Animal Core- The responsibilities of the Animal Core are 5-fold: (1) To coordinate the purchase and numbering of young and aged rats and monkeys for all four Projects;(2) To train rats and monkeys on the appropriate cognitive tasks (Projects 1, 2 and 4);(3) To perform neural implant aseptic surgeries for monkeys used in electrophysiological studies (Project 1), and rats receiving viral transfections in prefrontal cortex (Project 2);(4) To perform cognitive assessment of rats (Projects 2 and 4) and monkeys (Project 4) in order to evaluate the effects of viral transfection or chronic drug treatment;and (5) To assist with chronic drug treatment (Project 4). Cognitive testing will include several tests of spatial working memory. For Project 1, young and aged monkeys will be habituated to sitting in a primate chair while interacting with a computer monitor. They will then be trained on the oculomotor spatial delayed response task. Training aged monkeys to perform this task requires patience, but is feasible if done gradually. Projects 2 and 4 will require training of young and aged rats on the spatial delayed alternation task in a T maze. A separate group of rats will also be trained on a control task, spatial discrimination, in the same T maze, to examine the specificity of viral manipulations in prefrontal cortex on cognitive function. Finally, young and aged monkeys in Project 4 will be trained and tested on spatial delayed response in a Wisconsin General Test Apparatus, a classical test of dorsolateral prefrontal cortical function. Animals in chronic drug studies will be tested twice weekly. The experimenter testing the animals will be unware of the drug or viral treatment conditions. Cognitive data will be submitted to the Administrative Core for statistical analysis, to examine the relationships between cognitive, histological and /or biochemical data. LAY SUMMARY: The Animal Core will train and test young and aged animals on memory tasks. We will see if drugs or molecular manipulations in the brain of rats will slow the aging process and improve memory.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Program Projects (P01)
Project #
5P01AG030004-05
Application #
8377659
Study Section
Special Emphasis Panel (ZAG1-ZIJ-5)
Project Start
Project End
2014-02-28
Budget Start
2012-03-01
Budget End
2013-02-28
Support Year
5
Fiscal Year
2012
Total Cost
$354,986
Indirect Cost
$188,834
Name
Yale University
Department
Type
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520
Laubach, Mark; Caetano, Marcelo S; Narayanan, Nandakumar S (2015) Mistakes were made: neural mechanisms for the adaptive control of action initiation by the medial prefrontal cortex. J Physiol Paris 109:104-17
Carlyle, Becky C; Nairn, Angus C; Wang, Min et al. (2014) cAMP-PKA phosphorylation of tau confers risk for degeneration in aging association cortex. Proc Natl Acad Sci U S A 111:5036-41
Arnsten, Amy F T; Jin, Lu E (2014) Molecular influences on working memory circuits in dorsolateral prefrontal cortex. Prog Mol Biol Transl Sci 122:211-31
Gamo, N J; Duque, A; Paspalas, C D et al. (2013) Role of disrupted in schizophrenia 1 (DISC1) in stress-induced prefrontal cognitive dysfunction. Transl Psychiatry 3:e328
Yang, Yang; Paspalas, Constantinos D; Jin, Lu E et al. (2013) Nicotinic ?7 receptors enhance NMDA cognitive circuits in dorsolateral prefrontal cortex. Proc Natl Acad Sci U S A 110:12078-83
Narayanan, Nandakumar S; Cavanagh, James F; Frank, Michael J et al. (2013) Common medial frontal mechanisms of adaptive control in humans and rodents. Nat Neurosci 16:1888-1895
Paspalas, Constantinos D; Wang, Min; Arnsten, Amy F T (2013) Constellation of HCN channels and cAMP regulating proteins in dendritic spines of the primate prefrontal cortex: potential substrate for working memory deficits in schizophrenia. Cereb Cortex 23:1643-54
Wang, Min; Yang, Yang; Wang, Ching-Jung et al. (2013) NMDA receptors subserve persistent neuronal firing during working memory in dorsolateral prefrontal cortex. Neuron 77:736-49
Arnsten, Amy F T; Wang, Min J; Paspalas, Constantinos D (2012) Neuromodulation of thought: flexibilities and vulnerabilities in prefrontal cortical network synapses. Neuron 76:223-39
Wei, Lan; Simen, Arthur; Mane, Shrikant et al. (2012) Early life stress inhibits expression of a novel innate immune pathway in the developing hippocampus. Neuropsychopharmacology 37:567-80

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