The purpose of the research outlined in this proposal is to combine cell biological, electrophysiological, and behavioral techniques to probe the morphological basis of two fundamental issues central to the study of behavior: 1) the relation between nonassociative and associative learning and 2) the relation between the mechanisms of short- and long-term memory. Toward this end a model system will be used, the gill- and siphon-withdrawal reflex of the marine mollusc Aplysia californica which undergoes a form of associative learning -- classical conditioning as well as two elementary types of nonassociative learning -- habituation and sensitization -- both of which demonstrate a short- and long-term memory. Several aspects of the biophysical and biochemical mechanisms of these forms of learning and memory are known and involve changes in function at a common locus -- the synapses of identified sensory neurons. We have recently demonstrated that long-term habituation and sensitization also produce changes in structure at the sensory neuron synapses. We now propose to explore the mechanisms that underlie these morphological alterations as well as to begin an examination of the nature and extent of structural changes at sensory neuron synapses that may accompany classical conditioning and the short-term form of habituation and sensitization. The intracellular labeling and serial reconstruction approaches we have developed and the model system we plan to use provide the required specificity to address these problems directly. Results from these studies should increase our understanding of the role that morphological alterations at the synapse play in the initiation and maintenance of changes in functional efficacy that mediate various forms of learning and memory. In this fashion we hope to gain additional insights into the cellular relationships between both nonassociative and associative processes as well as the family of morphological events that may contribute to the progressive development of memory storage.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH037134-05
Application #
3376057
Study Section
(BPNB)
Project Start
1982-06-01
Project End
1988-05-31
Budget Start
1986-06-01
Budget End
1987-05-31
Support Year
5
Fiscal Year
1986
Total Cost
Indirect Cost
Name
New York State Psychiatric Institute
Department
Type
DUNS #
167204994
City
New York
State
NY
Country
United States
Zip Code
10032
Miniaci, Maria Concetta; Kim, Joung-Hun; Puthanveettil, Sathyanarayanan V et al. (2008) Sustained CPEB-dependent local protein synthesis is required to stabilize synaptic growth for persistence of long-term facilitation in Aplysia. Neuron 59:1024-36
Bailey, Craig H; Kandel, Eric R (2008) Synaptic remodeling, synaptic growth and the storage of long-term memory in Aplysia. Prog Brain Res 169:179-98
Hawkins, Robert D; Kandel, Eric R; Bailey, Craig H (2006) Molecular mechanisms of memory storage in Aplysia. Biol Bull 210:174-91
Barco, Angel; Bailey, Craig H; Kandel, Eric R (2006) Common molecular mechanisms in explicit and implicit memory. J Neurochem 97:1520-33
Udo, Hiroshi; Jin, Iksung; Kim, Joung-Hun et al. (2005) Serotonin-induced regulation of the actin network for learning-related synaptic growth requires Cdc42, N-WASP, and PAK in Aplysia sensory neurons. Neuron 45:887-901
Bailey, Craig H; Kandel, Eric R; Si, Kausik (2004) The persistence of long-term memory: a molecular approach to self-sustaining changes in learning-induced synaptic growth. Neuron 44:49-57
Kim, Joung-Hun; Udo, Hiroshi; Li, Hsiu-Ling et al. (2003) Presynaptic activation of silent synapses and growth of new synapses contribute to intermediate and long-term facilitation in Aplysia. Neuron 40:151-65
Bailey, C H; Giustetto, M; Zhu, H et al. (2000) A novel function for serotonin-mediated short-term facilitation in aplysia: conversion of a transient, cell-wide homosynaptic hebbian plasticity into a persistent, protein synthesis-independent synapse-specific enhancement. Proc Natl Acad Sci U S A 97:11581-6
Bailey, C H (1999) Structural changes and the storage of long-term memory in Aplysia. Can J Physiol Pharmacol 77:738-47
Casadio, A; Martin, K C; Giustetto, M et al. (1999) A transient, neuron-wide form of CREB-mediated long-term facilitation can be stabilized at specific synapses by local protein synthesis. Cell 99:221-37

Showing the most recent 10 out of 29 publications