Cerebellar control of saccades by the size of the active ...
Transcript of Cerebellar control of saccades by the size of the active ...
2/2/2018
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Laurent Goffart, PhD
CNRSINT, Marseille, France
A meeting honoring our memory of late David A. RobinsonMay 26-27, 2017Baltimore, USA
Cerebellar control of saccades by the size of the active population
in the caudal fastigial nucleus
Fastigio-reticular projections and the cerebellar control of visual saccades
Motoneurons(ABD)
Ponto-medullaryReticular
Formation(EBN, IBN)
Corticaleye
fields(LIP, FEF, SEF…)
DeepSuperiorColliculus
Thalamus Caudal Fastigial Nuclei
Visualcorticalareas
Lobules VIc-VII
Pontine Nuclei,NRTP, cMAO
Neck proprioception
Vestibular input
NPH
Extra-ocular muscle proprioception
EBNIBN
MN agonist
EBN IBN
For every saccade (horizontal, oblique or vertical), the left and right cFN regulate the dynamic balance of activity
between the excitatory and inhibitory input (from EBNs and IBNs)to the motor and internuclear neurons in the abducens nucleus.
(Goffart, Chen & Sparks Journal of Neurophysiology 2004)
Bilateral hypothesis
midline
contracFN
ipsicFN
EBNIBN
MN agonist
EBN IBN
Electrical microstimulation evokes a contralateral saccade
STIM
contracFN
ipsicFN
midline
Quinet J & Goffart L. Journal of Neurophysiology 2015 (head fixed monkey)
Cogdell B, Hassul M & Kimm J. Archives of Otolaryngology 1977
Noda H, Murakami S, Yamada J, Tamada J, Tamaki Y & Aso T. Journal of Neurophysiology 1988
Quinet J & Goffart L. Journal of Neurophysiology 2009 (head free monkey)
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EBNIBN
MN agonist
EBN IBN
STIM
contracFN
ipsicFN
EBNIBN
MN agonist
EBN IBN
STIM
contracFN
ipsicFN
highcurrent
smallcurrent
larger number ofexcited neurons
WORKING HYPOTHESIS : the cerebellar control of saccade dynamics consists of
regulating the size of the population of active prem otor burst neurons
EBNIBN
MN agonist
EBN IBN
cFN inactivation does not suppress contralateral saccades,but reduces their horizontal velocity and amplitude
contracFN
midline
muscimol
ipsicFN
Goffart L & Pélisson D. Journal of Neurophysiology 1994, 1998 (head free cat)
Ohtsuka K, Sato H & Noda H. Journal of Neurophysiology 1994
Robinson FR, Straube A & Fuchs AF Journal of Neurophysiology 1993
Goffart L, Chen LL & Sparks DL. Journal of Neurophysiology 2004
Quinet J & Goffart L. Journal of Neurophysiology 2005, 2007 (head free monkey)
EBNIBN
MN agonist
EBN IBN
contracFN
ipsicFN
midline
muscimol
cFN inactivation also affects ipsilateral saccades, making their horizontal amplitude hypermetric
Goffart L & Pélisson D. Journal of Neurophysiology 1994, 1998 (head free cat)
Ohtsuka K, Sato H & Noda H. Journal of Neurophysiology 1994
Robinson FR, Straube A & Fuchs AF Journal of Neurophysiology 1993
Goffart L, Chen LL & Sparks DL. Journal of Neurophysiology 2004
Quinet J & Goffart L. Journal of Neurophysiology 2005, 2007 (head free monkey)
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“planning noise” = “all noise sources that contribute to the variability of the planned saccade amplitude” (page 3)i.e., “non-motor noise affecting sensory processing, target selection, and cortical representations of the initial motor error” (page 3)
Fastigio-reticular projections and the cerebellar control of saccades
Motoneurons(ABD)
PremotorNeurons
(EBN, IBN)Cortical
eyefields
(LIP, FEF, SEF…)
DeepSuperiorColliculus
Thalamus Caudal Fastigial Nuclei
Visualcorticalareas
Lobules VIc-VII
Pontine Nuclei,NRTP, cMAO
Neck proprioception
Vestibular input
NPH
Extra-ocular muscle proprioception
Microstimulation (100Hz)
Horizontal position (deg) Horizontal position (deg)V
ertic
al p
ositi
on (
deg)
Evidence for an intrasaccadic, not planning disorder
ControlMuscimol
ControlStimulation
32
24
16
8
0
-8
-16
-24
-32-32 -24 -16 -8 0 8 16 24 32-32 -24 -16 -8 0 8 16 24 32
Muscimol injection
Right cFN (rebound saccades removed)
SEE ALSO : Goffart L, Chen LL & Sparks DL. Annals NY Academy of Sciences 2003
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Increased variability of starting positionsNOT EXACT
x 3.
Is the endpoint variance increasedfor ipsilesional saccades ?
Not position but amplitude !
InactivationControl
Increased variability of starting positions due to :- shifted centroid of positions AND- horizontal dysmetria of fixational saccades
Is the endpoint variance increasedfor ipsilesional saccades ?
NOT EXACTNot position
but amplitude !
x 3.
Hor
izon
tal l
andi
ng p
ositi
on (
°)
Trial #
16DOWN
16UP
HOR
10
0
-20
-10
10
20
0-10-20 20
Horizontal position (°)
Ver
tical
pos
ition
(°)
A26jun15_5
POST
POST
Other possible target locations(+/-8,0); (0,+/-8); (+/-8,+/-8)
A26jun15_5
POSTPRE
PREflashed target (100 ms)gap = 200 ms
No increase of endpoint variance for ipsilesional saccades
10
0
-20
-10
10
20
0-10-20 20
A26jun15_5
POSTPRE
POSTPRE
left cFN
Larger hypermetria
A09oct15_5
POSTPRE
Smaller hypermetria
0
-20
-10
10
20
100-10-20 20
Searching for symmetry
Horizontal position (°)
Ver
tical
pos
ition
(°)
Horizontal position (°)V
ertic
al p
ositi
on (
°)
right cFN
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5
10
0
-20
-10
10
20
0-10-20 20
A26jun15_5
POSTPRE
POSTPRE
left cFN
Increased endpoint variabilityfor contralesional saccades !!!
A09oct15_5
POSTPRE
100-10-20 20
0
-20
-10
10
20
Searching for symmetry
Horizontal position (°)V
ertic
al p
ositi
on (
°)Horizontal position (°)
Ver
tical
pos
ition
(°)
right cFN
100
0
-20
-10
10
20
0 300
right cFN
A09oct15_5
500200 400
0
-20
-10
10
20
-10-20
Trial #
100 20
POSTPRE
A09oct15_5
Other possible target locations(+/-8,0); (0,+/-8); (+/-8,+/-8)
Hor
izon
tal l
andi
ng p
ositi
on (
°)
Ver
tical
pos
ition
(°)
Horizontal position (°)
100
0
-20
-10
10
20
0 300 500200 400
Trial #
Other possible target locations(+/-8,0); (0,+/-8); (+/-8,+/-8)
A09oct15_5
right cFN
Weak time-dependence
Strong time-dependence
Time-dependent endpoint variability for contralesional saccades
0
-20
-10
10
20
-10-20 100 20
POSTPRE
A09oct15_5
Hor
izon
tal l
andi
ng p
ositi
on (
°)
Ver
tical
pos
ition
(°)
Horizontal position (°)
100
0
-20
-10
10
20
0 300 500200 400
Trial #
1000 300 500200 400
Trial #H
oriz
onta
l lan
ding
pos
ition
(°)
Hor
izon
tal l
andi
ng p
ositi
on (
°)
0
-20
-10
10
20
A02oct15_5A09oct15_5
right cFN
Strong time-dependence
Weak time-dependence
Stability
Stability
injection A7 injection A6
NOYES
Time-dependent endpoint variability for contralesional saccades depends upon the experiment
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For some injection, the magnitude of hypometria incre ases with the trial number.
The drug diffuses with the trial number.
As the drug diffuses, the number of inactivated neurons increases = the numbe r of active neurons diminishes
Reduced number of active neurons reduced peak velocityinsufficient duration enhanced hypometria
EBNIBN
MN agonist
EBN IBN
midline
EBNIBN
MN agonist
EBN IBN
midline
EBNIBN
MN agonist
EBN IBN
midline
muscimol
contracFN
ipsicFN
0
0
-30
-10
10
30
-10-20-30 20
Horizontal position (°)
Ver
tical
pos
ition
(°)
B02avr14
POSTPRE
POSTPRE
left cFN
10
-20
20
Trial #
Hor
izon
tal l
andi
ng p
ositi
on (
°)
-40
-30
-20
-10
0
10
20
-402000 300 400100
Time-dependent endpoint variability also possible for only ipsilesional saccades
POSTPRE
time-dependence
stability
EBNIBNEBN
OPN
contracFN
midline
EBNIBN
MN agonist
EBN IBN
ipsicFN
midline
muscimol
EBNIBN
MN agonist
EBN IBN
midline
MN agonist
IBN
Enhanced duration is due to : - desinhibited residual input from descending commands- due to prolonged inhibition of OPN by the agonist drive
Reduced number of active neurons enhanced duration
unchangedenhanced
enhanced hypermetriapeak velocity
As the drug diffuses, the number of active neurons diminishes
reduced feedback gainduring ipsilesional saccades longer H duration longer V duration
VERTICAL GENERATOR
HORIZONTAL GENERATOR
1+∆g2
1-∆g1
Goffart, Koene & Quinet SFN abstr . 2005
Goffart, Koene & Quinet 2005 rejected
Saccade duration and the local feedback control
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25 muscimol injections in the cFN of 4 monkeys
Oblique saccades
enhancedVduration
<
CONCLUSION
1. BOTH cFN contribute to accelerate AND decelerate the horizontal component of any saccade
reduccedH peakvelocity
enhancedH peakvelocity
1. BOTH cFN contribute to accelerate AND decelerate the horizontal component of any saccade2. The NUMBER of active neurons in BOTH cFN matters in the specification of saccade dynamics
EBNIBN
MN agonist
EBN IBNEBNIBN
MN agonist
EBN IBNEBNIBN
MN agonist
EBN IBN
muscimol
contracFN
ipsicFN
CONCLUSION : the bilateral mass hypothesis
EBNIBN
MN agonist
EBN IBN
contracFN
EBNIBN
MN agonist
EBN IBNEBNIBN
MN agonist
EBN IBN
ipsicFN
Saccade time course
activelate
active early
CONCLUSION : the bilateral mass hypothesis
1. BOTH cFN contribute to accelerate AND decelerate the horizontal component of any saccade2. The NUMBER of active neurons in BOTH cFN matters in the specification of saccade dynamics
3. The late burst of some neurons in the ipsilateral cFN is the signature of a RECRUITMENTOhtsuka K & Noda H. Journal of Neurophysiology 1991
Kleine JF, Guan Y & Büttner U. Journal of Neurophysiology 2003 Fuchs AF, Robinson FR & Straube A. Journal of Neurophysiology 1993
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1. BOTH cFN contribute to accelerate AND decelerate the horizontal component of any saccade2. The NUMBER of active neurons in BOTH cFN matters in the specification of saccade dynamics
3. The late burst of some neurons in the ipsilateral cFN is the signature of a RECRUITMENT4. Different evolutions of ipsi/contra-lesional dysmetria suggest DISTINCT ROUTES to EBN/IBNs
Trial #
Hor
izon
tal l
andi
ng p
ositi
on (
°)
-30
-20
-10
0
10
20
-402000 300 400100
Strong time-dependence ofIpsilesional dysmetria
stability
100
0
-20
-10
10
20
0 300 500200 400
Trial #A09oct15_5
Weak time-dependence
Strong time-dependence ofcontralesional dysmetria
Hor
izon
tal l
andi
ng p
ositi
on (
°)
CONCLUSION : the bilateral mass hypothesis
1. BOTH cFN contribute to accelerate AND decelerate the horizontal component of any saccade2. The NUMBER of active neurons in BOTH cFN matters in the specification of saccade dynamics
3. The late burst of some neurons in the ipsilateral cFN is the signature of a RECRUITMENT4. Different evolutions of ipsi/contra-lesional dysmetria suggest DISTINCT ROUTES to EBN/IBNs
5. Between the topographical and temporal "codes", the NEURONAL MASS "code"
TOPOGRAPHICAL "code" (e.g. deep Superior Colliculus)
TEMPORAL "code"(e.g. motoneurons)
NEURONALMASS"code"
Cerebello-reticularnetwork
neuronal mass = the number of active neurons contributing to the agonist burst
CONCLUSION : the bilateral mass hypothesis
Gratefulness and thanks for their support
Julie QUINET
Edward L. KELLER
Longtang L. CHEN
Ziad M. HAFED
Rich J. KRAUZLIS
Patrick CAVANAGH
POSITION (P. Cavanagh)
Clara BOURRELLY
Lorenzo GUERRASIO
Ulrich BÜTTNER
David L. SPARKS
Albert F. FUCHS
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