Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Molecule Awakens and Maintains Neural Connections

14.09.2004


A neuron from the brain in which DNA has been stained red and the Dasm1 protein, which controls mammalian dendrite development, has been stained green. Dasm1 is abundantly expressed in the dendrites of neurons, but not in the axons.


Researchers have discovered a critical protein that regulates the growth and activation of neural connections in the brain. The protein functions in the developing brain, where it controls the sprouting of new connections and stimulates otherwise silent connections among immature neurons, and potentially in the mature brain as well, where it may play a role in memory formation.

The researchers published their discovery of the protein, called dendrite arborization and synapse maturation 1, or Dasm1, in two papers in the September 7, 2004, issue of the Proceedings of the National Academy of Sciences. They were led by Howard Hughes Medical Institute investigators Yuh Nung Jan and Lily Yeh Jan. The first author on both papers was Song-Hai Shi in the Jans’ laboratory at the University of California, San Francisco.

Dendritic spines are mushroom-shaped protuberances that extend from the surface of the cable-like axon of a neuron. Dendrites receive chemical signals that trigger nerve impulses in the form of neurotransmitters launched from neighboring neurons. Growth of new dendrites can therefore increase the connection between neurons. Changes in the strength of connections, known as long-term potentiation, allow the brain to create memories.



In exploring the growth and development of dendritic spines, Shi, the Jans, and their colleagues first identified a gene in the fruit fly Drosophila that appears to play a role in regulating dendrite growth, or “arborization.” In comparing the fruit fly gene with databases of vertebrate genomes, they identified a similar homologue in mice, which they named Dasm1.

Their initial studies revealed that the gene was highly expressed in the brains of embryonic mice. “A major reason we became interested in this molecule is that when we used antibody markers to look at the distribution of the protein, we saw it primarily in the dendrites, with very little in the axons,” said Yuh Nung Jan. “If you look at areas of the hippocampus rich in dendrites, they just light up, whereas in axonal areas there is very little evidence for the presence of this protein.”

When the researchers blocked the activity of the version of the Dasm1 gene found in rats, they found dendrite arborization to be drastically reduced in cultured brain cells.

The researchers also studied the effects of Dasm1 on the maturation of neuronal connections, or synapses. Newly formed, immature synapses are silent, meaning they lack a type of receptor called AMPA receptors, which receive neurotransmitter molecules. However, these neurons do have other receptors, called NMDA receptors, which are associated with long-term changes in the strength of neuronal signaling. During maturation, dendrites acquire active AMPA receptors, and it was not known whether this process depended on Dasm1.

Shi, the Jans, and their colleagues found that interfering with Dasm1 function drastically decreased AMPA receptor function. Their experiments also revealed that Dasm1 was responsible for “awakening” silent synapses and promoting the maturation of the neuronal connections, a process that depends on dendrite development.

“While we expected that Dasm1 would contribute to dendrite arborization, the finding that reducing its activity caused a dysfunction in synaptic maturation was quite surprising,” Yuh Nung Jan said.

According to Lily Yeh Jan, the finding of a single control molecule for both maturation and arborization is significant. “It’s known that the ratio of AMPA to NMDA receptors increases during development, and it also increases during long-term potentiation,” she said. “So, Song-Hai’s identification of a molecule that is likely to be important for dendrite arborization and also to control synapse maturation is quite important.”

While the function of Dasm1 is not yet known, said Lily Yeh Jan, the protein’s structure hints that it is a receptor molecule. “The Dasm1 molecule has a large extracellular domain, a single transmembrane domain and a large cytoplasmic domain,” she said. “So that is characteristic of receptor molecules.” This suggests that, like other receptors, Dasm1 nestles in the cell membrane, receiving chemical signals that activate cellular processes.

Further evidence that Dasm1 is a receptor comes from an experiment in which Shi treated neurons with a molecule that mimicked Dasm1, but in which the portion of the molecule that extends into the cell had been replaced by a segment from another protein - rendering it unable to interact with Dasm1’s usual partners inside the cell. This treatment impaired dendrite growth, “which gives us hints that there is a signaling pathway within the cell activated by Dasm1 that we need to explore,” she said.

The next step, the researchers say, is to knock out the Dasm1 gene in mice to see whether the observations they have made in isolated brain tissue and cultured cells can be extended to neural development in vivo.

Jennifer Michalowski | EurekAlert!
Further information:
http://www.hhmi.org

More articles from Life Sciences:

nachricht Zap! Graphene is bad news for bacteria
23.05.2017 | Rice University

nachricht Discovery of an alga's 'dictionary of genes' could lead to advances in biofuels, medicine
23.05.2017 | University of California - Los Angeles

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Turmoil in sluggish electrons’ existence

An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.

We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...

Im Focus: Wafer-thin Magnetic Materials Developed for Future Quantum Technologies

Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.

Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...

Im Focus: World's thinnest hologram paves path to new 3-D world

Nano-hologram paves way for integration of 3-D holography into everyday electronics

An Australian-Chinese research team has created the world's thinnest hologram, paving the way towards the integration of 3D holography into everyday...

Im Focus: Using graphene to create quantum bits

In the race to produce a quantum computer, a number of projects are seeking a way to create quantum bits -- or qubits -- that are stable, meaning they are not much affected by changes in their environment. This normally needs highly nonlinear non-dissipative elements capable of functioning at very low temperatures.

In pursuit of this goal, researchers at EPFL's Laboratory of Photonics and Quantum Measurements LPQM (STI/SB), have investigated a nonlinear graphene-based...

Im Focus: Bacteria harness the lotus effect to protect themselves

Biofilms: Researchers find the causes of water-repelling properties

Dental plaque and the viscous brown slime in drainpipes are two familiar examples of bacterial biofilms. Removing such bacterial depositions from surfaces is...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

AWK Aachen Machine Tool Colloquium 2017: Internet of Production for Agile Enterprises

23.05.2017 | Event News

Dortmund MST Conference presents Individualized Healthcare Solutions with micro and nanotechnology

22.05.2017 | Event News

Innovation 4.0: Shaping a humane fourth industrial revolution

17.05.2017 | Event News

 
Latest News

Scientists propose synestia, a new type of planetary object

23.05.2017 | Physics and Astronomy

Zap! Graphene is bad news for bacteria

23.05.2017 | Life Sciences

Medical gamma-ray camera is now palm-sized

23.05.2017 | Medical Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>