The long-term objective is to analyze the cellular mechanisms underlying two important capabilities of the nervous system: (1) the ability to associate a given stimulus with a novel motor response (stimulus-response or S-R learning), and (2) long-term sensory modifiability. This objective requires the development of preparations, involving well-defined behavioral alterations and identified neuronal networks, that permit direct analysis of physiological mechanisms. Building on preliminary studies using the siphon, tail, head, and parapodia of the marine gastropod, Aplysia, intact and semi-intact preparations will be developed that show the acquisition of novel siphon responses after pairing parapodial stimulation with head or tail stimulation. Electrophysiological correlates of this S-R conditioning will be examined in identified siphon motor neurons and interneurons. Two hypotheses for the development of novel S-R connections will be tested using intracellular recording, voltage clamp, and quantal analysis techniques. Long-term sensory memory will be investigated in the central and peripheral processes of parapodial sensory neurons, which offer special advantages for sensory analysis. The general hypothesis that associative information storage in sensory systems makes use of mechanisms evolved for sensory compensation after injury will be tested. The contribution of a specific cellular associative mechanism - activity-dependent extrinsic modulation (ADEM) - to sensory modifiability will be tested. Several potential ADEM-related enhancements of signaling effectiveness produced by associative conditioning and by injury of the receptive field will be examined: synaptic facilitation, increased central and/or peripheral excitability, and sprouting of peripheral and/or central processes. These studies should provide basic information on general mechanisms of learning, sensory compensation, and neuronal regeneration that may eventually contribute to an understanding of normal and abnormal physiological plasticity within the human nervous system.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
2R01MH038726-07A1
Application #
3376835
Study Section
Neurosciences Research Review Committee (BPN)
Project Start
1987-02-01
Project End
1996-01-31
Budget Start
1991-03-01
Budget End
1992-01-31
Support Year
7
Fiscal Year
1991
Total Cost
Indirect Cost
Name
University of Texas Health Science Center Houston
Department
Type
Schools of Medicine
DUNS #
City
Houston
State
TX
Country
United States
Zip Code
77225
Walters, E T; Illich, P A; Weeks, J C et al. (2001) Defensive responses of larval Manduca sexta and their sensitization by noxious stimuli in the laboratory and field. J Exp Biol 204:457-69
Illich, P A; Walters, E T (1997) Mechanosensory neurons innervating Aplysia siphon encode noxious stimuli and display nociceptive sensitization. J Neurosci 17:459-69
Ambron, R T; Zhang, X P; Gunstream, J D et al. (1996) Intrinsic injury signals enhance growth, survival, and excitability of Aplysia neurons. J Neurosci 16:7469-77
Ambron, R T; Dulin, M F; Zhang, X P et al. (1995) Axoplasm enriched in a protein mobilized by nerve injury induces memory-like alterations in Aplysia neurons. J Neurosci 15:3440-6
Hickie, C; Walters, E T (1995) Motor neuronal control of tail-directed and head-directed siphon responses in Aplysia californica. J Neurophysiol 74:307-21
Steffensen, I; Dulin, M F; Walters, E T et al. (1995) Peripheral regeneration and central sprouting of sensory neurone axons in Aplysia californica following nerve injury. J Exp Biol 198:2067-78
Dulin, M F; Steffensen, I; Morris, C E et al. (1995) Recovery of function, peripheral sensitization and sensory neurone activation by novel pathways following axonal injury in Aplysia californica. J Exp Biol 198:2055-66
Illich, P A; Joynes, R L; Walters, E T (1994) Response-specific inhibition during general facilitation of defensive responses in Aplysia. Behav Neurosci 108:614-23
Walters, E T (1994) Injury-related behavior and neuronal plasticity: an evolutionary perspective on sensitization, hyperalgesia, and analgesia. Int Rev Neurobiol 36:325-427
Clatworthy, A L; Walters, E T (1994) Comparative analysis of hyperexcitability and synaptic facilitation induced by nerve injury in two populations of mechanosensory neurones of Aplysia californica. J Exp Biol 190:217-38

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