Dr. Glanzman 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 mechanisms that underlie the persistence of memory: how are memories maintained in our brains over long periods of time? Two phenomena related to memory persistence that have attracted significant interest in recent years are memory reconsolidation and memory erasure. Regarding memory reconsolidation, it has been found that when a long-term memory is reactivated through a reminder stimulus the memory becomes temporarily labile; during this period the memory can be permanently lost by various treatments, such as protein synthesis inhibition, until it reconsolidates and is once more stable. Memories can also be lost, apparently permanently, if a specific kinase, known as PKM, is inhibited. This suggests that the activity of PKM is critical for the maintenance of long-term memories. We are currently performing studies on Aplysia to try to unravel the mechanisms that underlie memory reconsolidation and memory erasure. These studies should provide insights into how memories persist. They may also facilitate treatments for such disorders of long-term memory as posttraumatic stress disorder (PTSD). Work on the zebrafish: 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. 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.
Roberts Adam C, Bill Brent R, Glanzman David L Learning and memory in zebrafish larvae Frontiers in neural circuits, 2013; 7: 126.
Glanzman David L PKM and the maintenance of memory F1000 biology reports, 2013; 5: 4.
Glanzman David L David L. Glanzman Current biology : CB, 2012; 22(21): R895-7. Cai Diancai, Pearce Kaycey, Chen Shanping, Glanzman David L Reconsolidation of long-term memory in Aplysia Current biology : CB, 2012; 22(19): 1783-8.
Glanzman David L Behavioral neuroscience: no easy path from genes to cognition Current biology : CB, 2012; 22(9): R302-4.
Glanzman David L Olfactory habituation: fresh insights from flies Proceedings of the National Academy of Sciences of the United States of America, 2011; 108(36): 14711-2.
Cai Diancai, Pearce Kaycey, Chen Shanping, Glanzman David L Protein kinase M maintains long-term sensitization and long-term facilitation in aplysia The Journal of neuroscience : the official journal of the Society for Neuroscience, 2011; 31(17): 6421-31.
Roberts Adam C, Reichl Jun, Song Monica Y, Dearinger Amanda D, Moridzadeh Naseem, Lu Elaine D, Pearce Kaycey, Esdin Joseph, Glanzman David L Habituation of the C-start response in larval zebrafish exhibits several distinct phases and sensitivity to NMDA receptor blockade PloS one, 2011; 6(12): e29132.
Issa Fadi A, O’Brien Georgeann, Kettunen Petronella, Sagasti Alvaro, Glanzman David L, Papazian Diane M Neural circuit activity in freely behaving zebrafish (Danio rerio) The Journal of experimental biology, 2011; 214(Pt 6): 1028-38.
Glanzman David L Common mechanisms of synaptic plasticity in vertebrates and invertebrates Current biology : CB, 2010; 20(1): R31-6.
Glanzman David L Ion pumps get more glamorous Nature neuroscience, 2010; 13(1): 4-5.
Esdin Joseph, Pearce Kaycey, Glanzman David L Long-term habituation of the gill-withdrawal reflex in aplysia requires gene transcription, calcineurin and L-type voltage-gated calcium channels Frontiers in behavioral neuroscience, 2010; 4(1): 181.
Glanzman David L Habituation in Aplysia: the Cheshire cat of neurobiology Neurobiology of learning and memory, 2009; 92(2): 147-54.
Villareal Greg, Li Quan, Cai Diancai, Fink Ann E, Lim Travis, Bougie Joanna K, Sossin Wayne S, Glanzman David L 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 The Journal of neuroscience : the official journal of the Society for Neuroscience, 2009; 29(16): 5100-7.
Bedi Supinder S, Cai Diancai, Glanzman David L Effects of axotomy on cultured sensory neurons of aplysia: long-term injury-induced changes in excitability and morphology are mediated by different signaling pathways Journal of neurophysiology, 2008; 100(6): 3209-24.
Fulton Daniel, Condro Michael C, Pearce Kaycey, Glanzman David L The potential role of postsynaptic phospholipase C activity in synaptic facilitation and behavioral sensitization in Aplysia Journal of neurophysiology, 2008; 100(1): 108-16.
Glanzman DL New tricks for an old slug: The critical role of postsynaptic mechanisms in learning and memory in Aplysia, Prog. Brain Res, 2008; 169C: 277-292.
Glanzman David L New tricks for an old slug: the critical role of postsynaptic mechanisms in learning and memory in Aplysia Progress in brain research, 2008; 169(12): 277-92.
Glanzman David L Octopus conditioning: a multi-armed approach to the LTP–learning question Current biology : CB, 2008; 18(12): R527-30.
Cai Diancai, Chen Shanping, Glanzman David L Postsynaptic regulation of long-term facilitation in Aplysia Current biology : CB, 2008; 18(12): 920-5.
Villareal Greg, Li Quan, Cai Diancai, Glanzman David L The role of rapid, local, postsynaptic protein synthesis in learning-related synaptic facilitation in aplysia Current biology : CB, 2007; 17(23): 2073-80.
Jami SA, Wright WG, Glanzman DL. 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, 2007; 27(12): 3064-8. Download
Glanzman, D. L Simple minds: the neurobiology of invertebrate learning and memory, Invertebrate Neurobiology, 2007; 347-380.
Villareal G, Li Q, Cai D, Glanzman DL The role of rapid, local, postsynaptic protein synthesis in learning-related synaptic facilitation in Aplysia, Curr. Biol, 2007; 17(23): 2073-2080. Download
Jami Shekib A, Wright William G, Glanzman David L Differential classical conditioning of the gill-withdrawal reflex in Aplysia recruits both NMDA receptor-dependent enhancement and NMDA receptor-dependent depression of the reflex The Journal of neuroscience : the official journal of the Society for Neuroscience, 2007; 27(12): 3064-8.
Glanzman DL. The cellular mechanisms of learning in Aplysia: of blind men and elephants, Biol Bull, 2006; 210(3): 271-9. Download
Glanzman David L The cellular mechanisms of learning in Aplysia: of blind men and elephants The Biological bulletin, 2006; 210(3): 271-9. Li Q,
Roberts AC, Glanzman DL. Synaptic facilitation and behavioral dishabituation in Aplysia: dependence on release of Ca2+ from postsynaptic intracellular stores, postsynaptic exocytosis, and modulation of postsynaptic AMPA receptor efficacy, J Neurosci, 2005; 25(23): 5623-37. Download
Li Quan, Roberts Adam C, Glanzman David L Synaptic facilitation and behavioral dishabituation in Aplysia: dependence on release of Ca2+ from postsynaptic intracellular stores, postsynaptic exocytosis, and modulation of postsynaptic AMPA receptor efficacy The Journal of neuroscience : the official journal of the Society for Neuroscience, 2005; 25(23): 5623-37.
Roberts AC, Glanzman DL. Learning in Aplysia: looking at synaptic plasticity from both sides, Trends Neurosci, 2003; 26(12): 662-70. Download Ezzeddine Y, Glanzman DL. Prolonged habituation of the gill-withdrawal reflex in Aplysia depends on protein synthesis, protein phosphatase activity, and postsynaptic glutamate receptors, J Neurosci, 2003; 23(29): 9585-94. Download
Chitwood RA, Li Q, Glanzman DL. Serotonin facilitates AMPA-type reponses in isolated siphon motor neurons of Aplysia in culture, J Physiol, 2001; 534(Pt 2): 501-10. Download
Murphy GG, Glanzman DL. Cellular analog of differential classical conditioning in Aplysia: disruption by the NMDA receptor antagonist DL-2-amino-5-phosphonovalerate, J Neurosci, 1999; 19(23): 10595-602. Download