Scientists control rapid re-wiring of brain circuits using patterned visual stimulation

by Anita Kar
Scientists control rapid re-wiring of brain circuits using patterned visual stimulation
Xenopus tadpoles. Credit: David Freiheit

(Medical Xpress)—In a new study, published in this week's issue of the journal Science, researchers show for the first time how the brain re-wires and fine-tunes its connections differently depending on the relative timing of sensory stimuli. In most neuroscience textbooks today, there is a widely held model that explains how nerve circuits might refine their connectivity based on patterned firing of brain cells, but it has not previously been directly observed in real time. This "Hebbian Theory", named after the McGill University psychologist Donald Olding Hebb who first proposed it in 1949 has been summarized as:

"Cells that fire together, wire together. Cells that fire out of sync, lose their link"

In other words, a nerve cell that fires at the same time as its nerve cell neighbors will cooperatively form strong, stable connections onto its partner cells. On the other hand, a nerve cell that fires out of synchrony with its neighbours, will end up destabilizing and withdrawing its connections. "For the first time, we have direct, real-time evidence from watching brain cells in an intact animal to support Hebb's model, but, we also provide surprising, new details, fundamentally updating the model for the 21st century," says Dr. Edward Ruthazer, senior investigator on the study at the Montreal Neurological Institute and Hospital –The Neuro at McGill University and the McGill University Health Centre.

The study, which used multiphoton laser-scanning microscopy to observe cells in the brains of intact animals, discovered that asynchronous firing, or "firing out of sync" not only caused to lose their ability to make other cells fire, but unexpectedly, also caused them to dramatically increase their elaboration of new branches in search of better matched partners. "The surprising and entirely unexpected finding is that even though nerve circuit remodeling from asynchronous stimulation actively weakens connections, there is a 60% increase in axon branches that are exploring the environment but these exploratory branches are not long-lived," said Dr. Ruthazer.

This video is not supported by your browser at this time.
Video showing the enhanced growth and branch dynamics of 2 ipsilateral retinal ganglion cells in response to asynchronous stimulation of the two eyes (green dot) . Upon presentation of the same visual stimulus, but temporally synchronized across the two eyes, leading to correlated firing, the growth is rapidly reduced.

Dr. Ruthazer's lab charts the formation of brain circuitry during development in the hopes of better understanding the rules that control healthy brain wiring and of advancing treatments for injuries to the nervous system and therapies for neurodevelopmental disorders such as autism and schizophrenia. Astoundingly, nearly one out of every 100 Canadians suffers from one of these disorders, estimated to cost the Canadian economy over $10 billion annually in addition to inflicting a devastating impact on patients and their families.

In the developing brain, initially imprecise connections between are gradually pruned away, leaving connections that are stronger and more specific. This refinement occurs in response to patterned stimulation from the environment. "The way we perceive the world as adults is directly impacted by what we saw when we were younger," says Dr. Ruthazer.

Scientists control rapid re-wiring of brain circuits using patterned visual stimulation
Credit: Science. 2014 May 23;344(6186):904-9. doi: 10.1126/science.1251593

Dr. Ruthazer's team studies brain development in Xenopus tadpoles, which have the distinct advantage of being transparent, enabling the team to clearly see the nervous system inside. They have developed a model that allows them to watch nerve cell remodeling in vivo, in real time, and to measure the efficacy of connections between . Optic fibers were used to stimulate the eyes of the tadpoles with different light patterns, while imaging and recording nerve cell branch formation. Asynchronous stimulation involved light flashes presented to each eye at different times, while synchronous stimulation involved simultaneous stimulation of both eyes.

Importantly, Dr. Ruthazer's group also has begun to identify the molecular mechanisms underlying these changes in the nervous system. They show that the stabilization of the retinal nerve cell branches caused by synchronous firing involves signaling downstream of the synaptic activation of a neurotransmitter receptor called the N-methyl-D-aspartate receptor. In contrast, the enhanced exploratory growth that occurs with asynchronous activity does not appear to require the activation of this receptor.

More information: "Rapid hebbian axonal remodeling mediated by visual stimulation." Science 23 May 2014: Vol. 344 no. 6186 pp. 904-909. DOI: 10.1126/science.1251593

add to favorites email to friend print save as pdf

Related Stories

Spinal nerve connections develop using simple rules

Jan 09, 2014

(Medical Xpress)—Repairing spinal injuries with stem cells may be a step closer thanks to scientists at the Universities of Bristol and Plymouth. A new study, published today in the Journal of Neuroscience, employ ...

No room for inaccuracy in the brain

Jul 20, 2011

Dr. Ed Ruthazer is a mapmaker but, his landscape is the developing brain - specifically the neuronal circuitry, which is the network of connections between nerve cells. His research at The Montreal Neurological Institute ...

Getting wired: How the brain does it

Aug 26, 2009

In a new study, researchers at the Montreal Neurological Institute and Hospital (The Neuro), McGill University have found an important mechanism involved in setting up the vast communications network of connections ...

Recommended for you

A new cause of mental disease?

1 hour ago

Astrocytes, the cells that make the background of the brain and support neurons, might be behind mental disorders such as depression and schizophrenia, according to new research by a Portuguese team from ...

Molecular basis of age-related memory loss explained

Jul 22, 2014

From telephone numbers to foreign vocabulary, our brains hold a seemingly endless supply of information. However, as we are getting older, our ability to learn and remember new things declines. A team of ...

The neurochemistry of addiction

Jul 22, 2014

We've all heard the term "addictive personality," and many of us know individuals who are consistently more likely to take the extra drink or pill that puts them over the edge. But the specific balance of ...

Study examines blood markers, survival in patients with ALS

Jul 21, 2014

The blood biomarkers serum albumin and creatinine appear to be associated with survival in patients with amyotrophic lateral sclerosis (ALS) and may help define prognosis in patients after they are diagnosed with the fatal ...

User comments

Adjust slider to filter visible comments by rank

Display comments: newest first

Whydening Gyre
1 / 5 (1) May 28, 2014
Think of all the TV we watch and get synched to... Frank Zappa had it right, back in the late 60's, with his "I'm the Slime" oozing out of your TV set... song...:-)