Our lab is interested in the molecular basis of neuroplasticity with an emphasis on the role of signal transduction crosstalk between the cAMP, calcium and the MAP kinase signaling pathways. Our lab uses an interdisciplinary approach which includes transgenic mouse technology, signaling mechanisms in cultured neurons, electrophysiology and behavioral studies.
Memory has two functionally and mechanistically distinct components: a short-term phase that lasts no more than several hours, and a long-term component that can continue for days or longer. The formation of long-term memory requires transcription of specific genes and de novo translation.
Another property of long-term memory is a dependency on the cAMP, calcium and MAP kinase signal transduction systems.
A key event in the generation of hippocampus-dependent long-term memory is activation of NMDA receptors with increases in intracellular free calcium. This triggers a series of events required for long-term changes at the synapse including the activation of calcium-stimulated adenylyl cyclases and MAP kinase. Transgenic ice lacking calcium-stimulated adenylyl cyclases do not develop long-term memory; mice overexpressing a calcium-stimulated adenylyl cyclase have superior memory for novel projects. Our recent data indicates that calcium-stimulated adenylyl cyclases are required for the activation and nuclear translocation of MAP kinase. These studies identify the calcium-stimulated adenylyl cyclase as a pharmacological window of opportunity for the development of drugs to enhance memory.