Associative Learning and the Monkey Medial Temporal Lobe Wendy A. Suzuki Center for Neural Science New York University.

Associative Learning and the Monkey Medial Temporal Lobe

Wendy A. Suzuki Center for Neural Science

New York University

Ventral View of Macaque Monkey Brain

rs

PR

ER

PH

RL

AP 14.5

HPC

EC PR

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

Experimental Question:

What are the neural correlatesof associative memory formation in

the medial temporal lobe?

Location-Scene Association Task

Gaffan (1994)

Murray and Wise (1996)

Murray et. al., (1998)

+

+

+

Location-scene association task

+ ++New Scenes

(n = 2-4)

+ ++

ReferenceScenesn = 4

Fixation/Baseline(300 ms)

Scene/TargetPresentation

(500 ms)

Delay(700 ms)

Eye MovementResponse

Working Hypothesis

Selective changes in the patterns of activity in hippocampal neurons underlie

the formation of new location-scene associations.

-300 0 500 1200

0

5

10

15

20

25

30

35

40

45

+

Response to 3 New Scenes

Baseline

+ +

Scene/Target EMDelay

Time from Scene Onset (ms)

Sp

ike

s/S

ec

C110600

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

Behavioral Learning Curve and Delay Activity Over Time for Reference Scene 67

C110600.4

0 21 41

Response (S

p ik es /Sec )

Trials

Pro

babi

lity

Cor

rect

-10

0

10

20

30

40

50

0

0.2

0.4

0.6

0.8

1

Are There Different Categoriesof Changing Cells?

2 Categories of Changing Cells

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

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

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

Categories of Changing Cells

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

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

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

Categories of Changing Cells

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

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

What Does the Change in Neural Activity Represent?

Degree of selectivity was measured

Using a selectivity Index (Moody et al., 1989)

λi is response to ith scene

λmax is maximal response for a cell

n is the total number of scenes

max1

( / ) /( 1)n

ii

SI n n

Measures of Selectivity: Sustained Changing Cells

Sel

ectiv

ity In

dex

Before AfterLearning

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7*

Response of a changing cell to all scenes

0

2

4

6

8

10

12

14

1 11 21 31 41 51 61 71 81 91 101 111

Res

pons

e (S

pike

s/S

ec)

Trials

Ref 1Ref 2Ref 3

Ref 4New 1New 2

0

0.2

0.4

0.6

0.8

1

Probability C

orrect

Learning Curve

Measures of Selectivity: Baseline Sustained Changing Cells

Sel

ectiv

ity In

dex

Before AfterLearning

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8*

What is The Time Course of the Changing Cells relative

to Learning?

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

esponse (Spikes/S

ec)

Pro

babi

lity

Cor

rect

-10

0

10

20

30

40

50

0 10 20 30 40 500

0.2

0.4

0.6

0.8

1

Baseline Activity

Trials C110600.4

Neurons that change after learning

Neurons that changebefore learning

Behavioral Change

0 10 20 30 40 50

Neu

rona

l Cha

nge

0

10

20

30

40

50

Neural Change vs. Learning

Ratio Index

Before – AfterBefore + After

Ratio Index =

Trials to Learn

-1.5

-1

-0.5

0

0.5

1

1.5

1 - 10 11 - 20 21 - 30 > 31

Ratio Index: Hippocampus

Rat

io I

ndex

Where are the changing cells located?

Anteroposterior20 18 16 14 12 10 8

Do

rsov

ent

ral

-18

-16

-14

-12

-10

-8

-6

AP 14.0

Hippocampal Recording Sites

Monkey 1

SustainedBaseline Sustained

Nonresponsive/nonselectiveSelective

Summary

Hippocampal Changing Cells:

1. Signal new learning with changes in their stimulus-selective response properties

2. Participate throughout the early learning process

3. Are located throughout the hippocampal region

2. Comparison with the Perirhinal Cortex

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)

Selective

PR Cortex(n = 2 monkeys)

Hippocampus(n = 2 monkeys)

89/145 (61 %) 67/104 (64 %)

Changing Cells

25/89 (28%)

19/67 (28%)

Sustained

Baseline Sustained

4/19 (21%)

15/19 (79%)

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

Learning-related cells in the Perirhinal Cortex

Sustained Changing Cell

Probability C

orrectRes

pons

e (S

pike

s/S

ec)

Trial Number

10 20 30 40

30

40

50

60

0.0

0.2

0.4

0.6

0.8

1.0

10 20 30

0.0

0.2

0.4

0.6

0.8

1.0

10

15

20

25r= -0.62

r= 0.58

Trial Number

Baseline Sustained Changing Cell

40

What is The Time Course of the Changing Cells relative

to Learning?

Behavioral Change

0 10 20 30 40 50

Neu

rona

l Cha

nge

0

10

20

30

40

50

Hippocampus Perirhinal Cortex

Behavioral Change

0 10 20 30 40 500

10

20

30

40

50

Trials to Learn

-1.5

-1

-0.5

0

0.5

1

1.5

1 - 10 11 - 20 21 - 30 > 31

Ratio Index: Hippocampus

Rat

io I

ndex

-1.5

-1

-0.5

0

0.5

1

1.5

1 - 10 11 - 20 21 - 30 > 31

Trials to Learn

Rat

io I

ndex

Perirhinal

Hippocampus

Ratio Index: Hippocampus vs. PR

Behavioral Change

0 10 20 30 40 50

Neu

rona

l Cha

nge

0

10

20

30

40

50

Hippocampus Perirhinal Cortex

Behavioral Change

0 10 20 30 40 500

10

20

30

40

50

Location-scene association task:

+ ++New Scenes

Fixation Scene/Target Delay Response

Within Trial Analysis

Nor

mal

ized

Res

pons

e

Time (ms)

+ +

Fixation Scene Delay Response

Within-Trial Analysis: Sustained Cells

Perirhinal

Hippocampus

0 200 400 600 800 1000 1200 1400 1600 1800-0.2

0.0

0.2

0.4

0.6

0.8

Nor

mal

ized

Res

pons

e

Perirhinal

Hippocampus

Within-Trial Analysis: Baseline Sustained Cells

+ +

Fixation Scene Delay Response

0 200 400 600 800 1000 1200 1400 1600 1800-0.2

0.0

0.2

0.4

0.6

0.8

1.0

Time (ms)

Behavioral Change

0 10 20 30 40 50

Neu

rona

l Cha

nge

0

10

20

30

40

50

Hippocampus Perirhinal Cortex

Behavioral Change

0 10 20 30 40 500

10

20

30

40

50

Learning Signals Across the Brain

HippocampusCahusac et al., 1993

Wirth et al., 2003

SEF & FEFChen and Wise, 1995a,b

Premotor CortexMitz et al, 1991

Brasted and Wise, 2004

StriatumBrasted and Wise, 2004

Prefrontal CortexAsaad et al., 1998

Perirhinal CortexYanike et al. 2005

Neurons that change after learning

Neurons that changebefore learning

Behavioral Change

0 10 20 30 40 50

Neu

rona

l Cha

nge

0

10

20

30

40

50

Neural Change vs. Learning

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

Lead SameTime

Lag

Pro

port

ion

PM

Putamen

SEF

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

Lead SameTime

Lag

HPC (Wirth)

HPC (Cahusac)

HPC (Wirth/Wise)

Population Response: Sustained cells

Neural activity relative to behavior

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

Lead SameTime

Lag

Pro

port

ion

PM

Putamen

SEF

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

Lead SameTime

Lag

HPC (Wirth)

HPC (Cahusac)

HPC (Wirth/Wise)

Population Response: Sustained cells

Neural activity relative to behavior

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

Lead SameTime

Lag

Perirhinal

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)

Summary

HPC and PR exhibit similar proportions and categories of changing cells.

HPC and PR exhibit a similar temporal relationship between learning and neural activity

PR signals learning during the scene period of the task while the HPC signals learning during the delay

Sylvia WirthMarianna Yanike

Suzuki Laboratory

Sylvia Wirth

Stephen Leonard

Postdoctoral Fellows Students

Technicians

Marianna Yanike

Nilda Nystrom

Cindy Chiu

CollaboratorsEmery N. BrownLoren M. FrankAnne C. Smith

Eric HargreavesEmin Avsar

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