Structure and function of vestibular
nerve afferents and efferents
Soroush Sadeghi
Structure and function of the auditory
and vestibular systems
Nov 2012
Vestibular system is an old system
Silcox et al. 2009
Peripheral vestibular system
Joseph Breuer
(1842 – 1925)
Multimodal integration of signals in the VN
Central vestibular pathways
VO
Vestibular reflexes:
Postural control
Normal human
Mouse after unilateral
labyrinthectomy
Vestibular reflexes:
Postural control
Normal
Unilateral labyrinthectomy
Courtesy of Mathieu Beraneck
Weber et al. 2009
Vestibular-nerve afferents
We used:
HC
SC
1) 2-4 weeks old rats,
2) whole tissue preparation,
3) either horizontal or
superior crista,
4) whole-cell patch clamp
recording.
Utricle
Scarpa’s
ganglion
Isabelle Roux
Elisabeth Glowatzki
Supporting cell to Type I hair cell (pigeon)
Weisleder et al .1995
Evidence from culture studies suggests that afferent
contact is not required for HC differentiation to type I
Synaptic currents are mediated by AMPA receptors
Different zones in the cristae
Goldberg 2000
Different zones in the cristae
Purcell and Perachio 1997
Two types of afferents: regular vs. irregular
• Vestibular organs have type I hair cells
with calyx endings and type II hair cells
with bouton endings.
• Calyx-only afferents have very
irregular resting discharge (CV>0.15)
•Bouton-only afferents have regular
resting discharge (CV<0.15)
• Calyx only afferents are only present in
amniotes (birds, reptiles, mammals) .
• Dimorphic afferents can have
regular or irregular resting discharges
• Most afferents have both calyx and
bouton endings.
Irregular
Regular
Goldberg and Fernandez 1971
Regular afferent
120
paffn67301b.mat: hhv - fr - - 1 -
120
Regular
100
100
1
Firing rate
(spikes/s)
80
80
60
60
40
Head velocity
(deg/s)
40
20
20
0
0
-20
-20
-40
-40
4.691
6.691
8.691
10.691
12.691
14.691
16.691
18.691
20.691
22.691
24.691
Irregular afferent
160
paffn70501b.mat: hhv - fr - - 1 -
160
140
Irregular
140
1
120
120
100
100
80
80
Firing rate
60
60
(spikes/s)
40
40
20
20
0
0
Head velocity
(deg/s)
-20
-20
-40
-40
29.992
34.992
39.992
44.992
49.992
54.992
Irregular afferents have high pass properties
Irregular
afferent
Irregular
Regular
Sadeghi et al., 2007
Dynamics of afferent responses do not parallel the
endolymph fluid dynamics
Fernandez and Goldberg, 1971
Torsion pendulum
Frequency of rotation (Hz)
Variability in the resting discharge of afferents
Sadeghi, Chacron, Taylor, and Cullen; J Neurosci 2007
Stimulus reconstruction in response to broad band stimulus
CF=1-(root mean squared error/stimulus SD)
MI=[-log2(1-C(f)]
C(f)=|Prs(f)|2/[Pss(f)Prr(f)]
Sadeghi, Chacron, Taylor, and Cullen; J Neurosci 2007
Stimulus reconstruction
Sadeghi, Chacron, Taylor, and Cullen; J Neurosci 2007
Population responses to broad band stimulus
MI=[-log2(1-C(f)]/fr
G(f)=|Prs(f)/Pss(f)|
Sadeghi, Chacron, Taylor, and Cullen; J Neurosci 2007
Is information about head movements carried in
the firing rate of the afferent (i.e., rate code) or
in the spike times (i.e., temporal code) ?
Adding jitter to spike times
Sadeghi, Chacron, Taylor, and Cullen; J Neurosci 2007
Adding jitter to spike times decreases information
carried by regular afferents
Regular afferent
Irregular afferent
Sadeghi, Chacron, Taylor, and Cullen; J Neurosci 2007
Detection thresholds
Sadeghi, Chacron, Taylor, and Cullen; J Neurosci 2007
Regular afferents have lower detection thresholds
Sadeghi, Chacron, Taylor, and Cullen; J Neurosci 2007
Two channels of information coding in the peripheral
vestibular system: functional implications
Regular afferents, with low detection thresholds, carry
information about the detailed time course of head
movement in their spike times.
Irregular afferents, with high detection thresholds, act as
detectors of high frequency transient features by using
rate codes.
The efferent vestibular system
The efferent pathway
Phasic
Tonic
Irregular
Regular
Goldberg and Fernandez 1971
Efferent cell group
Efferent vestibular
cells
VN
Goldberg and Fernandez 1980
1- About 300-400 efferent fibers
2- They project bilaterally
3- They are not specific for each end organ
Goldberg et al.,
Efferent neurons have changed through evolution
ACh is the main efferent neurotransmitter
Response of type II vestibular hair cells
to ACh (guinea pig)
Kong et al. 2005
Colocalization of ACh receptors and BK
channels
Kong et al. 2005
Vestibular efferents:
Studies in decerebrate chinchillas
Electrical stimulation of
contralateral nerve
Stim
Stim
Stimulation of
efferents by rotation
Rec
Response (spk/sec)
Rec
Electrical stimulation
of efferents
Time (sec)
Time (sec)
1- Excitatory responses for rotations in both directions (type III)
2- fast and slow components (nicotinic and muscarinic?)
3- larger in irregular compared to regular afferents
Time (sec)
Plotnik et al. 2001 and 2002
Marlinski et al. 2004
Recording from alert toad fish
Fish do not have type I hair
cells or afferents with calyx
endings
Toadfish: efferent activity
Highstein and Baker 1985
Toadfish: response of efferents to
touch
Highstein and Baker 1985
Toadfish: response of efferents to
auditory stimulus
Highstein and Baker 1985
Toadfish:
Afferent responses during escape reaction
1.
2.
Increase in resting discharge
Decrease in sensitivity
Boyle and Highstein 1985
Vestibular afferents respond similarly to active vs.
passive rotations
REGULAR
IRREGULAR
Passive
Active
Cullen and Minor 2002, Sadeghi et al. 2007
Is the efferent vestibular system
functional in alert primates?
Excitation of superior canal afferents
to pitch and yaw rotations
Finding the null plane of the superior canals
Efferent-mediated responses in normal animals
Type III response:
excitation during both CW and
CCW rotations
Sadeghi et al. 2009
Efferent-mediated responses:
contralateral labyrinthectomy & plugged HC & PC
Sadeghi et al. 2009
1.
The vestibular efferent system is functional in the alert primate.
2.
The efferent responses to rotations are abolished in the absence of
vestibular inputs.
3.
Efferent-mediated vestibular nerve afferent responses:
• are type III (i.e., excitatory for rotations in both directions),
• are symmetric,
• have two components: per- and post-stimulus responses,
• are larger in irregular units compared to regular units.
What is the functional role of the efferent
vestibular system?
Resting discharge of afferents do not
change after lesion
Sadeghi et al. 2007
Sensitivity and phase of the response
of afferents do not change after lesion
Sadeghi et al. 2007
Change in relative proportions of
regular and irregular afferents
There is also new evidence from α9
knock out mice! (Eron et al., sfn 2011)
Sadeghi et al. 2007
Do distinct central pathways exist?
Modified from Lasker et al. 1999
Two types of neurons based on intracellular
recordings
Type A (Tonic)
Type B (Phasic)
Type A: High and regular resting rate; low gain ; low sensitivity
Type B: low and irregular resting rate; high gain ; high sensitivity
Beraneck et al. 2003
Cullen et al. 2010