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