Sensitization and classical conditioning are two forms of learning, respectively non-associative and associative, that occur throughout the animal kingdom, including in man. In the marine mollusc Aplysia, both sensitization and classical conditioning involve increases in transmitter release, called heterosynaptic facilitation, from mechanoreceptor sensory neurons of the pathways that mediate defensive withdrawal behaviors. A number of cellular phenomena accompany this facilitation, among them a reduction in potassium current, an increase in spike duration and number, and an increase in calcium current. Earlier work showed that facilitation involves a rise in intracellular cyclic adenosine monophosphate (cAMP) and the consequent phosphorylation of neuronal substrates by cAMP-dependent protein kinase. More recent work suggests a role for C kinase also in facilitation. The proposed project has a threefold aim: 1. To re-examine the role of cAMP in facilitation. This question is prompted by recent findings that suggest that an increase in cAMP alone may be insufficient to account for facilitation. 2. To determine which of the cellular phenomena associated with facilitation are causal and which are not, and to determine how much of the facilitation can be accounted for by each process. 3. To examine the cellular phenomena associated with activity-dependent amplification of facilitation to determine whether, as has been proposed, classical conditioning involves only enhancement of processes that underlie sensitization, or whether new mechanisms are involved. These questions will be addressed by examining 1) the effects on facilitation of treating sensory neurons with substances that influence the cAMP cascade; 2) the time courses of, and the effects of different manipulations on, each of the facilitation-associated phenomena, compared to those of the facilitation itself; and 3) cellular correlates of activity-dependent amplification of facilitation, a mechanism underlying classical conditioning.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH045397-06
Application #
2246550
Study Section
Cognitive Functional Neuroscience Review Committee (CFN)
Project Start
1989-09-30
Project End
1996-08-31
Budget Start
1994-09-30
Budget End
1996-08-31
Support Year
6
Fiscal Year
1994
Total Cost
Indirect Cost
Name
Clinical Research Institute of Montreal
Department
Type
DUNS #
City
Montreal
State
QC
Country
Canada
Zip Code
H2 1-R7