Model for brain signaling flawed, new study finds

January 10, 2013, University of Rochester Medical Center

A new study out today in the journal Science turns two decades of understanding about how brain cells communicate on its head. The study demonstrates that the tripartite synapse – a model long accepted by the scientific community and one in which multiple cells collaborate to move signals in the central nervous system – does not exist in the adult brain.

"Our findings demonstrate that the tripartite synaptic model is incorrect," said Maiken Nedergaard, M.D., D.M.Sc., lead author of the study and co-director of the University of Rochester Medical Center (URMC) Center for Translational Neuromedicine. "This concept does not represent the process for transmitting signals between neurons in the brain beyond the ."

The central is home to many different cells. While neurons tend to garner the most attention, it is only recently that the function of the brain's other cells have been fully appreciated. Glial cells known as astrocytes, for example, had long been considered mainly the "glue" that helps hold all the other cells in the in place. Scientists now understand that that these cells are essential to maintaining a healthy environment in the brain by helping carry out functions such as removing waste.

"Neurons are like a racing car," said Nedergaard. "While the driver gets all the credit, there are often 20 people behind the scenes that are optimizing his or her success."

However, when it comes to moving signals between neurons in the brain it turns out that the scientists may have vastly exaggerated the role of the astrocyte.

Neurons are connected to each other via or "arms" that extend from the cell's main body. Communication between neighboring neurons takes place where axons meet other nerve cells – called a synaptic juncture – when an causes chemicals called neurotransmitters or glutamate to be released by one cell and "read" by receptors on the surface of the opposite. The two cells do not actually touch, so the chemicals messages must pass through a gap in the synaptic juncture. The space around this gap is insulated by astrocytes.

Under the tripartite synapse model, both astrocytes and neurons were believed to play a role in the "conversation" between cells. This understanding was largely based on animal models which showed active receptors and neurotransmission between not only the nerve cells but also the nearby astrocytes.

Specifically, a key neurotransmission receptor called metabotropic glutamate receptor 5 (mGluR5) was observed to be present and active in astrocytes at the synaptic juncture. It was also observed that when the mGluR5 receptor was activated, the astrocytes would release chemical transmitters that were in turn read by the . These findings led to the conclusion that must in some manner modulate the signaling process between .

While this model has held sway for decades, scientists have long been frustrated by their inability to influence this process by targeting it with drugs.

"If this concept was correct, it should have given rise to a clinical trial by now," said Nedergaard. "It has not, which tells us that with so many labs work on this for 20 years that there must be something wrong."

One of the barriers to understanding precise mechanics of passing signals from one neuron to another has been the inability to observe this process in the . The tripartite synapse model was based – in part – by examining the activity in the brains of very young rodents. Adult rodents could not be similarly studied because the synapses in the brain would die before they could be fully analyzed. This ultimately led to the presumption that the signaling process that was witnessed in the young brain carried over to adulthood.

Collaborating with researchers at the University of Rochester's Institute of Optics, Nedergaard and her team developed a new 2-photon microscope that enables researchers to observe glia activity in the living brain. Using both this method and by analyzing the gene and protein expression in the brain the researchers discovered that the mGluR5 largely disappear in the glial cells of adult mice meaning that these do not directly respond to synaptic neuronal signalling, thus calling into question the concepts that drive most of ongoing research in the field.

"The process of neuron-glial transmission as conceived by the tripartite synapse model appears to just be a simplistic signaling pathway that 'teaches' the synapse how to behave," said Nedergaard. "Once the matures, it goes away."

Explore further: Once considered mainly 'brain glue,' astrocytes' power revealed

More information: "Glutamate-Dependent Neuroglial Calcium Signaling Differs Between Young and Adult Brain," by W. Sun et al., Science, 2013.

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not rated yet Jan 10, 2013
The writer has me confused:
Scientists now understand that that these cells are essential to maintaining a healthy environment in the brain by helping carry out functions such as removing waste.


is assigned the function the writer assigns macroglia(astrocytes.)

Is mGluR5 (always/never/temporarily)present? In microglia?

not rated yet Jan 10, 2013
"Astrocytes (etymology: astron gk. star, cyte gk. cell), also known collectively as astroglia, are characteristic star-shaped glial cells in the brain and spinal cord."

Astrocytes are a specialized form of glial cell. This paper argues that mGluR5 is only present and active in young developing mouse brains, but not so much in adults.

1 / 5 (2) Jan 10, 2013
Blah bla bla blab blah blab blah bla bla blah bla, bla!
There... you may quote me. I am a Ph of D and a fabulous researcher
and pundit of obfuscation and demagogery. (I also can't spelladamn without my thirty G secretary. Wow.

PS. The real truth is the most juicy science stuffed in my career profile and vita, et al-chit... is due to my awesomely competent and really, really, smart graduate assistant and the two PhD candidates I superfise. They don't know how smart they really are they try too hard to be my clones. lol

Humans really think with their buttcells. Its all in thebutt. Yup. Inthebutt.
not rated yet Jan 10, 2013
What structures would host life?- Pn

From your first post.

Information is 'host' to everything.
Of course information theory is a frontier science.
The 'structures' of which have yet to be explored.

The proponents shy away from nothing:

As a proponent I can envision answers where the other sciences have fallen short or avoided.

not rated yet Jan 11, 2013
I hope you feel Ok . Do you have mental illness .
They did a great job about astrocytes and we need more research and investigate about this result
not rated yet Jan 11, 2013
I wonder if this has anything to do with the diminished plasticity of the brain with age? Recognizing certain sounds such as "L" in the english language is "programmed" when the human is a baby. Learning to discern "R" from "L" - for instance - is a difficult task for adult japanese, but comes naturally for all japanese-americans.

So, could it be that the lack of mGluR5 in the astrocytes of an adult brains is the cause of diminished learning capability?
not rated yet Jan 11, 2013
I do not know what diminished plasticity is.
I do not know what "recognition of sounds" is for a baby.
I do not know if "discerning" any sound is a process of cognitive "learning".
For example, I will assert that intact hearing and an intact brain will separate frequencies physically. (Tonotopy is the label used to describe that part of the process.)As a baby I had no way of assigning meanings that make sense to beings older than me from the functions arising from my senses delivered to my conscious state. My senses were busy morphing my brain ascribing my conscious state during awareness with never-before-put-to-test-after-birth senses. At birth, crying is the "big bang" of baby physics - without having the slightest cognitive meaning of what that event represented or caused.
The universe took shape. Your universe took shape.
"Meaning" 'condensed' from the input of your senses.

I hear the sounds of your words when I read them.
Everyone does this and no one is aware of this.
not rated yet Jan 13, 2013

Brain plasticity change every minutes and you can increase your brain's plasticity by learning more difficult task and I think we can maintain mGluR5 even after Puberty by improve your brain function ,so may be it plays role in be more smarter .
not rated yet Jan 14, 2013

Yes, but accordning to the above article, the astrocytes are only part of the synapse exchange of mGluR5 in very young animals. One has to wonder why that is... What I speculate is that this is related to the fantastic learning capabilities of (human) babies compared to human adults.
not rated yet Jan 14, 2013

I am not what you want to say, but I'll answer the one question that I found in your comment.

With "discern" I mean to recognize as a different sound. Adult japanese may know that "row" and "low" have different meanings, but their brains are not capable of separating the sound of "r" from the sound of "l". This has nothing to do with a cognitive knowledge of language.

Let me put it another way. If you would scan the brains of humans that were listening to "r-r-r-r-" and "l-l-l-l", you would find that in american subjects these two sound would elicit brain activity in different regions. In japanese subjects, it both sound would elicit reactions in only one brain region.

A young baby can separate all language sound from all languages, but it "un-learns" this for the sound that it does not encounter. It makes sense to prune the sound processing so that a brain can only separate the sound that make up his language. This makes the processing more efficient.
not rated yet Jan 15, 2013

I agree with you about what you said that babies brain can really separate the different sounds of language and I found an article that the babies can learn language when they are in womb so may be the mGluR5 have role in this processes and untill now we dont know if al human adult brain are lacking of mGluR5 we need to do more investigation especially for pepole who have ASD and other neurological dieases .

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