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TRANSCRIPT
Making Lasting Memories
James L. McGaugh
Center for the Neurobiology of
Learning and Memory
And
Department of Neurobiology and Behavior
“Memory is assisted by anything that makes an impression on a powerful passion, inspiring fear, for example, or wonder, shame or joy.” Francis Bacon, 1620
“The usefulness of all of the passions consists in their strengthening and prolonging in the soul thoughts which are good for it to conserve…
Descartes, The Passions of the Soul, 1650
Stress-Released Hormones
Arousal/Stress
Brain Activation
Anterior Pituitary Autonomic Nervous System
Adrenal Cortex Adrenal Medulla
Cortisol (corticosterone) Epinephrine (Adrenaline)
Inhibitory
Avoidance
Saline
Controls
Epinephrine
100
50
200
0
250
150 Retention Latencies
0 10 30 120
Epinephrine Administered
After Training Enhances Memory of
Inhibitory Avoidance Training
Time of Posttraining Injection (min)
Gold and van Buskirk, 1975
Amygdala
Object recognition test in rats
Interval
A3
?
B
Training trial
A1
Retention trial
A2
Roozendaal et al., 2008
Object Recognition Memory
Adrenal Corticosterone
Modulates Consolidation
Mediation via Basolateral Amygdala
Basolateral Amygdala NE Activation Required
-20
-10
0
10
20
30
40
50
Dis
cri
min
ati
on
in
de
x (
%)
Saline Propranolol (0.5 µg)
Intra-BLA infusion
Vehicle
Cort 0.3 mg/kg
Cort 1 mg/kg
Cort 3 mg/kg
BLA β-Adrenoceptors mediate corticosterone
effects on
object recognition memory
**
**
Okuda , Roozendaal and McGaugh PNAS 2006
No prior habituation
Norepinephrine Activation in the Amygdala
Influences Memory Consolidation
in vivo microdialysis
HPLC
Norepinephrine Release in the Amygdala After
Inhibitory Avoidance Training
0
100
200
300
400
500
600
700
800
1 2 3 4 5 IA 7 8 9 10 11 12 13 14
15 min sample
% o
f B
aselin
e N
E
600 SEC
600 SEC
600 SEC
600 SEC
342 SEC
227 SEC
10 SEC
McIntyre, Hatfield and McGaugh, 2000
Retention Latencies
Neuromodulatory and Amygdala Regulation of Memory in Human
Subjects
4
2
8
12
10
6
0.03 0.04 0.05 0.06 0.07 0.08
r = + 0.93
Number of Films Recalled
Amygdala Activity (PET)
During Encoding and Long-
Term Explicit Memory
Cahill, et al
1996
Right Amygdala Glucose
Learning
Experience Cortex
Hippocampus
Caudate Nucleus
Other Brain Regions
Basolateral
Amygdala
Adrenal Gland
Initiation of Memory Consolidation
Glucocorticoid Epinephrine
Modulating Influences
“The usefulness of all of the passions consists in their strengthening and prolonging in the soul thoughts which are good for it to conserve… And all the harm they can do consists in their strengthening and conserving these thoughts more than is necessary.”
Descartes, The Passions of the Soul, 1650
Preventing PTSD with drugs affecting norepinephrine?
Highly Superior Autobiographical Memory
Five new subjects
Testing for memory of events
Professional violinist
Subject’s discussion of the remembering process
Testing for dates
Testing for memory of sporting events
TV producer
Memory of an Italian event:
Hollywood actress Marilu Henner
Temporoparietal Junction
HSAM region > Control
region TBM
Some questions: Neurobiological bases –fMRI, genetics Importance of selectivity in memory? What possible insights concerning memory – a novel capacity? or, for most of us, a lost capacity? What “price” is paid for this ability?
With thanks to --
Benno Roozendaal
Larry Cahill
Christa McIntyre
Shoki Okuda
Emily Malin
Areg Barsegyan
Daniel Berlau
Ryan LaLumiere
John Guzowski
Craig Stark
Aaron Mattfeld
Frithjof Kruggel
Aurora LePort … and many others
The end