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Neuroscience: 2:00-3:00
Wednesday, February 25, 2009
Dr. Gamlin
MVN - Medial vestibular nucleus
NPH - Nucleus prepositus hypoglossi
EBN - Excitatory burst neuron
IBN - Inhibitory burst neuron
Neuroscience
Scribe: Sheena Harper
Proof: Patricia Fulmer
Page 1 of 6
This kind of picked up in the middle of what he was saying about the last hour:
a. Those are the eye movements you need to look between objects of interest whether it be two targets horizontally
or vertically. You are using them to read across a page. You make them all the time. As I said before the break
the motor neurons have to generate a pulse of activity to generate a muscle force that overcomes the viscous
drag. They have to generate a step to hold the eye in a new position.
I. Right Medial Rectus Motoneuron – Saccades [S29]
a. People have recorded over the years from alert, behaving monkeys during specific eye movements: saccadic
eye movements, vergence eye movements, smooth pursuit eye movements, and we have a monkey cartoon,
and we’ve animated it so when the eyes move they are moving twice as much as they would in real life.
b. The sound you hear is actually the sound of the neurons as they were recorded.
c. He plays the video.
d. This is a medial rectus motor neuron. You can hear the burst and the tonic firing rate.
II. Horizontal saccades are generated in the paramedian pontine reticular formation (PPRF) [S30]
a. As the eye is moved in the opposite direction they decrease their firing rate. Motor neurons can have very high
firing rates. They can have a firing rate of 100 spikes per second. They can easily reach firing rates of 300
action potentials per second in extreme gaze and maintain those firing rates. During the saccade, they may
burst to up to close to 1,000 action potentials per second. They are metabolically very active, and interestingly
they are the last motor neuron pool to be affected usually in conditions of ALS. The argument is maybe their
normal high metabolic rate of activity in some ways protects them a little bit against ALS. They are usually the
last motor neurons to be affected in ALS.
b. The horizontal saccades, which are driving the motor neuron, those pre-motor cells are in the paramedium
pontine reticular formation (PPRF), and the vertical saccade signals are generated in the rostral interstitial
nucleus of the medial longitudinal fasciculus (riMLF).
c. That’s the two pools of pre motor neurons. We are going to focus on the horizontal ones, but the vertical ones
are the same just for vertical movements.
III. Picture [S31]
a. The pre motor neurons that we are going to talk about are located in this region around the abducens nucleus
on the midline. The major players are excitatory burst neurons (EBN’s). They generate the pulse of firing that’s
seen on most motor neurons during saccades. EBN’s generate the burst of firing during saccades, and then
signals from the Nucleus Prepositus Hypoglossi are the tonic signals that hold the eye in the new position after
the saccade.
b. The burst comes from the EBN’s, the tonic firing rate comes from the nucleus prepositus.
c. The inhibitory burst neurons inhibit the contralateral abducens nucleus.
d. The excitatory excites and the inhibitatory inhibits during the saccade.
e. During a saccade, in the agonist there is a burst of activity, but in the antagonist they briefly stop the firing rate.
Hence that’s what the IBN’s do.
IV. Typical Neural Discharge Patterns [S32]
a. Recordings from this area in behaving animals have revealed the different classes of neurons.
b. The motor neuron generates a pulse during a saccade, so this is a horizontal eye movement, and it generates a
pulse during the movement and a tonic firing rate after the movement. The motor neuron has all the signals
appropriate for moving the eye, which is just as well since it is moving the eye.
c. There are also these tonic neurons, which are located in the nucleus prepositus hypoglossi, which do not burst
during the movement but increase their tonic activity with each new eye position.
d. We’re going to ignore this next category, this long-lead burst neuron.
e. We’re going to talk about the short-lead burst neuron which is the same thing as an excitatory or inhibitory burst
neuron.
f. They all behave the same way. They give a burst of activity right before the rapid saccadic eye movement, and
they don’t fire at any other time.
g. Omnipause neuron-These neurons fire at a resting rate of approximately 80-100 action potentials per second all
the time, and they pause for a brief period of time to allow a saccade to occur. If these cells are firing, they
Neuroscience: 2:00-3:00
Scribe: Sheena Harper
Wednesday, February 25, 2009
Proof: Patricia Fulmer
Dr. Gamlin
Neuroscience
Page 2 of 6
inhibit the burst neurons, and no saccade can occur. Pause neurons have to briefly stop firing to allow the
saccades to occur. They control the occurrence or nonoccurrence of saccadic eye movements.
V. OPN/ OMN [S33]
a. The omnipause neurons inhibit the burst neurons. There are many omnipause neurons that are on the midline
near the abducens nucleus. They pause only for saccades, and when they pause the burst neuron will generate
a burst of activity. The bigger the saccade, the bigger the burst.
b. If you want to move the eye further you generate a larger pulse of activity in the burst neurons and a larger
pulse of activity in the oculomotor nucleus or in this case either oculomotor or medial or lateral rectus motor
neurons, either one.
c. In addition this pulse of activity goes directly to the motor neurons. It also goes to regions of the brain, the
nucleus prepositus hypoglossi where the burst is turned into an increase of tonic firing rate. The burst gets
integrated in a neural fashion. The bigger the burst, the higher the firing rate after the movement. That’s what
holds the eye in the new position after the saccade.
d. The burst and the tonic signals, combine at the motor neuron to give a characteristic pulse step firing. The
players are the omnipause neurons, which are normally are firing. When they fire no saccades can occur. Then
the burst neurons and the tonic neurons in the NPH.
VI. Excitatory burst neuron- small saccade [S34]
a. This is a burst neuron that just fires for a saccade. That’s a small saccade. He shows the video.
VII. Excitatory burst neuron- medium saccade [S35]
VIII. Excitatory burst neuron - large saccade [S36]
a. Burst neurons only fire during a saccade, and that’s all they do.
b. They have that characteristic firing.
IX. GRAPH [S37]
a. Omnipause neurons do exactly the opposite. They shut down firing just before the saccadic eye movement.
b. This is showing the horizontal eye position. Just showing the omnipause neurons firing here. This one is firing
about 150 action potentials per second. Then it just shuts down. You have to really listen carefully to hear this
brief cessation of firing for about 40 ms.
c. This shows omnipause neurons. They fire all the time except for during a saccade.
d.
X. Omnipause neuron - various saccades [S38]
a. You should have heard a very brief 40ms gap, and then the rest of the time they’re firing action potentials.
b. It is believed that if those neurons are not behaving normally then you will make back-to-back saccades, which
as we started the first lecture with the opsiclonis with the child with the back-to-back saccades where they were
rapidly moving.
c. If the omnipause neurons are not behaving normally and maintaining their firing rate, then saccades will occur
back to back.
d. The omnipause neurons have to be turned off to allow a saccade to occur.
e. Since saccades are ballistic, you don’t’ want them occurring unless you are ready to make a saccade.
Omnipause neurons are really important for that.
XI. [S39]
a. The omnipause neuron is a critical player in this. This neuron receives a trigger signal from other parts of the
brain to make the saccade occur. That’s all they do. They turn off when a saccade occurs and they turn back on
after the saccade, but they don’t carry any information about the size of the saccade. They are just a switch.
Think of these as a switch.
b. In addition to starting a saccade or controlling the saccadic occurrence, there is also a signal that comes to the
PPRF that controls the size of the saccade.
c. There is a trigger signal, and then there is also a signal that tells the PPRF how large the saccade is supposed
to be.
XII. THE SUPERIOR COLLICULUS PROJECTS TO THE PPR [S40]
a. One of these signals is from the superior colliculus. Unlike the PPRF, which controls horizontal saccade and the
riMLF, which does vertical saccades, the superior colliculus has a map of all directions of eye movements into
the contralateral space.
b. The left colliculus has a map for rightward saccades. The right colliculus has a map for leftward saccades.
c. This map is really precisely organized, and this goes to one of the questions on the take home test.
Neuroscience: 2:00-3:00
Scribe: Sheena Harper
Wednesday, February 25, 2009
Proof: Patricia Fulmer
Dr. Gamlin
Neuroscience
Page 3 of 6
d.
XIII. SUPERIOR COLLICULUS MOTOR MAP [S41]
a. If you look at the map of the superior colliculus the anterior colliculus codes for small contralateral saccades.
The posterior colliculus codes for large contralateral saccades.
b. You can put a very thin electrode into the superior colliculus and pass a very small amount of stimulating current
for about 40 ms and you can elicit a saccade with microstimulation. You can elicit saccades that are in the
contralateral direction with different obliqueness.
c. These are small anteriorly and large posteriorly, and you can see that some are oblique. Some are horizontal.
Some are down, and some are up.
d. The map can be shown here. Small saccades are listed rostrally. Large saccades here. Horizontal saccades
are elicited along this horizontal meridian. As you go more medially or laterally the saccade will have an oblique
component.
e. If you get activity centered on 0/20 degrees, it will generate a saccade of 20 degrees horizontally into the
contralateral space.
f. When you record for the superior colliculus you learn there is a population of neurons that is active for any given
saccade. For any given saccade about 1/3 of the colliculus is active, but it’s like a mound of activity, and the
center of the mountain of activity is where the saccade is being specified. We know that from microstimulation
studies and from recording studies. There’s this 2-D map.
g. He didn’t bring his cartoon of the monkey, but if he had you would have heard specific bursts for specific
saccadic size and direction
h. The superior colliculus projects to the PPRF, and codes for saccadic eye movements.
i. In addition the most posterior part of the SC codes for eye movements and neck muscles that moves the head.
j. It’s hard to make a 70-degree saccade. The eyes won’t go that far. If you were to make an auditory sound over
to the side, you will make a combination head-eye movement- a gaze shift.
k. In fact, for primates they usually make 20-30 degree saccades, anything beyond this are done by a combined
head-eye movements. This is coded for in the most posterior part of the colliculus. This accounts for large gaze
shifts up to 70-80 degrees.
XIV.
A block diagram of the major structures that project to the brain [S42]
a. Eye movements involve quite a few different areas of the brain. Hence, they are susceptible to damage of those
areas of the brain.
b. Saccadic eye movements are no exception.
c. The brainstem saccade generator is the pre-motor area, which generates the signals to generate the saccade,
and it gets input from the superior colliculus.
d. There are other major players involved in rapid saccadic eye movements.
e. First there is a basal ganglia circuit. As is involved in any other movement control, which is dedicated to
controlling the timing of the saccade.
f. This is a basal ganglia circuit here. Damage to the basal ganglia, such as in Parkinson’s disease or in
Huntington’s disease, can affect eye movements and limb movements.
g. In addition there is a region in the parietal cortex, which projects to the superior colliculus and will control
saccadic eye movements.
h. A very important area involved in saccadic eye movement control is the frontal eye fields and supplementary
eye fields in humans.
i. Why might you want cortical control of voluntary eye movements? If you were to put a target up on the board
and you are told to look at it, now you are asked to keep track of another target and then remove your gaze
back to the first target. Many saccadic eye movements require that you have the location of a target in working
memory and you keep track of where that target is. Then you can make an eye movement to it later on. This
requires frontal cortex. Remembered eye movements, such as saccades, requires frontal cortex.
j. Antisaccades- look at the finger of the left hand and you are told to look in the opposite direction of another
target that is flashed. Most people can do this, but schizophrenic people have problems with antisaccades.
They generally look in the direction of the target. Antisaccades require that you suppress the initial saccadic
response to look at the target and then program a new movement. You need a normal frontal cortex for this.
k. Saccadic eye movements aren’t just simple reflexive eye movements all the time. That’s why it involves cortical
control and why damage or abnormalities in cortex can lead to abnormalities in saccadic control.
l. The circuit through the cerebellum is to ensure that eye movements are precise: neither hypo or hypermetric.
Just as in other cerebellar damage, if you have cerebellar damage for eye movements, they may overshoot or
undershoot.
Neuroscience: 2:00-3:00
Scribe: Sheena Harper
Wednesday, February 25, 2009
Proof: Patricia Fulmer
Dr. Gamlin
Neuroscience
Page 4 of 6
XV. Disorders of the saccadic pulse and step [S43]
a. Under normal circumstances the pulse and the step of the motor neurons are precisely matched so that the eye
stops on a dime and doesn’t drift. If there’s any mismatch between the pulse and the step, for example if the
pulse and the step are both too small, the saccade will be too small- a hypometric saccade. If the pulse is too
slow then the saccade will be too slow.
b. If the step is low or no step, they your eye go out and drift back to the original position. Even in normal
individuals, if there is an extreme gaze the eye tends to drift back. Any of these conditions can be affected with
cerebellum damage. People will report that the visual world is moving, and it can be quite disconcerting.
Normally the cerebellum produces saccades like the top ones, but cerebellar damage can cause any of the rest
of these.
XVI.
FUNCTIONAL CLASSES OF EYE MOVEMENTS [S44]
XVII.
Smooth pursuit [S45]
a. Smooth pursuit eye movements allow you to track objects of interest and maintain them on the fovea as they
move around.
XVIII. Video [S46]
a. Tracking a black dot across the screen.
XIX.
Smooth pursuit eye movements [S47]
a. You can’t track anything interesting without them.
b. If you move it slowly you should be able to track his laser pointer. If he moves it really quickly you won’t be able
to track it, and you are using saccadic eye movements.
c. The shortcoming of the smooth pursuit eye movement is that it only operates up to a target speed of about 100
degrees per second. Smooth pursuit requires that the target move at a reasonable speed.
XX. SMOOTH PURSUIT PATHWAYS [S48]
a. Smooth pursuit eye movements involve cortical areas that detect the motion of the stimulus on the retina. The
extrastriate visual areas, in humans it’s called HMT+, where neurons are sensitive to motion of the small targets
on the retina. Those cells project through the pontine nuclei and generate signals indirectly through the
cerebellum to control smooth pursuit eye movements.
b. In addition to these early striate visual area. There is another region of the frontal eye fields that is separate
from the region controlling saccades that also controls smooth pursuit eye movements. It turns out that tracking
this target here is easy, but you can do a little bit more than just track a visual target.
c. He had us track the laser pointer as it moved behind his hand. You should be able to track it even though it’s
briefly occluded.
d. You can track objects that go behind a tree. Even though the object disappears for about 100 ms, your eyes
can predict where it’s going to go. This requires the frontal cortex. The frontal cortex is the area of the brain
that allows you to predict where the target will reappear after it has disappeared. Damage to that can cause
problems with tracking objects when they go behind concluders.
e. Schitzophrenics also have problems with smooth pursuit. These are useful tools for looking at abnormal
individuals.
XXI.
FUNCTIONAL CLASSES OF EYE MOVEMENTS [S49]
a. Extra-ocular muscles
XXII. Vergence [S50]
a. Vergence: Eye movements in depth. Allows you to look at objects at different distances. They have a different
neural subsystem that controls them. They don’t share the MLF with the other eye movement systems that
we’ve talked about.
XXIII. Far and Near Viewing: Accommodation and Convergence (Both Eyes) [S51]
a. Vergence is linked to accommodation.
b. When you converge your eyes your lenses in the left and the right eye will also change their accommodation.
c. This diagram shows normal far viewing and the lenses focused for far.
d. If you bring a near target in, it will be blurred and its images fall off the fovea. In order to look at that near target
you need to converge your eyes and focus them. Under those conditions you will converge and change your
focus. Those two responses are coupled neurologically.
XXIV.
Far and Near Viewing: Accommodation and Convergence (Right Eyes only) [S52]
a. If the left eye is covered up and you bring a near target in so you have to focus on it, what will happen is that
you will change your focus in the right eye, and the other eye will also change focus since they are coupled. The
diagram isn’t quite right. They both change focus. You will accommodate to this target, and the non-viewing eye
will rotate as if it were viewing the target. This produces accommodation, but the convergence occurs because
you accommodate. Accommodation also produces accommodative convergence.
Neuroscience: 2:00-3:00
Scribe: Sheena Harper
Wednesday, February 25, 2009
Proof: Patricia Fulmer
Dr. Gamlin
Neuroscience
Page 5 of 6
b. Under normal circumstances. You can cover one eye, change focus, and you can see the non-viewing eye
converging toward the target. They are often coupled.
XXV. Picture [S53]
a. The areas that are involved in vergence and accommodation are not these regions that I’ve told you right now.
The cells are located right around the oculomotor nucleus, which is pre-motor for vergence and accommodation.
XXVI. [S54]
a. This is a horizontal diagram showing the vergence signals directly coming in to the oculomotor nucleus and
bypassing the abducencs and the MLF.
XXVII. Internuclear ophthalmoplegia [S55]
a. When you have damage to the MLF that is seen in internuclear ophthalmoplegia, the adduction during
convergence is not reduced because the vergence signal is coming in directly to the medial rectus motor
neurons and is not going through the MLF.
XXVIII. Class Demo (turned lights on and off and we looked at each other’s pupillary response.)
a. Pupillary light reflex- on TV when someone is in the ER and they shine a pen light in someone’s eyes to see if
they have a papillary light reflex.
XXIX. FUNCTIONAL CLASSES OF EYE MOVEMENTS [S56-61]
a. Under normal circumstances if you shine a light in one eye, you get the direct pupillary light reflex in that eye. In
addition in most normal individuals you will see an equal consensual pupillary response in the opposite eye. As
the light increases, the pupils get smaller. If you shine a light in the eye and there is no pupillary response,
there are a number of reasons. It doesn’t have to mean that the person is brain dead. It may not be that severe.
XXX.
Pupillary light reflex [S62]
a. If it’s absent, there’s a problem.
b. You can look at the PLR and see where the problem might be.
c. AFFERENT DEFECTS: May be due to, the extreme case is if you were blind in one eye, you are not likely to
show a pupil response from that eye. Signals reaching the brain will be abnormal.
d. EFFERENT DEFECTS: If you have damage to CNIII, you would probably have an abnormal papillary response.
You would also see oculomotor signs. You can see pupil deficits with damage to the Edinger Wesphnal nucleus.
In cases of tertiary syphilis, there would be an absence of papillary light reflex but the pupil would still constrict
when you looked near. (Side note- Argyll Robertson’s pupil) possibly because of damage to some of these
preganglionic neurons.
e. You can look at the pathway of the papillary light reflex. We will look at where potential damage might be that
accounts for the abnormality in the pupil. You can have either afferent or efferent defects. You can normally
distinguish between the two. If there’s afferent defect, then the signals reaching the brain from either one eye or
the other eye will be abnormal if this is a unilateral afferent defect.
f. In efferent defects the signals reaching the (in this instance the sphincter muscle). These signals will be
abnormal so the abnormality will tend to localize to the pupil of the affected eye.
g. If CN III is damaged going to the left eye, the direct and consensual response in that eye will be affected.
XXXI. Pupillary light reflex: Afferent deficit [S63]
a. When you shine a light in the right eye, it produces a good direct (right eye) and consensual (left eye) response.
When you shine a light in the left eye, you get a reduced direct and consensual response, but they are not
asymmetric. They are about the same size. Therefore the effect is in the afferent defect of the left eye.
b. You can see that both pupils respond normally in the first case, so there’s no efferent problem. In the second
case the direct response and the consensual response is reduced. Notice that there is no difference in pupil
size. That would be called an anisochoria. There is no anisochoria here.
XXXII. Pupillary light reflex: Afferent deficit [S64]
a. You can quantify this defect by putting neutral density filters over the light source illuminating the good eye. You
can see how much you can reduce that light until you get the same pupil response as in the affected eye. For
example if you drop this down by half a log unit this would be reported as a relative afferent pupillary defect of
0.5. You may well see a RAPD- relative afferent papillary defect.
b. This person has a relative afferent defect in the left eye, assuming they’re looking at us, of about 0.5 log units.
XXXIII. Pupillary light reflex: Efferent deficit [S65]
a. This is characterized by anisochoria (different dilation or constriction of the pupils between the two eyes).
b. There’s two possibilities for what caused this: it could be an abnormality in the sympathetic system, which he
isn’t going to talk about now called Horner’s Syndrome. We are going to assume that this is a parasympathetic
problem.
c. When you shine the light in the right eye, you get a strong direct response but a weak consensual response.
d. When you shine the light in the left eye, you get a weak direct and a strong consensual. It looks as though the
efferent signals to this left eye are not normal. There is an efferent deficit.
Neuroscience: 2:00-3:00
Scribe: Sheena Harper
Wednesday, February 25, 2009
Proof: Patricia Fulmer
Dr. Gamlin
Neuroscience
Page 6 of 6
e. You would normally do a swinging flashlight test. They will move the light from one eye to the other, and in this
case if you go back and forth in this direction, since there’s an efferent defect, those pupils don’t change in size
too much, but if you go back here to swing the light from the right to the left eye, then the pupils would change
as you swing the light from the right eye to the left eye. You would see them small and then they’d go larger.
f. When you do a swinging flashlight test, a normal individual’s pupils won’t change too much, and the pupils
shouldn’t show any anisochoria. They should be equal in size.
g. There are benign conditions where there is an anisochoria between the two eyes. If it’s a recent onset then it
needs to be looked at. If it has always been around it’s not a big deal.
XXXIV. TOP TEN LIST [S66]
a. 1. Pupillary light reflex. If it’s absent, there’s a problem.
b. 2. Vergence. Without it, you can’t get a closer look.
c. 3. Smooth pursuit eye movements. You can’t track anything interesting without them
d. 4. Saccadic eye movements. You can’t look at anything interesting without them.
e. 5. Optokinetic responses. The world drifts without them.
f. 6. Vestibular responses. You can’t read without them.
g. 7. Eye movements are controlled by distinct neurological subsystems.
h. 8. Except for changes in viewing distance, normal eye movements are yoked.
i. 9. The stretch reflex is absent. Gently press on your eye and you’ll see the world move.
j. 10. Movements of the eyes are produced by six extra-ocular muscles. If they, or the neural pathways
controlling them, are not functioning normally, eye movements are abnormal.
[end 40 min]