Individual differences in aged rodent models of executive function and decision making

1. 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.

2. Inter-temporal Choice

3. Inter-temporal Choice choice of delayed reward delay to reward delivery

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

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

6. Inter-temporal choice in young and aged rats Young Adult (6 mo.) 100 80 60 % Choice of Large Reward 40 20 0 0s 10s 20s 40s 60s Delay Simon et al 2010, Neurobiology of Aging

7. Young Adult (6 mo.) 100 Aged (24 mo.) 80 60 % Choice of Large Reward 40 20 0 0s 10s 20s 40s 60s Delay Inter-temporal choice in young and aged rats Simon et al 2010, Neurobiology of Aging

8. Reward Equalized 100 80 Young Adult 60 Aged % Choice of Delayed Reward 40 20 0 60s 40s 20s 10s 0s Delay Controls for reward and delay perception/responses Simon et al 2010, Neurobiology of Aging

9. Reward Equalized Delay Equalized 100 100 80 80 Young Adult 60 60 Aged % Choice of Large Reward % Choice of Delayed Reward 40 40 20 20 0 0 60s 40s 20s 10s 0s 0s 0s 0s 0s 0s Delay Delay Controls for reward and delay perception/responses Simon et al 2010, Neurobiology of Aging

10. Young Adult (6 mo.) Aged (24 mo.) Inter-temporal choice in young and aged rats 100 80 60 % Choice of Large Reward 40 20 0 0s 10s 20s 40s 60s Delay Simon et al 2010, Neurobiology of Aging

11. Young Adult (6 mo.) Aged (24 mo.) Inter-temporal choice in young and aged rats 100 80 60 % Choice of Large Reward 40 20 0 0s 10s 20s 40s 60s Delay - similar to findings in human subjects Simon et al 2010, Neurobiology of Aging

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

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

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

15. Age differences in inter-temporal choice • Hippocampus? • Hippocampus implicated in inter-temporal choice

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

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

18. Age differences in inter-temporal choice • 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

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

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

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

22. Age differences in inter-temporal choice • 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 • Neural/behavioral mechanisms • Longitudinal studies (behavior and neuroimaging)

23. 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

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

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

26. Age differences in inter-temporal choice α4β2 nicotinic receptors α7 nicotinic receptors Mendez et al 2013, Neuroscience

27. 250 Young Adult Aged 200 150 Lever Presses 100 50 0 FR1 FR3 FR10 FR20 FR40 Response Schedule Control for motivational deficits Simon et al 2010, Neurobiology of Aging

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

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

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

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