Cerebellar control of gaze orientation toward visual targets: studies in the non-human primate

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Submitted on 20 Mar 2019

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Cerebellar control of gaze orientation toward visual targets: studies in the non-human primate

Laurent Goffart

To cite this version:

Laurent Goffart. Cerebellar control of gaze orientation toward visual targets: studies in the non-

human primate. Cerebellum-Striatum-Hippocampus network: bridging the gap between basic science

and clinical research, Mar 2019, Paris, France. �hal-02073990�

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Laurent Goffart

Cerebellar control of gaze orientation toward visual targets:

studies in the non-human primate

Institut de Neurosciences de la Timone, CNRS – Aix-Marseille Université, Marseille, France Contact: laurent.goffart@univ-amu.fr

2 6

4 3

5 1

1

2 3 1. Superior Rectus 6

2. Inferior Rectus 3. Lateral Rectus 4. Medial Rectus 5. Inferior Oblique 6. Superior Oblique 9. Optic nerve

5

6

MOVE: contract Leftward: LR Rightward: MR Upward: SP + IO Downward: IR + SO

IBN IBN

MN MN

EBN

AIN MN EBN

AIN MN

LR muscle

MR muscle

LR muscle

Left Eye Right Eye

IO

IR SRSO SOSRIOIR

Right/Upward saccade

Rightward saccade

OPN

IBN IBN

MN MN

EBN

AIN MN EBN

AIN MN

EBN EBN MN

MN MN

MN

MN MN MN MN

IBN IBN

EBN EBN

Pontomedullary Reticular Formation

Mesencephalic Reticular Formation

EBN EBN MN

MN MN

MN

MN MN MN MN

IBN IBN

EBN EBN

IO

IR SRSO SOSRIOIR

LR muscle

MR muscle

LR muscle

Upward saccade

SACCADE GENERATORS

caudal Fastigial nucleus STIM

Lobules VIc-VII (vermis)

Microstimulation (100Hz)

Horizontal position (°) Horizontal position (°)

V e rt ic a l p o si ti o n ( °)

Control M uscimol

Control Stimulation

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

ELECTRICALLY-INDUCED INHIBITION OF cFN FIRING RATE OF

SACCADE-RELATED NEURONS

Lobules VIc-VII (vermis)

caudal Fastigial nucleus

- -

Purkinje cells

Nuclear cells

Muscimol (gaba-A)

MUSCIMOL INACTIVATION OF cFN

ACKNOWLEDGMENTS

10 stimulation pulses

TIME WINDOW OF SACCADE DYSMETRIA OCULOMOTOR DISORDER

NEURONAL RECRUITMENT

MEDIO-POSTERIOR CEREBELLUM

Caudal Fastigial Nuclei

proprioceptive signals

vestibular signals Lobules VIc-VII

rostral

20°

0°

-20°

-40°-60°

2°

5°

10°

20°

30°

40°

2°

5°

10°

20°

30°

40°

20°

0°

-20°

-40°

-60°

caudal 60°

40°

60°

lateral rostral

caudal

IBN EBN

MN leftward Saccade

Generator EBN IBN IBN EBN

IBN EBN

Leftward Saccade Generator

saccade toward the right

MN Rightward Saccade Generator Colliculus Supérieur profond droit

Up/downward Saccade Generator

Abducens Nuclei

Up/downward Saccade Generator

contra cFN

ipsi cFN IBN EBN

MN _agonist

Dynamic balance

EBN IBN

Caudal Fastigial Nucleus

Caudal Fastigial Nucleus OPN OPN

BILATERAL CONTROL

Spinal Cord

IBN IBN EBN RSN

NECK MUSCLES MN

EBN RSN

EXTRA-OCULAR MUSCLES

MN MN MN Spinal

Cord Reticular

Formation

NECK MUSCLES

Reticular Formation Caudal

Fastigial Nucleus

HEAD ORIENTATION

rostral

20°

0°

-20°

-40°-60°

2°

5°

10°

20°

30°

40°

2°

5°

10°

20°

30°

40°

20°

0°

-20°

-40°

-60°

caudal 60°

40°

60°

lateral Colliculus Supérieur profond droit rostral

caudal Colliculus Supérieur profond gauche

FASTIGIO-COLLICULAR DISORDER

MUSCIMOL INJECTION IN ROSTRAL SUPERIOR COLLICULUS

Spinal Cord

IBN IBN EBN RSN

OPN OPN

NECK MUSCLES MN

EBN RSN

MN MN MN Spinal

Cord Reticular

Formation

NECK MUSCLES

Reticular Formation Caudal

Fastigial Nucleus

FIXATION OFFSET + MICROSACCADE DYSMETRIA

EXTRA-OCULAR MUSCLES

IPSILESIONAL SACCADES AND PURSUIT CONTRALESIONAL SACCADES AND PURSUIT

BRAIN CONTROL OF TRACKING EYE MOVEMENTS

FIXATION AS EQUILIBRIUM

NO SACCADE symmetrical commands

NO SLOW MOVEMENT symmetrical commands

>

100 0

-20 -10 10 20

0 200 300 400 500

Trial #

Horizontal eye position (°)

A09oct15_5

Strong time-dependence Weak time-dependence

100

0 200 300 400 500

Trial #

0

-20 -10 10 20

A02oct15_5

Stability Stability

IBN EBN MN agonist

EBN IBN

contra cFN

EBN IBN

ipsi cFN muscimol

Trial #

-30 -20 -10 0 10 20

-40

200

0 100 300 400

EBN IBN

midline contra

cFN IBN EBN

MN agonist

EBN IBN

ipsi cFN

midline muscimol

EBN IBN

midline

For some injection (not all), the size of the dysmetria increases with the trial number.

EXPLANATION:

The drug diffuses with the trial number.

As the drug diffuses, the number of inactivated neurons increases;

the number of active neurons diminishes CONTRALESIONAL SACCADES

Reduced number of active neurons reduced peak velocity unchanged duration size of hypometria increases

IPSILESIONAL SACCADES

Reduced number of active neurons unchanged/enhanced peak velocity enhanced duration size of hypermetria increases IBN EBN

MN

agonist

EBN

IBN

STIM contra

cFN

ipsi cFN

midline IBN EBN

MN

agonist

EBN

IBN

STIM contra

cFN ipsi

cFN

midline

Vertical eye position (°)

Control Muscimol (right cFN)

% %

Vertical eye position (°)

Horizontal eye position (°) Horizontal eye position (°)

FIXATION OFFSET

Evidence from pharmacological experiments Evidence from

microstimulation experiments

TRACKING A MOVING TARGET

HYPOTHESIS : PURSUIT ALSO AS EQUILIBRIUM

- Theory of neural control of movement which is strictly neurophysiological and does not embed kinematic notions (position, amplitude, velocity etc.) within the inner functioning of the brain.

Monkey E Monkey B

STRENGTH and NOVELTY

Drs David L. Sparks and Lewis L. Chen Drs Ulrich Büttner and Lorenzo Guerrasio, Drs Richard Krauzlis and Ziad Hafed, Drs Julie Quinet and Clara Bourrelly Dr Patrick Cavanagh Injection Bi

Injection A6

Injection A7

LIMITS and PERSPECTIVES

- Extension to binocular eye movements

- Connections with reticulo- and vestibulo-spinal tracts (eye-head coupling) - Extension to spatial cognition and the neural correlates of loci - Inclusion of the climbing fiber input from cMAO - Extension to basal ganglia and DA neurons

In the caudal fastigial nucleus (cFN), saccade-related neurons exhibit a

a burst of action potentials during saccades and a sustained firing rate between them. Electrophysiologists tried to relate the timing of the bursts to the acceleration and deceleration of saccades, i.e., with kinematic parameters. The dysmetria observed after cFN inactivation was considered as the outcome of the suppression of the burst; the pre-saccadic sustained firing rate was not considered for unjustified reasons. Therefore I searched for the critical time window during which an imbalance of cFN activity leads to horizontal dysmetria.

Goffart, Chen & Sparks Journal of Neurophysiology2004

Bourrelly, Quinet & Goffart Journal of Neurophysiology2018a

Quinet & Goffart Journal of Neurophysiology2007

Bourrelly, Quinet & Goffart Journal of Neurophysiology2018b Quinet & Goffart Journal of Neurophysiology2015