Columbia University

Amy Hale

Won Yung Choi

Yaniv Eyny

Johannes Schwaninger

Princeton University

Barry Jacobs, Ph.D.

Tripp Stewart

A photo-emitter -detector reports each head entry into the food compartment

Movement of the rat is detected as its infrared body heat crosses compartments of a mounted lens.

Sprague-Dawley rats received 16 days of drug-free training (28 trials/day).

On day 17, rats were pretreated with vehicle, D1 antagonist SCH23390 or D2 antagonist raclopride.

Pellets drop, on average, every 70 sec.

Each pellet delivery is preceded by a 400 ms, 78 dB sound.

28 trials are presented during each session

Drug freeSubject 31

Seconds (relative to CS onset)

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4

8

12

16

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24

28

Trial

-16 0 10

D1 antagonistSCH 23390

Subject 31

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28

-16 0 10

Trial

Selective D2 dopamine receptor blockade

VEH, Day 16

-16 0

Trial

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20

24

28

10

Subject 7

RAC 0.4 (Day 17)

-16 0

Time (sec relative to food delivery)

Trial

0

4

8

12

16

20

24

28

10

from Horvitz and Eyny 2000

Dopamine is needed to execute internally-generated responses,

but not for responses to a well-acquired conditioned stimulus

Saline, Rat 41

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10

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30

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-15

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-10 -9 -8 -7 -6 -5 -4 -3 -2 -1 0 1 2 3 4 5 6 7 8 9

Time (sec)

Tri

al

Day 3 of training

SCH23390 0.16 mg/kg, Rat 32

0

5

1015

20

25

30

Time (sec)

Tri

al

D1 receptor blockade increases the frequency of missed trials early but not late in training

Missed trials (proportion of

total)

Days of training

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3 17

Veh0.04 SCH0.08 SCH0.16 SCH

But is necessary to execute responses to a conditioned stimulus during early stages of learning

Dopamine is not needed to execute responses to a well-acquired conditioned stimulus

Test

CS-Food sessions

3-3 group

3-7 groupTest

7-7 group

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Training Sessions/Days

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CS-Food sessions

3-3 group

3-7 groupTest

7-7 group

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SCH 0.16

CORTEX

Motor planning

(anterior frontal lobe)Motor strip

Striatum

DA neurons

Thalamus Gl Pall

sensory

Dopamine neurons respond to salient auditory and visual stimuli

click click signals reward

click click signals reward

1

43

2

Dopamine neuronal response to a click is enhanced when the click signals reward delivery

0

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-10 -9 -8 -7 -6 -5 -4 -3 -2 -1

TONE ONSET 1 2 3 4 5

TONE END 7 8 9 10 11 12 13 14 15

He

ad

-in

(p

rop

ort

ion

of

tria

ls)

Unpaired

Veh

D1 receptor blockade disrupts acquisition of head-entry response to food cue

0

0.1

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0.5

0.6

He

ad-i

n (

pro

po

rtio

n o

f tr

ials

) Unpaired

Veh

.08 SCH

.16 SCH

D1 receptor blockade disrupts acquisition of head-entry response to food cue

14 15

0

0.1

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-10 -9 -8 -7 -6 -5 -4 -3 -2 -1

TONE ONSET 1 2 3 4 5

TONE END 7 8 9 10 11 12 13

He

ad

-in

(p

rop

ort

ion

of

tria

ls)

Unpaired

Veh

.2 Rac

.4 Rac

D2 receptor blockade promotes acquisition of head-entry response to food cue

Dopamine plays a critical role in the acquisition of responses to new environmental stimuli, and D1 and D2 receptors appear to play opposing roles in this process.

Somehow, learned responses become dopamine-independent with overtraining.

00.10.20.30.40.50.60.70.80.9

1

3 17

Veh

0.04 SCH0.08 SCH0.16 SCH

Dopamine transmission is needed for the execution of internally generated responses,

but not for the execution of responses to well-acquired conditioned stimuli

0

4

8

12

16

20

24

28

-16 0 10

Tria

l

Thalamus

Striatum Gl Pall

cortex