A Gene Linked to Disease Found to Play a Critical Role in Normal Memory Development

A Gene Linked to Disease Found to Play a Critical Role in Normal Memory Development JUPITER, FL, August 12, 2014 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:doi/10.1371/journal.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.

About The Scripps Research Institute

The Scripps Research Institute (TSRI) is one of the worlds largest independent, not-for-profit organizations focusing on research in the biomedical sciences. TSRI is internationally recognized for its contributions to science and health, including its role in laying the foundation for new treatments for cancer, rheumatoid arthritis, hemophilia, and other diseases. An institution that evolved from the Scripps Metabolic Clinic founded by philanthropist Ellen Browning Scripps in 1924, the institute now employs about 3,000 people on its campuses in La Jolla, CA, and Jupiter, FL, where its renowned scientists including three Nobel laureates work toward their next discoveries. The institutes graduate program, which awards PhD degrees in biology and chemistry, ranks among the top ten of its kind in the nation. For more information, see www.scripps.edu.

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