Transcript Spinal axial microcircuits in fish provide evolutionary basis for limb

Vestibular circuitry and physiology
Martha Bagnall, Ph.D.
Asst. Professor, Anatomy & Neurobiology
[email protected]
Today’s plan
1. Lecture
2. Small group problem set
solving
3. Discussion of problem set
Vestibular sensation: your sixth sense
...doesn’t include interoceptive senses:
vestibular, proprioceptive
Questions
How do vestibular organs sense head movement and orientation?
What cellular and circuit properties account for the remarkable speed
and linearity of vestibular reflexes?
How do other sensory modalities affect central vestibular processing?
Vestibular end-organs come in two flavors
Otoliths
saccule,
utricle
Vestibular end-organs come in two flavors
Semicircular canals
superior,
posterior,
horizontal
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.
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.
Spikes/s
Firing of neurons innervating otoliths reports orientation
Spikes/s
Firing of neurons innervating otoliths reports orientation
viewed from back of head
Utricle
Saccule
Semicircular canals report head rotation
Canals are filled with fluid
(endolymph); at the base, the
cupula contains a mass of hair cells
all with the same directionality
During head rotation, endolymph moves
inertially, more slowly than the head itself,
causing a deflection of the hair cells in the
cupula.
The directionality of the hair cells dictates
which direction of head movement is
excitatory, and which is inhibitory. For
horizontal canals, ipsiversive is excitatory,
contraversive inhibitory.
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
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
Vestibulo-ocular reflex (VOR)
Fuchs and Kimm 1975
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
VOR is very, very fast
Gaze
Head
Eyes
Head
Latency from head to eye mvt: 5-6ms
Cf saccade or smooth pursuit delay of
initiation: 100-200 ms
Huterer and Cullen, 2002
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
Central vestibular firing in vivo
“Vestibular-only” neurons (~40% of population)
Fuchs and Kimm 1975
Linear spike generation in vestibular nucleus neurons
Recording vestibular nucleus
neuron in slice preparation,
injecting sinusoidal current
du Lac and Lisberger, 1995
Linear spike generation in vestibular nucleus neurons
Recording vestibular nucleus
neuron, injecting sinusoidal
current: linearity of responses both
in scale and in additivity
Line: Fourier prediction. Dots:
data
du Lac and Lisberger, 1995
Central vestibular firing in vivo
Current injection
“Vestibular-only” neurons (~40% of population)
Fuchs and Kimm 1975
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
Linear synaptic processing from vestibular afferents
Stimulating vestibular nerve afferents at varying
instantaneous rate (top). Ignoring first few pulses, which
show system adapting out of quiescence, EPSC
amplitude is invariant.
Synaptic stim of vestibular nerve
also produces linear changes in
postsynaptic FR
Bagnall et al, 2008
Linear synaptic processing is unusual!
Hippocampal
CA3  CA1
synapse
Klyachko and Stevens 06
Synaptic transmission is a dynamic process. Postsynaptic responses wax and wane as
presynaptic activity evolves. This prominent characteristic of chemical synaptic
transmission is a crucial determinant of the response properties of synapses and, in turn,
of the stimulus properties selected by neural networks and of the patterns of activity
generated by those networks....Virtually all types of synapses are regulated by a variety of
short-lived and long-lasting processes, some of which lead to a decrease in synaptic
strength and others that lead to synaptic enhancement.
Zucker and Regehr 02
Linear synaptic processing is unusual!
Abbott et al Science 97
Cortical synapse: exponential decay of EPSC amplitude with respect to rate,
yielding a “normalization” function: total charge transfer (B, dashed line) quickly
maxes out.
Vestibular synaptic linearity indicates that synapses don’t HAVE to be nonlinear—instead, that’s a typical function that may be “valued” by a given circuit.
Here, the demands of behavior are towards linearity.
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
Central vestibular processing in vivo
Cerebellum
Thalamus,
hippocampus,
oculomotor
Vestibular nuclei
(brainstem)
Abducens
Vestibular nuclei
(brainstem)
Abducens
Spinal cord
Vestibular
afferents
(canals and
otoliths)
Central vestibular firing in vivo
“Position-vestibular-pause” neurons (~50% of population):
carrying both vestibular and eye movement info
Fuchs and Kimm 1975
Central vestibular processing
Cerebellum
Thalamus,
hippocampus,
oculomotor
Vestibular nuclei
(brainstem)
Vestibular nuclei
(brainstem)
Vestibular
afferents
(canals and
otoliths)
Eye position info
Abducens
Abducens
Spinal cord
Passive and active head movement encoding
Cullen 2011
Passive and active head movement encoding
Cullen 2011
Central vestibular processing: it’s complicated
Cerebellum
Thalamus,
hippocampus,
oculomotor
Vestibular nuclei
(brainstem)
Vestibular nuclei
(brainstem)
Vestibular
afferents
(canals and
otoliths)
Eye position info
Abducens
Proprioceptive neck/
body or movement
planning info
Abducens
Spinal cord
Summary
Two types of vestibular end-organs have different encoding properties
Vestibular circuits are also responsible for distinguishing between intentional and
unintentional head movement
Unusual linearity of cellular and synaptic properties in the vestibular nucleus may be
related to the unusual linearity of vestibular reflexes
Vestibulo-ocular reflex is stunningly rapid and highly accurate; relies on high firing rates
at baseline and distinctive forms of cellular and synaptic plasticity to maintain
throughout life
Vestibular sensation also influences many other systems: spinal reflexes, heart rate,
blood pressure, etc