A Spiking Model of Hippocampus for Guiding Behavior

Summary

Principal Investigator: Michael Hasselmo
Abstract: [unreadable] DESCRIPTION (provided by applicant): The proposed research focuses on development of a detailed and realistic model of how neural firing patterns in the hippocampus, entorhinal cortex, prefrontal cortex and ventral tegmental area mediate goal directed behavior in specific behavioral tasks. These projects explore the interaction of goal activation, response selection and episodic memory for guiding behavior. Understanding these processes of motivated behavior should prove important for understanding the drug addiction processes. In particular this work allows modeling of how alterations in glutamatergic, GABAergic cholinergic and dopaminergic processes within numerous interacting regions could influence addictive behavior. The proposed research will further develop existing software that allows a direct interface between a neural simulation and behavior of a virtual rat in a virtual environment, a model simultaneously constrained by requirements about behavioral function and biologically realistic structure. The neural simulation uses dynamics based on extensive physiological data on rhythmic field potentials (EEG) and firing patterns of individual neurons (unit recording). The research proposed here will involve a continuous interaction between three groups: [unreadable] 1. The group in Edinburgh (Robert Cannon and Nigel Goddard) will provide ongoing development of a flexible, graphics based simulation package (CATACOMB), which allows construction of neural simulations for guiding behavior of a virtual rat in a variety of different experimental tasks, including spatial memory tasks and operant tasks. [unreadable] 2. The Hasselmo group will continue development of simulations of how the hippocampus, entorhinal cortex, prefrontal cortex and ventral tegmental area are involved in goal directed movements in behavioral tasks. This work will generate clear experimental predictions about the timing of spikes relative o behavior and relative to theta rhythm EEG based on hypotheses about the physiological interaction. [unreadable] 3. The Eichenbaum group will analyze data from a spatial alternation task to test specific predictions of the simulation about the timing of spikes during behavior. [unreadable] This project will have a synergistic interaction with a separate collaboration between the Hasselmo and Kantak laboratories at B.U., which focuses on modeling operant tasks used in experimental studies of drug self-administration phenomena, in work supported by a supplement to a previous grant from NIDA. [unreadable] [unreadable]
Funding Period: 2002-09-30 - 2008-06-30
more information: NIH RePORT

Top Publications

  1. pmc Working Memory Performance Correlates with Prefrontal-Hippocampal Theta Interactions but not with Prefrontal Neuron Firing Rates
    James M Hyman
    Seamans Laboratory, Department of Psychiatry, Brain Research Center, University of British Columbia Vancouver, BC, Canada
    Front Integr Neurosci 4:2. 2010
  2. pmc Arc length coding by interference of theta frequency oscillations may underlie context-dependent hippocampal unit data and episodic memory function
    Michael E Hasselmo
    Center for Memory and Brain, Department of Psychology and Program in Neuroscience, Boston University, Boston, Massachusetts 02215, USA
    Learn Mem 14:782-94. 2007
  3. pmc Modeling the role of working memory and episodic memory in behavioral tasks
    Eric A Zilli
    Program in Neuroscience, Departmentof Psychology, Center for Memory and Brain, Boston University, Boston, Massachusetts 02215, USA
    Hippocampus 18:193-209. 2008
  4. ncbi Neuromodulation by glutamate and acetylcholine can change circuit dynamics by regulating the relative influence of afferent input and excitatory feedback
    Lisa M Giocomo
    Program in Neuroscience, Center for Memory and Brain, Boston University, 2 Cummington Street, Boston, MA 02215, USA
    Mol Neurobiol 36:184-200. 2007
  5. pmc Grid cell firing may arise from interference of theta frequency membrane potential oscillations in single neurons
    Michael E Hasselmo
    Center for Memory and Brain and Program in Neuroscience, Boston University, Boston, Massachusetts, USA
    Hippocampus 17:1252-71. 2007
  6. pmc Interoperability of neuroscience modeling software: current status and future directions
    Robert C Cannon
    Textensor Limited, Edinburgh, UK
    Neuroinformatics 5:127-38. 2007
  7. pmc Consequences of parameter differences in a model of short-term persistent spiking buffers provided by pyramidal cells in entorhinal cortex
    Randal A Koene
    Center for Memory and Brain, Department of Psychology and Program in Neuroscience, Boston University, 64 Cummington Street, Boston, MA 02215, USA
    Brain Res 1202:54-67. 2008
  8. pmc Temporal frequency of subthreshold oscillations scales with entorhinal grid cell field spacing
    Lisa M Giocomo
    Center for Memory and Brain, Department of Psychology, Program in Neuroscience, Boston University, 2 Cummington Street, Boston, MA 02215, USA
    Science 315:1719-22. 2007
  9. ncbi Spatial representations of hippocampal CA1 neurons are modulated by behavioral context in a hippocampus-dependent memory task
    Amy L Griffin
    Center for Memory and Brain, Boston University, Boston, Massachusetts 02215, USA
    J Neurosci 27:2416-23. 2007
  10. pmc Reversed and forward buffering of behavioral spike sequences enables retrospective and prospective retrieval in hippocampal regions CA3 and CA1
    Randal A Koene
    Center for Memory and Brain, Department of Psychology, Boston University, Boston, MA 02215, USA
    Neural Netw 21:276-88. 2008

Scientific Experts

Detail Information

Publications43

  1. pmc Working Memory Performance Correlates with Prefrontal-Hippocampal Theta Interactions but not with Prefrontal Neuron Firing Rates
    James M Hyman
    Seamans Laboratory, Department of Psychiatry, Brain Research Center, University of British Columbia Vancouver, BC, Canada
    Front Integr Neurosci 4:2. 2010
    ....
  2. pmc Arc length coding by interference of theta frequency oscillations may underlie context-dependent hippocampal unit data and episodic memory function
    Michael E Hasselmo
    Center for Memory and Brain, Department of Psychology and Program in Neuroscience, Boston University, Boston, Massachusetts 02215, USA
    Learn Mem 14:782-94. 2007
    ..Arc length coding could contribute to episodic encoding of trajectories as sequences of states and actions...
  3. pmc Modeling the role of working memory and episodic memory in behavioral tasks
    Eric A Zilli
    Program in Neuroscience, Departmentof Psychology, Center for Memory and Brain, Boston University, Boston, Massachusetts 02215, USA
    Hippocampus 18:193-209. 2008
    ..When a delay is imposed, simulations with both episodic memory and WM can solve all of the tasks except a disambiguation of odor sequences task...
  4. ncbi Neuromodulation by glutamate and acetylcholine can change circuit dynamics by regulating the relative influence of afferent input and excitatory feedback
    Lisa M Giocomo
    Program in Neuroscience, Center for Memory and Brain, Boston University, 2 Cummington Street, Boston, MA 02215, USA
    Mol Neurobiol 36:184-200. 2007
    ..Modulation of afferent versus intrinsic processing could contribute to the role of neuromodulators in regulating attention, learning, and memory effects in behavior...
  5. pmc Grid cell firing may arise from interference of theta frequency membrane potential oscillations in single neurons
    Michael E Hasselmo
    Center for Memory and Brain and Program in Neuroscience, Boston University, Boston, Massachusetts, USA
    Hippocampus 17:1252-71. 2007
    ..These same mechanisms of subthreshold oscillations may play a more general role in memory function, by providing a method for learning arbitrary time intervals in memory sequences...
  6. pmc Interoperability of neuroscience modeling software: current status and future directions
    Robert C Cannon
    Textensor Limited, Edinburgh, UK
    Neuroinformatics 5:127-38. 2007
    ..cnsorg.org ). We assess the current state of interoperability of neural simulation software and explore the future directions that will enable the field to advance...
  7. pmc Consequences of parameter differences in a model of short-term persistent spiking buffers provided by pyramidal cells in entorhinal cortex
    Randal A Koene
    Center for Memory and Brain, Department of Psychology and Program in Neuroscience, Boston University, 64 Cummington Street, Boston, MA 02215, USA
    Brain Res 1202:54-67. 2008
    ....
  8. pmc Temporal frequency of subthreshold oscillations scales with entorhinal grid cell field spacing
    Lisa M Giocomo
    Center for Memory and Brain, Department of Psychology, Program in Neuroscience, Boston University, 2 Cummington Street, Boston, MA 02215, USA
    Science 315:1719-22. 2007
    ....
  9. ncbi Spatial representations of hippocampal CA1 neurons are modulated by behavioral context in a hippocampus-dependent memory task
    Amy L Griffin
    Center for Memory and Brain, Boston University, Boston, Massachusetts 02215, USA
    J Neurosci 27:2416-23. 2007
    ..Our results suggest that trial-phase-selective coding is common in tasks that require rapid alternation between encoding and retrieval processes...
  10. pmc Reversed and forward buffering of behavioral spike sequences enables retrospective and prospective retrieval in hippocampal regions CA3 and CA1
    Randal A Koene
    Center for Memory and Brain, Department of Psychology, Boston University, Boston, MA 02215, USA
    Neural Netw 21:276-88. 2008
    ..Associations are formed between buffered episodic cues, unique temporal context specific representations in dentate gyrus, and episodic memory in the CA3 recurrent network...
  11. pmc A model of behavioral treatments for self-mutilation behavior in Lesch-Nyhan syndrome
    Eric A Zilli
    Program in Neuroscience, Department of Psychology, Center for Memory and Brain, Boston University, Boston, MA 02215, USA
    Neuroreport 19:459-62. 2008
    ..Simulations of this model reproduce findings on the results of behavioral treatments for dealing with self-mutilation behaviors...
  12. pmc Neuroscience. The scale of experience
    Michael E Hasselmo
    Center for Memory and Brain, Department of Psychology and Program in Neuroscience, Boston University, Boston, MA 02215, USA
    Science 321:46-7. 2008
  13. pmc Evaluation of the oscillatory interference model of grid cell firing through analysis and measured period variance of some biological oscillators
    Eric A Zilli
    Department of Psychology, Boston University, Boston, Massachusetts, USA
    PLoS Comput Biol 5:e1000573. 2009
    ..However, oscillatory interference models can tolerate small amounts of noise, suggesting the utility of circuit level effects which might reduce oscillator variability. Further implications for grid cell models are discussed...
  14. pmc Grid cell mechanisms and function: contributions of entorhinal persistent spiking and phase resetting
    Michael E Hasselmo
    Center for Memory and Brain, Department of Psychology and Program in Neuroscience, Boston University, Boston, Massachusetts 02215, USA
    Hippocampus 18:1213-29. 2008
    ..Science, 2008), and a hairpin maze task...
  15. pmc Computation by oscillations: implications of experimental data for theoretical models of grid cells
    Lisa M Giocomo
    Center for Memory and Brain, Program in Neuroscience, and Psychology Department, Boston University, Boston, Massachusetts 02215, USA
    Hippocampus 18:1186-99. 2008
    ..Mechanisms of oscillatory interference and attractor dynamics may make complementary contributions to the properties of grid cell firing in entorhinal cortex...
  16. pmc Temporally structured replay of neural activity in a model of entorhinal cortex, hippocampus and postsubiculum
    Michael E Hasselmo
    Center for Memory and Brain, Department of Psychology and Program in Neuroscience, Boston University, 2 Cummington St, Boston, MA 02215, USA
    Eur J Neurosci 28:1301-15. 2008
    ..These mechanisms could be important for episodic memory of trajectories...
  17. pmc Time constants of h current in layer ii stellate cells differ along the dorsal to ventral axis of medial entorhinal cortex
    Lisa M Giocomo
    Center for Memory and Brain, Program in Neuroscience and Department of Psychology, Boston University, Boston, Massachusetts 02215, USA
    J Neurosci 28:9414-25. 2008
    ..Differences in h current could underlie differences in membrane potential oscillation properties and contribute to grid cell periodicity along the dorsal-ventral axis of medial entorhinal cortex...
  18. pmc mGluR-dependent persistent firing in entorhinal cortex layer III neurons
    Motoharu Yoshida
    Center for Memory and Brain, Boston University, Boston, MA 02215, USA
    Eur J Neurosci 28:1116-26. 2008
    ....
  19. pmc Linking cellular mechanisms to behavior: entorhinal persistent spiking and membrane potential oscillations may underlie path integration, grid cell firing, and episodic memory
    Michael E Hasselmo
    Center for Memory and Brain, Department of Psychology and Program in Neuroscience, Boston University, 2 Cummington Sreet, Boston, MA 02215, USA
    Neural Plast 2008:658323. 2008
    ..The interaction of oscillations and persistent firing could contribute to encoding and retrieval of trajectories through space and time as a mechanism relevant to episodic memory...
  20. pmc The influence of Markov decision process structure on the possible strategic use of working memory and episodic memory
    Eric A Zilli
    Center for Memory and Brain, Boston University, Boston, Massachusetts, United States of America
    PLoS ONE 3:e2756. 2008
    ..This may provide a basis for a quantitative behavioral stoichiometry of memory tasks...
  21. ncbi Switching between "On" and "Off" states of persistent activity in lateral entorhinal layer III neurons
    Babak Tahvildari
    Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada
    Hippocampus 17:257-63. 2007
    ..The neuronal ability to switch "On" and "Off" persistent activity may facilitate the concurrent representation of temporally segregated information arriving in the EC and being directed toward the hippocampus...
  22. ncbi Cholinergic modulation of cortical function
    M E Hasselmo
    Center for Memory and Brain, Boston University, Boston, MA 02215, USA
    J Mol Neurosci 30:133-5. 2006
    ..Interference from prior memory is reduced by suppressing synapses modified by prior learning (Sevilla et al., 2002; Linster et al., 2003)...
  23. pmc An analysis of the mean theta phase of population activity in a model of hippocampal region CA1
    Eric A Zilli
    Program in Neuroscience, Center for Memory and Brain, Boston University, Boston, MA 02215, USA
    Network 17:277-97. 2006
    ..The analyses also reveal that the model's learning rule results in stability and normalization of synaptic weights and show how dysfunction of neuromodulatory systems might lead to epileptic or amnestic type conditions...
  24. ncbi Nicotinic modulation of glutamatergic synaptic transmission in region CA3 of the hippocampus
    Lisa M Giocomo
    Department of Psychology, Center for Memory and Brain, 2 Cummington Street, Boston University, Boston, MA, 02215, USA
    Eur J Neurosci 22:1349-56. 2005
    ....
  25. ncbi What is the function of hippocampal theta rhythm?--Linking behavioral data to phasic properties of field potential and unit recording data
    Michael E Hasselmo
    Department of Psychology, Center for Memory and Brain, Program in Neuroscience, Boston University, Boston, MA 02215, USA
    Hippocampus 15:936-49. 2005
    ..g., "splitter cells"), (3) the cholinergic regulation of sustained activity in entorhinal cortical neurons, and (4) the phasic timing of prefrontal cortical neurons relative to hippocampal theta rhythm...
  26. pmc A model of prefrontal cortical mechanisms for goal-directed behavior
    Michael E Hasselmo
    Department of Psychology, Center for Memory and Brain, Boston University, Boston, MA 02215, USA
    J Cogn Neurosci 17:1115-29. 2005
    ....
  27. ncbi A model of STDP based on spatially and temporally local information: derivation and combination with gated decay
    Anatoli Gorchetchnikov
    Department of Cognitive and Neural Systems, Boston University, 677 Beacon St, Boston, MA 02215, USA
    Neural Netw 18:458-66. 2005
    ..The results show that the advantages of using these gatings are transferred to the new rule without sacrificing its dependency on spike-timing...
  28. ncbi Medial prefrontal cortex cells show dynamic modulation with the hippocampal theta rhythm dependent on behavior
    James M Hyman
    Center for Memory and Brain, Department of Psychology, Boston University, Boston, MA 02215, USA
    Hippocampus 15:739-49. 2005
    ..mPFC neurons have the capability to respond to behaviorally relevant elements by dynamically alternating between hippocampal theta entrained and nonphasic firing...
  29. ncbi An integrate-and-fire model of prefrontal cortex neuronal activity during performance of goal-directed decision making
    Randal A Koene
    Center for Memory and Brain, Department of Psychology and Program in Neuroscience, Boston University, 64 Cummington Street, Boston, MA 02215, USA
    Cereb Cortex 15:1964-81. 2005
    ..The spiking activity shows properties similar to recordings of orbitofrontal neurons during task performance...
  30. ncbi Encoding and retrieval in the CA3 region of the hippocampus: a model of theta-phase separation
    Steve Kunec
    Center for BioDynamics, Department of Mathematics and Statistics, Boston University, 111 Cummington Street, Boston, Massachusetts 02215, USA
    J Neurophysiol 94:70-82. 2005
    ..Slow inhibitory neurons (O-LM cells) play a role in the disambiguation during retrieval. We compare and contrast our computational results with existing experimental data and other contemporary models...
  31. ncbi The role of hippocampal regions CA3 and CA1 in matching entorhinal input with retrieval of associations between objects and context: theoretical comment on Lee et al. (2005)
    Michael E Hasselmo
    Boston University, Boston, MA 02215, USA
    Behav Neurosci 119:342-5. 2005
    ..Along with recent electrophysiological data, this provides a framework for more specifically modeling the role of CA3 and CA1 in matching sensory input with context-dependent retrieval for memory-guided behavior in different tasks...
  32. ncbi Scopolamine reduces persistent activity related to long-term encoding in the parahippocampal gyrus during delayed matching in humans
    Karin Schon
    Department of Psychology, Boston University, Boston, Massachusetts 02215, USA
    J Neurosci 25:9112-23. 2005
    ..The results are consistent with computational modeling data and behavioral pharmacological studies, suggesting that long-term encoding-related activity may be reduced if cholinergic receptors are blocked by scopolamine...
  33. pmc Hippocampal mechanisms for the context-dependent retrieval of episodes
    Michael E Hasselmo
    Department of Psychology Center for Memory and Brain, Program in Neuroscience, Boston University, 2 Cummington St, Boston, MA 02215, USA
    Neural Netw 18:1172-90. 2005
    ..The model links data at the cellular level to behavior at the systems level, describing a physiologically plausible mechanism for the brain to recall a given episode which occurred at a specific place and time...
  34. ncbi Muscarinic suppression in stratum radiatum of CA1 shows dependence on presynaptic M1 receptors and is not dependent on effects at GABA(B) receptors
    T Kremin
    Department of Psychology, Center for Memory and Brain, Boston University, Boston, MA 02215, USA
    Neurobiol Learn Mem 85:153-63. 2006
    ..These findings support a role for presynaptic m1 mAChRs in modulation of synaptic transmission in CA1, but indicate that other muscarinic receptor subtypes, such as M2, are also involved in suppression of synaptic potentials...
  35. ncbi Difference in time course of modulation of synaptic transmission by group II versus group III metabotropic glutamate receptors in region CA1 of the hippocampus
    Lisa M Giocomo
    Program in Neuroscience, Center for Memory and Brain, Boston University, Boston, MA 02214, USA
    Hippocampus 16:1004-16. 2006
    ..The difference in time course for group II vs. group III mGluRs suggests a different functional role, with group II playing a potential role in making synapses act as low pass filters...
  36. ncbi First-in-first-out item replacement in a model of short-term memory based on persistent spiking
    Randal A Koene
    Center for Memory and Brain, Department of Psychology and Program in Neuroscience, Boston University, Boston, MA 02215, USA
    Cereb Cortex 17:1766-81. 2007
    ..As noise increases, the simulated buffer provides robust output that may underlie episodic encoding...
  37. pmc Mechanisms underlying working memory for novel information
    Michael E Hasselmo
    Center for Memory and Brain, Department of Psychology and Program in Neuroscience, Boston University, 2 Cummington Street, Boston, MA 02215, USA
    Trends Cogn Sci 10:487-93. 2006
    ..These intrinsic mechanisms in parahippocampal cortices provide an important alternative to theories of working memory based on recurrent synaptic excitation...
  38. pmc The role of acetylcholine in learning and memory
    Michael E Hasselmo
    Center for Memory and Brain, Boston University, 2 Cummington Street, Boston, MA 02215, USA
    Curr Opin Neurobiol 16:710-5. 2006
    ..These effects might enhance different types of encoding in different cortical structures. In particular, the effects in entorhinal and perirhinal cortex and hippocampus might be important for encoding new episodic memories...
  39. ncbi Gradual translocation of spatial correlates of neuronal firing in the hippocampus toward prospective reward locations
    Inah Lee
    Center for Memory and Brain, Boston University, 2 Cummington Street, Boston, MA 02215, USA
    Neuron 51:639-50. 2006
    ..The within-session shifts in preferred firing locations in the absence of any changes in the environment suggest that certain cognitive factors can significantly alter the location-bound coding scheme of hippocampal neurons...
  40. pmc The ion channel inverse problem: neuroinformatics meets biophysics
    Robert C Cannon
    Department of Psychology Center for Memory and Brain, Boston, Massachusetts, USA
    PLoS Comput Biol 2:e91. 2006
    ..We review the current state of channel modeling and explore the developments needed for its conclusions to be integrated into whole-cell modeling...
  41. ncbi Hippocampal CA1 spiking during encoding and retrieval: relation to theta phase
    Joseph R Manns
    Center for Memory and Brain, Boston University, Boston, MA 02215, USA
    Neurobiol Learn Mem 87:9-20. 2007
    ..The modeling results obtained here demonstrated that the experimentally observed phase differences are consistent with different levels of CA3 synaptic input to CA1 during recognition of repeated items...
  42. ncbi Mechanism of graded persistent cellular activity of entorhinal cortex layer v neurons
    Erik Fransen
    School of Computer Science and Communication, Royal Institute of Technology, SE 100 44 Stockholm, Sweden
    Neuron 49:735-46. 2006
    ..The model is consistent with detailed experimental observations and provides a mechanism for maintenance of memory-related activity in individual neurons...
  43. ncbi Unraveling the attentional functions of cortical cholinergic inputs: interactions between signal-driven and cognitive modulation of signal detection
    Martin Sarter
    Department of Psychology, University of Michigan, 525 E University Ave, Ann Arbor, MI 48109 1109, USA
    Brain Res Brain Res Rev 48:98-111. 2005
    ....