Principles of Memory Organization in the Monkey Medial Temporal Lobe

Wendy A. Suzuki Center for Neural Science

New York University

24/25/32Pi

Ia

Id

Ig

Frontal Lobe Temporal Lobe InsularCortex

CingulateGyrus

ParietalLobe

V4

23/29/30

7a/LIP

STSd STG

TE

STSv

TEO

11/1246

13

DG

SubHPC

30-60%18-29%5-17%<5%

Entorhinal

ParahippocampalPerirhinal

Suzuki and Amaral, 1994

Take Home Message:• All structures of the MTL appear to

provide a similar complement of associative learning-related signals.

24/25/32Pi

Ia

Id

Ig

Frontal Lobe Temporal Lobe InsularCortex

CingulateGyrus

ParietalLobe

V4

23/29/30

7a/LIP

STSd STG

TE

STSv

TEO

11/1246

13

DG

SubHPC

30-60%18-29%5-17%<5%

Entorhinal

ParahippocampalPerirhinal

Suzuki and Amaral, 1994

Take Home Message:• All structures of the MTL appear to provide a

similar complement of associative learning-related signals.

• There appears to be a conditionally dynamic relationship between different MTL structures such that depending on task demands different MTL structure can either contribute in similar/cooperative ways or in more clearly distinct way to mnemonic functions.

Location-Scene Association TaskGaffan (1994), Murray and Wise (1996), Murray et. al., (1998)

+ ++New Scenes

(n = 2-4)

Fixation/Baseline(300 ms)

Scene/TargetPresentation

(500 ms)

Delay(700 ms)

Eye MovementResponse

Pro

babi

lity

Cor

rect

0 10 20 30 40 500

0.2

0.4

0.6

0.8

1

Behavioral Learning Curve and Delay Activity Over Time to Scene 653 R

esponse (Spikes/S

ec)

-10

0

10

20

30

40

50

Baseline Activity

Trials C110600.4 Wirth et al., 2003

Pro

babi

lity

Cor

rect

Behavioral Learning Curve and Delay Activity Over Time to Scene 386 R

esponse (Spikes/S

ec)

Trials

0

0.2

0.4

0.6

0.8

1

1 4 7 10 13 16 19 22 25 28 31 34 37

0

2

4

6

8

10

12

14

16

Wirth et al., 2003

2 Categories of Changing Cells

A. Sustained Changing cells: 56% of all changing cells

B. Baseline Sustained Changing cells: 44% of all changing cells

What about the Perirhinal cortex?

Yanike et al., 2008, In press

Selective

Hippocampus(n = 2 monkeys)

89/145 (61 %)

Changing Cells

25/89 (28%)

Sustained

Baseline Sustained

PR Cortex(n = 2 monkeys)

83/128 (65 %)

26/83 (31%)

8/26 (31%)

18/26 (69%)

14/25 (56%) 11/25 (44%)

Yanike et al., 2008, In press

Early

Late Early

Late+

+ +

+

Object 1 Object 2

Place 1

Place 2

Object-Place Association Task

Wirth et al, 2009

Fixation500ms

Cue500ms

Delay700ms

Early500ms

Late500ms

Reward ITI2000ms

++ ++ ++ ++ ++

Bar Release Period

Fixation500ms

Cue500ms

Delay700ms

Early500ms

Late500ms

Reward ITI2000ms

++ ++ ++ ++ ++

Bar Release Period

Fixation500ms

Cue500ms

Delay700ms

Early500ms

++ ++ ++ ++Reward

Release

Fixation500ms

Cue500ms

Delay700ms

Early500ms

Late500ms

++ ++ ++ ++ ++ Release No Reward

ITI

ITI

Correct Trial

Incorrect Trial

Wirth et al, 2009

50% are outcome-selective

Do hippocampal cells differentiate between correct and error trials?

Time from Release (ms)

-500 0 500 1000 1500

Nor

mal

ized

Firi

ng R

ate

(Spi

kes/

Sec

)

-4

-2

0

2

4

6

8

10

12

Time from Release (ms)

-500 0 500 1000 1500

Nor

mal

ized

Firi

ng r

ate

(Spi

kes/

Sec

)-4

-2

0

2

4

6

8

10

12 CorrectError

CorrectError

N=16 N=18

A B

Correct Up CellsN = 30

Error Up CellsN = 38

Wirth et al, 2009

A

Time from Release or Random Drop (ms)-500 0 500 1000 1500 2000

Spi

kes/

Sec

0

5

10

15

20

25

Correct

Error

Random reward

B

Lat

enc

ies

(ms)

0

200

400

600

800

Standard Delayedwith Sound

DelayedNo Sound

*

Wirth et al, 2009

++ + ++

Fixation500ms

Cue500ms

Delay700ms

Reward ITI2000ms

Fixation500ms

Cue500ms

Delay700ms

Early500ms

Late500ms

Reward ITI2000ms

++ ++ ++ ++ ++

Bar Release Period

Standard Trials

Fixation Only Trials

Time from Release (ms)

-500 0 500 1000 1500

Nor

mal

ized

Firi

ng R

ate

(Spi

kes/

Sec

)

-4

-2

0

2

4

6

8

10

12

Time from Release (ms)

-500 0 500 1000 1500

Nor

mal

ized

Firi

ng r

ate

(Spi

kes/

Sec

)-4

-2

0

2

4

6

8

10

12 CorrectError

CorrectError

N=16 N=18

A B

Correct Up CellsN = 30

Error Up CellsN = 38

Wirth et al, 2009

++ + ++

Fixation500ms

Cue500ms

Delay700ms

Reward ITI2000ms

Fixation500ms

Cue500ms

Delay700ms

Early500ms

Late500ms

Reward ITI2000ms

++ ++ ++ ++ ++

Bar Release Period

Standard Trials

Fixation Only Trials

Time from Trial End (ms)

-500 0 500 1000 1500

Firi

ng R

ate

(Spi

kes/

Sec

)

6

8

10

12

14

16

18

20

Time from End of Fixation (ms)

-500 0 500 1000 1500F

iring

Rat

e (S

pike

s/S

ec)

0

10

20

30

40Completed FixationBreake Fixation

N=9N=13 Rewarded TrialsOmit

A B

Wirth et al, 2009

Time from Release (ms)

-500 0 500 1000 1500

Nor

mal

ized

Firi

ng R

ate

(Spi

kes/

Sec

)

-4

-2

0

2

4

6

8

10

12

Time from Release (ms)

-500 0 500 1000 1500

Nor

mal

ized

Firi

ng r

ate

(Spi

kes/

Sec

)-4

-2

0

2

4

6

8

10

12 CorrectError

CorrectError

N=16 N=18

A B

Correct Up CellsN = 30

Error Up CellsN = 38

Wirth et al, 2009

Early

Late Early

Late+

+ +

+

Object 1 Object 2

Place 1

Place 2

Object-Place Association Task

Wirth et al, 2009

Fixation500ms

Cue500ms

Delay700ms

Early500ms

Late500ms

Reward ITI2000ms

++ ++ ++ ++ ++

Bar Release Period

Fixation500ms

Cue500ms

Delay700ms

Early500ms

Late500ms

Reward ITI2000ms

++ ++ ++ ++ ++

Bar Release Period

Sessions without learning

BEFORE AFTERS

elec

tivity

Inde

x

0.35

0.40

0.45

0.50

0.55

0.60

0.65CORRECT UPERROR UPCONTROL

Sessions with learning

BEFORE AFTER

Sel

ectiv

ity In

dex

0.35

0.40

0.45

0.50

0.55

0.60

0.65CORRECT UPERROR UPCONTROL

*

Sessions without learning

Differential Selectivity

-0.7 -0.5 -0.3 -0.1 0.1 0.3 0.5 0.7 0.9

Inci

denc

es (

perc

enta

ge o

f ca

ses)

0

10

20

30

40

50

60

A B

C DSessions with learning

Differential Selectivity

-0.7 -0.5 -0.3 -0.1 0.1 0.3 0.5 0.7 0.9

Inci

denc

es (

perc

enta

ge o

f ca

ses)

0

10

20

30

40

Control cellsError up cellsCorrect up cells

Control cellsError up cellsCorrect up cells

Wirth et al, 2009

24/25/32Pi

Ia

Id

Ig

Frontal Lobe Temporal Lobe InsularCortex

CingulateGyrus

ParietalLobe

V4

23/29/30

7a/LIP

STSd STG

TE

STSv

TEO

11/1246

13

DG

SubHPC

30-60%18-29%5-17%<5%

Entorhinal

ParahippocampalPerirhinal

Suzuki and Amaral, 1994

Take Home Message:• All structures of the MTL appear to provide a

similar complement of associative learning-related signals.

• There appears to be a conditionally dynamic relationship between different MTL structures such that depending on task demands different MTL structure can either contribute in similar/cooperative ways or in more clearly distinct way to mnemonic functions.

Temporal Order Task

0.3 s 0.9 s 0.3 s 0.5 s0.4 s

1.0 s > 4.0 s

Encoding Phase

Retrieval Phase

1st Cue 2nd Cue

1st Choice 2nd Choice

SmallReward

LargeReward

0.7-1.5 s

Pre-responseDelay

Inter-phaseDelay

Naya and Suzuki, SFN 2008

24/25/32Pi

Ia

Id

Ig

Frontal Lobe Temporal Lobe InsularCortex

CingulateGyrus

ParietalLobe

V4

23/29/30

7a/LIP

STSd STG

TE

STSv

TEO

11/1246

13

DG

SubHPC

30-60%18-29%5-17%<5%

Entorhinal

ParahippocampalPerirhinal

Suzuki and Amaral, 1994

Findings

• The most stimulus selective response are found in area TE and the perirhinal cortex.

• Perirhinal cortex has the strongest proportion of order and stimulus selective responses

• The hippocampus has the highest proportion of trial outcome selective responses.

Take Home Message:• All structures of the MTL appear to provide a

similar complement of associative learning-related signals.

• There appears to be a conditionally dynamic relationship between different MTL structures such that depending on task demands different MTL structure can either contribute in similar/cooperative ways or in more clearly distinct way to mnemonic functions.

Sylvia WirthMarianna Yanike

Emin Avsar

Eric Hargreaves Yuji Naya