Breaking News
February 21, 2018 - Researchers discover brain pathway that dissociates opioid addiction from analgesia
February 21, 2018 - Scientists uncover how newly discovered gene helps grow blood vessels
February 21, 2018 - Brain’s quality control process holds clues to obesity’s roots
February 21, 2018 - Researchers to study whether menstrual cups can help prevent vaginal infections
February 21, 2018 - MS patients who feel stigmatized more likely to suffer from depression
February 21, 2018 - Vitamin D supplementation during pregnancy could protect against childhood obesity
February 21, 2018 - Lower-Quality Medical Tx Might Have Skewed Key PCI vs CABG Trials
February 21, 2018 - Love and fear are visible across the brain instead of being restricted to any brain region
February 21, 2018 - Adults with congenital heart disease have increased risk for dementia, study finds
February 21, 2018 - Clinical trial studying type 1 diabetes reaches full enrollment
February 21, 2018 - Father’s stress affects the brain development of offspring, mice study shows
February 21, 2018 - ESRD Death Declines in Vasculitis Patients
February 21, 2018 - Taking ibuprofen for long periods found to alter human testicular physiology
February 21, 2018 - Google AI device could predict a person’s risk of a heart attack
February 20, 2018 - FDA Approves Domestic Source for Tc-99m Isotopes
February 20, 2018 - Sanofi rejects refund demand faces Philippine suit over dengue vaccine (Update)
February 20, 2018 - Researchers discover that activation of specific enzyme may help suppress tumor metastasis
February 20, 2018 - Blood or marrow transplantation survivors have higher risk of cognitive impairment
February 20, 2018 - Booze Beats Pot at Being Unhealthy: Oregon Poll
February 20, 2018 - Morning Break: ’20 Years Late’; Drugs in the Dirt; Catching Flu in the Dorm
February 20, 2018 - Another piece to the puzzle in naked mole rats’ long, cancer-free life
February 20, 2018 - Scientists identify four viruses that can produce insulin-like hormones
February 20, 2018 - New e-Health solution developed to prevent cardiovascular disease, dementia in senior citizens
February 20, 2018 - New genetic risk score could help guide screening decisions for prostate cancer
February 20, 2018 - Study finds higher risk of stroke among blacks with atrial fibrillation than whites
February 20, 2018 - Physical activity could be used as strategy for diabetes prevention
February 20, 2018 - Researchers develop sensing method for early detection of cancer and diabetes
February 20, 2018 - New wearable electronics could be game-changer for stroke rehabilitation
February 20, 2018 - Immune history influences person’s response to flu vaccine
February 20, 2018 - Research findings could help develop new drugs to prevent, treat dry eye disease
February 20, 2018 - Serenity Now! Learn to Have Patience with Patients
February 20, 2018 - Computer simulation addresses the problem of blood clotting
February 20, 2018 - Women with type 1 diabetes not protected against coronary artery disease
February 20, 2018 - Persistent bloating can be a sign of ovarian cancer, warns charity
February 20, 2018 - Trump administration proposes rule to loosen curbs on short-term health plans
February 20, 2018 - Key protein involved in epigenetic regulation of gene expression guides skin cell renewal
February 20, 2018 - Heart attack symptoms often missed in women
February 20, 2018 - Diagnosis of celiac disease takes 3.5 years for patients who do not report GI symptoms
February 20, 2018 - Study reveals functional dynamics of ion channels
February 20, 2018 - Study explores link between mortality risk and combustible tobacco use
February 20, 2018 - ‘She Trusted Me, and I’d Turned Her Away’
February 20, 2018 - AbbVie and Voyager Therapeutics collaborate to develop new treatments for tauopathies
February 20, 2018 - Fast food makes the immune system more aggressive in the long term
February 20, 2018 - Therapeutic target for glaucoma could have treatment ramifications for Alzheimer’s and Parkinson’s
February 20, 2018 - Overcoming Negative Reviews | Medpage Today
February 20, 2018 - MyD88—villain of allergies and asthma
February 20, 2018 - Food scientists develop rapid screening technique to detect pesticide residue in vegetables
February 20, 2018 - Lab-grown cerebellar cells may help explain how ASD develops at molecular level
February 20, 2018 - Scientists explore connection between bad sleep habits and stiff blood vessels
February 20, 2018 - New Treatment Apalutamide (Erleada) Approved for Prostate Cancer That Resists Hormone Therapy
February 20, 2018 - Do You Really Need My Signature on That?
February 20, 2018 - HIV-1 genetic diversity is higher in vaginal tract than in blood during early infection
February 20, 2018 - Diabetes does not increase work-loss years due to early retirement
February 20, 2018 - Researchers aim to find out how PTSD affects decisions of police
February 20, 2018 - UH Cleveland Medical Center explores novel treatments for uterine fibroids
February 20, 2018 - Flu Vax Efficacy 25% Against Predominant H3N2 Strain So Far
February 20, 2018 - HIV screening most optimal at 25 years of age if no risk factors
February 20, 2018 - Loyola Medicine primary care physician offers advice to minimize risk of flu
February 20, 2018 - Safe sleep recommendations for parents that may help reduce child’s risk of SUID
February 20, 2018 - Why Do So Few Docs Have Buprenorphine Waivers?
February 20, 2018 - Low levels of alcohol good for the brain
February 20, 2018 - Experimental treatment improves invisible symptoms of a man with spinal cord injury
February 20, 2018 - Myriad’s EndoPredict offers better prediction of breast cancer recurrence, analysis shows
February 20, 2018 - Researchers identify fifteen genes that determine our facial features
February 20, 2018 - Morning Break: New Health IT Player; Luxturna No Bargain; Nuclear Freakout
February 20, 2018 - How does it compare? Hospice care at home, at assisted living facility, at nursing home
February 19, 2018 - Scientists develop water-soluble warped nanographene for bioimaging
February 19, 2018 - It’s Not Your Imagination: You’re Hungrier After Losing Weight
February 19, 2018 - Antihypertensive Use At Delivery Rising in Preeclampsia
February 19, 2018 - A centuries-old math equation used to solve a modern-day genetics challenge
February 19, 2018 - Liquid biopsies could be used as new predictive marker for metastatic TNBC
February 19, 2018 - Russian researchers develop new multi-layered biodegradable scaffolds
February 19, 2018 - Are ‘Vaccine Skeptics’ Responsible for Flu Deaths?
February 19, 2018 - Hidden genetic effects behind immune diseases may be missed, study suggests
February 19, 2018 - Emergency nurses experience regular verbal and physical abuse
February 19, 2018 - Study sheds light on biology that guides behavior across different stages of life
February 19, 2018 - Morning Break: Transgender Breast Feeding; Brazilian ‘Pro-Vaxxers’; Post-Stroke Exercise
February 19, 2018 - Meningitis vaccination strategy in Africa found to be effective, economical
February 19, 2018 - Researchers uncover how excess calcium may influence development of Parkinson’s disease
February 19, 2018 - Psoriasis drug also effective at reducing aortic inflammation
New microscope optimized to perform studies using optogenetic techniques

New microscope optimized to perform studies using optogenetic techniques

image_pdfDownload PDFimage_print

A newly developed microscope is providing scientists with a greatly enhanced tool to study how neurological disorders such as epilepsy and Alzheimer’s disease affect neuron communication. The microscope is optimized to perform studies using optogenetic techniques, a relatively new technology that uses light to control and image neurons genetically modified with light-sensitive proteins.

“Our new microscope can be used to explore the effects of different genetic mutations on neuronal function,” said Adam Cohen from Harvard University, USA, and the leader of the research team that developed the microscope. “One day it could be used to test the effects of candidate drugs on neurons derived from people with nervous system disorders to try to identify medicines to treat diseases that do not have adequate treatments right now.”

The new microscope, called Firefly, can image a 6-millimeter-diameter area, more than one hundred times larger than the field of view of most microscopes used for optogenetics. Rather than studying the electrical activity of one neuron, the large imaging area makes it possible to trigger the electrical pulses neurons use to communicate and then watch those pulses travel from cell to cell throughout a large neural circuit containing hundreds of cells. In the brain, each neuron typically connects to one thousand other neurons, so viewing the larger network is important to understanding how neurological diseases affect neuronal communication.

In The Optical Society (OSA) journal Biomedical Optics Express, Cohen and his colleagues report how they assembled the new microscope for less than $100,000 using components that are almost all commercially available. The microscope not only images a large area, but also collects light extremely efficiently. This provides the high image quality and fast speed necessary to watch neuronal electrical pulses that each last only one-thousandth of a second.

Using light to see neurons fire

The new microscope is ideal for studying human neurons grown in the laboratory. In the past decade, scientists have developed human cell models for many nervous system disorders. These cells can be genetically modified to contain light-sensitive proteins that allow scientists to use light to make neurons fire or to control variables such as neurotransmitter levels or protein aggregation. Other light-sensitive fluorescent proteins turn the invisible electrical pulses coming from neurons into brief flashes of fluorescence that can be imaged and measured.

These techniques have made it possible for scientists to study the input and output of individual neurons, but commercially available microscopes aren’t optimized to fully utilize the potential of optogenetics approaches. To fill this technology gap, the researchers designed the Firefly microscope to stimulate neurons with a complex pattern containing a million points of light and then record the brief flashes of light fluorescence that correspond to electrical pulses fired by the neurons.

Each pixel of the light pattern can independently stimulate a light-sensitive protein. Because the pixels can be many distinct colors, different types of light-sensitive proteins can be triggered at once. The light pattern can be programmed to cover an entire neuron, stimulate certain areas of a neuron or be used to illuminate multiple cells at once.

“This optical system provides a million inputs and a million outputs, allowing us to see everything that’s going on in these neural cultures,” explained Cohen.

After stimulating the neurons, the microscope uses a camera imaging at a thousand frames a second to capture the fluorescence induced by the extremely short electrical pulses. “The optical system must be highly efficient to detect good signals within a millisecond,” said Cohen. “A great deal of engineering went into developing optics that can not only image a large area but do so with very high light collection efficiency.”

To efficiently collect light over a large area, the Firefly microscope uses an objective lens about the size of a soda can rather than the thumb-sized objective lens used by most microscopes. The researchers also used an optical setup that increases the amount of light stimulating the neurons to help ensure the neurons emit bright fluorescence when firing.

“The one custom element in the microscope is a small prism placed between the neurons and the objective lens,” explained Cohen. “This important component causes the light to travel along the same plane as the cells rather than entering the sample perpendicularly. This keeps the light from illuminating material above and below the cells, decreasing background fluorescence that would make it hard to see fluorescence actually coming from the neurons.”

Watching 85 neurons at once

The researchers demonstrated their new microscope by using it to optically stimulate and record the fluorescence from cultured human neurons. “The neurons were a big tangled mess of spaghetti,” said Cohen. “We showed that it was possible to resolve 85 individual neurons at the same time in a measurement that took about 30 seconds.”

After the initial stimulation and imaging, the researchers were able to find 79 of those 85 cells a second time. This capability is important for studies that require each cell to be imaged before and after exposure to a drug, for example.

In a second demonstration, the researchers used the microscope to map the electrical waves propagating through cultured heart cells. This showed that the microscope could be used to study abnormal heart rhythms, which occur when the electrical signals that coordinate heartbeats do not work properly.

“The system we developed is designed for looking at a relatively flat sample such as cultured cells,” said Cohen. “We are now developing a system to perform optogenetics approaches in intact tissue, which would allow us to look at how these neurons behave in their native context.”

The researchers have also started a biotech company called Q-State Biosciences that is using an improved version of the microscope to work with pharmaceutical companies on drug discovery.

Source:

http://www.osa.org/en-us/about_osa/newsroom/news_releases/2017/innovative_microscope_poised_to_propel_optogenetic/

Tagged with:

About author

Related Articles