Post on 17-Dec-2015
transcript
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 ChoiceInter-temporal Choice
Inter-temporal ChoiceInter-temporal Choice
delay to reward delivery
cho
ice
of
del
ayed
rew
ard
Inter-temporal ChoiceInter-temporal Choice
delay to reward delivery
cho
ice
of
del
ayed
rew
ard
addiction
Inter-temporal ChoiceInter-temporal Choice
Choice Trial
LeverOne
LeverTwo
Delay
(0, 10, 20, 40, 60 s)
Small Reward Delivery
Large Reward Delivery
No Delay
Inter-temporal choice in young and aged rats
0s 10s 20s 40s 60s0
20
40
60
80
100Young Adult (6 mo.)
Delay
% C
ho
ice
of
Lar
ge
Rew
ard
Simon et al 2010, Neurobiology of Aging
Inter-temporal choice in young and aged rats
0s 10s 20s 40s 60s0
20
40
60
80
100Young Adult (6 mo.)
Aged (24 mo.)
Delay
% C
ho
ice
of
Lar
ge
Rew
ard
Simon et al 2010, Neurobiology of Aging
Controls for reward and delay perception/responses
Reward Equalized
60s 40s 20s 10s 0s0
20
40
60
80
100Young Adult
Aged
Delay
% C
ho
ice
of
De
lay
ed R
ewar
d
Simon et al 2010, Neurobiology of Aging
Controls for reward and delay perception/responses
Reward Equalized
60s 40s 20s 10s 0s0
20
40
60
80
100Young Adult
Aged
Delay
% C
ho
ice
of
De
lay
ed R
ewar
d
Delay Equalized
0s 0s 0s 0s 0s0
20
40
60
80
100
Delay
% C
ho
ice
of
La
rge
Rew
ard
Simon et al 2010, Neurobiology of Aging
Inter-temporal choice in young and aged rats
0s 10s 20s 40s 60s0
20
40
60
80
100Young Adult (6 mo.)
Aged (24 mo.)
Delay
% C
ho
ice
of
Lar
ge
Rew
ard
Simon et al 2010, Neurobiology of Aging
Inter-temporal choice in young and aged rats
0s 10s 20s 40s 60s0
20
40
60
80
100Young Adult (6 mo.)
Aged (24 mo.)
Delay
% C
ho
ice
of
Lar
ge
Rew
ard
Simon et al 2010, Neurobiology of Aging
- similar to findings in human subjects
Individual differences in inter-Individual differences in inter-temporal choice in agingtemporal choice in aging
Individual differences ininter-temporal choice in aging
0
25
50
75
100
10 20 40 600
Delay to large reward (s)% C
ho
ice
of
larg
e, d
ela
ye
d r
ew
ard
Simon et al 2010, Neurobiology of Aging
Individual differences in inter-Individual differences in inter-temporal choice in agingtemporal choice in aging
Individual differences ininter-temporal choice in aging
0
25
50
75
100
10 20 40 600
Delay to large reward (s)% C
ho
ice
of
larg
e, d
ela
ye
d r
ew
ard
Simon et al 2010, Neurobiology of Aging
Inter-temporal choice vs.working memory
% Choice of Large Delayed RewardM
ea
n %
Co
rre
ct
(wo
rkin
g m
em
ory
)
0 20 40 60 80 10070
80
90
100
r=0.58, p<0.05
Shimp et al. in press, Neurobiol Learning & Memory
Individual differences in inter-Individual differences in inter-temporal choice in agingtemporal choice in aging
Individual differences ininter-temporal choice in aging
0
25
50
75
100
10 20 40 600
Delay to large reward (s)% C
ho
ice
of
larg
e, d
ela
ye
d r
ew
ard
Simon et al 2010, Neurobiology of Aging
- individual differences don’t account for young vs. aged differences
Inter-temporal choice vs.working memory
% Choice of Large Delayed RewardM
ea
n %
Co
rre
ct
(wo
rkin
g m
em
ory
)
0 20 40 60 80 10070
80
90
100
r=0.58, p<0.05
Shimp et al. in press, Neurobiol Learning & Memory
Age differences in inter-Age differences in inter-temporal choicetemporal choice
Hippocampus?Hippocampus?– Hippocampus implicated in inter-Hippocampus implicated in inter-
temporal choicetemporal choice
Age differences in inter-Age differences in inter-temporal choicetemporal choice
Hippocampus?Hippocampus?– Hippocampus implicated in inter-Hippocampus implicated in inter-
temporal choicetemporal choice– Some hippocampal functions decline Some hippocampal functions decline
with agewith age
Age differences in inter-Age differences in inter-temporal choicetemporal choice
Hippocampus?Hippocampus?– Hippocampus implicated in inter-Hippocampus implicated in inter-
temporal choicetemporal choice– Some hippocampal functions decline Some hippocampal functions decline
with agewith age– Age-related alterations in hippocampal Age-related alterations in hippocampal
neurochemical signalingneurochemical signaling
Age differences in inter-Age differences in inter-temporal choicetemporal choice
Hippocampus?Hippocampus?– Hippocampus implicated in inter-temporal Hippocampus implicated in inter-temporal
choicechoice– Some hippocampal functions decline with ageSome hippocampal functions decline with age– Age-related alterations in hippocampal Age-related alterations in hippocampal
neurochemical signalingneurochemical signaling– Nicotinic cholinergic receptors?Nicotinic cholinergic receptors?
Decline with ageDecline with age Decline associated with impaired hippocampal-Decline associated with impaired hippocampal-
dependent learning/memorydependent learning/memory
Age differences in inter-Age differences in inter-temporal choicetemporal choice
Dorsal Hippocampus
25 50 75 1004.5
5.0
5.5
6.0
Mean % Choice of Large Reward
4
2 n
AC
hR
Den
sity
(nC
i/mg
)
r=-.87, p<.001
α4β2 nicotinic receptors
Mendez et al 2013, Neuroscience
Age differences in inter-Age differences in inter-temporal choicetemporal choice
What does this mean?What does this mean?– an improvement in cognitive function in aging?an improvement in cognitive function in aging?
OR…OR…
Age differences in inter-Age differences in inter-temporal choicetemporal choice
What does this mean?What does this mean?– an improvement in cognitive function in aging?an improvement in cognitive function in aging?
OR…OR…– perhaps exaggerated preference for delayed perhaps exaggerated preference for delayed
gratification is not a good thinggratification is not a good thing
Age differences in inter-Age differences in inter-temporal choicetemporal choice
What does this mean?What does this mean?– an improvement in cognitive function in aging?an improvement in cognitive function in aging?
OR…OR…– perhaps exaggerated preference for delayed perhaps exaggerated preference for delayed
gratification is not a good thinggratification is not a good thing
Future directionsFuture directions– Neural/behavioral mechanismsNeural/behavioral mechanisms– Longitudinal studies (behavior and Longitudinal studies (behavior and
neuroimaging)neuroimaging)
AcknowledgementsAcknowledgementsNick Simon, PhDNick Simon, PhDSofia BeasSofia BeasIan Mendez, PhDIan Mendez, PhDKristy ShimpKristy ShimpCristina Bañuelos, PhDCristina Bañuelos, PhDMarci Mitchell, PhDMarci Mitchell, PhDCandi LaSarge, PhDCandi LaSarge, PhDKarienn Montgomery, PhDKarienn Montgomery, PhDJoanne Damborsky, PhDJoanne Damborsky, PhDCaitlin Orsini, PhDCaitlin Orsini, PhDJoseph McQuail, PhDJoseph McQuail, PhD
Dr. Jennifer BizonDr. Jennifer BizonDr. Ursula Winzer-SerhanDr. Ursula Winzer-Serhan
National Institute on AgingNational Institute on Aging
Individual differences in inter-Individual differences in inter-temporal choice in agingtemporal choice in aging
Simon et al 2010, Neurobiology of Aging
Nucleus AccumbensD2 Dopamine Receptor
40 60 80 100
0.6
0.8
1.0
1.2
% Choice of Large Delayed Reward
D2
mR
NA
Ex
pre
ss
ion
(nC
i/mg
pro
tein
)
r=0.88, p<0.01
Beas et al. in press
Inter-temporal choice vs.working memory
% Choice of Large Delayed Reward
Me
an
% C
orr
ec
t(w
ork
ing
me
mo
ry)
0 20 40 60 80 10070
80
90
100
r=0.58, p<0.05
Shimp et al. in press, Neurobiol Learning & Memory
Individual differences ininter-temporal choice in aging
0
25
50
75
100
10 20 40 600
Delay to large reward (s)% C
ho
ice
of
larg
e, d
ela
ye
d r
ew
ard
Individual differences in inter-Individual differences in inter-temporal choice in agingtemporal choice in aging
Individual differences ininter-temporal choice in aging
0
25
50
75
100
10 20 40 600
Delay to large reward (s)% C
ho
ice
of
larg
e, d
ela
ye
d r
ew
ard
Simon et al 2010, Neurobiology of Aging
Nucleus AccumbensD2 Dopamine Receptor
40 60 80 100
0.6
0.8
1.0
1.2
% Choice of Large Delayed RewardD
2 m
RN
A E
xp
res
sio
n(n
Ci/m
g p
rote
in)
r=0.88, p<0.01
Beas et al. in press
Age differences in inter-Age differences in inter-temporal choicetemporal choice
Dorsal Hippocampus
25 50 75 1004.5
5.0
5.5
6.0
Mean % Choice of Large Reward
4
2 n
AC
hR
Den
sity
(nC
i/mg
)
r=-.87, p<.001
Dorsal Hippocampus
25 50 75 100
0.4
0.6
0.8
Mean % Choice of Large Reward
7
nA
Ch
R D
ensi
ty (n
Ci/m
g)
r=-.22, p=.42
α4β2 nicotinic receptors α7 nicotinic receptors
Mendez et al 2013, Neuroscience
Control for motivational deficits
FR1 FR3 FR10 FR20 FR400
50
100
150
200
250Young Adult
Aged
Response Schedule
Le
ver
Pre
sse
s
Simon et al 2010, Neurobiology of Aging
Inter-temporal ChoiceInter-temporal Choice
delay to reward delivery
cho
ice
of
del
ayed
rew
ard
addiction0
20
40
60
80
100
0 2 4 16 32
CocaineControl
Delay (s)C
ho
ice
of
La
rge
Re
wa
rd (
%)
Mitchell et al in press, Behavioral Neuroscience
Individual differences in inter-Individual differences in inter-temporal choice in agingtemporal choice in aging
Simon et al 2010, Neurobiology of Aging
0
25
50
75
100
10 20 40 600
Delay to large reward (s)% C
ho
ice
of
larg
e, d
ela
ye
d r
ew
ard
Individual differences in inter-Individual differences in inter-temporal choice in agingtemporal choice in aging
0
25
50
75
100
10 20 40 600
Delay to large reward (s)% C
ho
ice
of
larg
e, d
ela
ye
d r
ew
ard
Simon et al 2010, Neurobiology of Aging
Nucleus AccumbensD2 Dopamine Receptor
40 60 80 100
0.6
0.8
1.0
1.2
Mean % Choice of Large Reward
D2
mR
NA
Ex
pre
ss
ion
(nC
i/mg
pro
tein
)r=0.88, p<0.01
Beas et al. in press
Individual differences in inter-Individual differences in inter-temporal choicetemporal choice
Shimp et al. in press, Neurobiology of Learning and Memory
Inter-temporal choice vs.working memory
% Choice of Large,Delayed Reward
Me
an
% C
orr
ec
t(w
ork
ing
me
mo
ry)
0 20 40 60 80 10070
80
90
100
r=0.58, p<0.05