It has been more than 20 years since scientists discovered that mutations in the gene huntingtin cause the devastating progressive neurological condition Huntington's disease, which involves involuntary movements, emotional disturbance and cognitive impairment. Surprisingly little, however, has been known about the gene's role in normal brain activity.
Now, a study from The Scripps Research Institute's (TSRI's) Florida campus and Columbia University shows it plays a critical role in long-term memory.
"We found that huntingtin expression levels are necessary for what is known as long-term synaptic plasticity—the ability of the synapses to grow and change—which is critical to the formation of long-term memory," said TSRI Assistant Professor Sathyanarayanan V. Puthanveettil, who led the study with Nobel laureate Eric Kandel of Columbia University.
In the study, published recently by the journal PLOS ONE, the team identified an equivalent of the human huntingtin protein in the marine snail Aplysia, a widely used animal model in genetic studies, and found that, just like its human counterpart, the protein in Aplysia is widely expressed in neurons throughout the central nervous system.
Using cellular models, the scientists studied what is known as the sensory-to-motor neuron synapse of Aplysia—in this case, gill withdrawal, a defensive move that occurs when the animal is disturbed.
The study found that the expression of messenger RNAs of huntingtin—messenger RNAs are used to produce proteins from instructions coded in genes—is increased by serotonin, a neurotransmitter released during learning in Aplysia. After knocking down production of the huntingtin protein, neurons failed to function normally.
"During the learning, production of the huntingtin mRNAs is increased both in pre- and post-synaptic neurons—that is a new finding," Puthanveettil said. "And if you block production of the protein either in pre- or post-synaptic neuron, you block formation of memory."
The findings could have implications for the development of future treatments of Huntington's disease. While the full biological functions of the huntingtin protein are not yet fully understood, the results caution against a therapeutic approach that attempts to eliminate the protein entirely.
The first author of the study, "Huntingtin Is Critical Both Pre- and Postsynaptically for Long-Term Learning-Related Synaptic Plasticity in Aplysia," is Yun-Beom Choi of Columbia University. Other authors include Beena M. Kadakkuzha, Xin-An Liu and Komolitdin Akhmedov of TSRI. For more information on the study, see http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0103004
The work was supported by the Howard Hughes Medical Institute, the National Institutes of Health (Grant NS053415), the Whitehall Foundation and the State of Florida.
Eric Sauter | Eurek Alert!
Strong Evidence – New Insight in Muscle Function
27.04.2015 | Austrian Science Fund FWF
Cell fusion ‘eats up’ the ‘attractive cell’ in flowering plants
27.04.2015 | Institute of Transformative Bio-Molecules (WPI-ITbM), Nagoya University
KAIST researchers published an article on the development of a novel technique to precisely track the 3-D positions of optically-trapped particles having complicated geometry in high speed in the April 2015 issue of Optica.
Daejeon, Republic of Korea, April 23, 2015--Optical tweezers have been used as an invaluable tool for exerting micro-scale force on microscopic particles and...
A very small and rare species of shark is swimming its way through scientific literature. But don't worry, the chances of this inches-long vertebrate biting...
Ever since computers have been small enough to be fixtures on desks and laps, their central processing has functioned something like an atomic Etch A Sketch, with electromagnetic fields pushing data bits into place to encode data.
Unfortunately, the same drawbacks and perils of the mechanical sketch board have been just as pervasive in computing: making a change often requires starting...
How is lightning initiated in thunderclouds? This is difficult to answer - how do you measure electric fields inside large, dangerously charged clouds? It was discovered, more or less by coincidence, that cosmic rays provide suitable probes to measure electric fields within thunderclouds. This surprising finding is published in Physical Review Letters on April 24th. The measurements were performed with the LOFAR radio telescope located in the Netherlands.
How is lightning initiated in thunderclouds? This is difficult to answer - how do you measure electric fields inside large, dangerously charged clouds? It was...
Max Planck researcher Buhalqem Mamtimin determines how much nitrogen oxide is released into the atmosphere from agriculturally used oases.
In order to make statements about current and future air pollution, scientists use models which simulate the Earth’s atmosphere. A lot of information such as...
23.04.2015 | Event News
23.04.2015 | Event News
13.04.2015 | Event News
27.04.2015 | Life Sciences
27.04.2015 | Power and Electrical Engineering
27.04.2015 | Life Sciences