Collaborative Research: Evolutionary Origins of the Brain Energetics and Adaptive Plasticity of Humans

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The human brain is distinguished by costly energetic demands and enhanced plasticity. This combination of factors underlies some of the most unique cognitive capacities of our species. The brain's capacity for learning is greatest during childhood and involves the formation and refinement of new neuronal connections. This process is driven by high rates of energy consumption. This research project will identify the genetic changes during evolution that brought about the human brain and explore the causal link between the development of brain plasticity and metabolism. A major aim of this project involves charting the changes in the brain's energy utilization during the different maturational stages of humans. To accomplish this goal, the interdisciplinary team is using positron emission tomography scans of brain glucose consumption over the course of development from birth to adult stages. These results will be integrated with the patterns presented by RNA and protein data on the thousands of genes that are expressed at changing levels in different brain regions across the same developmental stages. Comparative data on the developmental expression of proteins and neuron morphology in great apes and macaque monkeys are also being obtained to determine whether the progression of molecular and cellular changes in human brain development are distinctively different from our close relatives. The investigators expect to find coordinated expression patterns in brain energetic and brain plasticity genes showing evidence that adaptive evolution occurred in their regulatory machinery during the origin of humans. The results should provide important clues about the organization and function of the molecular machinery that underpins the type of human brain plasticity that gives our species its exceptional capacity to incorporate experience and learning into the production of culture. By focusing attention on brain energetic and brain plasticity genes that show adaptive evolution during recent human ancestry but are currently fixed across human populations, this project's focus on shared genes that define human cognitive abilities reinforces the conclusion of a common humanity. Thus the results of this project should be of interest to the general public and to scientists across a wide variety of disciplines, including anthropology, neuroscience, molecular evolution, bioenergetics, endocrinology and pediatrics. Experimental determination of total brain energetics during growth will enhance our ability to understand the age-specific tradeoffs that the acquisition of larger brains would have required during human evolutionary history, while also providing a new context in which to understand metabolic diseases such as diabetes. Furthermore, this project will advance research and education by providing training opportunities for individuals at the undergraduate, graduate and postdoctoral levels.