The swimming activity of the staggerer mutant mouse

Behavroural Processes, Elsewer

THE SWIFMING ACTIVITY G. GOODALL, J.-H.

OF THE STAGGERER MUTANT MOUSE

GUASTAVINO and 6.

GHEUSI

Unit: Associge au C.N.R.S. no667, d'Ethologie, Avenue J.B. Clement, 93430 Villetaneuse FRANCE

Laboratoire Paris XIII, (Accepted

287

13 (1986) 281-299

University

10 July 1986)

ABSTRACT Goodall, activity

G., Guastavino, of the Staggerer

J.-M., and Gheusi, G., 1986. The swimming mutant mouse. Behav. Processes 13. 287-299.

Four experiments investigated the swimmng behaviour of staggerer previous reports that a mutant mice. The results partially confirmed mouse's swimming is unaffected by the staggerer mutation. In terms of speed and distance there are indeed no measurable differences between The stagnormal and staggerer mice, when first placed in the water. gerer's resistance was however shown to be much lower than a normal's and the genetic difference was also associated with different styles of whereas the normal mouse's swimming behaviour swimming. Furthermore, evolves with increased time in the water, the staggerer's remains constant. The differences are interpreted on the basis of abnormal novelty Thus, swimming appears to be a reactions by the staggerer mutants. better tool for investigating the higher-level cognitive functions of this mutant than terrestrial locomotion.

KEY YOROS:

Staggerer,

Mutant,

Swirrming Behaviour,

Novelty

Reactions

INTRODUCTION The staggerer of

investigations

through

embryology

involves cerebellar Changeux, disruption

the

mutation in to

laminar

cortex

0376-6357/86/$03

50

life

ethology. organization

(Crepe1 et al.,

1980, Sidman of the

in mice has been the source of a wide variety

the

et al.,

lamination

sciences

ranging

The only

reported

of,

and

the

1980; Mallet

number

the degenerative

0 1986 Elsevler Science Pubhshers

neuro-anatomy

of cells

defect in the

et al., 1975; Mariani

1962, Sax et al.,

and

from

physiological

1968). Apparently cell

B V (Blomedlcal

loss are

Dwslon)

and the

secon

288

dary effects between

of the mutation.

the parallel

The primary effect

fibers and the PurkinJe

involves

cells

synaptogenesis

(Sotelo and Changeux,

1974).

The mutation's linked

of behavioural

social 1983,

behaviour

staggerers,

et

shown to be a particularly tional recovery

Despite hors

of

a number

these

terpretation are

effects

induced

example,

certain

artefacts during

due

deficient

to

the

copulation.

be side-effects

Swining

differentiating

neurological

details

were given.

such as learning apparently

mal ambulation. corroborate

Sidman

staggerer's

swimnlng

distance during

and

of swlmmng

which

the patterns

efficient

of

to

locomotor

aut-

the

behavioural

deficits.

behaviour

may

For

be only

its

behaviour

in-

results

balance may also

as a diagnostic

Sidman

mutant

that certain suitably

(1962)

claim

while

also

chose

to

time

(1962) reported

normal,

although

investigated

periods,

during

no

using the abnor-

series of experiments

for

examine

in

higher level functions

the

examining

swirmiing was observed, movements

tool

rather than the blatently

al.' s

fixed

et al.

appeared

present

of whole-body

by the

of social

ln the

over

of func-

analyses

in maintaining

sought

we

been

(Guastavlno,

ObJection

sexual

used

may be more

ability

1978,

also

patterns

these

primary

mice.

as a support

In particular

behaviour.

mutant

and memory

that

frequently

It thus appeared

We thus

recurrlng

difficulty

the staggerer

normal swlmmng

has

abnormalltles.

is very

that in this respect,

mutant

in-depth

some aspects

of locomotor

ability

a been

components

Similarly,

to more

Guastavino,

1985).

by the

animal's

dlsrupt-

behaviour

1982,

behavlour

and

studies, has

are also severely

This

number

that a large number

tool for the investigation

of precautions,

results

of balance

gait. A growing

al.,

1986).

and Goodall,

behavloural

is loss

individual

et

of abnormal

of their

secondary

from

al.,

valuable

of a variety

1983, 1984a,b; Guastavino

patterns

(Bulloch

Misslin

effect

have revealed

ranging

relationships

1984a;

behavioural

and a "staggering"

in recent years

integrated

ed in homozygous complex

sallent

posture

reports

of more complex

1982,

most

to an abnormal

normality

the details

four

aspects:

stamina and style

swimming.

of

to the

of this

speed

and

or the duration as revealed

by

289

METHODS

SubJects

Ten

adult

experiments animals

were

initially

the four

staggerers

obtained

based

Dr. L. Guenet

vulsive

male

(sg/sg)

as well as ten normal

on

from a

the

pair

studies,

two

+/sg

ln each

went

in the water,

mice

of the

four

(t/t or +/sg). All

breeding

C57BL/6

Institute.

lmnediately

fit when placed

used

laboratory's

of

of the Pasteur

were

adult male controls

colony kindly

which

was

donated

by

Of the forty staggerers

used ln

into what appeared

to be a con-

and so were returned

to their home

cages and replaced.

The staggerers conditions (1978).

modified

The

weaning

were housed to ensure

normals

were

in group cages after weaning their

survival

separated

and were maintained

from

in unmodified

as described

their

with rearing by Guastavino

staggerer

siblings

at

group cages.

Apparatus

The swlmnlng high,

filled

paper

on

dlvlding wlthln

the

pool consisted

to a depth outside,

of

of a glass box,

10 cm. The walls

on which

were

the pool into 100 squares

20 of 270C.

of

drawn

1 metre square and 20 cm were

lines

lOOcm*.

obscured at

10 cm

The water

with

white

intervals,

was malntained

290

For Experiment first,

creating

wall was level.

2, an additional

a peripheral

raised

5cm from

No mouse

alley

the base,

(normal

wall

was inserted

with

a width

of

and proJected

or staggerer)

ever

10 cm inside 10 cm.

This

5 cm above

managed

to climb

the

inner

the water over

this

inner wall or to swim under it.

Recording which

was effected

records

press.

These

2-digit data

with a portable

data

were

codes

then

puter on which subsequent

and

down-loaded

analyses

data recorder

the

associated

(Datamyte

time

to a Thompson

1006)

of each

Micro-Mega

key com-

were performed.

Procedure

Experiments ten staggerers

took place during the light phase. Four separate and ten normals were run in different

tions with differents introduced

aspects

Experiment

the

1: The mice were order

(ABBA),

introduced,

and their

figure

to

the

2: The

for ten minutes wall

walls.

into

to the main

an analysis

SubJects the

pool.

in terms of direction line.

Experiment

3: Slow motion

term resistance swianning pool.

of swimming The only

the mouse's

seconds.

video

head

As soon as this

from the swlmnlng

were

walls,

Introduced alley

recorded Tnversion

recording

recorded

dropped

below

criterion

pool and returned

recorded

on the basis

of

period.

The analysis

of

defined

intermediate

of swimming portayed

in

and central

zones.

in a counterbalanced

order

created

by adding

the

inner

permitted

and the speed of swimnlng

was

used to observe and normals

involved the

as

(time and location)

of the staggerers

data

2, in which

stood.

swum and the location

zones

peripheral

The data

a straight

before

were

situa-

Mice were

one at a time and in a counter-

observation

Four

1: these were the corners,

Experiment

in experiment

traJectones

10x10 grid for a thirty-minute

relation

recorded.

on the side where the observer

the data was in terms of the distance in

behaviour

into the centre of the pool, except

they were placed centrally

balanced

of swlmning

sets of

experimental

was reached

the long

in the square

the total

surface

in

time

elapsed

for ten consecutive

the subJect

to Its home cage.

was

removed

291

Experiment

4:

In order

swlrrunlng traJectory duced

for

patterns mals:

a ten-minute

straight

line

swinmnlng 3-

in

were

for at least circles

maintaining

finer

the mice

of

details

of this

period

recorded

traJectones,

lannoblllty, in which

surface,

analyse

speed,

observation

of locomotion

l- straight

to

and

into the

both

in which

for

the

diameter

no

its position

the

patterns

of

were

lntro-

pool.

Three

staggerers

and

nor-

swims ln a fairly

traJectorles,

greater

remains

the

square

SubJect

30 cm, 2- circular

the mouse

of

experiment

than

about

virtually

defined 30

cm

motionless

only by very occasional

as and

on the

flutterlngs

of

the tail or limbs.

RESULTS The data

from

the four

experiments

but regrouped

into behavloural

ality

reported

of

mental

the

conditions.

measures,

Statistics

are

categories

presented

separately

so as to underline

irrespective

of the

used were t-tests

specific

and analyses

below,

the generexperl-

of variance

as appropriate.

A- Distance

Experiments a given shows

1 and 2 generated

time by normal

the

ten-minute significant

average

distance

swum

test of experiment difference

df= 18, p>.O5),

despite

the

Iwmr El*-

two

A

and

normals

peripheral

alley.

groups

this

a very slight advantage

70.

to the distance

swum ln

The left portion of figure

by staggerers

Metrem A

mice.

2, ln the

between

Metros 100.

data pertinent

and staggerer

ln

dunng There

test

2

the is no

(t=1.43

for the staggerers.

292

The results

in the unrestricted

1 offer a more accurate normals.

These

data,

that the normals time when

the

presented

in the

slightly

further

swim

first introduced

gresslvely

less

distance

distance

swum

.05). Dunng

right than

into the water. as the

by the

the final

fact swam on average

environment

presented

picture of the difference

time

further

panel

the staggerers

Whereas

remains

of the

and

2 reveal

per unit of

the normals

swim pro

increases,

however,

constant

30-minute

than the normals

ln Experiment staggerers

of figure

in the water

staggerers

period

between

(F(5,45)=3.17

test, the

staggerers

(t=3.47, df=18,

pC ln

pd.01).

B- Speed

The only cerning

one

The other

experiments

the SubJect

changes tation

four

contain

provldlng

1s Experiment data concerning

estimate

were explicitly

only which

It is possible

of speed

both of fastest

(or distance). speed

panel,

of speed.

recorded,

Figure

and the average

panel, for staggerers

and normals.

grid

con-

alley. posltlon

recorded

to

which

In Experiment 2 any dlrectlon

3 presents

continuous

any underthese

The difference

data

loop around

speed over ten-minutes

both cases 1s small and lnslgnlflcant

data

for the SubJects

movement

thus eliminating

(for a 4-metre

reliable

2 ln the peripheral

a given square, with no additional

a minimum-biased

in the left

experiments

is in at any given time.

circle wlthln yields

of the

the speed of swlmnlng

between

(t=1.03, df=18,

represenin terms

the alley), ln the right

the groups

p>.O5).

Frgure 3 he mean fastest speed O”~P a 4 mtce loop around the perzpke*y for nomtzt and stnggerer rmce TV ekown m the left panel The ngkt speeds over the entrre 10 nnn test Em,or bars show standard e~mn.6.

dunng Erpenmt prnel shows the

2 mean

ln

293

Resistance

Figure and

reveals

normals

The normals a

a

terms

of

or

difference

reslstance

staggerers

fatigue

in

can

sufficient

of

efficiency

swimming

to

afloat

average

significant

for

of

hours

six the

water

is at whereas reach

the the

for

exhaustion

only

119

This

therefore

a

first

in

staggerer's

Ptgure4 Re mean tm,e m m.nute~ for eubjectsof the tm groupsto attatn the cntenon for t-eeastancze as defmed by berngsubmerged for ten con~ecut~oe seconde These resulte were

which

swimming

obtamed

from Ezpenment 3.

to be deflclent

can be

when compared

to a normal's.

D- Style

Experiments

1,

2 and

overall

style or strategy

of

swirnnlng obtained

the

transformed

to account

and are presented between

4

~tgure

contained

in

the

30-minute

for the different

test

surface

5. This figure

and normals.

5 The the four to acxount

measures

relevent

of swirrming. The data concerning

in figure

the staggerers

each

Whereas

of

the

the locations

Experiment

areas

to

1 were

of the 4 zones,

shows a very clear difference the normals

tend to stay

percent of trmespentby staggerers and nomule tn regrons of the pod Thp persentages were watghted for the dsfferentsurfacearea of each regton

294 close to the walls the

centre,

the

(the corners

staggerers

areas of the swimming An

aspect

concerns

of the

6. There

and the normals. rate of decline

Finally, confirm

the

further

dlstrlbute

in Experiment

obtained

IS again

The groups

results

of

differences

engaged

in the

differ

difference

straight

styles.

The staggerers

the

in

all

to

between

the

style, of time

staggerers and the

test.

4, conducted

patterns

of

in the

swimmng

1 m2 pool, displacement

mice. The mean time spent by the two groups

(along

for the two groups,

2 related

in terms both of the number

Experiment

swimming

similar

equally

The data are shown as a function

a clear

in

and to avoid

pL.05).

of U-turns over the lo-minute

three

movements

data

normal and staggerer

swlmning

their

favoured)

3.93,

between

spent

especially

pool (F(3,18)=

the number of U-turns.

1r-1figure

being

styles

is shown

a wall

or

across

but they differed

circled

much more

almost four times as long in the immobile

in

than

figure the

widely

7. The

pool)

time

was

very

for the other

the normals,

which

two

spent

posture.

aoauu

400

300

Frgure 7 durcng

Tke mean ttnw &p”t Ezpercment 4 eneach of the three dtstrnctrva patterns of evvmnrng styts normale and by etaggorers

gaged ti

100

100

295

Furthermore, reveals ence

that

figure

8

the dlffer-

between

the

in terms of immobility strongly

the

groups

is

the

minutes, the

KM

between

but

gressively

em

thereafter

more

staggerers

9.

four

spend

this attitude

m4g.rr

--1Lrrrl

observed

first

normals

stant

CJ- - -0

is

time-dependent.

Little difference

over

1%

groups

M

pro-

time

whereas remain

/ o_--

_-

--_

--O-_--_O____-o

in the

i?rgure B The ttmespentrmobtle

con-

(~(4,18)=5.73

by

the

WV, gwqs

cn ezpen”mt

of ttme

ae a functwn 4

p'

.Ol).

DISCUSSION

The results of the the

staggerer's

inclusion

normal

reported

this mutant's

concern

new

gait.

significant

movements.

and

Their

et al.'s extend

The present

results

totally

in resistance

resistance

displayed

description the

confirm

of the staggerer's

differences

of

by

apparently

the severe disruption

on the basis

elements

reported

and patterns

by staggerers

of

that contrast

swimming

and speed. The additional

The measured

basic description

this

description

with that concerning

the normality

of distance

Sidman

behaviour,

elements.

contrasted

by demonstrating of measures

swimming

of

swimnlng

here confirm

here

of swimning was less than

a third of that by normals. One

tempting

explanation

linked to the difference respect

was

remaining

the

motionless

quit-es more quickly.

that

energy

Another

staggerers as

possibility

of staggerers

more

saturation

buoyancy.

do

the

expenditure,

fur density rapid

for

the

of style.

tend

It is conceivable

to

normals. and the

swim One

the

fur

in the

resistance

difference

may

assume would

water,

that if the resistance

that

resistance

producing measure

instead this

of re

thus tire more

from that of normals,

with

is

in the latter

in circles

staggerer

for the differential

is different of

difference

The clearest

is that the leading

to

decreased

were in terms

296

of distance

swum,

there would Quite

apart

different,

or energy

from

the

the absence

remarkable.

This

staggerer's

handicap

instead

of

nature

that should both depend functlonning

walking

and swimmng),

whereas

III the other

Even

heavily

of the vestibular

sInking,

demonstrably

the extent

the neurological

"second-order"

very

defi-

similar

on the cerebellum, mechanism

1s

of the

This underlines

considering

in one case the behavlour only

are

locomotion.

between

lmpalrment.

appropriate

that

one considers

of the relationship

behaviours,

before

the groups.

in terms of speed and distance

so when

in terms of terrestrial

behavioural

of time

between

behavlour

of a difference

cit

the

aspects

1s especially

the selective and

consumed,

have been little or no difference

and on an

(as IS the case for

IS severely

behavloural

disturbed,

abnormalltles

are

observed. The different

swimming

number

of U-turns

longer

lmnobility

made

patterns

by the

by normals

for these style differences expression abnormal

reported

staggerers

that

one should

suggests

ments

involved We

movements. the way the

structure.

be able in

are

mice

swimming,

a greater

peripheral

pool. A tempting

locomotor

or

at present

involve

alley

and

explanation

that they are simply a second-order

This

to detect

use their

II-Ithe

in the square

of a directly-produced cerebellar

prlmarlly

dlsfunctlon

analysis

leads

abnormalities at

least

in

investigating

different

limbs

caused

to

the

by the

prediction

in the muscular the

this and

sequencing

of

possibility, tail when

movesuch

based

swimming

on and

walking. A

second

explanation

abnormalities have

of

suggested

(Goodall,

a

for

higher-order

abnormalities

1985; Misslin

attributed

to the

in this direction,

to time-dependent reported same

constant

same

of

whereas

explanation

for

this

unable

to

distinguish

Whether

this should

may be variable,

the

A

in

number

staggerer's

and

factor.

of

IS based between

recent

results

on

results

reactions

could

also be

of aspects

of the

those measures

related was

( distance, U-turns and imnoblllty),

the

the

normals on the new

staggerers'

behavlour

changes

over

time.

notion

that

the

and

known

events

result in all or no situations

but in either

based

of swimming

appears:

of the

1s

novelty

A number

in particular

style

In each case that a feature

of time

results that

function. in

underlying

measures.

as a function

pattern

differences

et al. 1986). The present

data

point

these

case any behaviour

One

remains possible

staggerers or

being treated influenced

are

situations. as new

by a recog

291

nltion

of novelty

novelty tic

reaction

would could

differences,

be expected

to be

thus directly

and

indirectly

abnormal.

explain

be

Such

an

abnormal

the time dependent

involved

in

some

or

stylis-

all

of

the

others. One

of the

establish

primary

concerns

the validity

tigation

of

functions.

of this

of swimming

staggerers,

especially

The reported

results

as

may be more valid than walking.

for the

investigation

genetics

and learning

and

Le Pape,

based

on

aquatic

than terrestrial for

the

plasticity,

shown

movements

study

by these

investigations

water

These

higher-level

suggest

knowledge

of

was

cognitive

that, where

(Morris,

Lassalle authors escape

could

possible,

of cerebellar

1979; Lassale tasks

recovery function

using mutant mice as experimental

could

reinforcement,

then form a valuable

functional

useful

1985) or behaviour

et al.,

learning as

to

lnves-

This could be especially

1973a,b,

with

locomotion.

ethological

physiological

of spatial

1983). As

of experiments

concerns

do indeed

swimming

(Festing,

series

as a tool for the behavioural

and

related

be

rather

framework

for

neuro-

to synaptic

models.

ACKNOWLEDGEMEMTS

The first

author's

Fondation

Fyssen.

these

experiments,

figures,

participation We

I.

thank Gale111

and an anonymous

A.

was made Ly

for

for typing

reviewer

possible his

by a grant

technical

the manuscript

for his helpful

from the

assistance

with

and drawing

the

comments.

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