One of the great challenges in neurobiology is to decipher the molecular mechanisms that integrate synaptic plasticity, learning and memory. Dr. Franke's project examines the protein kinase called Akt, which is a key molecule at the interphase between the extracellular environment and intracellular homeostasis. The project seeks to clearly define the role Akt signaling as a new molecular pathway at the center of neuronal cell biology, synaptic plasticity and cognition. By expanding Dr. Franke's previous research on the identification and characterization of Akt, this project will examine novel implications of the Akt kinase in higher brain function using genetically modified mice. The project is based on the hypothesis that the Akt-dependent regulation of specific receptors in the brain is involved in mediating its role in learning and synaptic plasticity. To test this hypothesis, behavioral, electrophysiological, biochemical and cell biological experiments will be performed in an innovative and interdisciplinary project team that combines diverse scientific know-how and technical expertise. Considering the crucial role of Akt in neuronal cell biology, the results of the study will provide significant new insights into the cellular basis for the processing of memories. Thus, the project will reveal important new information about basic mechanisms contributing to higher brain function that have not yet been investigated. The project includes training opportunities for pre- and post-doctoral students, and involves high school and undergraduate students as active participants in the research. In addition, the investigators will present their research findings at local schools and undergraduate colleges. A special emphasis will be placed on the integration of students from underrepresented population groups by including summer students from minority-based institutions such as Hunter College (City University of New York) and Long Island University (Brooklyn).
"What are the critical neurobiological mechanisms linking cellular signals to behavior?" One of the great challenges in neurobiology is to decipher the molecular mechanisms underlying synaptic plasticity, learning and memory. One signaling pathway with significant implications in neuronal function is the intracellular cascade leading to the activation of the Akt serine/threonine kinase. Mainly by the use of pharmacological inhibitors, research has suggested a role for Akt and its upstream regulators in memory processing and long-lasting synaptic plasticity. These results motivated us to directly address the involvement of Akt by analyzing Akt-mutant mice in biochemical, behavioral and electrophysiological assays. Results of our studies have provided us with significant insights into basic molecular mechanisms of learning and point out the highly selective involvement of Akt1 in hippocampal synaptic plasticity. The broad impact of the project was achieved by including high school, undergraduate and graduate students as active participants in the project. We also offered high school students research opportunities during the summer months and provided research opportunities for under-represented minorities. Students engaged in these activities were assigned to a small project in the lab under supervision of more senior staff, with an emphasis of doing actual research at the bench such as genotyping, image analysis and behavioral testing. Undergraduate students had the opportunity to present their findings at scientific meetings incuding the Annual Meeting of the Society for Neuroscience. The project’s training value was underscored by the year-long participation of undergraduate students. 12 undergraduates participated in this research over the course of the project at the NYU School of Medicine, many of who had the chance to present during journal clubs and group meetings, and also submit abstract for consideration at undergraduate research conferences and scientific meetings. Participants in the study included underrepresented minorities at all levels including faculty colleagues. Over half of all participants of the project were female. Educational outreach activities related to the performed research included presentations to K-12 students; presentations at scientific meetings including posters given by undergraduates; and symposia related to the funded research that were held at national and international meetings. Other activities included regularly scheduled journal clubs and neuroscience seminars.
