A great deal of research has been devoted to understanding the functions of forebrain acetylcholine (ACh) in mammalian cognitive processes. However, conclusions from many of the studies have been tempered by caveats related to the inherent limitations of pharmacological and lesion approaches. Thus, specific functions of ACh remain equivocal. In order to look directly at the role of ACh in learning, we will develop a conditional genetic approach which will allow us to eliminate ACh from discrete regions of the brain with spatial and temporal precision. Specifically, mice carrying a loxP modification of the gene encoding choline acetyltransferase (ChAT) will be generated by standard gene targeting techniques. Adult homozygous mice will be administered a viral vector encoding Cre recombinase. Infected neurons will functionally inactivate their ChAT genes, and thus will no longer be able to synthesize ACh. Once the parameters of the methodology are worked out, we will determine if loss of basal forebrain ACh alters either basic behavioral or cognitive functions. If successful, this system will have general applicability for re-examination of many putative functions of ACh in mammals.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32GM019519-02
Application #
6018389
Study Section
Special Emphasis Panel (ZRG1-NEUC (01))
Program Officer
Tompkins, Laurie
Project Start
1998-09-01
Project End
Budget Start
1999-09-01
Budget End
1999-09-30
Support Year
2
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Salk Institute for Biological Studies
Department
Type
DUNS #
005436803
City
La Jolla
State
CA
Country
United States
Zip Code
92037