Fields of Research
- Memory Consolidation
- Chemosensory Mechanisms
Molecular basis of neuroplasticity; cAMP and calcium signal transduction mechanisms in the central nervous system; regulation of adenylyl cyclases; calmodulin- and calcium-regulated systems; regulation of neuron growth.
Our lab has been 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. culturedneurons, 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 memohas as asss bee.
Awards and Honors
NIH Javits Neuroscience Award
Mahan KL, Phan, T, Han, S, Wang, H, Chan, G, Scheiner, ZS, and Storm, DR. Circadian Oscillation of MAPK Activity and cAMP in the Hippocampus: Implications for Memory Persistence. Nature Neuroscience 11, 1074-1082
Shimizu, K, Phan T, Mansuy, I, and Storm, DR. Proteolytic Degradation of SCOP in the Hippocampus Contributes to Activation of MAP Kinase and Memory For Novel Objects. Cell 128:1219-1229.
Sindreu, CB, Scheiner, ZS & Storm, DR. Ca2+-Stimulated Adenylyl Cyclases Regulate ERK-Dependent Activation of MSK1 During Fear Conditioning. Neuron 53:79-89.
Chen, X, Garelick, M, Wang, H, Athos, J, Li, V and Daniel R. Storm. PI3 Kinase Signaling is Required for Retrieval and Extinction of Contextual Memory. Nature Neuroscience 8: 925-931.
Trinh, K and Storm, DR. Disruption of the Type 3 adenylyl cyclase reveals detection of odorants by the vomeronasal organ Nature Neuroscience 6: 519-525.