A shared role for CREB in declarative and procedural memory

Different parts of the mammalian brain are associated with different forms of memory. Of these, the hippocampus is involved in memory for events and ideas, collectively known as declarative memory; the striatum is involved in the formation of habits. Dynamic modulation of synaptic strength (synaptic plasticity) is widely believed to be the mechanism by which memories are stored in the brain. It has been hypothesized that similar mechanisms of synaptic plasticity in different brain regions may underlie different forms of memory.; The transcription factor CREB is critical for long-lasting synaptic plasticity and long-term memory in the invertebrates Aplysia and Drosophila. In mammals, the evidence for a role for CREB in learning and synaptic plasticity is less strong. In this thesis, I have used transgenic mice to examine the role of CREB and related transcription factors in hippocampus-dependent spatial learning and striatum-dependent habit learning. My study attempts to improve on previously published work in several ways, with better spatial restriction, better temporal control, and a broader interference with CREB-family transcription factors than earlier studies.; In the hippocampus, I find that interference with CREB in area CA1 of the dorsal hippocampus disrupts spatial memory. This deficit is specific to long-term memory. Strikingly, I find no deficit in context conditioning, a hippocampus-dependent learning task that is not specifically dependent on the dorsal hippocampus, as spatial learning is. This dissociation focuses attention on the functional distinction between the dorsal and ventral hippocampus, a distinction that has been neglected in the study of learning and memory in genetically modified mice. Finally, I find a deficit in some forms of long-lasting synaptic plasticity but not in others, emphasizing that synaptic plasticity has many forms.; In a separate line of transgenic mice, I examine the role of CREB-family transcription factors in striatum-dependent habit learning. I find a deficit in habit learning, but no deficit in hippocampus-dependent spatial learning in these mice. These data represent the first examination of striatum-dependent learning in genetically modified mice, to my knowledge. Together, my findings support a shared role for CREB-family transcription factors in declarative and procedural learning factors in striatum-dependent habit learning. I find a deficit in habit learning, but no deficit in hippocampus-dependent spatial learning in these mice. These data represent the first examination of striatum-dependent learning in genetically modified mice, to my knowledge. Together, my findings support a shared role for CREB-family transcription factors in declarative and procedural learning.