Emmanuel Landau, MD, PhD
- PROFESSOR EMERITUS | Psychiatry
- PROFESSOR EMERITUS | Pharmacological Sciences
PhD, Australian National University
Harvard University School of Medicine
Connecticut Valley Hospital
Yale University School of Medicine
Study the role of the cyclic AMP (cAMP) signaling pathway in long-term potentiation (LTP).
One goal of the Landau and Blitzer Laboratory is to study the role of the cyclic AMP (cAMP) signaling pathway in long-term potentiation (LTP), and important example of neuronal plasticity and learning. Synaptic potentials are measured in slices of rat hippocampus, employing various types of electrophysiological recording (patch, intracellular, field). High frequency stimulation of the presynaptic fibers induces prolonged enhancement of synaptic transmission (LTP). The role of protein phosphatases in LTP, and their regulation by the cAMP pathway is studied by bath and intracellular application of enzyme inhibitors. Protein substrates of intracellular phosphatases and kinases are identified through labeling with specific antibodies. These studies are aimed at discovering the biochemical machinery of neuronal plasticity and finding pharmacological tools that influence learning and memory.
A second research area in the lab is to define a receptor for amyloid peptide (Ab). Ab is a major component of the plaques in Alzheimer's disease, and is implicated in the neurotoxicity of the illness. Using Xenopus oocytes injected with brain RNA, we have obtained evidence that Ab activates a receptor linked to phospholipase C (PLC). Since PLC activation has been shown to inhibit the formation of Ab such a receptor may play an important role in the pathogenesis and treatment of Alzheimer's disease. The aim of these studies is to characterize and clone the receptor for Ab.
Tsokas P, Ma T, Iyengar R, Landau EM, Blitzer RD. Mitogen-activated protein kinase upregulates the dendritic translation machinery in long-term potentiation by controlling the mammalian target of rapamycin pathway. J Neurosci 2007 May 30; 27(22): 5885-5894.
Garcia-Osta A, Tsokas P, Pollonini G, Landau EM, Blitzer R, Alberini CM. MuSK expressed in the brain mediates cholinergic responses, synaptic plasticity, and memory formation. J Neurosci 2006 July 26; 26(30): 7919-7932.
Tsokas P, Grace EA, Chan P, Ma T, Sealfon SC, Iyengar R, Landau EM, Blitzer RD. Local protein synthesis mediates a rapid increase in dendritic elongation factor 1A after induction of late long-term potentiation. J Neurosci 2005 Jun 15; 25(24): 5833-43.
Giovannini MG, Blitzer RD, Wong T, Asoma K, Tsokas P, Morrison JH, Iyengar R, Landau EM. Mitogen-activated protein kinase regulates early phosphorylation and delayed expression of Ca2+/calmodulin-dependent protein kinase II in long-term potentiation. J Neurosci 2001 Sep 15; 21(18): 7053-7062.
Brown GP, Blitzer RD, Connor JH, Wong T, Shenolikar S, Iyengar R, Landau EM. Long-term potentiation induced by theta frequency stimulation is regulated by a protein phosphatase-1-operated gate. J Neurosci 2000 Nov 1; 20(21): 7880-7887.
Blitzer RD, Wong T, Giovannini MG, Pangalos MN, Robakis NK, Landau EM. Amyloid beta peptides activate the phosphoinositide signaling pathway in oocytes expressing rat brain RNA. Brain Res Mol Brain Res 2000 Mar 10; 76(1): 115-20.