The objective of the proposed research is to identify cellular mechanisms underlying associative learning and to relate these mechanisms to general principles of information processing by sensory systems. Building on the recent demonstration of activity-dependent associative plasticity in individual sensory neurons mediating afferent input for the tail withdrawal reflex in Aplysia, the proposed experiments will test the hypothesis that this associative plasticity is a mechanism for classical conditioning of tail withdrawal. Differential classical conditioning of tail withdrawal will be examined in a semi-intact preparation in which behavioral and cellular alterations in identified neurons within the reflex circuit can be measured simultaneously. Alterations both in the monosynaptic connections to identified tail motor neurons and in the electro-physiological properties of the sensory neuron soma will be measured. Both classes of assciative modification will be compared to associative plasticity produced by pairing intracellular activation of sensory neurons with application of the presumed reinforcing neuromodulator (serotonin) in both the semi-intact preparation and the isolated sensory neuron soma. The possible interactions of associatively specific activity-dependent neuromodulation with changes in membrane potential and lateral inhibition will be examined in an attempt to identify sensory processes that may contribute to more complex features of associative learning such as sequence specificity, overshadowing, and blocking. By precisely defining conditioning and test stimuli in the semi-intact preparation and relating the effects of conditioning with these stimuli to the details of cellular associations measured under analogous conditions in the isolated soma, the groundwork for an eventual quantitative model of associative processing in this sensory system will be laid. Since learning is one of the fundamental capabilities of most if not all nervous systems, these studies may shed light on general mechanisms involved in both the normal function and some of the dysfunctions of the human brain.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH038726-02
Application #
3376836
Study Section
(BPNB)
Project Start
1983-12-01
Project End
1986-11-30
Budget Start
1984-12-01
Budget End
1985-11-30
Support Year
2
Fiscal Year
1985
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
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
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
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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