email: dglanzman@physci.ucla.edu
phone: (310) 206-9972
office: 2506C Gonda (Goldschmied) Center
research interests: Cellular and Molecular Mechanisms of Learning and Memory
Research Interests
My laboratory is interested in the cell biology of learning and memory in simple organisms. In our research we use two animals, the marine snail Aplysia californica, and the zebrafish (Danio rerio). Work on Aplysia: This invertebrate has a comparatively simple nervous system (~ 20,000 neurons) that provides a valuable experimental model for understanding the cellular mechanisms that underlie simple forms of learning, such as habituation, sensitization, and classical conditioning. Another experimental advantage of Aplysia is that sensory and motor neurons that mediate specific reflexes of the animal can be placed into dissociated cell culture where they will reform their synaptic connections. These in vitro sensorimotor synapses are extremely useful for cellular and molecular studies of short- and long-term learning-related synaptic plasticity. Currently, my laboratory is investigating the modulation of AMPA-type glutamate receptors during learning in Aplysia. We have found that serotonin, an endogenous monoamine that plays a central role in learning, modulates the efficacy of AMPA receptors in the motor neurons. Our current evidence indicates that serotonin modulates the trafficking of AMPA receptors in the motor neurons, causing additional receptors to be delivered to postsynaptic sites via exocytosis. We also wish to know whether long-term learning in Aplysia involves changes in the expression of glutamate receptors. We have cloned and sequenced ten AMPA-type and one NMDA-type glutamate receptor from the CNS of Aplysia. Currently, we are using the techniques of in situ hybridization and quantitative RT-PCR to examine whether long-term sensitization and long-term habituation are accompanied by changes in glutamate receptor expression. Work on the zebrafish: The zebrafish has been used extensively in studies of development. It has not been commonly used in behavioral studies, however. This is unfortunate, because the zebrafish has significant advantages for genetic and molecular studies of behavior, including studies of learning and memory. The zebrafish is amenable to both forwards and reverse genetics. Furthermore, although it is a vertebrate with a complex vertebrate nervous system, it possesses reflexive behaviors that are mediated by relatively simple neural circuits in the spinal cord and brainstem. One such reflex, the startle reflex, is under the control of a pair of large command neurons in the brainstem, the Mauthner cells. Finally, zebrafish larvae are transparent, which facilitates the use of imaging techniques to study learning-related neural activity within the intact animal. We are interested in the neural basis of nonassociative and associative behavioral modification of the startle reflex. In particular, we wish to know what changes occur in the Mauthner cell circuit during learning. In our current experiments we are using electrophysiological, genetic, and imaging techniques to analyze the mechanisms of habituation and sensitization of the startle reflex. In future experiments we hope to investigate the neural basis of classical conditioning of the reflex.
Press
NSN Short A Memorable Snail NOVA Vodcast published 08-21-2009 13:00:00
Video interview on learning and consciousness (scroll down for David Glanzman video)
Audio interview in The DNA Files show "Minding the Brain"
Selected Publications
Villareal, G. V., Li, Q., Cai, D., Fink, A. E., Lim, T., Bougie, J. K., Sossin, W. S., and Glanzman, D. L.. 2009. Role of protein kinase C in the induction and maintenance of serotonin-dependent enhancement of the glutamate response in isolated siphon motor neurons of Aplysia californica J. Neurosci 29 5100-5107 [link].
Bedi, S. S., Cai, D., and Glanzman, D. L.. 2008. Effects of axotomy on cultured sensory neurons of Aplysia: long-term injury-induced changes in excitability and morphology are mediated by different signaling pathways J. Neurophysiol 100 3209-3204 [link].
Cai, D., Chen, S., and Glanzman, D.L.. 2008. Postsynaptic regulation of long-term facilitation in Aplysia Curr Biol 18 920-925 [link].
Fulton, D., Condro, M.C., Pearce, K., and Glanzman, D.L.. 2008. The potential role of postsynaptic phospholipase C activity in synaptic facilitation and behavioral sensitization in Aplysia J Neurophysiol 100 108-116 [link].
Jami, S.A., Wright, W.G. and Glanzman, D.L. 2007. Differential classical conditioning of the gill-withdrawal reflex in Aplysia recruits both NMDA receptor-dependent enhancement and NMDA receptor-dependent depression of the reflex J Neurosci 27 3064-3068 [link].
Glanzman, D.L.. 2007. Simple minds: the neurobiology of invertebrate learning and memoryin Invertebrate Neurobiology (ed. G. North & R.J. Greenspan) 347-380 (Cold Spring Harbor Laboratory Press, Woodbury, NY) .
Villareal, G., Li, Q., Cai, D. & Glanzman, D.L. 2007. The role of rapid, local postsynaptic protein synthesis in learning-related synaptic faciliation in Aplysiain Curr Biol 17 2073-2080 [link].
Glanzman, D.L.. 2006. The cellular mechanisms of learning in Aplysia: of blind men and elephants Biol Bull 210 271-279 [link].
Li, Q., Roberts, A.C. and Glanzman, D.L.. 2005. Synaptic facilitation and behavioral dishabituation in Aplysia: dependence upon release of Ca2+ from postsynaptic intracellular stores, postsynaptic exocytosis and modulation of postsynaptic AMPA receptor efficacy J Neurosci 25 5623-5637 [link].
Ezzeddine, Y. and Glanzman, D.L.. 2003. Prolonged habituation of the gill-withdrawal reflex in Aplysia depends upon protein synthesis, protein phosphatase activity and postsynaptic glutamate receptors J. Neurosci 23 9585-9594 .