The findings could shed new light on human learning and neurological and psychiatric disorders
A team led by a Scripps Research Institute scientist has for the first time identified a new gene that is required for memory formation in Drosophila, the common fruit fly. The gene may have similar functions in humans, shedding light on neurological disorders such as Alzheimer's disease or human learning disabilities.
The study was published in the September 9, 2010 edition (Vol. 67, No. 5) of the journal Neuron.
"This is the first time we have a new memory and learning gene that lies outside what has been considered the most fundamental signaling pathway that underlies learning in the fruit fly," said Ron Davis, chair of Scripps Research Department of Neuroscience who led the study. "Since many of the learning and memory genes originally identified in the fruit fly are clearly involved in human neurological or psychiatric diseases, this discovery may offer significant new insights into multiple neurological disorders. We're definitely in the right ballpark."
The study shows that different alleles or mutant forms of the gene, known as gilgamesh (gish), are required for short-term memory formation in Drosophila olfactory associative learning - learning that links a specific odor with a negative or positive reinforcer.
Because Drosophila learning genes are known to be conserved in higher organisms including humans, they often provide new insights into human brain disorders. For example, the Drosophila gene known as dunce, which Davis helped identify several years ago, provided clues to the genetics of the devastating psychiatric condition of schizophrenia. Recent studies have revealed that the human version of the dunce gene is a susceptibility determinant for schizophrenia. In a similar way, any new learning gene identified in Drosophila, including gilgamesh, may provide new clues to genes involved in human neurological or psychiatric disorders.
"We're still early in the process of making connections between Drosophila memory and learning genes and the pathology of human disease," Davis said, "but it's already clear that many of these genes will provide important conceptual information and potential insights into human brain disorders. In addition, there is every reason to believe that their gene products will be one day become the target of new drugs to enhance cognition. Uncovering this new gene and its signaling pathway helps bring us that much closer to this goal."
New Gene, New Pathway
To identify the new gene, Davis and his colleagues used a novel screen for new memory mutants, looking for lines that showed abnormal learning when only one of two copies of the gene was mutant.
"We used a dominant screen because we realized that behavior such as learning and memory are very sensitive to gene dosage," Davis said. "That is, the mutation of just one copy of a gene involved in behavior is often sufficient to produce an abnormality."
The formation of new memories occurs, in part, through the activation of molecular signaling pathways within neurons that comprise the neural circuitry for learning, and for storing and retrieving those memories.
One of the things that makes the function of gish so interesting, Davis noted, is the fact that it is independent of mutations of the rutabaga gene, a Drosophila memory-learning pathway that is known to be essential for memory formation. The rutabaga mutants convert ATP, the energy chip of cells, into cyclic AMP or cAMP, which plays a critical role in olfactory learning in Drosophila.