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brain circuits

Everybody knows that it’s important to stay alert behind the wheel or while out walking on the bike path. But our ability to react appropriately to sudden dangers is influenced by whether we feel momentarily tired, distracted, or anxious. How is it that the brain can transition through such different states of consciousness while performing the same routine task, even as its basic structure and internal wiring remain unchanged?

A team of NIH-funded researchers may have found an important clue in zebrafish, a popular organism for studying how the brain works. Using a powerful new method that allowed them to find and track brain circuits tied to alertness, the researchers discovered that this mental state doesn’t work like an on/off switch. Rather, alertness involves several distinct brain circuits working together to bring the brain to attention. As shown in the video above that was taken at cellular resolution, different types of neurons (green) secrete different kinds of chemical messengers across the zebrafish brain to affect the transition to alertness. The messengers shown are: serotonin (red), acetylcholine (blue-green), and dopamine and norepinephrine (yellow).

What’s also fascinating is the researchers found that many of the same neuronal cell types and brain circuits are essential to alertness in zebrafish and mice, despite the two organisms being only distantly related. That suggests these circuits are conserved through evolution as an early fight-or-flight survival behavior essential to life, and they are therefore likely to be important for controlling alertness in people too. If correct, it would tell us where to look in the brain to learn about alertness not only while doing routine stuff but possibly for understanding dysfunctional brain states, ranging from depression to post-traumatic stress disorder (PTSD).


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Cells of a mouse retina

Caption: Neuronal circuits in the mouse retina. Cone photoreceptors (red) enable color vision; bipolar neurons (magenta) relay information further along the circuit; and a subtype of bipolar neuron (green) helps process signals sensed by other photoreceptors in dim light.
Credit: Brian Liu and Melanie Samuel, Baylor College of Medicine, Houston.

When most people think of reprogramming something, they probably think of writing code for a computer or typing commands into their smartphone. Melanie Samuel thinks of brain circuits, the networks of interconnected neurons that allow different parts of the brain to work together in processing information.

Samuel, a researcher at Baylor College of Medicine, Houston, wants to learn to reprogram the connections, or synapses, of brain circuits that function less well in aging and disease and limit our memory and ability to learn. She has received a 2016 NIH Director’s New Innovator Award to decipher the molecular cues that encourage the repair of damaged synapses or enable neurons to form new connections with other neurons. Because extensive synapse loss is central to most degenerative brain diseases, Samuel’s reprogramming efforts could help point the way to preventing or correcting wiring defects before they advance to serious and potentially irreversible cognitive problems.


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A stylized rocket headed toward a moon made of a human brain

Moonshot to the BRAIN

Some have called it America’s next moonshot. Indeed, like the historic effort that culminated with the first moon landing in 1969, the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative is a bold, ambitious endeavor that will require the energy of thousands of our nation’s most creative minds working together over the long haul.

Our goal? To produce the first dynamic view of the human brain in action, revealing how its roughly 86 billion neurons and its trillions of connections interact in real time. This new view will revolutionize our understanding of how we think, feel, learn, remember, and move, transforming efforts to help the more than 1 billion people worldwide who suffer from autism, depression, schizophrenia, epilepsy, traumatic brain injury, Parkinson’s disease, Alzheimer’s disease, and other devastating brain disorders.


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