Robert D Blitzer, PhD
- ASSOCIATE PROFESSOR | Pharmacological Sciences
- ASSOCIATE PROFESSOR | Psychiatry
Research Topics:Brain, Electrophysiology, Memory, Neurophysiology, Protein Translation, RNA Transport & Localization, Signal Transduction, Synapses, Synaptic Plasticity
The Blitzer Laboratory studies the cellular mechanisms that give rise to stable forms of synaptic plasticity in the brain, with a particular interest in the signaling pathways that regulate protein synthesis following synaptic stimulation.
Multi-Disciplinary Training AreasNeuroscience [NEU], Pharmacology and Therapeutics Discovery [PTD]
BS, Rutgers University
MS, Purdue University
PhD, University of Rhode Island
Research in the Blitzer Laboratory addresses the mechanism of memory formation through the phenomenon of synaptic plasticity. In particular, we are interested in a persistent form of increased synaptic efficiency, termed long-term potentiation (LTP), which can be induced in the hippocampus, a brain structure concerned with memory formation and retrieval. LTP is induced by physiological stimulation, and is a highly regulated process involving numerous signaling pathways. Current projects include:
1) The detailed analysis of the roles of signaling pathways in LTP induction. This is a broad topic, and includes such topics as interactions between MAP kinase and Ca2+/calmodulin kinase II and the inhibition of protein phosphatases by the cAMP pathway.
2) The mechanism of LTP maintenance. Memories tend to be persistent, but the correspondingly persistent phase of LTP remains relatively unexplored. The underlying processes are only beginning to be understood, but are clearly different from those of LTP induction. We are gaining insight into maintenance processes using manipulations, both physiological and pharmacological, that can reverse well-established LTP.
3) The synaptic locus of LTP. LTP induction requires both presynaptic and postsynaptic events. However, a major unresolved issue in the field is whether the expression of LTP reflects a pre- or postsynaptic change. A presynaptic change might be increased glutamate release, while postsynaptic possibilities include recruitment of new glutamate channels to the membrane and regulation of existing receptors phenomenon. We are using quantal analysis methods to address this issue.
Most of our projects are collaborative and interdisciplinary in design, including biochemical, molecular biological, and imaging techniques in addition to the lab's core expertise in neurophysiology.
LTP, memory, neurophysiology, hippocampus, signaling
Ma T, Tzavaras N, Tsokas P, Landau EM, Blitzer RD. Synaptic stimulation of mTOR is mediated by Wnt signaling and regulation of glycogen synthetase kinase-3. J Neurosci 2011 Nov; 31(48): 17537-17546.
Chen DY, Stern SA, Garcia-Osta A, Saunier-Rebori B, Pollonini G, Bambah-Mukku D, Blitzer RD, Alberini CM. A critical role for IGF-II in memory consolidation and enhancement. Nature 2011 Jan; 469(7331): 491-497.
Ma T, Hoeffer CA, Capetillo-Zarate E, Yu F, Wong H, Lin MT, Tampellini D, Klann E, Blitzer RD, Gouras GK. Dysregulation of the mTOR pathway mediates impairment of synaptic plasticity in a mouse model of Alzheimer's disease. PLoS One 2010 Sep; 5(5): e12845.
Neves SR, Tsokas P, Sarkar A, Grace EA, Rangamani P, Taubenfeld SM, Alberini CM, Schaff JC, Blitzer RD, Moraru II, Iyengar R. Cell shape and negative links in regulatory motifs together control spatial information flow in signaling networks. Cell 2008 May; 133(4): 666-680.
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; 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 Jul; 26(30): 7919-7932.
Ma'ayan A, Jenkins SL, Neves S, Hasseldine A, Grace E, Dubin-Thaler B, Eungdamrong NJ, Weng G, Ram PT, Rice JJ, Kershenbaum A, Stolovitzky GA, Blitzer RD, Iyengar R. Formation of regulatory patterns during signal propagation in a Mammalian cellular network. Science 2005 Aug; 309(5737): 1078-1083.
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; 25(24): 5833-5843.
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; 21(18): 7053-7062.