New findings in memory research reveal the role of dendritic translation in learning, identifying thousands of micropeptides and key regulatory proteins, offering insights into intellectual disabilities and broader neurological functions. Credit: SciTechDaily.com
Activity taking place within the dendrites that branch off of neuron cell bodies is key to memory formation.
Less than twenty minutes after finishing this article, your brain will begin to store the information that youve just read in a coordinated burst of neuronal activity. Underpinning this process is a phenomenon known as dendritic translation, which involves an uptick in localized protein production within dendrites, the spiny branches that project off the neuron cell body and receive signals from other neurons at synapses. Its a process key to memoryand its dysfunction is linked to intellectual disorders.
That makes the inner workings of dendritic translation a holy grail for understanding memory formation, says Rockefellers Robert B. Darnell, whose team just published a study in Nature Neuroscience describing a new platform capable of identifying the specific regulatory mechanisms that drive dendritic translation. The team leveraged a method, dubbed TurboID, to discover an entire suite of previously unknown factors in memory formation, revealing now mechanisms that underlie how protein synthesis in dendrites contributes to learning and memory. The findings may also have implications for intellectual disabilities, such as Fragile X syndrome.
Technological limitations have long prevented a comprehensive inventory of the activity at the synapse involved in memory formation, says lead author Ezgi Hacisuleyman, who conducted the research as a postdoctoral researcher in Darnells laboratory. She is now an assistant professor at The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology. Our new techniques can accomplish this with extremely high resolution to look at neurons in vitro that are closely mimicking what we see in the brain.
Hacisuleymans work defines a whole new biochemical pathway which fits with, complements, and vastly expands what we already knew about memory and learning, adds Darnell, the Robert and Harriet Heilbrunn professor.
Memory formation centers around the hippocampus, a brain region so central to learning that, when surgeons removed it from people with epilepsy in the 1940s, the patients remembered their childhoods but lost the ability to form new memories. It has since become clear that memories form, in part, because of new protein synthesis made locally in the dendrites of the hippocampus.
Darnell, a physician-scientist, observed the importance of dendritic translation firsthand while working with patients whose immune systems had attacked the hippocampus. I would talk to a patient for 30 minutes, leave the room, walk back in, and it was like they had never seen me before, he says. Thats when I began focusing on why neurons of the hippocampus have their own system for regulating RNA metabolisma system that no other cell in the body uses.
That system, it turns out, lies at the heart of how our brains form memories and learn new information, and became a focus for the Darnell lab, culminating in his teams 2003 development of CLIP, a method that allowed researchers to study the proteins that bind and influence RNA. But limitations remained. Many details about how neurons respond to stimuli at the dendrites were still missing, Hacisuleyman says. We needed that information, because that plays a role in determining how neurons functionand where things often go awry in neurologic disease.
To get a better idea of the role that changes in dendrites play in learning, Hacisuleyman extended the TurboID platform to works in concert with RNA-sequencing, CLIP, translation and protein analysis. The platform allowed the team to track activity in dendrites before, during, and several minutes after the neuron activates, capturing the moments critical to protein synthesis in the cell and, more importantly, the stage considered key to memory formation.
An analysis of these crucial moments revealed a microscopic upheaval in the dendrite. Upon activation, local ribosomes jump onto mRNAs, an action that has all the biochemical hallmarks of memory formation, and which models predicted will cause the dendrite to produce not only new proteins, but 1,000 small proteins known as micropeptides, with as-yet unknown function. The team also identified an RNA-binding protein that helps seal the connection between these ribosomes and mRNA, and demonstrated that if that protein is disabled, the proposed micropeptides and their associated downstream proteins will not form.
We never knew these micropeptides might even exist, Darnell says. It opens a new field of study, where we can ask what these peptides might be doing and how they could play into memory formation. Its such a vast discovery that there are dozens if not hundreds of avenues in which to pursue this.
Among the many observations that researchers will unpack in future studies, one stood out: the team noted that a certain protein stood out for its prolific binding of mRNA in the dendrite. The protein, called FMRP, is key to brain development and function, and genetic mutations that adversely impact FMRP contribute to Fragile X syndrome, one of the most common genetic causes of intellectual disability. Our findings fit nicely with the molecular biology of FMRP, and also open the door to future insights into what is going wrong in Fragile X, Darnell says.
Beyond the papers immediate findings, dendritic-TurboID could also allow researchers to examine RNA regulation and protein synthesis in other brain regions and apply the findings to different diseases. We can now begin to look at many other sites with a fine-toothed comb, Hacisuleyman says.
When you develop a new technique as Hacisuleyman did, you enter a room that nobody has ever been in before, Darnell adds. The light turns on, and the findings just take your breath away.
Reference: Neuronal activity rapidly reprograms dendritic translation via eIF4G2:uORF binding by Ezgi Hacisuleyman, Caryn R. Hale, Natalie Noble, Ji-dung Luo, John J. Fak, Misa Saito, Jin Chen, Jonathan S. Weissman and Robert B. Darnell, 8 April 2024, Nature Neuroscience. DOI: 10.1038/s41593-024-01615-5
Go here to read the rest:
Neuroscience Breakthrough Unveils How We Learn and Remember - SciTechDaily
- Unlocking Flow: The Neuroscience of Creative Bliss - Neuroscience News - April 15th, 2024 [April 15th, 2024]
- Revolutionizing Glioblastoma Treatment - Neuroscience News - April 15th, 2024 [April 15th, 2024]
- Decoding spontaneous thoughts from the brain via machine learning - EurekAlert - April 15th, 2024 [April 15th, 2024]
- Reducing Toxic AI Responses - Neuroscience News - April 15th, 2024 [April 15th, 2024]
- Advancing the neuroscience of human pregnancy - Nature.com - April 15th, 2024 [April 15th, 2024]
- Angela Bryan Awarded Hazel Barnes Prize | Psychology and Neuroscience - University of Colorado Boulder - April 15th, 2024 [April 15th, 2024]
- How Old Are You in Your Head? The Neuroscience of Subjective Age Reveals How to Stay Mentally Young - Inc. - April 15th, 2024 [April 15th, 2024]
- Biohaven Showcases Innovative Neuroscience Portfolio with 20 Presentations at the 2024 American Academy of ... - PR Newswire - April 15th, 2024 [April 15th, 2024]
- Those Who Use Willpower Deemed More Trustworthy - Neuroscience News - April 15th, 2024 [April 15th, 2024]
- How Sex and Gender Shape Our Cognition - Neuroscience News - April 15th, 2024 [April 15th, 2024]
- War's Toll on the Brain: Widespread PTSD and Anxiety Among Ukrainians - Neuroscience News - April 15th, 2024 [April 15th, 2024]
- Paints and Pesticides Linked to ALS Risk - Neuroscience News - April 15th, 2024 [April 15th, 2024]
- AI STORIES: A New Vision for AI and Narratives - Neuroscience News - April 15th, 2024 [April 15th, 2024]
- Pregnancy's Toll: Accelerated Aging in Young Mothers - Neuroscience News - April 15th, 2024 [April 15th, 2024]
- Learning and Memory Formation's Molecular Basis - Neuroscience News - April 15th, 2024 [April 15th, 2024]
- Acetaminophen in Pregnancy Not Linked to Autism, ADHD Risk - Neuroscience News - April 15th, 2024 [April 15th, 2024]
- Childhood Loneliness Linked to Later Psychosis - Neuroscience News - April 15th, 2024 [April 15th, 2024]
- Vigil Neuroscience, Inc. (NASDAQ:VIGL) Expected to Post Q1 2024 Earnings of ($0.58) Per Share - Defense World - March 29th, 2024 [March 29th, 2024]
- International Brain Research Organisation (IBRO) Diversity Grants 2024 Opportunity Desk - Opportunity Desk - March 29th, 2024 [March 29th, 2024]
- Hereditary Alzheimer's Transmitted Via Bone Marrow Transplants - Neuroscience News - March 29th, 2024 [March 29th, 2024]
- Household Chemicals Linked to Brain Health Risks - Neuroscience News - March 29th, 2024 [March 29th, 2024]
- Cheers to Longevity: Couples Who Drink Together, Live Longer - Neuroscience News - March 29th, 2024 [March 29th, 2024]
- Sleeplessness Makes You Feel Up To Ten Years Older - Neuroscience News - March 29th, 2024 [March 29th, 2024]
- Aging Brain Cells Have Prolonged Death Process - Neuroscience News - March 29th, 2024 [March 29th, 2024]
- Anxiety Drives Wishful Thinking to Risky Levels - Neuroscience News - March 29th, 2024 [March 29th, 2024]
- Prolonged Progestogen Use Linked to Brain Tumor Risk - Neuroscience News - March 29th, 2024 [March 29th, 2024]
- The Genetic Secrets of Neuron Formation - Neuroscience News - March 29th, 2024 [March 29th, 2024]
- Vigil Neuroscience Reports Fourth Quarter and Full Year 2023 Financial Results and Provides Business Update - Yahoo Finance - March 29th, 2024 [March 29th, 2024]
- Big research, little time: Medical neuroscience student wins 3 Minute Thesis finals - Dal News - March 29th, 2024 [March 29th, 2024]
- The new NeuroAI - Nature.com - March 29th, 2024 [March 29th, 2024]
- Exploring Aphantasia: The Mind Without a Mental Picture - Neuroscience News - March 29th, 2024 [March 29th, 2024]
- Altered Brain pH Linked to Cognitive Disorders - Neuroscience News - March 29th, 2024 [March 29th, 2024]
- Emotion vs. Reason: Rethinking Decision-Making - Neuroscience News - March 29th, 2024 [March 29th, 2024]
- DNA Damage and Inflammation Key to Memory Formation - Neuroscience News - March 29th, 2024 [March 29th, 2024]
- Embracing Neurodiversity: Beyond Stigma to Strength - Neuroscience News - March 29th, 2024 [March 29th, 2024]
- Devil in the Details: The Visual World of Prosopometamorphopsia - Neuroscience News - March 29th, 2024 [March 29th, 2024]
- Rockefeller Neuroscience Institute receives $2M grant for ultrasound drug addiction treatments - Health Imaging - March 29th, 2024 [March 29th, 2024]
- Empathy Begins in Infancy - Neuroscience News - March 29th, 2024 [March 29th, 2024]
- Mapping Brain Activity with Brain-Computer Interface Technology - Neuroscience News - March 29th, 2024 [March 29th, 2024]
- Want Better Mental Focus? Neuroscience Just Found This Simple, Joyful Activity Helps Your Brain Concentrate - Inc. - March 29th, 2024 [March 29th, 2024]
- The neuroscience of groove: Why certain rhythms make us want to dance - PsyPost - March 29th, 2024 [March 29th, 2024]
- High Rates of Suicidal Ideation in Rural Black Men - Neuroscience News - March 29th, 2024 [March 29th, 2024]
- Harmony in Chaos: How BPD Influences Music Tastes - Neuroscience News - March 29th, 2024 [March 29th, 2024]
- WVU Rockefeller Neuroscience Institute receives $2M Grant - WDTV - March 29th, 2024 [March 29th, 2024]
- Study Links Diet, Diabetes, and Alzheimers - Neuroscience News - March 29th, 2024 [March 29th, 2024]
- Neuroscience and Society Series: Aligning Science with the Public's Values - The Hastings Center - March 29th, 2024 [March 29th, 2024]
- Hardwiring Your Brain: The Neuroscience Of Behaviour Change | TheHealthSite.com - TheHealthSite - March 29th, 2024 [March 29th, 2024]
- Refined Carb Intake's Effect on Facial Attractiveness - Neuroscience News - March 11th, 2024 [March 11th, 2024]
- Linking Childhood Adversity to Adult Mental Health - Neuroscience News - March 11th, 2024 [March 11th, 2024]
- Overnight neuronal plasticity and adaptation to emotional distress - Nature.com - March 11th, 2024 [March 11th, 2024]
- Less Obesity and Depression in NPD Individuals - Neuroscience News - March 11th, 2024 [March 11th, 2024]
- Unlocking Creative Flow: How the Brain Enters the Zone - Neuroscience News - March 11th, 2024 [March 11th, 2024]
- Self-Control, Not Impulsivity, Paves the Way to Power - Neuroscience News - March 11th, 2024 [March 11th, 2024]
- 3D Maps Reveal Molecular Complexities of the Brain - Neuroscience News - March 11th, 2024 [March 11th, 2024]
- Loneliness Linked to Personality Disorders - Neuroscience News - March 11th, 2024 [March 11th, 2024]
- Gen Z's Climate Anxiety: A Call for Action and Hope - Neuroscience News - March 11th, 2024 [March 11th, 2024]
- Decoding Emotions: Beyond Senses in the Human Brain - Neuroscience News - March 11th, 2024 [March 11th, 2024]
- Brain Circuit Balances Speech and Breath - Neuroscience News - March 11th, 2024 [March 11th, 2024]
- Schizophrenia and Aging Share Brain Changes - Neuroscience News - March 11th, 2024 [March 11th, 2024]
- Monitoring Spinal Cord Activity During Surgery in Real-Time - Neuroscience News - March 11th, 2024 [March 11th, 2024]
- Scientists team up with jazz musicians to reveal the neuroscience of creative flow - PsyPost - March 11th, 2024 [March 11th, 2024]
- Peer Pressure Persists Through Adulthood - Neuroscience News - March 11th, 2024 [March 11th, 2024]
- Mary Bartlett Bunge, 92, Dies; Pioneer in Spinal Injury Treatment - The New York Times - March 11th, 2024 [March 11th, 2024]
- Rethinking Reminiscence: Theater's Ageism Dilemma Unveiled - Neuroscience News - March 11th, 2024 [March 11th, 2024]
- PTSD: Virtual Reality and Magnetic Stimulation Provide Relief - Neuroscience News - March 11th, 2024 [March 11th, 2024]
- The Partisan Morality Divide: When Politics Shapes Right and Wrong - Neuroscience News - March 11th, 2024 [March 11th, 2024]
- Biological Sciences Professor Terrence Sejnowski Wins Brain Prize - University of California San Diego - March 11th, 2024 [March 11th, 2024]
- Pioneering work in computational and theoretical neuroscience is awarded the world's largest brain research prize - afp.com - March 11th, 2024 [March 11th, 2024]
- Substance Abuse Beyond Dopamine and Impulsivity - Neuroscience News - March 11th, 2024 [March 11th, 2024]
- Pioneering work in computational and theoretical neuroscience is awarded the world's largest brain research prize - Business Wire - March 11th, 2024 [March 11th, 2024]
- Dal study of football players sheds light on how concussions affect the brain - Yahoo Canada Sports - March 11th, 2024 [March 11th, 2024]
- Hebrew University's Haim Sompolinsky awarded prestigious Brain Prize for pioneering neuroscience research - The Times of Israel - March 11th, 2024 [March 11th, 2024]
- Harvard neuroscientist Haim Sompolinsky awarded Brain Prize - EurekAlert - March 11th, 2024 [March 11th, 2024]
- Rhythm in the Brain: Music Exposure Influences Rhythmic Interpretation - Neuroscience News - March 11th, 2024 [March 11th, 2024]
- Physicist Haim Sompolinsky first Israeli to win largest brain science research prize - The Times of Israel - March 11th, 2024 [March 11th, 2024]
- Prestigious 2024 Brain Prize awarded to Hebrew University's Prof. Haim Sompolinsky by Lundbeck Foundation - EurekAlert - March 11th, 2024 [March 11th, 2024]
- Pioneering work in computational and theoretical neuroscience is awarded the world's largest brain research prize - EurekAlert - March 11th, 2024 [March 11th, 2024]
- Role of AI in Neuroscience Research and Understanding of the Human Brain - Medriva - February 13th, 2024 [February 13th, 2024]
- Healis selected to present at key biotechnology and neuroscience investor conferences in Amsterdam, New York, - EIN News - February 13th, 2024 [February 13th, 2024]
- Brain's Method for Preserving Cognition in Aging Revealed - Neuroscience News - February 13th, 2024 [February 13th, 2024]