Molecular Mechanisms of Memory: Identification and Modeling

ABSTRACT (i) Understanding how memory is formed is an essential question in Neuroscience and is necessary to treat memory disorders, like Alzheimer’s disease. Biological assays are used to identify the molecular mechanisms responsible for memory formation, while computer-simulated models of neural networks are created to investigate how hippocampal networks encode memory. Few studies investigated, however, how learning-induced neuronal molecular alterations identified by biologists influence these computer-simulated networks, due to the lack of scientific interaction between these two types of investigations. (ii) We therefore created a consortium of biologists, biophysicians and mathematicians to bridge these two disciplines and begin to fill this gap. We will combine our knowledge to create more realistic computer CA1 neuron models. Also, we will identify how hippocampal activation of CREB, a transcription factor highly implicated in memory, results in better memory formation as previously reported by the biologists. (iii) To accurately model CREB-dependent neuronal alterations that lead to better memory formation, we propose additional biological experiments identifying how CREB modulates afterhyperpolarization and GABAergic transmission. Also, we will create new highly realistic BAM neural networks to evaluate how CREB-dependent alterations affect the critical capacity of these networks. (iv) The outcome of this research will be three-fold: 1) we will provide new and more realistic models of CA1 pyramidal neurons and complex BAM networks 2) we will identify new neuronal alterations resulting from CREB-dependent transcription 3) we will evaluate the influence of these and previously identified CREB-dependent neuronal adaptations on the memory critical capacity of these networks.