Posts classified under: Joint Faculty

Research

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.

Publications

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

Biography

Dr. Frye began his research career at Union College, then received his PhD at the University of Washington. As a postdoctoral fellow at Berkeley and then at Caltech, he began to work on multi-sensory processing and motor control of flight in fruit flies. He is currently a member of the Department of Physiological Science, and teaches courses in integrative and comparative animal physiology. He is the reciepient of a Sloan Foundation Fellowship, and his laboratory examines sensory fuison and sensory-motor integration for the control of walking and flight in fruit flies.

Publications

Duistermars BJ Frye MA A magnetic tether system to investigate visual and olfactory mediated flight control in Drosophila JoVE, 2008; 23: .

Theobald, JC Frye, MA Animal Behavior: flying back-to-front, Curr. Biol. , 2008; 18(4): r169. Chow DM Frye MA Context dependent olfactory enhanced optomotor flight control in Drosophila, J. Exp. Biol. , 2008; 211: 2478-2485.

Duistermars, BJ Frye, MA Cross-modal visual input for odor tracking during fly flight, Curr. Biol. , 2008; 18(4): 270-275.

Theobald JC Duistermars BJ Ringach DL Frye MA Flies see second order motion, Curr. Biol. , 2008; 18(11): r464. Duistermars, B.J. Reiser, M.B. Zhu, Y. Frye, M.A. Dynamic properties of large-field and small-field optomotor flight responses in Drosophila, Journal of Comparative Physiology A, 2007; in press: .

Reynolds, A. Frye, M.A. Free-flight odor tracking in Drosophila is consistent with a mathematically optimal intermittent scale-free search, PLoS ONE, 2007; 2(4): 354.

Frye, MA The neuromechanics of fly flight control, Invertebrate Neurobiology, 2007; 209-229.

Duistermars, BJ Chow, D Condro, M Frye, MA The spatial, temporal, and contrast properties of expansion and rotation flight optomotor responses in Drosophila, J. Exp. Biol. , 2007; 210: 3218-3227. Frye, MA Dickinson, MH Visual edge orientation shapes free-flight behavior in Drosophila, Fly, 2007; 3: 153-154.

Humbert, J.S. Frye, M.A. Extracting behaviorally relevant retinal image motion cues via wide-field integration, Proc. IEEE American Controls Conference, 2006; 2724-2729.

Frye, MA Dickinson, MH Closing the loop between neurobiology and flight behavior in Drosophila Current opinion in neurobiology. , 2004; 14(6): 729-36.

Frye, MA Dickinson, MH Fly flight: a model for the neural control of complex behavior Neuron. , 2001; 32(3): 385-8.

Research

The mind is thought to be the emergent property of the activities of ensembles of neurons. The nature of these emergent properties and how they arise are unknown. This is the focus of our research. In particular, our current research addresses the following fundamental questions in Neurophysics: 1. How is information about the physical world represented by ensembles of neurons? In particular, what are the neural mechanisms of perceiving space-time? 2. How do the neural representations evolve with learning? 3. What is the role of brain rhythms in learning and memory? 4. How does sleep influence learning? To address these questions we use both experimental and theoretical approaches as follows: 1. Develop hardware to measure and manipulate neural activity and behavior. 2. Measure the activity of ensembles of well isolated neurons from many hippocampal and neocortical areas simultaneously during learning and during sleep. 3. Develop data analysis tools to decipher the patterns of neural activity and field potentials, and their relationship to behavior. 4. Develop biophysical theories of synapses, neurons and neuronal networks that can explain these experimental finding, relate them to the underlying cellular mechanisms, and make experimentally testable predictions. The results would not only provide fundamental understanding of neural ensemble dynamics but also point to novel ways of treating learning and memory disorders.

Publications

Jason J. Moore, Pascal M. Ravassard, David Ho, Lavanya Acharya, Ashley L. Kees, Cliff Vuong, Mayanak R. Mehta.  Dynamics of Cortical Dendritic Membrane Potential and Spikes in Freely Behaving Cats.  Science, vol 335, issue 6331, 1281 (2017), 24 March 2017.

Acharya Lavanya, Aghajan Zahra M, Vuong Cliff, Moore Jason J, Mehta Mayank R Causal Influence of Visual Cues on Hippocampal Directional Selectivity Cell, 2016; 164(1-2): 197-207.

Mehta Mayank R From synaptic plasticity to spatial maps and sequence learning Hippocampus, 2015; 25(6): 756-62.

Aghajan Zahra M, Acharya Lavanya, Moore Jason J, Cushman Jesse D, Vuong Cliff, Mehta Mayank R Impaired spatial selectivity and intact phase precession in two-dimensional virtual reality Nature neuroscience, 2015; 18(1): 121-8.

Ravassard Pascal, Kees Ashley, Willers Bernard, Ho David, Aharoni Daniel, Cushman Jesse, Aghajan Zahra M, Mehta Mayank R Multisensory control of hippocampal spatiotemporal selectivity Science (New York, N.Y.), 2013; 340(6138): 1342-6.

Cushman Jesse D, Aharoni Daniel B, Willers Bernard, Ravassard Pascal, Kees Ashley, Vuong Cliff, Popeney Briana, Arisaka Katsushi, Mehta Mayank R Multisensory control of multimodal behavior: do the legs know what the tongue is doing? PloS one, 2013; 8(11): e80465.

Ghorbani Maryam, Mehta Mayank, Bruinsma Robijn, Levine Alex J Nonlinear-dynamics theory of up-down transitions in neocortical neural networks Physical review. E, Statistical, nonlinear, and soft matter physics, 2012; 85(2 Pt 1): 021908.

Ahmed Omar J, Mehta Mayank R Running speed alters the frequency of hippocampal gamma oscillations The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012; 32(21): 7373-83.

Hahn Thomas T G, McFarland James M, Berberich Sven, Sakmann Bert, Mehta Mayank R Spontaneous persistent activity in entorhinal cortex modulates cortico-hippocampal interaction in vivo Nature neuroscience, 2012; 15(11): 1531-8.

Resnik Evgeny, McFarland James M, Sprengel Rolf, Sakmann Bert, Mehta Mayank R The effects of GluA1 deletion on the hippocampal population code for position The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012; 32(26): 8952-68.

Mehta Mayank R Contribution of Ih to LTP, place cells, and grid cells Cell, 2011; 147(5): 968-70.

McFarland James M, Hahn Thomas T G, Mehta Mayank R Explicit-duration hidden Markov model inference of UP-DOWN states from continuous signals PloS one, 2011; 6(6): e21606.

Kumar Arvind, Mehta Mayank R Frequency-Dependent Changes in NMDAR-Dependent Synaptic Plasticity Frontiers in computational neuroscience, 2011; 5(5): 38.

Chen Zhiping, Resnik Evgeny, McFarland James M, Sakmann Bert, Mehta Mayank R Speed controls the amplitude and timing of the hippocampal gamma rhythm PloS one, 2011; 6(6): e21408.

Ahmed Omar J, Mehta Mayank R The hippocampal rate code: anatomy, physiology and theory Trends in neurosciences, 2009; 32(6): 329-38. Mehta Mayank R Cortico-hippocampal interaction during up-down states and memory consolidation Nature neuroscience, 2007; 10(1): 13-5.

Hahn Thomas T G, Sakmann Bert, Mehta Mayank R Differential responses of hippocampal subfields to cortical up-down states Proceedings of the National Academy of Sciences of the United States of America, 2007; 104(12): 5169-74.

Hoffman Kari L, Battaglia Francesco P, Harris Kenneth, MacLean Jason N, Marshall Lisa, Mehta Mayank R The upshot of up states in the neocortex: from slow oscillations to memory formation The Journal of neuroscience : the official journal of the Society for Neuroscience, 2007; 27(44): 11838-41.

Hahn Thomas T G, Sakmann Bert, Mehta Mayank R Phase-locking of hippocampal interneurons’ membrane potential to neocortical up-down states Nature neuroscience, 2006; 9(11): 1359-61.

Mehta Mayank R Role of rhythms in facilitating short-term memory Neuron, 2005; 45(1): 7-9.

Mehta Mayank R Cooperative LTP can map memory sequences on dendritic branches Trends in neurosciences, 2004; 27(2): 69-72.

Petersen Carl C H, Hahn Thomas T G, Mehta Mayank, Grinvald Amiram, Sakmann Bert Interaction of sensory responses with spontaneous depolarization in layer 2/3 barrel cortex Proceedings of the National Academy of Sciences of the United States of America, 2003; 100(23): 13638-43.