Download Review (11/01/16)

11/01/16
What are some differences between
rods and cones
Rod and Cone Photoreceptors
Rods:
A. High Sensitivity
B. Slow Response
C. Monochromatic
Cone Opsin
Cones:
A. Low Sensitivity
B. Faster Responses
C. Color Vision
Be careful with the ones in boxes. If he asks a test
question about differences in phototransduction
between rods and cones, C is not an answer. Color
vision comes from having multiple cones that
preferentially respond to different wavelengths.
Photocurrent (pA)
Comparison of Rod and Cone Physiology
CONE
ROD
0
0
-5
-20
-10
-40
-15
0
4
8
12
0
4
t (s)
8
12
t (s)
ROD
CONE
Normalized Response
1.0
0.5
0.0
1
10
2
10
3
10
PIGM* / cell
4
10
5
10
Which ion is important for adaptation
in photoreceptors
Which ion is important for adaptation
in photoreceptors
• It is always calcium
– We will talk about why/how next week
Calcium and Photoreceptor Adaptation
Baylor 1996
Light Adaptation Reduces Cone Sensitivity
Dark
1.0
8.8 X 103
0.8
R/Rmax
4.0 X 104
0.6
0.4
0.2
0.0
1
2
3
4
Log Light Intensity
5
6
Liu
• Afferent fibers (from periphery to spinal cord)
have their cell bodies in the _____
– Dorsal Root Ganglion (DRG)
• These fibers have a ______
geometry/morphology
– Pseudounipolar
• Pseudounipolar means______
– The axon spilts at the soma and goes in two
directions. The cell body is in the DRG, the axon splits,
one goes to the periphery, one goes into the dorsal
horn of the spinal cord
• Nociceptive fibers, also called ___-fibers, lack
_____ and have a _____ diameter. As a
consequence, the conduction velocity of these
fibers is _____.
– C-fibers Myelin
Small Slow (~1 m/s)
• Which of the A-fibers can also be considered
nociceptive?
– A-delta
• Starting from a pinprick on the skin of your
hand, describe the circuit that leads to
withdrawal of the hand.
• Rank the following in order of conduction
velocity. Fastest to slowest
–
–
–
–
A-delta
A-Beta
C
A-alpha
• Alpha, beta, delta, C
• Would you have to change your answer if she
asked you to order them based on axon
diameter?
– No. The fast ones have larger axon diameters than the
slow ones, just as you would expect.
• Which fibers are associated with the initial,
“sharp” response to a painful stimulus and
which are associated with “second pain”, the
slower component that sticks around for a
while after the painful stimulus.
– A-delta sharp response
– C second pain
• What does WDR stand for?
– Wide dynamic range.
• What does that mean?
These neurons respond to a wide range of stimulus
strengths and their response is dynamic (the
response changes in proportion to the strength of
the stimulus).
• What are the synaptic targets of A-delta and C
fibers?
A. nociceptive-specific neurons
B. wide-dynamic range neurons
C. Both of them
D. None of them
• What are the synaptic targets of A-delta and C
fibers?
A. nociceptive-specific neurons
B. wide-dynamic range neurons
C. Both of them
D. None of them
• What is windup
• In the central sensitization "wind-up", which
statements are true?
A. In addition to glutamate, the release of substance P by
C fibers also plays an important role in wind-up.
B. The activation of NMDA leads to the opening of
AMPA-R
C. wind-up causes an increased sensitivity of the
nociceptive-specific neurons, which now fire action
potentials more readily
D. Wind-up can persist long after an injury has healed
• In the central sensitization "wind-up", which
statements are true?
A. In addition to glutamate, the release of substance P
by C fibers also plays an important role in wind-up.
B. The activation of NMDA leads to the opening of
AMPA-R
C. wind-up causes an increased sensitivity of the
nociceptive-specific neurons, which now fire action
potentials more readily
D. Wind-up can persist long after an injury has healed
• Please explain how a tissue injury causes
thermal allodynia.
These sensitize
TRPV1 channels or
upregulate their
expression. TRPV1
channels are
temperature
sensitive.
• Please explain how a tissue injury causes a
thermal allodynia.
• Answer: Tissue injury leads to the release of
inflammatory molecules, such as bradykinin and
prostaglandins, which sensitize TRPV1 channel.
In addition, nerve growth factor NGF secreted
from immune cells can increase the expression
of TRPV1 channels (more channels on
membrane), and enhance the thermal
sensitivity of nociceptive neurons.
• Under chronic pain conditions
A.
B.
Nociceptive neurons adapt and respond less strongly to stimuli
Sensitize and respond more strongly to a stimulus.
B
•
What happens to ion channels during this process
–
•
What is the difference between allodynia and hyperalgesia
–
•
More excitatory, fewer inhibitory (through modulation or through
change in expression at membrane). Lowers response threshold
Hyperalgesia is a stronger pain response to a stimulus that is always
painful. Allodynia is responding to a stimulus that is normally not
painful as though it were painful.
What kinds of transmitter-like things are associated with
sensitization?
–
Neuropeptides
choose excitatory or inhibitory
• According to the gate control theory of pain,
large-diameter fibers make _____ connections
onto WDR neurons and small-diameter
(nociceptive) neurons make _____ connections
onto WDR neurons.
• According to the gate control theory of pain,
large-diameter fibers make _____ connections
onto inhibitory interneurons and small-diameter
(nociceptive) neurons make _____ connections
onto inhibitory interneurons.
choose excitatory or inhibitory
• According to the gate control theory of pain,
large-diameter fibers make excitatory
connections onto WDR neurons and smalldiameter (nociceptive) neurons make excitatory
connections onto WDR neurons.
• According to the gate control theory of pain,
large-diameter fibers make excitatory
connections onto inhibitory interneurons and
small-diameter (nociceptive) neurons make
inhibitory connections onto inhibitory
interneurons.
• If only large-diameter fibers are activated,
inhibitory interneurons are ________, which
means they _______ the pain pathway, so you
_______ experience pain, because ________.
• If only small-diameter fibers are activated,
inhibitory interneurons are _______, which
means they ________ the pain pathway, so
you _____ experience pain, because ______.
Answers: see her slide if you find the
words confusing. The diagram is easier
to follow
• If only large-diameter fibers are activated, inhibitory
interneurons are activated, which means they inhibit
the pain pathway, so you will not experience pain,
because even though the large-diameter fibers are
excitatory and excite the pain pathway, this is
countered by the inhibtion that they also activate.
• If only small-diameter fibers are activated, inhibitory
interneurons are inhibited, which means they do
nothing to the pain pathway, so you will experience
pain, because there is no inhibition and the smalldiameter fibers will activate the pain pathway.
• What are the three itch coding models?
– Intensity
– Labeled-line
– Occlusion
• Describe each
– Intensity – same neurons carry information about both
pain and itch. The perception of pain vs itch just depends
on the strength (firing rate) of the response of the neurons
carrying this information.
– Labeled-line – separate pathways (neurons). There are
neurons that only sense itch and others that only sense
pain.
– Occlusion – There are neurons that code for pain and
others that code for itch and pain (labeled-line like), but in
the presence of significant pain and itch, the pain response
is more significant and occludes(inhibits) the itch neurons.
• Which is the favored model
– Occlusion
Bagnall
• Name two modalities/types of information
that influence vestibular nucleus neurons
besides vestibular sensation.
• Name two modalities/types of information
that influence vestibular nucleus neurons
besides vestibular sensation.
– Vision
– Proprioception
• Many neurons in the vestibular circuit operate
around high baseline firing rates as discussed
in lecture. What do you think are the
advantages of this feature? What are some
disadvantages?
Vestibular sensation: your sixth sense
...doesn’t include interoceptive senses:
vestibular, proprioceptive
Vestibular end-organs come in two flavors
Otoliths
saccule,
utricle
I would know that there
are two otoliths
Vestibular end-organs come in two flavors
Semicircular canals
superior,
posterior,
horizontal
I would know
that there are 3
semicircular
canals
Otoliths report head translation...and gravity
The saccule and utricle contain a
gel-like mesh with suspended
crystals (otoconia). Both contain
hair cells with two dominant
orientations.
I would know how otoliths work in
3d even though there are only two
In response to accelerative forces, this gel
slides in the corresponding direction, opening
some hair cells and closing others.
Scarpa’s ganglion contains cell bodies of 8th
nerve neurons.
• Signals processed by the otolith and semicircular canal end-organs
differ in which of the following ways? Circle all that apply.
a) Hair cells innervating an otolith are all aligned in the same direction,
whereas those innervating a semicircular canal have mixed orientations.
b) Hair cells innervating a semicircular canal are all aligned in the same
direction, whereas those innervating an otolith have mixed orientations.
c) Afferents innervating semicircular canals have low baseline firing rates,
but those innervating otoliths have high firing rates.
d) Both otoliths and semicircular canals report head translation.
e) Semicircular canals provide a transient signal about head rotation and
cannot report gravity, unlike otoliths.
• Signals processed by the otolith and semicircular canal end-organs
differ in which of the following ways? Circle all that apply.
a) Hair cells innervating an otolith are all aligned in the same direction,
whereas those innervating a semicircular canal have mixed orientations.
b) Hair cells innervating a semicircular canal are all aligned in the same
direction, whereas those innervating an otolith have mixed orientations.
c) Afferents innervating semicircular canals have low baseline firing rates,
but those innervating otoliths have high firing rates.
d) Both otoliths and semicircular canals report head translation.
e) Semicircular canals provide a transient signal about head rotation and
cannot report gravity, unlike otoliths.
Crucial differences in end-organ function
Semicircular canals
Report head rotation
Otoliths
Report head translation
Fluid eventually catches up  movement only
reported transiently
Gel only returns to original position when forces let
up; therefore, reports both gravity and translation
Have single excitatory direction
Have mix of hair cell orientations, not single direction
Both are conveyed by nerve fibers with high baseline firing rates
Which are recordings from otoloiths
and which are from semicircular canals
Spikes/s
Firing of neurons innervating otoliths reports orientation
Firing of neurons innervating canals reports rotation
Sinusoidal stimulation
J Neurophys 1971 a, b, c
Vestibular and auditory afferents are really different
Auditory nerves
Much lower baseline firing rates
Response to sound (pure tones) often involves phase
locking: all spikes fired at particular phase of sound
oscillation.
Dreyer and Delgutte J Neurophys 2006
• Turning your head to the left (excites/inhibits)
vestibular nucleus neurons on the left side of
your head?
• Which direction do your eyes move?
Circuit of horizontal angular VOR
Push-pull action: excitation from one side and inhibition
(and decrease in excitation) from the other
Straka and Dieringer 2004
• You implant a small micro-pump in a rat’s right medial
vestibular nucleus (responsible mostly for horizontal VOR).
You infuse a small amount of the glutamate receptor
antagonist NBQX. Briefly, what do you predict will happen to
the VOR when you rotate the animal back and forth on a
turntable? You can draw results if you wish, but label
everything.
Circuit of horizontal angular VOR
Push-pull action: excitation from one side and inhibition
(and decrease in excitation) from the other
Straka and Dieringer 2004
• You implant a small micro-pump in a rat’s right medial
vestibular nucleus (responsible mostly for horizontal
VOR). You infuse a small amount of the glutamate
receptor antagonist NBQX. Briefly, what do you predict
will happen to the VOR when you rotate the animal
back and forth on a turntable? You can draw results if
you wish, but label everything.
• NBQX decreased firing in the right MVN  failure
to make VOR to the left, AND an exaggerated VOR to
the right due to loss of commissural inhibition.
Which would respond in each case and
which would be suppressed
Passive head motion
Active head motion
Vestibular afferents
Central vestibular neurons
In 1-2 sentences, provide a possible explanation for the source of suppression:
• In 1-2 sentences, provide a possible
explanation for the source of suppression:
• Possible explanation: cerebellar inhibition of
predicted signal, using motor command
and/or proprioceptive information. It’s not
known for sure so would accept other
reasonable ideas.
Passive and active head movement encoding
This is a great paper. Read it for fun.
https://courses.cit.cornell.edu/bionb4240/Documen
ts/Holst_Mittelsteadt_1950_English.pdf
Cullen 2011
Keeping neurons firing fast: crucial role of Kv3
Primary dissociated medial vestibular nucleus neurons
Slower firing
Faster firing (projection
(GABAergic)
neuron)
Injecting action potential waveform
during voltage clamp to isolate
different currents flowing during a
spike
Faster-firing neuron has a narrower
spike and a 2x larger Kv3 component
Gittis et al. 2010, J
Neurophys
Tail currents: a read-out of open, non-inactivated
channels
With a long depolarization, Na
currents inactivate
With brief depolarization, fewer Na
channels inactivate. Tail current (arrow)
is measure of channels that were open
(ie not inactivated) when the cell was
repolarized.
Keeping neurons firing fast: crucial role of Kv3
Primary dissociated medial vestibular nucleus neurons
Slower firing
Faster firing (projection
(GABAergic)
neuron)
Injecting action potential waveform
during voltage clamp to isolate
different currents flowing during a
spike
Faster-firing neuron has a narrower
spike and a 2x larger Kv3 component
Artificially broadening the spike,
mimicking TEA application to block
Kv3, yields diminished Na current on
subsequent spike.
Tail
current
Gittis et al. 2010, J
Neurophys
• Vestib nu. neurons express the Ca-gated K
channel known as SK. You apply a known
agonist of SK channels while recording from a
slice prep of vestib nu. neurons.
– What is gain, in the cellular sense? The behavioral
sense?
– What do you expect to happen to the gain in the
cell you’re recording when an SK agonist is
applied?
Vestibulo-ocular reflex (VOR)
The VOR and its necessity were
described by a physician whose
inner ear had been severely
damaged by excessive
streptomycin therapy. He could
read in bed only by bracing his
head against the headboard;
otherwise the printed page
jumped with each heartbeat.
When walking he was unable to
recognize faces or read signs
unless he stood still.
https://kin450-neurophysiology.wikispaces.com/VOR
Changing the input/output relationship (gain)
Blockade of BK channels with
iberiotoxin  increased gain
Step currents in slice
preparation to measure cellular
gain
Bidirectional changes in gain with ambient
[Ca]
Smith et al 2002