Think global, act local: New roles for protein synthesis at synapses

May 10, 2012

(Medical Xpress) -- How do we build a memory in the brain? It is well known that for animals (and humans) new proteins are needed to establish long-term memories. During learning information is stored at the synapses, the junctions connecting nerve cells. Synapses also require new proteins in order to show changes in their strength (synaptic plasticity). Historically, scientists have focused on the cell body as the place where the required proteins are synthesized. However, in recent years there has been increasing focus on the dendrites and axons (the compartments that meet to form synapses) as a potential site for protein synthesis.

Protein synthesis machines have been observed there as well as a limited number of their templates, the messenger . The limited number of mRNAs observed in dendrites and axons placed constraints on the constellation of proteins that could be synthesized to help work and change. Researchers from Erin Schuman's lab at the Max Planck Institute (MPI) for Brain Research used new-generation sequencing to directly identify a very large number (over 2500) of new that are present at the axons and dendrites. Using high-resolution imaging techniques they were able to both quantify and visualize individual mRNA molecules. They published their findings in the latest issue of Neuron.

This video is not supported by your browser at this time.
Erin Schuman and her colleagues describe how they were able to detect numerous new mRNAs in the processes of neurons with unprecedented sensitivity. Video: Neuron.

Using microarray approaches and/or in situ hybridization techniques, many different groups had each identified a hundred or so mRNAs that might reside in the dendrites. By analyzing and comparing these studies the Schuman team discovered something surprising: it seems that not a single mRNA type was found in all three studies. This observation made the scientist at the MPI for wonder whether the already discovered mRNAs are just the tip of the iceberg and whether there were many more mRNA molecules waiting to be discovered.

In order to find out the researchers dissected the neuropil layer of the rat hippocampus. This layer comprises a high concentration of axons and dendrites, but lacks the cell bodies of pyramidal neurons (the principal cell type in the hippocampus and other brain areas). By using sensitive high-resolution sequencing techniques, mRNAs could be detected which, due to their lower concentrations, were not discovered before. The researchers found an impressive number of 2550 unique mRNAs present at the dendrites and/or axons. To determine the relative abundance in the neuronal cells, the scientists at Erin Schuman's lab used the Nanostring nCounter, a new technique allowing the high-resolution visualization and quantification of single mRNA molecules. They found that the concentration of mRNAs in the euronal cells varies by three orders of magnitude. Additionally, the researchers were able to classify many of the mRNAs and determine their function in synaptic plasticity. These include signaling molecules, scaffolds and the receptors for neurotransmitter molecules. In addition, many mRNAs coding for protein implicated in diseases like autism were discovered in the dendrites and axons. Finally, by using advanced imaging techniques, the researchers could directly visualize some of the mRNAs in the neuronal dendrites, hundreds of micrometers from the cell body.

These results reveal a previously unappreciated enormous potential for the local machinery to supply, maintain and modify the dendritic and synaptic protein population. It seems that neurons use a local control mechanism much in the same way that modern societies have learned that the most efficient means to distribute goods to the population is to use local distribution centers.

More information: Iván J. Cajigas, Georgi Tushev, Tristan J. Will, Susanne tom Dieck, Nicole Fuerst & Erin M. Schuman, The Local Transcriptome in the Synaptic Neuropil Revealed by Deep Sequencing and High- Resolution Imaging. Neuron 74: 1-14, May 10, 2012

Related Stories

Recommended for you

Surprising similarity in fly and mouse motion vision

July 29, 2015

At first glance, the eyes of mammals and those of insects do not seem to have much in common. However, a comparison of the neural circuits for detecting motion shows surprising parallels between flies and mice. Scientists ...

Research grasps how the brain plans gripping motion

July 28, 2015

With the results of a new study, neuroscientists have a firmer grasp on the way the brain formulates commands for the hand to grip an object. The advance could lead to improvements in future brain-computer interfaces that ...

New research rethinks how we grab and hold onto objects

July 28, 2015

It's been a long day. You open your fridge and grab a nice, cold beer. A pretty simple task, right? Wrong. While you're debating between an IPA and a lager, your nervous system is calculating a complex problem: how hard to ...

It don't mean a thing if the brain ain't got that swing

July 27, 2015

Like Duke Ellington's 1931 jazz standard, the human brain improvises while its rhythm section keeps up a steady beat. But when it comes to taking on intellectually challenging tasks, groups of neurons tune in to one another ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.