The Role of Phosphorylated Creb in the Preferential Recruitment of Immature Dentate Granule Neurons into Learning and Memory Circuitry

................................................................................................................................... ii ACKNOWLEDGEMENTS ........................................................................................................... iii LIST OF FIGURES ....................................................................................................................... vi LIST OF TABLES ........................................................................................................................ vii LIST OF ABBREVIATIONS ...................................................................................................... viii 1.0. GENERAL INTRODUCTION ................................................................................................ 1 1.1. Learning and Memory .................................................................................................. 1 1.2. Neurogenesis: A Historical Perspective ....................................................................... 2 1.3. The Neurogenic Brain .................................................................................................. 4 1.4. Functional Consequence of Hippocampal Neurogenesis ............................................. 7 1.5. Unique Physiological Properties of Newly Generated Dentate Granule Neurons ..... 11 1.6. Accelerated Functional Integration of 4-8 Week Old Dentate Granule Neurons ...... 12 1.7. Role of CREB in Intrinsic Neuronal Excitability....................................................... 13 1.8. Memory Allocation as a Competitive Process: Role of CREB and Intrinsic Neuronal Excitability ................................................................................................. 14 1.9. CREB and the Preferential Recruitment of 4-8 week Old Dentate Granule Neurons into Memory Circuitry ................................................................................. 16 1.10. Current Experiment .................................................................................................. 17 2.0. METHODS ............................................................................................................................ 17 2.1. Subjects ...................................................................................................................... 17 2.2. BrdU Administration .................................................................................................. 18 2.3. Water Maze Procedure ............................................................................................... 18 2.4. Tissue Preparation ...................................................................................................... 20 2.5. BrdU+pCREB Double-Label Immunofluorescence .................................................. 21 2.6. Quantification ............................................................................................................. 22 3.0. RESULTS .............................................................................................................................. 23 3.1. Water Maze Results ................................................................................................... 23 3.2. BrdU+pCREB Immunofluorescence ......................................................................... 26