P oc.
Na l.
Acad.
Sci.
USA
Vol.
91,
pp.
807-811,
Janua y
1994
Neu obiology
Eye
posi ion
and
eye
eloci y
in eg a o s
eside
in
sepa a e
b ains em
nuclei
(gaze
s abiliza ion/mo o
pe o mance/in eg a o
hy hmici y/p eposi us
nudeus/lidocaine
inac i a ion)
ANGEL
M.
PASTOR*,
ROSA
R.
DE
LA
CRUZ*,
AND
ROBERT
BAKER
*Labo a o y
o
Neu oscience,
Depa men
o
Physiology
and
Biology,
Uni e si y
o
Se ille,
41012
Se ille,
Spain;
and
Depa men
o
Physiology
and
Biophysics,
New
Yo k
Uni e si y
Medical
Cen e ,
New
Yo k,
NY
10016
Communica ed
by
R.
Llinds,
Augus
25,
1993
ABSTRACT
Two
ypes
o
cen al
ne ous
sys em
in eg a-
o s
a e
c i ical
o
oculomo o
pe o mance.
The
is
in e-
g a es
eloci y
commands
o
c ea e
posi ion
signals
ha
hold
ixa ion
o
he
eye.
The
second
s o es
ela i e
eloci y
o
he
head
and
isual
su ound
o
s abilize
gaze
bo h
du ing
and
a e
he
occu ence
o
con inuous
sel
and
wo ld
mo ion.
We
ha e
used
eco dings
om
single
neu ons
o
es ablish
ha
he
"posi ion"
and
" eloci y"
in eg a o s
o
ho izon al
eye
mo e-
men
occupy
adjacen ,
bu
nono e lapping,
loca ions
in
he
gold ish
medulla.
Lidocaine
inac i a ion
o
each
in eg a o
esul s
in
he
eye
mo emen
de ici s
expec ed
i
ho izon al
eye
posi ion
and
eloci y
signals
a e
p ocessed
sepa a ely.
These
obse a ions
also
indica e
ha
each
b ains em
compa men
gene a es
and
s o es
hese
signals.
Consequen ly,
each
in eg a-
o
exhibi s
unc ional
au onomy.
The e o e,
we
p opose
ha
he
in insic
elec ophysiological
p ope ies
o
he
cons i uen
neu ons
in
each
b ains em
subnucleus
may
be
su icien
o
p oducing
in eg a o
hy hmici y.
Main aining
gaze
on
a ge s
ha
mo e
ela i e
o
he
ob-
se e
equi es
ha
es ibula
and
isual
e lexes
de ec ing
bo h
sel
and
wo ld
mo ion
espond
wi h
app op ia e
eye
and/o
head
mo emen s.
Neu al
in eg a o s
ac ing
as
com-
pu a ional
elemen s
a e
essen ial
building
blocks
wi hin
his
senso y-mo o
ans o ma ion
(1-3).
The
concep
o
a
"neu-
onal"
in eg a o
whose
inpu -ou pu
cha ac e is ics
could
be
desc ibed
by
a
ma hema ical
in eg al
was
i s
en isioned
a e
obse ing
he
ac i i y
o
abducens
mo oneu ons
du ing
changes
in
ho izon al
eye
posi ion
(4).
Cu en
hypo heses
equi e
neu al
ne wo ks
o
cascading,
e e be a ing
colla -
e als
wi h
posi i e
and/o
nega i e
eedback;
howe e ,
pu-
a i e
neu onal
mechanisms,
le
alone
causal
chains
o
syn-
ap ic
connec ions,
a e
s ill
no ional
in
he
ope a ion
o
in eg a o s
o
ei he
spinal
o
b ains em
ci cui s
(5-7).
He e
we
desc ibe
he
p ecise
loca ion
o
hindb ain
neu ons
ha
a e
necessa y
and
su icien
o
accomplishing
wo
dis inc
ypes
o
in eg a ion
in
he
oculomo o
sys em.
In
mammals,
he
p eposi us
hypoglossi
nucleus
was
ini-
ially
p oposed
o
ul ill
he
c i e ia
pos ula ed
as
necessa y
o
he
" eloci y
o
posi ion"
ans o ma ion
(8-11).
Recen
pha macological
and
lesion
s udies
implica e
bo h
he
es i-
bula
and
p eposi us
egions
o
he
b ains em
(12-14).
Join ly
hese
da a
sugges
ha
all
ho izon al
eye
mo emen - ela ed
subsys ems
(e.g.,
saccadic,
es ibula ,
and
isual)
p obably
sha e
a
common
posi ion
in eg a o
(15,
16).
Un o una ely,
i
has
no
been
possible
o
causally
place
any
iden i ied
es ibula
o
p eposi us
neu on
wi hin
his
ci cui
(5).
The
obse a ions
ha
es ibula
and
isual
senso y
signals
ela ed
o
sel
o
ex e nally
gene a ed
mo emen
a e
la gely
encoded
in
a
eloci y
domain
(17,
18)
led
o
iden i ica ion
o
a
second
ype
o
in eg a o
ha
could
accumula e
eye
eloc-
The
publica ion
cos s
o
his
a icle
we e
de ayed
in
pa
by
page
cha ge
paymen .
This
a icle
mus
he e o e
be
he eby
ma ked
"ad e isemen "
in
acco dance
wi h
18
U.S.C.
§1734
solely
o
indica e
his
ac .
i y
in
he
ho izon al
plane
(19,
20).
In
his
case,
neu al
in o ma ion
p opo ional
o
he
eloci y
o
he
head
and/o
isual
su ound
is
compiled
and
p ese ed
cen ally
(i.e.,
s o ed
up).
By
discha ging
he
s o ed
eloci y
a e
cessa ion
o
he
ini ia ing
senso y
s imulus,
his
in eg a o
ex ends
he
ime
o
oculomo o
compensa ion
o
ei he
head
o
isual
wo ld
mo ion.
The
loca ion
o
his
in eg a o ,
le
alone
i s
ope a ion,
has
emained
qui e
elusi e,
al hough
mos
e i-
dence
sugges s
a
c ucial
ole
o
he
es ibula
nuclei
(14,
21).
In
his
pape ,
he
posi ion
and
eloci y
in eg a o s
will
be
shown
o
occupy
spa ially
sepa a e,
non es ibula ,
loci
in
he
gold ish
medulla
ha
can
be
accu a ely
iden i ied,
eco ded
om,
and
e e sibly
inac i a ed.
MATERIALS
AND
METHODS
Gold ish
(Ca assius
au a us)
we e
p epa ed
unde
gene al
anes hesia
( icaine
me hanesul ona e;
1:20,000,
w / ol)
o
eye
mo emen
and
neu onal
eco ding.
Su ge y
consis ed
o
implan ing
an
ac ylic
pedes al
o
head
s abiliza ion
and
ephining
a
hole
in
he
occipi al
bone
o
eco ding
b ains em
neu al
ac i i y
(22).
Eye
posi ion
was
moni o ed
wi h
scle al
sea ch
coils.
A e
a
eco e y
pe iod
o
se e al
days,
ully
ale
animals
we e
es ed
in
a
e ical-axis
op okine ic
and
es ibula
s imula o .
This
sys em
consis ed
o
a
se o-
con olled
plane a ium
and
o a ing
able
in e aced
by
a
wa e o m
gene a o
ha
p oduced
any
desi ed
in e ac ion
in
phase
and/o
ela i e
eloci y
be ween
he
wo
s imuli
(23).
Compensa o y
eye
eloci y
is
nea ly
o
equal
ampli ude,
bu
opposi ely
di ec ed,
o
head
eloci y
and
exhibi s
nea ly
1800
phase
shi
wi h
espec
o
he
s imulus
[e.g.,
es ibuloocula
e lex
(VOR)
gain
o
1.0
in
Fig.
2
B
and
D].
Neu onal
ac i i y
was
eco ded
du ing
spon aneous
and/o
isual- es ibula -induced
e lex
eye
mo emen s
(see
Fig.
2).
Ins an aneous
i ing
a e
his og ams
we e
con-
s uc ed
as
he
ecip ocal
o
he
in e spike
in e al
( e .
22;
see
Fig.
2
A
and
B,
FR).
To
p oduce
local
anes hesia,
mic opipe es
illed
wi h
4%
lidocaine
and
be eled
o
a
ip
size
o
10
,Am
we e
si ua ed
a
he
physiological
cen e
o
each
iden i ied
a ea
by
eco ding
he
su ounding
ex acellula
ac i i y.
On
a e age,
1
nl
o
lidocaine
was
injec ed
wi h
5-
o
10-ms,
200-kPa
ai
p essu e
pulses
o e
30
s
(see
Figs.
3
and
4).
Fo
bila e al
inac i a ion,
wo
sepa a e
injec ions
we e
comple ed
wi hin
2
min.
Biocy in
dissol ed
in
0.1
M
phospha e
bu e
was
ei he
p essu e
injec ed
o
ion opho esed
in o
he
caudal
lobe
o
he
ce ebellum
o
label
b ains em
nuclei
(see
Fig.
1
B-E).
A e
pe usion
wi h
eleos
saline
and
aldehyde
ixa i e,
50-,um
sec ions
we e
eac ed
wi h
a idin-bio in-pe oxidase
com-
plex
(Vec o
Labo a o ies)
ollowed
by
diaminobenzidine
his ochemical
analysis
( e .
22;
see
Fig.
1
C-F).
Abb e ia ion:
VOR,
es ibuloocula
e lex.
807
P oc.
Na l.
Acad.
Sci.
USA
91
(1994)
RESULTS
Fou
hindb ain
nuclei
dis ibu ed
pe iodically
a
-500-,um
in e als
be ween
he
obex
and
he
abducens
nucleus
we e
designa ed
om
caudal
o
os al
as
a eas
I-IV
(Fig.
1
A
and
B).
Each
subg oup
con ained
a
o al
o
25-40
neu ons
ha
we e
in ol ed
in
ei he
posi ion
(a eas
I
and
III)
o
eloci y
(a eas
II
and
IV)
in eg a ion
o
oculomo o
(a eas
I
and
II)
and
pos u al
(a eas
III
and
IV)
con ol.
Biocy in
injec ions
in
he
es ibuloce ebella
lobe
selec i i y
labeled
neu ons
in
he
in e io
oli e
and
a ea
II
(Fig.
1
C-F).
Elec ical
s imula ion
o
he
ce ebellum
(Fig.
1B,
CL)
p oduced
an id omic
ac i-
a ion
o
a ea
II
eye
eloci y-only
neu ons
desc ibed
in
Fig.
2
(32).
A eas
I
and
II
we e
si ua ed
di ec ly
abo e
he
in e io
oli e
as
shown
in
bo h
sagi al
(Fig.
1
C
and
F)
and
co onal
(Fig.
1
D
and
E)
iews
o
he
b ains em.
The
longi udinal
dis ibu ion
o
he
ou
hindb ain
nuclei
could
be
ecognized
in
ela ionship
o
a
se
o
epea ing
ascula
b anches
ha
was
con i med
by
neu ophysiological
co ela es
in
e e y
animal.
Neu ons
we e
iden i ied
in
each
o
he
ho izon al
eye
mo emen - ela ed
a eas
I-IV
wi h
ex acellula
single
uni
eco dings
(Fig.
2).
Discha ge
p ope ies
we e
highly
co e-
la ed
in
he
wo
pos e io
a eas
(I
and
II)
wi h
eye
mo emen
pa ame e s,
while
ela ionships
we e
less
ob ious
in
he
wo
os al
a eas
(III
and
IV).
In
he
mos
caudal
subnucleus
(a ea
I),
neu onal
i ing
a e
du ing
spon aneous
eye
mo emen s
inc eased
in
p opo ion
o
he
angle
o
eye
de ia ion
owa d
he
ipsila e al
side
o
eco ding.
Du ing
di e gen
saccades,
_
F
P...
o
p.X_S
.. .. w. .. s
C
IV ..
..............
a ea
I
neu ons
encoded
he
posi ion
o
he
ipsila e al
eye
(Fig.
2A;
dashed
lines).
The
majo i y
o
a ea
I
neu ons
(70%)
demons a ed
a
sensi i i y
p opo ional
o
he
eloci y
o
he
eyes
du ing
saccades
(Fig.
2A,
a ow).
Some
o
hese
neu-
ons
we e
pu ely
posi ion ela ed
(30%)
since
he
eloci y
sensi i i y
du ing
apid
eye
mo emen s
was
negligible
(Fig.
2B,
a ows).
Du ing
he
slow
phase
o
ei he
es ibula
(Fig.
2B)
o
op okine ic
nys agmus,
i ing
a e
o
neu ons
in
a ea
I
was
p opo ional
o
eye
posi ion,
exhibi ing
li le
eye
eloci y
sensi i i y.
A ea
II
was
loca ed
immedia ely
os al
o
a ea
I.
Neu ons
in
his
a ea
ei he
emained
silen
o
showed
a
s eady
i ing
a e
du ing
spon aneous
saccadic
eye
mo emen
(Fig.
2C).
A ea
II
neu ons
modula ed
in
phase
wi h
eye
eloci y
di-
ec ed
owa d
he
ipsila e al
side
o
eco ding
du ing
he
slow
componen
o
ei he
op okine ic
(Fig.
2D)
o
es ibula
nys agmus.
The
wo
main
ypes
o
neu onal
esponses
de-
ec ed
in
a ea
II
we e
eye
eloci y
only
(51%)
and
eye
combined
wi h
a
head
eloci y
sensi i i y
measu ed
du ing
isual
supp ession
o
he
VOR
(49%).
Some
o
hese
neu ons
also
paused
o
all
as
phases
(eye
eloci y
pause,
25%).
Du ing
ei he
sinusoidal
op okine ic
o
es ibula
s imula-
ion,
he
i ing
a e
o
neu ons
in
a ea
I
peaked
in
phase
wi h
eye
posi ion
(Fig.
2B,
do ed
line),
while
neu ons
in
a ea
II
modula ed
in
phase
wi h
eye
eloci y
(Fig.
2D,
do ed
line).
Thus,
he
main
physiological
di e ence
be ween
a eas
I
and
II
was
an
exquisi e
seg ega ion
o
eye
posi ion
and
eye
eloci y
signals.
Ne e heless,
neu ons
in
bo h
a eas
we e
conside ed
p emo o
since
hey
i ed
15-20
ms
p io
o
he
FIG.
1.
O ganiza ion
o
hind-
::
:b ain
nuclei
in
he
gold ish.
Whole
+
b ain
(A)
and
sagi al
Nissl
sec-
ions
(B)
showing
he
os ocaudal
and
en al
loca ion
o
he
majo
$-
FL
V:
j
es ibula
subdi isions
(24)
and
'.
'
.i3-..a eas
I-IV.
(C-F)
Neu ons,
ax-
ons,
and
p ocesses
labeled
a e
biocy in
injec ion
in o
he
es ib-
uloce ebellum
(CL).
(C)
Pa asag-
i al
sec ion
300
Pm
om
he
mid-
line
showing
he
os al
in e io
oli e
(TO)
decussa ion
and
neu-
*g
_
s
ons
in
a ea
II.
Mossy
ibe
pa h-
ways
(a)
and
g anule
cell
(g)
clus-
e s
a e
ma ked.
(F)
High
magni-
S
#
::
ica ion
o
a ea
II
(s a
in
C)
illus a ing
soma
and
dend i es
o
pu a i e
eye
eloci y
in eg a o
neu ons.
(D)
Co onal
sec ion
showing
axons
(a)
o
labeled
con-
ala e al
IO
neu ons
c ossing
he
midline
and
he
ipsila e al
en o-
medial
loca ion
o
pu a i e
a ea
IT
eye
eloci y
neu ons.
(E)
Clus-
e ed
somas
(s)
and
dend i es
(d)
o
a ea
II
neu ons
a e
shown
a
highe
magni ica ion
(s a
in
D).
A,
D,
P,
M,
and
T,
an e io ,
de-
scending,
pos e io ,
magnoceliu-
la ,
and
angen ial
subdi isions
o
es ibula
nuclei;
VC,
CL,
CC,
and
CB,
al ula,
caudal
lobe,
ce -
-4i*
d
s
¢
¢ *
<
ebella
c es ,
and
co pus
o
he
ce ebellum;
ABD,
abducens;
OC
and
T,
oculomo o
and
ochlea
nuclei;
FL,
acial
lobe;
I-IV,
a eas
I-IV
o
he
hindb ain;
OT,
op ic
ec um;
SC,
spinal
co d;
TE,
elencephalon;
VIIIn,
oc a ola -
e alis
ne e;
Xn,
agal
ne e;
VL,
agal
lobe.
808
Neu obiology:
Pas o
e
al.
P oc.
Na l.
Acad.
Sci.
USA
91
(1994)
809
C
I
D
3000ms
#
~~~~~~~~~~~~~
L
Z
.
*.
100~~~~~~~~~~~~~~~~~oSp/s.
.~0
FIG.
2.
Discha ge
cha ac e is-
ics
o
a ea
I
(A
and
B)
and
a ea
II
(C
and
D)
neu ons.
(A)
Fi ing
a e
(FR)
o
an
a ea
I
neu on
du ing
spon aneous
eye
mo emen s.
Dis-
cha ge
was
co ela ed
o
le
eye
posi ion
(LE)
du ing
ixa ion
(dashed
lines)
and
some
neu ons
also
exhibi ed
saccade
sensi i i y
(a ow).
(B)
FR
o
a
pu ely
posi-
ion- ela ed
a ea
I
neu on
(a ows)
du ing
sinusoidal
head
o a ion
( i)
in
he
da k.
Head
eloci y
is
in e ed
in
B
and
D
o
acili a e
compa ison
o
eye
eloci y.
FR
was
associa ed
wi h
ho izon al
eye
posi ion
(LE)
bu
no
eye
e-
loci y
(do ed
line).
(C)
A ea
II
neu ons
we e
no
modula ed
du -
ing
spon aneous
eye
mo emen s.
(D)
Du ing
head
o a ion
a ea
II
neu ons
modula ed
in
phase
wi h
eye
eloci y
(1:E,
do ed
line)
bu
no
eye
posi ion
(LE).
Calib a-
ions
a e
indica ed.
occu ence
o
saccades,
as
phases,
o
eye
esponses
o
sudden
s ep
o a ions
o
he
head
(da a
no
shown).
Du ing
spon aneous
eye
mo emen s,
mos
neu ons
in
a ea
III
(75%)
exhibi ed
an
i egula
i ing
a e
poo ly
co ela ed
(
<
0.7)
wi h
ipsila e al
eye
posi ion.
A
weak
eye
eloci y
sensi i i y
was
de ec ed
du ing
es ibula
and
op okine ic
e lexes.
The
second
ype
(25%)
exhibi ed
a
simila
p o ile
bu
paused
o
saccades
and
as
phases
in
all
di ec ions.
A ea
IV
(100%)
was
composed
o
eye
eloci y-like
neu ons
ha
inc eased
i ing
du ing
con ala e al
eye
mo emen .
Th ee
sepa a e
clus e s
o
medially
loca ed
bu s ing
neu ons
we e
si ua ed
be ween
a eas
I
and
IV.
E e y
bu s
neu on
be ween
a ea
I
and
II
i ed
30-40
ms
be o e
he
occu ence
o
all
ipsila e ally
di ec ed
as
phases
and
saccades.
Bu s
neu ons
loca ed
be ween
a eas
II
and
III
exhibi ed
a
a iable
la ency
and
co ela ion
wi h
saccades
while
hose
be ween
a eas
III
and
IV
we e
bidi ec ional.
Selec i e
lidocaine
inac i a ion
o
he
ou
medulla y
a eas
was
used
o
assess
he
po en ial
con ibu ion
o
cons i uen
neu ons
o
he
in eg a ion
p ocess.
The
inac i a ion
o
ei he
a ea
I
o
II,
bu
no
a ea
III
o
IV,
p oduced
quali a i ely
dis inc
changes
in
eye
mo emen
pa ame e s
(Figs.
3
and
4).
Bila e al
lidocaine
injec ion
o
a ea
I
p oduced
se e e
gaze-
holding
de ici s
o
ho izon al
eye
mo emen s.
By
2
min
a e
he
injec ion,
and
du ing
he
20
min
o
e ec i e
inac i a ion,
ho izon al
saccades
o
bo h
eyes
and
in
bo h
di ec ions
we e
ollowed
by
an
exponen ial
d i
di ec ed
asymp o ically
owa d
a
null
poin
(Fig.
3A).
The
exponen ial
ime
cou se
o
he
d i
can
be
in e p e ed
as
he
passi e
ecen e ing
o
he
eye
due
o
o bi al
iscoelas ic
issue
o ces.
The
ime
con-
s an
o
he
exponen ial
d i
was
p og essi ely
sho ened
owa d
a
minimum
o
0.3
s
o e
he
i s
10
min
(Fig.
3B,
10
min).
Then
he
ime
cons an
p og essi ely
eco e ed
o
con ol
o e
he
nex
20
min
(Fig.
3B,
30
min).
Thus,
inac i a ion
o
he
in eg a o
appea s
o
emo e
he
posi ion
signals
a ailable
o
he
mo oneu ons
o
main aining
he
ho izon al
angle
o
gaze.
Bila e al
inac i a ion
o
a ea
I
also
p oduced
de as a ing
e ec s
on
bo h
he
VOR
and
op okine ic
e lex.
Sinusoidal
s imula ion
a
low
equency
(s0.25
Hz)
g ea ly
educed
VOR
gain
om
1.0
o
an
a e age
o
0.2
and
eye
eloci y
led
able
eloci y
by
70°
(Fig.
3C,
do ed
lines).
A
highe
o a ional
equencies,
gain
and
phase
p og essi ely
ap-
p oached
ypical
alues
(Fig.
3D,
do ed
line).
Consequen ly,
VOR
measu emen s
a
w1
Hz
exhibi ed
a
no mal
senso y
o
mo o
ans o ma ion
in
he
absence
o
any
cen al
neu onal
p ocessing
o
eloci y
o
posi ion
signals.
Eye
mo emen
de ici s
induced
a e
unila e al
lidocaine
inac i a ion
o
a ea
I
we e
ne e
as
ma ked
as
hose
ollowing
bila e al
injec ion
and
he
ime
cons an
o
he
pos saccadic
d i
was
ne e
lowe ed
o
<1.0
s.
Compa ison
o
da a
a e
many
e e sible
uni-
and/o
bila e al
inac i a ions
demon-
s a ed
ha
a
single
in ac
a ea
I
could
p ocess
posi ion
signals
capable
o
d i ing
bo h
eyes.
Independen
in eg i y
o
he
bila e ally
loca ed
posi ion
in eg a o s
implies
ha
he
in e connec ions
be ween
he
wo
a e
no
c i ical
o
he
eloci y
o
posi ion
ans o ma ion.
By
con as ,
unila e al
es ibula
and/o
p eposi us
lesions
in
mammals
we e
e-
po ed
as
su icien
o
p oduce
a
o al
gaze-holding
ailu e
(21,
25).
Lidocaine
inac i a ion
o
a ea
II
also
p oduced
dis inc
oculomo o
abno mali ies.
A
single
unila e al
lidocaine
in-
jec ion
in
a ea
II
caused
a
nys agmus
o
he
wo
eyes
wi h
as
phases
always
di ec ed
owa d
he
side
o
he
inac i a ion
(Fig.
4A).
The
saw oo h
mo emen
o
he
eyes
likely
o igi-
na ed
om
imbalancing
he
eloci y
ou pu
om
he
bila e al
a ea
II
nuclei
(Fig.
2).
The
esul ing
eye
eloci y
bias
was
maximal
in
he
da k,
16-22°/s du ing
he
slow
phase
o
nys agmus;
howe e ,
in
he
p esence
o
an
illumina ed
s a-
iona y
backg ound,
he
bias
was
educed
o
:4°/s,
indica -
ing
isual
supp ession
h ough
he
in ac
a ea
II
(Fig.
4A,
dashed
line).
This
amp-like
eye
mo emen
(Fig.
4B)
was
clea ly
dis inguishable
om
he
exponen ial
d i
in
eye
posi ion
ollowing
inac i a ion
o
a ea
I
(Fig.
3B).
Du ing
sinusoidal
head
o a ion
in
he
da k,
he
eloci y
bias
shi ed
he
eye
eloci y
by
a
cons an
alue
o
=20O/s
(Fig.
4C,
a ows).
All
he
as
phases
o
nys agmus
occu ed
in
he
di ec ion
opposi e
he
eloci y
bias
because
eye
eloci y
could
no
c oss
ze o
alue
(Fig.
4C,
LE).
A e
bila e al
lidocaine
inac i a ion
o
a ea
II,
saccades
and
ixa ions
exhibi ed
li le
sign
o
ei he
bias
o
gaze-
holding
ailu e
(Fig.
4D).
Ne e heless,
bila e al
anes hesia
o
a ea
II
maximally
comp omised
bo h
he
VOR
and
he
op okine ic
e lex.
Eye
eloci y
p ocessing
was
o ally
abol-
ished
du ing
ei he
sinusoidal
o
s ep
o a ion
o
he
head.
The
no mal
ime
cons an
o
he
eloci y
s o age
in eg a o
was
educed
om
10-12
s
(Fig.
4E,
a ow)
o
0.3
s
(Fig.
4F,
a ows).
By
con as ,
he
posi ion
in eg a o
con inued
o
pe o m
one-s ep
in eg a ion
o
he
eloci y- ela ed
signals
because
bo h
eyes
ollowed
wi h
an
eye
posi ion
s ep
esem-
bling
he
s imulus
eloci y
p o ile
(Fig.
4F,
RE
and
LE).
B
Neu obiology:
Pas o
e
al.
50SP/
W%l
i
P oc.
Na l.
Acad.
Sci.
USA
91
(1994)
B
1oo.
0-
100-
50
50
50]
16~
O-
w
~~~~.
500ms,
6E
FIG.
3.
E ec s
o
bila e al
lidocaine
injec ion
in
a ea
I.
(A)
Ho izon al
posi ion
o
he
le
(LE)
and
igh
(RE)
eyes
12
min
a e
a ea
I
inac i a ion.
A e
saccades
in
bo h
di ec ions
he
eyes
d i ed
cen ipe ally
wi h
an
exponen ial
p o ile
exhibi ing
a
ime
cons an
o
0.3
s.
(B)
Time
cou se
in
minu es
illus a ing
inac i a ion
and
eco e y
a e
bila e al
a ea
I
lidocaine
injec ion.
Saccades
o
simila
size
di ec ed
le wa d
we e
supe imposed
a
he
poin
o
peak
ampli ude
o
illus a e
sho ening
o
he
eloci y
o
posi ion
in eg a-
o
ime
cons an .
(C
and
D)
E ec s
o
a ea
I
inac i a ion
on
he
VOR
a
low
(0.125
Hz;
C)
and
high
(1
Hz;
D)
equency.
Lidocaine
injec ions
o
1
nl
in o
ei he
a ea
III
o
a ea
IV
did
no
in luence
eye
mo emen s.
La ge
amoun s
(10
nl)
p oduced
some
d i
and
eloci y
bias,
likely
due
o
sp ead
in o
adjacen
nuclei
and/o
ibe
ac s.
Lidocaine
injec ions
o
1
nl
in o
he
medial
bu s
neu ons
be ween
a ea
I
and
II
nea ly
abolished
saccades
and
as
phases
bu
did
no
a ec
in eg a o
ope a ion.
Inac i a ion
o
a ea
II
did
no
in e up
he
es ibula
con-
nec ion
o
he
posi ion
in eg a o .
These
esul s
a e
no
consis en
wi h
models
(26)
o
lesion
s udies
(21)
ha
place
he
si e
o
eloci y
s o age
in
a
sys em
o
ecip ocal
com-
missu al
connec ions
be ween
he
es ibula
complex.
DISCUSSION
Ou
da a
demons a e
ha
he
neu al
mechanisms
equi ed
o
bo h
eloci y
o
posi ion
and
eloci y
s o age
in eg a ion
eside
in
adjacen
medulla y
nuclei
clea ly
isola ed
om,
bu
likely
in ima ely
connec ed
o,
he
es ibula
nuclei.
The
spa ial
disc e eness
o
hese
in eg a o s
co esponds
o
con-
s an
mo phological
landma ks
in
he
gold ish
medulla
ha
e lec
he
adul
e en ion
o
a
segmen al
bluep in
desc ibed
in
la al
zeb a ish
(27).
We
p opose
ha
hese
hindb ain
nuclei
in
gold ish
a e
analogous
in
unc ion
o
he
mammalian
p eposi us
nuclei
and
ha
homologous
neu onal
ypes
can
be
e en ually
ecognized.
The e o e,
he
hindb ain
opog aphy
in
eleos s
(Fig.
1
A
and
B)
is
mo e
ad an ageous
o
esol ing
neu ophysiological
co ela es
as
well
as
in es iga ing
he
de elopmen al
and
gene ic
plans
unde lying
assembly
o
hindb ain
ho izon al
eye
mo emen
pa hways
(28).
In
each
disc e e
nono e lapping
compa men ,
he
quan-
i a i e
analysis
o
discha ge
cha ac e is ics
and
oculomo o
de ici s
a e
lidocaine
injec ions
we e
complemen a y.
A ea
I
and
a ea
II
neu ons
we e
co ela ed
wi h
eye
posi ion
and
eloci y,
espec i ely.
Signal
p ocessing
appea ed
o
be
au onomous
o
each
nucleus.
Since
a ea
I
esponses
we e
co ela ed
o
saccades,
VOR,
and
isually
induced
e lexes,
he
posi ion
in eg a o
is
indeed
common
o
all
eye
mo e-
men s
(15).
Ne e heless,
a ea
I
p obably
ep esen s
he
summing
junc ion
o
wo
qui e
di e en
modali ies
o
eye
eloci y
signal
because
as
phases
and
spon aneous
saccadic
eye
mo emen s
we e
spa ed
a e
bila e al
lidocaine
inac i-
a ion
o
a ea
II
(Fig.
4D).
Thus,
es ibula
and
op okine ic
eye
eloci y
signals
p ocessed
in
a ea
II
each
a ea
I
by
a
pa hway
dis inc
om
ha
o
bu s
neu ons
p oducing
sac-
cades.
An
equally
likely
supposi ion
is
ha
a ea
II
also
ep esen s
a
summing
junc ion
o
es ibula
and
isual
eye
eloci y,
because
hese
neu ons
do
no
i e
o
ei he
sac-
cades
o
as
phases
(Fig.
2
C
and
D).
Homogenei y
o
discha ge
pa e n
and
inac i a ion
wi h
lidocaine
a gues
ha
a ea
II
plays
wo
sequen ial
oles
in
eye
mo emen .
We
sugges
ha
he
neu ons
i s
gene a e
and
hen
s o e
eye
eloci y
since
lidocaine
inac i a ion
no
only
abolished
eloci y
s o age
bu
also
educed
he
VOR
ime
cons an
o
alues
less
han
he
a e age
es ibula
a e en
ime
cons an
(0.3
s
s.
3-4
s,
espec i ely).
Inac i a ion
o
a ea
II
g ea ly
impai s
bo h
es ibula
and
op okine ic
e-
lexes
because
all
neu ons
in
a ea
II
exhibi
a
con inuous
le el
o
onic
ac i i y
(Fig.
2C).
Hence,
he
VOR
ime
cons an s
a e
lowe
han
ha
expec ed
om
p edic ions
based
on
a e aged
p ima y
a e en
discha ges
(29),
and,
in
ac ,
many
species
o
eleos
exhibi
ypical
VOR
ime
cons an s
a
less
han
mean
a e en
alues
(30).
This
lowe ed
VOR
ime
cons an
was
accompanied
by
a
ma ked
comp omise
in
he
VOR
when
es ed
wi h
lowe
equency
sinusoidal
s imuli.
By
con as ,
he
di ec ,
p esumed
h ee-neu on,
VOR
pa h-
way
emained
in ac
as
indica ed
by
he
la ency
and
ampli-
ude
o
he
eye
posi ion
s ep
( e .
23;
Fig.
4F).
We
sugges
ha
a ea
II
eloci y
neu ons
comp ise
a
b ains em
loop
ha
suppo s
he
di ec
VOR
pa hway
loca ed
in
he
descending
oc a al
nucleus
(Fig.
1
A-C).
O e all,
he
mos
s aigh o wa d
a gumen
is
ha
a ea
I
and
a ea
II
a e
independen
eye
posi ion
and
eloci y
gen-
e a o s.
Assu edly,
a ea
I
is
he
equisi e
posi ion
in eg a o .
P incipally,
a ea
II
con e s
senso y
signal
eloci y
( es ib-
ula
and
isual)
o
mo o
(eye)
commands
as
well
as
assuming
he
impo an
ole
o
eye
eloci y
s o age.
The e o e,
he
pa e ns
o
neu al
ac i i y
wi hin
each
in eg a o
can
be
p oposed
o
a ise
om
in insic
p ope ies
o
hei
cons i uen
neu ons
as
opposed
o
in e ac ions
wi h
ex insic
synap ic
ci cui y.
One-s ep
signal
gene a ion
and
s o age
is
an
a ac i e
idea
because
he
same
neu ons
used
o
c ea e
can
also
s o e
he
neu al
ac i i y
co ela ed
wi h
ei he
posi ion
o
eloci y.
Such
neu onal
beha io
is
p edic ed
based
on
he
s uc u al
uniqueness,
homogenei y,
and
clea
sepa a ion
o
he
indi-
idual
a eas
om each
o he
and
he
es ibula
nuclei
(Fig.
810
Neu obiology:
Pas o
e
al.
P oc.
Na l.
Acad.
Sci.
USA
91
(1994)
811
100]
0
D
LE
l
A,
80
I
RE
ls
1).
Midline
sagi al
lesions
be ween
hese
a eas
do
no
block
ei he
posi ion
o
eloci y
s o age
(da a
no
shown);
howe e ,
es ibula
pa hways
a e
highly
p obable
h ough
mo e
os al
commissu es
(Fig.
1B).
The
medio en al
loca ion
o
hese
hindb ain
nuclei
and
hei
sepa a e
inac i a ion
clea ly
dem-
ons a e
ha
nei he
axonal
pa hways
no
neu ons
wi hin
he
es ibula
complex
we e
a ec ed
by
lidocaine
(Figs.
3
and
4).
We
belie e,
he e o e,
ha
all
o
he
s uc u al
and
unc ional
cha ac e is ics
expec ed
o
each
in eg a o
a e
embodied
by
neu ons
cen alized
wi hin
a
single
nucleus.
Since
hese
unusual
compa men s
a e
necessa y
and
p e-
sumed
su icien
o
p ocess
he
neu onal
ope a ions
elemen-
a y
o
in eg a ion,
we
hypo hesize
ha
ans o ma ions
wi hin
each
compa men
con e
au o hy hmic
cha ac e is-
ics
ha
a e
la gely
modula ed,
no
commanded,
by
ex e nal
synap ic
ci cui y.
In
p inciple,
he
inhe en
elec o espon-
si e
p ope ies
o
he
neu ons
alone
may
be
su icien
o
p oduce
in eg a ion
(31).
The e o e,
we
p opose
ha
signal
ans o ma ions
may
la gely
a ise
om
he
in insic
elec o-
physiological
p ope ies
o
cons i uen
neu ons
(32).
The
di e si y
o
eye
mo emen s
and
he
a ied
in eg a o
ime
cons an s
ha
exis
be ween
eleos ean
species
should
pe mi
hese
s uc u al
and
neu ophysiological
hypo heses
o
be
sa is ac o ily
se led.
We
hank
D s.
M.
U.
L.
Benne ,
B.
Cohen,
and
T.
Raphan
o
discussion
and
commen s
on
his
manusc ip .
1.
Robinson,
D.
A.
(1%8)
Science
161,
1219-1224.
2.
Raphan,
T.,
Ma suo,
V.
&
Cohen,
B.
(1979)
Exp.
B ain
Res.
35,
229-248.
3.
Raphan,
T.
&
Cohen,
B.
(1981)
in
Models
o
Oculomo o
Beha io
and
Con ol,
ed.
Zube ,
B.
L.
(CRC,
Boca
Ra on,
FL),
pp.
91-109.
4.
Ska enski,
A.
A.
&
Robinson,
D. A.
(1973)
J.
Neu ophysiol.
36,
724-738.
5.
Robinson,
D.
A.
(1989)
Annu.
Re .
Neu osci.
12,
33-45.
6.
Cannon,
S.
C.,
Robinson,
D. A.
&
Shamma,
S.
(1983)
Biol.
Cybe n.
49,
127-136.
7.
Anas asio,
T.
J.
&
Robinson,
D.
A.
(1989)
Biol.
Cybe n.
61,
79-89.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
22.
23.
24.
25.
26.
27.
28.
29.
30.
31.
32.
10°-
O-
4s
.
J
FIG.
4.
E ec s
o
unila e al
(A-C)
I
and
bila e al
(D-F)
lidocaine
inac i-
a ion
o
a ea
II.
(A)
Unila e al
inac-
i a ion
o
he
le
a ea
II
p oduced
nys agmus
o
he
le
in
he
da k,
bu
slow
phases
we e
a enua ed
in
he
ligh
(dashed
line).
(B)
Supe imposi-
ion
o
as
phases
demons a es
J
amp-like
eye
mo emen s
a e
inac-
1
11
I
i a ion.
(C)
Du ing
head
o a ion
in
4s
.
he
da k
eloci y
bias
added
o
he
sinusoidal
nys agmus
in
bo h
eyes.
l
(D)
Bila e al
lidocaine
injec ion
p o-
8
duced
nei he
d i
no
eloci y
bias
du ing
spon aneous
eye
mo emen s.
(E)
Pe - o a o y
nys agmus
(a ow)
du ing
cons an
head
eloci y
exhib-
1
i ed
a
no mal
ime
cons an
o
10-12
s.
H
320/s
(F)
Bila e al
lesion
o
a ea
II
i ually
]
elimina ed
eloci y
s o age
in
bo h
di ec ions
(VOR
ime
cons an
shown
l /;
by
a ows)
bu
eloci y
o
posi ion
in eg a ion
was
una ec ed
[le
eye
(LE)
and
igh
eye
(RE)].
L6pez-Ba neo,
J.,
Da lo ,
C.,
Be hoz,
A.
&
Bake ,
R.
(1982)
J.
Neu ophysiol.
47,
329-352.
Bake ,
R.
&
Be hoz,
A.
(1975)
B ain
Res.
86,
121-127.
Delgado-Ga c a,
J.
M.,
Vidal,
P.
P.,
G6mez,
C.
&
Be hoz,
A.
(1989)
Neu oscience
29,
291-307.
Bake ,
R.
(1977)
in
Eye
Mo emen s,
eds.
B ooks,
B.
A.
&
Bajandas,
F.
J.
(Plenum,
New
Yo k),
pp.
145-178.
Che on,
G.,
Godaux,
E.,
Laune,
J.
M.
&
Vande kelen,
B.
(1986)
J.
Physiol.
(London)
372,
75-94.
Cannon,
S.
C.
&
Robinson,
D.
A.
(1987)
J.
Neu ophysiol.
57,
1383-1409.
Kaneko,
C.
R.
S.
(1992)
Ann.
N.
Y.
Acad.
Sci.
656,
408-427.
Robinson,
D.
A.
(1975)
in
Basic
Mechanisms
o
Ocula Mo ili y
and
Thei
Clinical
Implica ions,
eds.
Lenne s and,
G.
&
Bach-y-Ri a,
P.
(Pe gamon,
New
Yo k),
pp.
337-374.
Tomlinson,
R.
D.
&
Robinson,
D. A.
(1984)
J.
Neu ophysiol.
51,
1121-1136.
Simpson,
J.
I.
(1984)
Annu.
Re .
Neu osci.
7,
13-41.
Goldbe g,
J.
M.
&
Fe nandez,
C.
(1975)
Annu.
Re .
Physiol.
37,
129-162.
Collewijn,
H.
(1972)
B ain
Res.
36,
71-88.
Cohen,
B.,
Ma suo,
V.
&
Raphan,
T.
(1977)
J.
Physiol.
(Lon-
don)
270,
321-344.
S aube,
A.,
Ku zan,
R.
&
Bu ne ,
U.
(1991)
Exp.
B ain
Res.
86,
347-358.
Pas o ,
A.
M.,
To es,
B.,
Delgado-Ga c a,
J.
M.
&
Bake ,
R.
(1991)
J.
Neu ophysiol.
66,
2125-2140.
Pas o ,
A.
M.,
de
la
C uz,
R.
R.
&
Bake ,
R.
(1992)
J.
Neu-
ophysiol.
68,
2003-2015.
Highs ein,
S.
M.,
Ki ch,
R.,
Ca ey,
J.
&
Bake ,
R.
(1992)
J.
Comp.
Neu ol.
319,
501-518.
Che on,
G.
&
Godaux,
E.
(1987)
J.
Physiol.
(London)
394,
267-290.
Galiana,
H.
L.
&
Ou e b idge,
J.
S.
(1984)
J.
Neu ophysiol.
51,
210-241.
Kimmel,
C.
B.,
Me cal e,
W.
K.
&
Schab ach,
E.
(1985)
J.
Comp.
Neu ol.
233,
365-376.
T e a ow,
B.,
Ma ks,
D.
L.
&
Kimmel,
C.
B.
(1990)
Neu on
4,
669-679.
Boyle,
R.
&
Highs ein,
S.
M.
(1990)
J.
Neu osci.
10,
1570-
1582.
Die inge ,
N.,
Reichenbe ge ,
I.
&
G a ,
W.
(1992)
B ain
Beha .
E ol.
39,
289-304.
Llinis,
R.
R.
(1988)
Science
242,
1654-1664.
De
la
C uz,
R.
R.,
Pas o ,
A.
M.
&
Bake ,
R.
(1993)
Soc.
Neu osci.
Abs .
19,
858.
Neu obiology:
Pas o
e
al.
L-------