aquatic heat-loving bacteria to cows – to create hybrid ion channels that open when animated by light. Ion channels enable excitable cells like neurons to generate and transport electrical signals, by allowing charged ions to pass in and out through the cell surface.

“By engineering specific neurons to express these channels, we can switch them on and off using light,” explains Nagel.

Optogenetics was first born when Nagel and longtime collaborator Peter Hegemann isolated from green algae two light-activated channels called ‘channelrhodopsins’. These allow positively-charged ions – particularly Na+ – to enter and excite neurons.

Following the success of channelrhodopsins, another natural optogenetic ion channel ‘halorhodopsin’ was developed for use as a neuron silencer. When illuminated, halorhodopsin inhibits neuronal signals with light-induced inflow of negatively charged Cl- ions.

With huge demand for still more optogenetic tools, Nagel and others now use gene editing techniques to create synthetic light-activated channels with new properties.

“Channelrhodopsins have low Ca2+ permeability, and Cl- channels like halorhodopsin can actually excite cells that have a high Cl- content. Despite a growing number of synthetic alternatives, highly-permeable light-sensitive channels that selectively allow Ca2+ into cells – or inhibit them by letting K+ out – remain high on many wish lists.”

Engineering new control switches

To construct new light-activated tools for Na+/Ca2+ and K+ movement in and out of cells, the group took two existing ion channels activated by a universal cell messenger molecule called ‘cAMP’ and fused each with a bacterial enzyme that produces cAMP in response to light.

“We tried fusing the DNA segments in different ways, to find the configuration with the highest light-activated ion permeability,” says senior study author and Nagel protégé Dr Shiqiang Gao.

The results were a highly Ca2+-permeable channel, and a highly permeable K+-selective channel, each activated by blue light.

With collaborators Dr Dennis Pauls from the University of Würzburg, Professor Robert Kittel and Dr Nadine Ehmann from Leipzig University, the Nagel group set about testing these newly created channels in Drosophila (fruit fly) neurons and with Dr Christine Gee and PhD student Oana Constantin from the ZMNH Hamburg in rat neurons.

“These new channels when illuminated activated or inhibited isolated rat neurons, respectively” reports Dr. Gee, “and caused body contraction or relaxation when expressed in motor neurons in whole fruit fly larvae,” adds Dr Pauls.

Worthy additions to the optogenetic toolkit

The authors highlight the potential drawbacks of using cAMP to mediate light-responsiveness in these channels.

“cAMP itself is an important messenger in many cell processes, so controls expressing only the bacterial cAMP-producing enzyme are needed to discriminate between the effects of light-induced cAMP, Ca2+ and K+.

“Furthermore, cAMP produced by other enzymes native to the cell could directly activate the channels. This likely explains why the fruit fly larvae engineered to express the new channels are smaller, move slightly slower, and fail to mature into adult flies.

Gao and Nagel are nonetheless confident that their latest contributions are a valuable addition to the optogenetic toolkit, worthy of further characterization and development.

“In summary, we have generated new and efficient tools for optogenetic manipulation of Ca2+ or K+ permeability, which open new possibilities for probing the function of complex neuronal systems. These could be applied in adult flies – and perhaps eventually, mammals – by developing mutant channels with lower cAMP sensitivity, better localization to sites in neurons that send and receive electrical signals, and inducible expression – with genes switched on by temperature changes, for example.”

Source:

https://www.frontiersin.org/

Tagged with:

About author

Related Articles