Human forebrain circuits under construction -- in a dishApril 26, 2017
National Institutes of Health (NIH)-funded neuroscientists have created a 3D window into the human brain's budding executive hub assembling itself during a critical period in prenatal development. What's more, they used it to discover and experimentally correct -- in a petri dish -- defective cell migration caused by an autism-related disorder.
Sergiu Pasca, M.D., of Stanford University, Stanford, California, a grantee of the NIH's National Institute of Mental Health (NIMH), and colleagues, report on experiments with forebrain spheroids April 26, 2017 online in the journal Nature.
The study advances a fast-developing "disease-in-a-dish" technology, in which cultured neurons derived from an individual's readily-accessible skin cells connect with each other to form 3D brain organoids or "spheroids." Although tiny, these replicate rudimentary circuitry that can reveal that person's brain's unique secrets -- even from when it was still under construction.
During mid-to-late gestation, neurons migrate from deep brain structures to their appointed places and organize themselves into the key working tissue of what will become the human cortex, the outer layer of the brain and seat of higher-order mental functions. This building process is complex and especially vulnerable to genetic and environmental insults that can set the stage for autism, schizophrenia, and other neurodevelopmental brain disorders.
Previous studies by Pasca's team produced relatively primitive cortex spheroids that didn't show how different regions of the forming structure interacted. In this study, Pasca's team coaxed 3D cell cultures to become spheroids representing two specific regions of the forebrain and fused them together. They then tracked neuronal migrations from a deep brain spheroid to a cortex spheroid that mimicked those seen during normal development.
For the first time, this new model reveals the developing human forebrain, maturing by building circuits that balance excitatory with inhibitory brain systems. Neurons from spheroids resembling tissue in the lower forebrain region are seen migrating to create cortex circuitry with neurons from spheroids resembling tissue in the upper region. The former communicate a slowing-down (inhibition) of neural activity, while the latter communicate a speeding-up (excitation) of neural activity.
In spheroids derived from skin cells of patients with Timothy syndrome, an autism-related disorder of known genetic cause, they discovered a defect in the migration of patients' neurons that caused them to move more frequently but less efficiently -- and experimentally reversed it in the dish with a drug.
"Today's recapitulation of a pivotal stage in the cortex's formation demonstrates the technique's promise for discovery - and even for testing potential interventions, explained NIMH Director Dr. Joshua Gordon. "It moves us closer to realizing the goal of precision medicine for brain disorders."
"The exquisite timing and placement of these different neuron cell types is critical for establishing a balance between excitation and inhibition within brain circuits. This balance is thought to be disrupted in brain disorders," explained Dr. David Panchision, chief of the NIMH Developmental Neurobiology Program that supports the project. "Re-playing these developmental processes with a patient's own cells can allow us to determine what distinguishes these different disorders at a molecular and cellular level."
"Our research provides a proof-of-concept for understanding the interaction of specific cell types and for building -- as well as probing - circuits within personalized human microphysiological systems," said Pasca.
iPS Cells & Organoids - Sci Fi vs Reality https://youtu.be/mqt-8qdoDj0
Birey F, Andersen J, Makinson CD, Islam S Wei W, Huber N, Gan HC, Metzler KRC, Panagiotakos G, Thom N, O'Rourke NA, Steinmetz LM, Bernstein JA, Hallmayer J, Huguenard JR, Pasca SP. "Assembly of Functionally-Integrated Human Forebrain Spheroids" Nature, April 26, 2017
About the National Institute of Mental Health (NIMH): The mission of the NIMH is to transform the understanding and treatment of mental illnesses through basic and clinical research, paving the way for prevention, recovery and cure. For more information, visit http://www.nimh.nih.gov.
About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.
NIH/National Institute of Mental Health
Related Neurons Articles:
One of the big challenges in the Neuroscience field is to understand how connections and communications trigger our behavior.
In a new study published in Neuron, investigators report on a transcription factor that they have found that can help certain neurons regenerate, while simultaneously killing others.
When many individual neurons collect data, how do they reach a unanimous decision?
Individual neurons can learn not only single responses to a particular signal, but also a series of reactions at precisely timed intervals.
Putting a turbo engine into an old car gives it an entirely new life -- suddenly it can go further, faster.
Turning the theory of how the human brain perceives time on its head, a novel analysis in mice reveals that dopamine neuron activity plays a key role in judgment of time, slowing down the internal clock.
Researchers have identified a large population of previously unrecognized young neurons that migrate in the human brain during the first few months of life, contributing to the expansion of the frontal lobe, a region important for social behavior and executive function.
For decades, scientists have struggled to develop a comprehensive census of cell types in the brain.
In the brain, patterns of neural activity are perfectly balanced.
University of Alberta researchers have developed a method of connecting neurons, using ultrashort laser pulses -- a breakthrough technique that opens the door to new medical research and treatment opportunities.
Related Neurons Reading:
From Neuron to Brain
by John G. Nicholls (Author), A. Robert Martin (Author), David A. Brown (Author), Mathew E. Diamond (Author), David A. Weisblat (Author), Paul A. Fuchs (Author)
From Neuron to Brain, Fifth Edition, provides a readable, up-to-date book for use in undergraduate, graduate, and medical school courses in neuroscience. As in previous editions, the emphasis is on experiments made by electrical recordings, molecular and cellular biological techniques, and behavioral studies on the nervous system, from simple reflexes to cognitive functions. Lines of research are followed from the inception of an idea to new findings being made in laboratories and clinics today.
A major change is that this edition begins with the anatomy and physiology of the... View Details
The Neuron: Cell and Molecular Biology
by Irwin B. Levitan (Author), Leonard K. Kaczmarek (Author)
The Fourth Edition of The Neuron provides a comprehensive first course in the cell and molecular biology of nerve cells. The book begins with properties of the many newly discovered ion channels that have emerged through mapping of the genome. These channels shape the way a single neuron generates varied patterns of electrical activity. Covered next are the molecular mechanisms that convert electrical activity into the secretion of neurotransmitter hormones at synaptic junctions between neurons. The following section examines the biochemical pathways that are linked to the action of... View Details
The Neuron: Cell and Molecular Biology
by Irwin B. Levitan (Author), Leonard K. Kaczmarek (Author)
The third edition of The Neuron provides a comprehensive first course in the cell and molecular biology of nerve cells. The first part of the book covers the properties of the many ion channels that shape the way a single neuron generates varied patterns of electrical activity, as well as the molecular mechanisms that convert electrical activity into the secretion of neurotransmitter hormones at synaptic junctions between neurons. The second part covers the biochemical pathways that are linked to the action of neurotransmitters and can alter the cellular properties of neurons or... View Details
From Photon to Neuron: Light, Imaging, Vision
by Philip Nelson (Author)
A richly illustrated undergraduate textbook on the physics and biology of light
Students in the physical and life sciences, and in engineering, need to know about the physics and biology of light. Recently, it has become increasingly clear that an understanding of the quantum nature of light is essential, both for the latest imaging technologies and to advance our knowledge of fundamental life processes, such as photosynthesis and human vision. From Photon to Neuron provides undergraduates with an accessible introduction to the physics of light and offers a unified view... View Details
The 7 Secrets of Neuron Leadership: What Top Military Commanders, Neuroscientists, and the Ancient Greeks Teach Us about Inspiring Teams
by W. Craig Reed (Author), Gordon R. England (Foreword)
Leadership techniques backed by the world's most effective teams
The 7 Secrets of Neuron Leadership offers a diverse collection of wisdom and practical knowledge to help you build and lead your most effective team yet. Written by a former U.S. Navy diver, this book draws from the author's experiences and beyond to reveal key truths about the nature of teamwork, and expose the core of effective team leadership. You'll go back to ancient Greece to discover the nine personality types and the seven types of love that form the foundation of human interaction, and learn how... View Details
Neurons In Action 2: Tutorials and Simulations using NEURON
by John W. Moore (Author), Anne E. Stuart (Author)
Neurons in Action 2 is the second version of a unique CD-ROM-based learning tool that combines hyperlinked text with NEURON simulations of laboratory experiments in neurophysiology. Version 2 features nine new tutorials introducing new channel types, single-channel simulations, and a redesigned interface. Neurons in Action s moving graphs provide insight into nerve function that is simply not possible with conventional, static text and figure presentations. Students discover how changing parameters such a neuronal geometry, ion concentrations, ion channel densities, and degree of myelination... View Details
From Neurons to Neighborhoods : The Science of Early Childhood Development
by Committee on Integrating the Science of Early Childhood Development (Author), Youth, and Families Board on Children (Author), National Research Council (Author), Committee on Integrating the Science of Early Childhood Development (Author), Jack P. Shonkoff (Editor), Deborah A. Phillips (Editor)
How we raise young children is one of today's most highly personalized and sharply politicized issues, in part because each of us can claim some level of "expertise." The debate has intensified as discoveries about our development-in the womb and in the first months and years-have reached the popular media.
How can we use our burgeoning knowledge to assure the well-being of all young children, for their own sake as well as for the sake of our nation? Drawing from new findings, this book presents important conclusions about nature-versus-nurture, the impact of being born into a... View Details
From Neuron to Cognition via Computational Neuroscience (Computational Neuroscience Series)
by Michael A. Arbib (Editor), James J. Bonaiuto (Editor)
A comprehensive, integrated, and accessible textbook presenting core neuroscientific topics from a computational perspective, tracing a path from cells and circuits to behavior and cognition.
This textbook presents a wide range of subjects in neuroscience from a computational perspective. It offers a comprehensive, integrated introduction to core topics, using computational tools to trace a path from neurons and circuits to behavior and cognition. Moreover, the chapters show how computational neuroscience -- methods for modeling the causal interactions underlying neural... View Details
The Myth of Mirror Neurons: The Real Neuroscience of Communication and Cognition
by Gregory Hickok (Author)
An essential reconsideration of one of the most far-reaching theories in modern neuroscience and psychology.In 1992, a group of neuroscientists from Parma, Italy, reported a new class of brain cells discovered in the motor cortex of the macaque monkey. These cells, later dubbed mirror neurons, responded equally well during the monkey’s own motor actions, such as grabbing an object, and while the monkey watched someone else perform similar motor actions. Researchers speculated that the neurons allowed the monkey to understand others by simulating their actions in its... View Details
I of the Vortex: From Neurons to Self
by Rodolfo R. Llinas (Author)
A highly original theory of how the mind-brain works, based on the author's study of single neuronal cells.
In I of the Vortex, Rodolfo Llinas, a founding father of modern brain science, presents an original view of the evolution and nature of mind. According to Llinas, the "mindness state" evolved to allow predictive interactions between mobile creatures and their environment. He illustrates the early evolution of mind through a primitive animal called the "sea squirt." The mobile larval form has a brainlike ganglion that receives sensory information about the... View Details