Plastic properties of the brain that allow its function to change adaptively in response to experience are one of the most important functions of the CNS. Electrophysiological phenomena, like long-term potentiation, inwhich the response of the stimulated pathway is modified by its preceding activity, are likely to underlie neuronal plasticity. The dentate fascia yeilds hours, even days lasting potentiation following brief tetanic stimulation of its entorhinal afferents. Electron microscopy of the dentate fascia neuropile shows a long-lasting volume increase of the dentate dendritic spines on which the stimulated pathway terminates. Since such a change can profoundly affect electrical properties of the neuronal elements involved, it has been postulated that the dendritic spine enlargement might be the underlying mechanism of long-term potentiation. Furthermore, in stimulated preparations, dentate perikarya show structural changes which indicate an enhancement of protein synthesis. Experiments are, therefore, proposed which would bring conclusive evidence that structural changes observed in the dentate perikarya and dendritic spines are the underlying mechanism of long-term potentiation. This should be brought about by experiments in which both phenomena will be simultaneously observed and simultaneously suppressed by a protein synthesis blocking drug - Anisomycin. Such an experiment will furthermore provide support for the protein hypothesis as a mechanism of spine enlargement. Since the time course of long-term potentiation is comparable to that of a learned response, it has been assumed that long-term potentiation and memory formation may have a common mechanism. It follows that by establishing the mechanism of long-term potentiation one could come close to the identification of the neural mechanism of memory trace formation. Indeed, in a classical conditioning paradigm, spine enlargement similar to that observed following tetanic stimulation has been found. Should the dendritic spine enlargement in the dentate be viewed as a general neural mechanism of learning and memory, it has to occur in other behavioral tasks as well. Experiments are, therefore, proposed which will include a reward magnitude shift paradigm and aversive conditioning.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH027240-10
Application #
3374987
Study Section
(BPNB)
Project Start
1978-09-01
Project End
1986-12-31
Budget Start
1985-07-01
Budget End
1986-12-31
Support Year
10
Fiscal Year
1985
Total Cost
Indirect Cost
Name
University of Colorado at Boulder
Department
Type
Schools of Arts and Sciences
DUNS #
City
Boulder
State
CO
Country
United States
Zip Code
80309