Breaking News
September 24, 2018 - A new approach for finding Alzheimer’s treatments
September 24, 2018 - USC research uncovers previously unknown genetic risk factor for dementia
September 24, 2018 - Study examining mental health among students finds significant disparities in treatment across race
September 24, 2018 - Breakthrough discovery paves way for future test to identify drowsy drivers
September 24, 2018 - Transcatheter mitral-valve repair in patients with heart failure
September 24, 2018 - Study opens new avenues for treatment of Laing distal myopathy
September 24, 2018 - Stroke Facts | cdc.gov
September 24, 2018 - Sarcolipin tricks muscle cells into using more energy, burning fat
September 24, 2018 - Enrollment in opioid controlled substance agreement reduces primary care visits
September 24, 2018 - UTA researchers patent new smart seat cushion technology that helps prevent painful ulcers
September 24, 2018 - Second HPV-Related Primary Cancers Common in Survivors
September 24, 2018 - How a virus destabilizes the genome
September 24, 2018 - Old letters provide insight into Spanish flu pandemic horror
September 23, 2018 - Smart textile-based soft robotic exosuit helps wearers save energy and traverse difficult terrain
September 23, 2018 - New research hub to drive radical change in development and manufacturing of vaccines
September 23, 2018 - AHA: For Hispanics, Neighborhood May Be Key Factor in Heart Disease Risk
September 23, 2018 - Excessive airway nerves tied to more severe asthma symptoms, study finds
September 23, 2018 - Study highlights need to remain vigilant in maintaining key infection control processes
September 23, 2018 - Novel therapeutic strategy for blood vessel related disorders, such as cancer and retinopathy
September 23, 2018 - New naturally occurring antibiotic found effective against Mycobacterium tuberculosis
September 23, 2018 - First-in-human phase 0 study shows clinically-relevant activity of new drug in glioblastoma
September 23, 2018 - Removing tobacco product display from shops reduced number of children buying cigarettes
September 23, 2018 - Random fraction of specialized immune cells leads the charge in battling invaders
September 23, 2018 - Few minutes of sprinting exercise may be as effective as longer exercise sessions
September 23, 2018 - Researchers use neutrons to make first direct observations of water in lipid bilayers
September 23, 2018 - Researchers demonstrate pre-clinical success for universal flu vaccine in new paper
September 23, 2018 - Study reveals surprising gaps in some HIV medical providers’ knowledge of ACA
September 23, 2018 - Oxehealth secures European medical device accreditation for vital signs measurement software
September 23, 2018 - HTN Tx Intensification Common Upon Discharge in U.S. Vets
September 23, 2018 - Fibre can strengthen the intestinal barrier
September 23, 2018 - New platform examines infectious pathogens that may spread from animals to humans
September 23, 2018 - Demographers create detailed color map of population aging in Europe
September 23, 2018 - New type of fatty acid can slow down overreactive immune system
September 23, 2018 - Innovative procedure could provide breakthrough in treating early-stage lung cancer
September 23, 2018 - Research finds drop in number of measles cases in the EU/EEA since March 2018
September 23, 2018 - Researchers acquire new insights into DNA polymerases
September 23, 2018 - Alzheimer’s diagnosis might become simpler with new brain imaging method
September 23, 2018 - Reports Warn of Growing Opioid Crisis Among Seniors
September 23, 2018 - Researchers unravel why people with HIV suffer from more neurologic diseases
September 23, 2018 - Human brain structured to make best possible decision with limited resources
September 23, 2018 - KHN’s ‘What the Health?’ Health on the hill
September 23, 2018 - Bad air and inadequate data prove an unhealthy mix
September 23, 2018 - Regular bedtime and wake time important for heart, metabolic health even among adults
September 23, 2018 - HIV and a tale of a few cities
September 23, 2018 - NIH launches clinical trial to test infusions of combination antibodies in people with HIV
September 23, 2018 - Researchers develop new system to detect consumption of synthetic cannabinoids
September 23, 2018 - Vax-Hub to influenze radical change in development and manufacturing of vaccines
September 23, 2018 - People who have slept lesser than seven hours have higher risks of car crashes
September 23, 2018 - an ancient art may work best to prevent falls in old age
September 23, 2018 - Consumption of foods with lower nutritional quality related to increased cancer risk
September 23, 2018 - Patient Health Information Often Shared Electronically
September 23, 2018 - Can machine learning bring more humanity to health care?
September 23, 2018 - Body organs undergo structural changes in response to diet
September 23, 2018 - Genetic polymorphisms linked with muscle injury and stiffness
September 23, 2018 - As states try to rein in drug spending, feds slap down one bold Medicaid move
September 22, 2018 - Why Eczema Is Tougher to Treat for Black Patients
September 22, 2018 - Team reveals that human genome could contain up to 20 percent fewer genes
September 22, 2018 - USC research uncovers previously unknown genetic risk factor for Alzheimer’s disease
September 22, 2018 - Novel method achieves accurate and precise temperature estimation in fat-containing tissues
September 22, 2018 - BSI accredits Oxehealth’s vital signs measurement software as Class IIa medical device
September 22, 2018 - Evolution of psychiatric disorders and human personality traits
September 22, 2018 - Obesity in early puberty doubles asthma risk for boy’s future offspring
September 22, 2018 - World’s most advanced real-time patient monitoring platform receives key US patent
September 22, 2018 - Study explores connection between sexuality and cognitive status in older adults
September 22, 2018 - LSTM partners with TB Alliance to develop novel TB drug regimens
September 22, 2018 - Annual wellness visits improve delivery of preventive services in elderly population
September 22, 2018 - CHMP provides positive opinion to Cabometyx for previously-treated patients with hepatocellular carcinoma
September 22, 2018 - Hispanic communities with high proportions of Hispanics face more cardiovascular-related death
September 22, 2018 - Vici syndrome – Genetics Home Reference
September 22, 2018 - Single-dose drug can shorten flu symptoms by about a day, studies suggest
September 22, 2018 - AMSBIO launches circulating tumor DNA Reference Standards
September 22, 2018 - Sandalwood mimicking odorant could stimulate hair growth in humans
September 22, 2018 - Overlooked immune cells could play a key role in cancer immunotherapy, claims new study
September 22, 2018 - Study reveals prevalence of diagnosed type 1 and type 2 diabetes among American adults
September 22, 2018 - Researchers develop fast detection strategy to know type of virus acquired by patients
September 22, 2018 - Global Prevalence of Insufficient Activity 27.5 Percent
September 22, 2018 - Strategies to protect bone health in hematologic stem cell transplant recipients
September 22, 2018 - Brigham Genomic Medicine program unravels 30 medical mysteries
September 22, 2018 - New system harnesses power of bubbles to destroy dangerous biofilms
September 22, 2018 - Inflammation plays crucial role in preventing heart attacks and strokes, study reveals
Researchers uncover surprising new role for inhibition in the cerebellum

Researchers uncover surprising new role for inhibition in the cerebellum

image_pdfDownload PDFimage_print

Almost everyone is familiar with the unique mixture of surprise and confusion that occurs after making a mistake during an everyday movement. It’s a fairly startling experience – stumbling on a step or accidentally missing your mouth when taking a drink. These actions are so ingrained that any mishap is almost always followed by the question “Why in the world did I just do that?” This momentary bewilderment is due to the fact that our brains have an extraordinary capacity for learning skilled movements. So much so that our routine actions, such as climbing stairs, become second nature. For the most part we don’t even consciously think about them…that is until we make a mistake.

While mistakes (errors in motor performance) don’t occur very frequently once we’ve picked something up, they are the tool used by the brain to evaluate and adjust our movements in hopes that next time, we won’t stumble or spill our drinks so easily. As the saying goes “We learn from our mistakes,” but how do our brains turn the motor errors we make into meaningful and reliable learning?

In a recent publication in Neuron, researchers from the lab of Dr. Jason Christie, Research Group Leader at the Max Planck Florida Institute for Neuroscience (MPFI), have discovered part of the answer to this longstanding question. Uncovering a surprising new role for inhibition in the cerebellum, Dr. Christie’s team has broadened the current understanding of neural computation and provided fundamental insights into the mechanisms and principles underlying motor learning.

“Learning isn’t a monolithic event, that either happens or doesn’t,” describes Dr. Christie. “It’s a much more complex behavior that can vary in duration, magnitude and direction. Our findings demonstrate that in the cerebellum, motor learning can occur along a continuum and what seems to be the key, is the influence of an inhibitory cell class called molecular layer interneurons.”

An anatomically unique region of the brain, the cerebellum plays a critically important role in regulating motor control and coordination. Despite its relatively small size- only about 10% of the entire brain- the cerebellum houses roughly half of our total neurons, around 50 billion. While receiving many inputs from various regions of the brain, the cerebellum integrates and sends refined information out through a single type of specialized neuron called a Purkinje cell. These cells receive two well characterized excitatory inputs and a lesser studied inhibitory input, helping to guide motor behavior and facilitate learning.

“Thousands of excitatory inputs by parallel fibers, set the stage for Purkinje cell activation by providing sensory and motor context for actions,” describes Audrey Bonnan, a Postdoctoral Researcher in the Christie Lab and one of the publication’s first authors. “It’s these inputs that activate Purkinje cells and maintain normal coordination and movement. When we make a mistake however, a second excitatory input from a climbing fiber, arrives simultaneously and delivers an instructive signal. This new information detailing motor error, weakens the synaptic connections between parallel fibers and Purkinje cells; producing a change in behavior and ultimately allowing for learning to occur. But the function of inhibitory inputs in this process, was still largely unknown.”

This alteration in synaptic strength, known as synaptic plasticity, is thought to be the mechanistic correlate of learning. Uncovering how inhibitory interneurons influence plasticity is the first step in gaining insights into their role in motor learning. To address this question, the team performed simultaneous electrical stimulation of the excitatory inputs encoding contexts and those encoding signaling errors, simulating the events that occur during learning. Using electrophysiology to record the output of the Purkinje cell, the researchers then precisely activated inhibitory interneurons by use of a light-based approach for neural stimulation (optogenetics). This approach benefited from a collaboration with MPFI’s Taniguchi lab that allowed optogenetic targeting of only molecular layer interneurons.

“We found that inhibition allows for an entire spectrum of outcomes,” notes Dr. Christie. “Without inhibition, Purkinje cells showed the expected synaptic weakening caused by co-activation of parallel fibers and climbing fibers. By strongly activating molecular layer interneurons, there was a complete reversal of plasticity where synapses were strengthened with the addition of inhibition. Surprisingly with weak activation of these interneurons, plasticity seemed to be negated where no change occurred at all.”

Taking the investigation one step further, inhibition produced a similar type of reversal on learning behavior. Using dual color optogenetics, the MPFI researchers evaluated the effect of molecular layer activation during adaptive vestibulo-ocular reflex or VOR, which helps to maintain a stable gaze by moving the eyes in the opposite direction of head movement. With training, the VOR can undergo learned adaptation where eye movement during the reflex increases (gain increase). Consistent with plasticity findings, strong activation of MLIs produced a complete reversal in learning of VOR, causing dramatically less eye movement (gain decrease). With weak activation of MLIs, little to no change occurred, matching animals with untrained VORs.

“Inhibition seems to dramatically broaden the range with which cells can respond to stimuli,” explains Dr. Christie. “Instead of the brain having only two options -learning or not learning- there can be a tremendous amount of variation in between. For example, learning a little or learning a lot. It’s like black and white versus shades of gray, where the shades of gray allow for a greater amount of behavioral flexibility.”

Dr. Christie notes that the work was a tremendous effort between first authors Matt Rowan, Ph.D., now an Assistant Professor at Emory University; Audrey Bonnan, Ph.D., and Ke Zhang, a graduate student in the International Max Planck Research School for Brain and Behavior, and that their surprising findings have opened up a whole new avenue of inquiry for the future.

Source:

Newly Identified Role for Inhibition in Cerebellar Plasticity and Behavior

Tagged with:

About author

Related Articles