Therefore, we sought to identify molecules that promote learning and memory by studying the THA phenotype. Since the THA rat strain was established through repeated mating for more than 100 generations to date 10, 11, we speculate that specific molecular factors are underlying the rats’ high learning ability. Owing to their abilities to learn and remember by quickly adapting to previously inexperienced conditions and environments, THA rats have exceptional results in various behavioral tests when compared to Wistar rats 4, 5, 6, 7, 8, 9. THA rats are unique experimental animals with a connaturally guaranteed high learning ability, strong memory, rapid acquisition of behavioral skills, and minor interindividual differences 4, 5, 6. THA rats were generated via the selective mating of sibling rats that exhibited a high avoidance rate in the free-operant behavioral task based on the Sidman avoidance schedule. We previously established and maintained Tokai high avoider (THA) rats, a unique rat strain without any genetic manipulation, which is derived from JCL-Wistar rats 4, 5, 6. As the molecular mechanisms involved in learning and memory formation in the brain share considerable similarities between humans and rodents 3, novel approaches for the prevention and treatment of learning deficits can be developed through studying animal models of excellent learning ability. Rodents are suitable for performing behavioral tests to evaluate cognitive ability and thus, are indispensable experimental models in the field of behavioral science. Rodent models are of particular relevance for investigating the molecular pathophysiology of and developing treatments for higher brain dysfunction conditions such as Alzheimer’s and Parkinson’s diseases, traumatic brain injury, posttraumatic stress disorder, and other neurological conditions 1. Identifying appropriate BCAA nutritional supplements and activation methods may thus hold potential for the prevention and amelioration of higher brain dysfunction, including learning disabilities and dementia.īehavioral studies utilize experimental rodent models to explore brain function, including learning and memory processes 1, 2. Feeding THA rats with a BCAA-reduced diet decreased acetylcholine levels and learning ability, thus, maintaining high BCAA levels while their proper metabolism in the hippocampus is the mechanisms underlying the high learning ability in THA rats.
THA rats maintained high blood BCAA levels via uptake of BCAAs in the small intestine and suppression of BCAA catabolism in the liver. Higher branched-chain amino acid (BCAA) levels and enhanced activation of BCAA metabolism-associated enzymes were observed in THA rats, suggesting that acetyl-CoA and acetylcholine are synthesized through BCAA catabolism. In the current study, we compare the hippocampi of parental strain Wistar rats to those of THA rats via metabolomic analysis in order to identify molecules specific to the THA rat hippocampus.
THA rats established by crossing those with high learning capacity exhibit excellent learning and memory abilities, but the factors underlying their phenotype are completely unknown.
To fully understand the mechanisms governing learning and memory, animal models with minor interindividual variability and higher cognitive function are required.