Spatial relational learning persists following neonatal hippocampal lesions in macaque monkeys

Pierre Lavenex, Pamela Banta Lavenex, and David G Amaral

Volume 10|Number 2| February 2007| Nature Neuroscience

Background

1. Procedural learning: The unconscious learning of a skill, such as a series of actions or perceptual processing functions (for example, learning to ride a bike), which typically results in increased speed or accuracy with repetition.

2. Primining: A behavioral change that is manifested in the speed or accuracy with which a stimulus is processed following prior exposure to the same stimulus

3. Classical conditioning: If the CS and the US are repeatedly paired, eventually the two stimuli become associated and the organism begins to produce a behavioral response to the CS.

Nat Rev Neurosci. 9:182-94. 2008

2. Semantic memory refers to the memory of meaning, understandings, and other concept-based knowledge unrelated to specific experiences.

1. Episodic memory is the memory of unique personal experiences (events, times, places, and associated emotions) that can be put in language.

Nat Rev Neurosci. 9:182-94. 2008

Nat Rev Neurosci. 9:182-94. 2008

1. Spatial memory involves allocentric (spatial relational) and egocentric coding of space.

2. Spatial memory has often been considered in the context of episodic memory, and has also been considered in the context of semantic memory.

Objective

• Previously, they showed that selective hippocampal damage prevented spatial relational learning in freely moving adult monkey.

• Here, they test the ability of juvenile monkeys with neonatal hippocampal lesions to learn new spatial relational information.

Materials and methods

• 16 infant macaque monkeys (8 controls, 8 lesions).• Hippocampal-lesion surgeries performed 12-16 d after

birth.• Reared in a cohort consisting of six mother-infant pairs

and one adult female, and they met >3 h/day, 5 d/week. • Weaned when the youngest one reached at 6 months,

and then housed in a cohort with one adult male and a new adult female.

• Tested each day (5 d/week), between 7:30-11am (Monkeys were about 18.6 years old).

Pre-training 5d

1. Pre-training: Monkeys were pre-trained in temporary holding cages for 5 d (20 trials per day until they successfully retrieved grapes in <30 s on all trials) to displace a cup to retrieve grapes.

Each, 61X66X81cm

Pre-training 5d

2. Acclimation: Monkeys were free to explore the open-field arena for 5 d, 5 min each day (no cups, no grapes). Monkeys randomly entered and exited the arena from one of the four entrances.

Acclimation 5d

Pre-training 5d

Acclimation 5d

Local cue conditioning

3 trials/day, 2 w

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3. Local cue conditioning: To test the ability to find food at fixed locations, blue cups (4, 8, 12) marked potentially-baited locations on the outer array, red cups (13, 15, 17) on the inner array. Others were covered with neutral cups.

Poster

Mainly egocentric

Pre-training 5d

Acclimation 5d

Local cue conditioning

3 trials/day, 2 w

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5. Spatial relational condition: To assess monkeys’ reliance on a spatial relational memory to discriminate these locations in relation to distal environmental cues, (such as posters). Neutral cups covered all locations.

Spatial relational conditioning

3 trials/day, 2 w

Poster

Only allocentric

Pre-training 5d

Acclimation 5d

Local cue conditioning

3 trials/day, 2 w

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6. Two steps repeated

Probe trial 1 trial

Spatial relational conditioning

3 trials/day, 2 w

Spatial relational conditioning

Local cue conditioning

3 trials/day, 2 w

Pre-training 5d

Acclimation 5d

Local cue conditioning

3 trials/day, 2 w

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4. Probe trial (no grapes): To assess monkeys’ reliance on the local cues (colored cups) versus spatial relational information (surrounding environment). Colored cups were shifted 60º from the usual locations. Blue (2,6,10); Red(14,16,18).

Poster

Egocentric

Allocentric

Local cue conditioning

3 trials/day, 2 w

Probe trial 1 trial

Spatial relational conditioning

3 trials/day, 2 w

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Analysis (I)

Pot in (PI)--three inner baited locations (13,15,17) .

Pot out(PO)--three outer baited locations (4,8,12).

Equ in (EI)--three inner never-baited corner locations (14,16,18).

Equ out (EO)--three outer never-baited corner locations (2,6,10).

Other (O)--six never-baited side locations (1,3,5,7,9,11).

PO

PO PO

PI

PI PI

EI

EI

EI

EO EO

EO

O

O O

O

OO

(I) local cue and relational conditions (II) Probe trial Space in (SI)

Space out (SO)

Color in (CI)

Color out (CO)

Other (O)

• To identify strategies monkey used--The first four choice for the local cue and spatial relational trial, and all choice made during the probe trial.

• To assess activity level--The number of cups being open in the each trial.

• To examine lesion size and placement -Magnetic resonance images (MRI).

Analysis (II)

How to get this?

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Analysis (III)PO

PO PO

PI

PI PI

EI

EI

EI

EO EO

EO

O

O O

O

OO

All choices

PI PO EI EO O

0.4

Nu

mb

er

of c

ho

ice

s

0.2

0.6

0.8

1.0

PI PO EI EO O

0.4

Nu

mb

er

of c

ho

ice

s

0.2

0.6

0.8

1.0First four choices

I

II

IV

III

V

VIII

VIIVI

Results

Hyperactivity caused by hippocampal lesions

AcclimationLocal cue and spatial relational conditioning

Number of the monkey’s position among eight zones every 5s during the 5-min session

?

No difference in the local cue conditioning

Neonatal hippocampal lesions Adult hippocampal lesions

First Four Choices

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PO

PO PO

PI

PI PI

EI

EI

EI

EO EO

EO

O

O O

O

OO

~ 18.6 months 10~13 year old

No difference in the spatial relational conditioning

Neonatal hippocampal lesions Adult hippocampal lesions

First Four Choices

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PO

PO PO

PI

PI PI

EI

EI

EI

EO EO

EO

O

O O

O

OO

~ 18.6 months 10~13 year old

No difference in the probe trial

Neonatal hippocampal lesions Adult hippocampal lesions

All Choices

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SO

SO SO

SI

SI SI

CI

CI

CI

CO CO

CO

O

O O

O

OO

~ 18.6 months 10~13 year old

??

Lesion regions shown by MRI

Coronal Horizontal Sagittal

Con

trol

H

ippo

cam

pal

Conclusions• Selective hippocampal prevented allocentric

spatial relational learning in freely moving adult monkeys. However, new allocentric spatial relational information were unimpaired in monkeys that received lesions shortly after birth.

Local cue conditioning Probe trialRelational conditioning

Egocentric Allo- & Egocentric Allocentric

Discussion1.Spatial memory--episodic memory The adult hippocampus is critical for the acquisition of new allocentric representations of space.

2. Spatial memory--episode-free semantic memoryThe adult hippocampal lesion showed impaired episode-free semantic memory.

3. However, juvenile monkey brain with hippocampal lesions shortly after birth will undergo a functional reorganization to enable the acquisition of these memories. They propose that the extra-hippocampal cortical regions, which are specialized for the maintenance and retrieval of long-term, episode-free memories will take over it.

Thank you!