This is a request for five years of support under the ADAMHA Research Scientist Development Award Program. The long-term objective of this research project is to analyze the cellular and molecular mechanisms of an example of associative learning and memory. The studies proposed in this grant will provide insights into general principles underlying memory for an associative experience following one-trial conditioning, and contribute to the elucidation of the events critical for the transformation of memory into a more enduring form, long-term memory. Toward these goals, a multidisciplinary approach to the study of associative learning and memory will be carried out in the marine mollusc Hermissenda, a preparation that has proven useful in biophysical and molecular studies of learning. The research will use a combination of cellular neurophysiological, biophysical, biochemical, and behavioral techniques to study short and long-term memory in intact and isolated nervous systems. One primary goal of the research is an investigation of the contribution of protein phosphorylation to the time-dependent processes underlying the induction, maintenance and expression of short- and long-term memory. The recent discovery that inhibiting protein kinase C with broad spectrum kinase inhibitors or depleting kinase levels by down-regulation, blocks the induction of short-term, but not long-term memory provides additional evidence that different molecular mechanisms may underlie these two phases of memory. Studies are proposed to further investigate the dissociation between short and long-term memory and the contribution that protein kinases and protein phosphorylation may make to the induction, maintenance, and expression of different memory stages. A second goal of this project is to analyze the specific membrane conductances that are modified by one-trial conditioning, and identify the contribution of enhanced excitability and modifications in synaptic strength to the expression of long-term memory. The third major goal is to identify the neural circuitry underlying locomotion and develop a semi-intact preparation for simultaneously recording from motor neurons and measuring conditioned modification of behavior. These studies should help to elucidate basic mechanisms of short and long-term memory and how such mechanisms may be related to clinical disorders of memory.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Scientist Development Award - Research (K02)
Project #
5K02MH001363-04
Application #
2889869
Study Section
Cognitive Functional Neuroscience Review Committee (CFN)
Program Officer
Asanuma, Chiiko
Project Start
1996-06-01
Project End
2001-05-31
Budget Start
1999-06-01
Budget End
2000-05-31
Support Year
4
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of Texas Health Science Center Houston
Department
Neurosciences
Type
Schools of Medicine
DUNS #
City
Houston
State
TX
Country
United States
Zip Code
77225
Crow, Terry; Tian, Lian-Ming (2002) Morphological characteristics and central projections of two types of interneurons in the visual pathway of Hermissenda. J Neurophysiol 87:322-32
Crow, T; Xue-Bian, J J; Siddiqi, V et al. (2001) Serotonin activation of the ERK pathway in Hermissenda: contribution of calcium-dependent protein kinase C. J Neurochem 78:358-64
Crow, T; Tian, L M (2000) Monosynaptic connections between identified A and B photoreceptors and interneurons in Hermissenda: evidence for labeled-lines. J Neurophysiol 84:367-75
Crow, T; Xue-Bian, J J (2000) Identification of a 24 kDa phosphoprotein associated with an intermediate stage of memory in Hermissenda. J Neurosci 20:RC74
Crow, T; Xue-Bian, J J; Siddiqi, V (1999) Protein synthesis-dependent and mRNA synthesis-independent intermediate phase of memory in Hermissenda. J Neurophysiol 82:495-500
Crow, T; Xue-Bian, J J; Siddiqi, V et al. (1998) Phosphorylation of mitogen-activated protein kinase by one-trial and multi-trial classical conditioning. J Neurosci 18:3480-7
Frysztak, R J; Crow, T (1997) Synaptic enhancement and enhanced excitability in presynaptic and postsynaptic neurons in the conditioned stimulus pathway of Hermissenda. J Neurosci 17:4426-33
Crow, T; Siddiqi, V; Dash, P K (1997) Long-term enhancement but not short-term in Hermissenda is dependent upon mRNA synthesis. Neurobiol Learn Mem 68:343-50
Crow, T; Siddiqi, V (1997) Time-dependent changes in excitability after one-trial conditioning of Hermissenda. J Neurophysiol 78:3460-4