Individual differences in aged rodent models of executive function and decision making McKnight Brain Research Foundation 2014 Inter-Institutional Meeting Barry Setlow, PhD Dept. of Psychiatry University of Florida College of Medicine No financial disclosures or conflicts of interest.

Inter-temporal Choice

delay to reward delivery choice of delayed reward

Inter-temporal Choice delay to reward delivery choice of delayed reward addiction

Inter-temporal Choice Choice Trial Lever One Lever Two Delay (0, 10, 20, 40, 60 s) Small Reward Delivery Large Reward Delivery No Delay

Inter-temporal choice in young and aged rats 0s10s20s40s60s Young Adult (6 mo.) Delay % Choice of Large Reward Simon et al 2010, Neurobiology of Aging

Inter-temporal choice in young and aged rats 0s10s20s40s60s Young Adult (6 mo.) Aged (24 mo.) Delay % Choice of Large Reward Simon et al 2010, Neurobiology of Aging

Controls for reward and delay perception/responses Reward Equalized 60s40s20s10s0s Young Adult Aged Delay % Choice of Delayed Reward Simon et al 2010, Neurobiology of Aging

Controls for reward and delay perception/responses Reward Equalized 60s40s20s10s0s Young Adult Aged Delay % Choice of Delayed Reward Delay Equalized 0s Delay % Choice of Large Reward Simon et al 2010, Neurobiology of Aging

Inter-temporal choice in young and aged rats 0s10s20s40s60s Young Adult (6 mo.) Aged (24 mo.) Delay % Choice of Large Reward Simon et al 2010, Neurobiology of Aging

Inter-temporal choice in young and aged rats 0s10s20s40s60s Young Adult (6 mo.) Aged (24 mo.) Delay % Choice of Large Reward Simon et al 2010, Neurobiology of Aging - similar to findings in human subjects

Individual differences in inter- temporal choice in aging Simon et al 2010, Neurobiology of Aging

Individual differences in inter- temporal choice in aging Simon et al 2010, Neurobiology of AgingShimp et al. in press, Neurobiol Learning & Memory

Individual differences in inter- temporal choice in aging Simon et al 2010, Neurobiology of Aging - individual differences don’t account for young vs. aged differences Shimp et al. in press, Neurobiol Learning & Memory

Age differences in inter- temporal choice Hippocampus? Hippocampus? –Hippocampus implicated in inter-temporal choice

Age differences in inter- temporal choice Hippocampus? Hippocampus? –Hippocampus implicated in inter-temporal choice –Some hippocampal functions decline with age

Age differences in inter- temporal choice Hippocampus? Hippocampus? –Hippocampus implicated in inter-temporal choice –Some hippocampal functions decline with age –Age-related alterations in hippocampal neurochemical signaling

Age differences in inter- temporal choice Hippocampus? Hippocampus? –Hippocampus implicated in inter-temporal choice –Some hippocampal functions decline with age –Age-related alterations in hippocampal neurochemical signaling –Nicotinic cholinergic receptors?  Decline with age  Decline associated with impaired hippocampal- dependent learning/memory

Age differences in inter- temporal choice α4β2 nicotinic receptors Mendez et al 2013, Neuroscience

Age differences in inter- temporal choice What does this mean? What does this mean? –an improvement in cognitive function in aging? OR…

Age differences in inter- temporal choice What does this mean? What does this mean? –an improvement in cognitive function in aging? OR… –perhaps exaggerated preference for delayed gratification is not a good thing

Age differences in inter- temporal choice What does this mean? What does this mean? –an improvement in cognitive function in aging? OR… –perhaps exaggerated preference for delayed gratification is not a good thing Future directions Future directions –Neural/behavioral mechanisms –Longitudinal studies (behavior and neuroimaging)

Acknowledgements Nick Simon, PhD Sofia Beas Ian Mendez, PhD Kristy Shimp Cristina Bañuelos, PhD Marci Mitchell, PhD Candi LaSarge, PhD Karienn Montgomery, PhD Joanne Damborsky, PhD Caitlin Orsini, PhD Joseph McQuail, PhD Dr. Jennifer Bizon Dr. Ursula Winzer-Serhan National Institute on Aging

Individual differences in inter- temporal choice in aging Simon et al 2010, Neurobiology of AgingBeas et al. in pressShimp et al. in press, Neurobiol Learning & Memory

Individual differences in inter- temporal choice in aging Simon et al 2010, Neurobiology of AgingBeas et al. in press

Age differences in inter- temporal choice α4β2 nicotinic receptorsα7 nicotinic receptors Mendez et al 2013, Neuroscience

Control for motivational deficits FR1FR3FR10FR20FR Young Adult Aged Response Schedule Lever Presses Simon et al 2010, Neurobiology of Aging

Inter-temporal Choice delay to reward delivery choice of delayed reward addiction Mitchell et al in press, Behavioral Neuroscience

Individual differences in inter- temporal choice in aging Simon et al 2010, Neurobiology of Aging

Individual differences in inter- temporal choice in aging Simon et al 2010, Neurobiology of Aging Beas et al. in press

Individual differences in inter- temporal choice Shimp et al. in press, Neurobiology of Learning and Memory