6/1/2010
The Cochlear Nucleus
Salamanca
June 2010
Maria E. Rubio
University of Pittsburgh
Cajal
The Cochlear Nucleus
The cochlear nucleus (CN) contains the circuits through
which information about sound is coupled to the brain.
In the CN, fibers of the auditory nerve contact neurons
that form multiple, parallel representations of the
acoustic environment. These circuits vary from simple
synapses that preserve the timing of auditory events to
complex neuropils that are sensitive to features that
identify sounds. The parallel pathways each perform a
different analysis of the auditory signal. Thus
calculations such as the localization of a sound source
in the space or the identification of a sound
so nd are
separated in the CN and performed in parallel as signals
ascend through the brainstem auditory nuclei.
(Young and Oertel)
Schematic View of the
Human Auditory Pathway
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The Cochlear Nucleus
Gross Anatomy
Pathways (afferents and efferents)
Cell types
Synaptic Circuitries (intrinsic connections)
Specialized Synapses
Plasticity: deafness and hearing loss
Cajal
Rat Brain: Gross Anatomy
Lateral view: dissection
Superior view
Ventral view
Dorsal view:
dissection
Auditory Nerve (AN)
Ventral cochlear nucleus (VCN)
Dorsal cochlear nucleus (DCN)
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Sectional Anatomy of the Cochlear Nucleus and Auditory Nerve Fibers Distribution
AN: Ascending and descending branches
Lateral view
DCN
AVCN
R t l
Rostral
AN
PVCN
Caudal
A sagittal slice of the cochlear nucleus of a mouse, with the auditory nerve entering from the bottom leftt, the anteroventral cochlear nucleus in the top left, and the dorsal cochlear nucleus in the top right. Auditory nerve fibers were labelled by injecting dextran‐conjugated Alexa488 into the cochlea. They label frequency‐specific bands in the AVCN. The molecular layer of the dorsal cochlear nucleus is labelled with an antibody against the cannabinoid receptor CB1 (courtesy of Dr. Ken Mackie, UWash). Cell nuclei are labelled with a DAPI counterstain. The scale bar is 200 µm.
Cat CN (Ryugo and Parks, 2003)
Cochlear Nucleus & Auditory Nerve Fibers Distribution
Tonotopy!!!
Lateral view
The innervation of the CN by AN fibers
is orderly and reflects the tonotopic
organi ation of the cochlea
organization
R t l
Rostral
Auditory Nerve (Type I fibers):
Low frequencies: ventral & lateral
g frequencies:
q
dorsal & medial
High
Caudal
Cat CN (Ryugo and Parks, 2003)
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Ventral Cochlear Nucleus (VCN)
1
The Core
The granular cell domain (GCD; cap)
2
3
Dorsal Cochlear Nucleus (DCN; layered)
1 Molecular layer
2 Fusiform cell layer
3 Deep layer
Oertel D et al. PNAS 2000
Ventral Cochlear Nucleus (VCN): Subdivisions
The Core
The granular cell domain (GCD; cap)
Photomicrograph (A) and drawing (B) illustrating the GCD of the CN in the rat. Granule cells were retrogradely labeled by placing an extracellular injection of diamidino yellow in the DCN. The labeled cell bodies form a shell along the lateral, dorsal, and dorsomedial surface of the VCN. This distribution is coincident with the distribution of the GCD as previously described (Mugnaini et al 1980).Scale bar=100um.
Zhang and Ryugo, 2007 JCN
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Targets of the Cochlear Nucleus
Cant and Benson 2003 The figure is based on degeneration studies in the cat by Warr and Fernandez and Karapas with additional details gleaned from studies done using a variety of different retrograde and anterograde tracing techniques.
AVCNa: anterior part of the anteroventral cochlear nucleus; AVCNp: posterior part of the AVCN; CN: central nucleus of the inferior colicullus; DAS: dorsal acoustic stria; DC: dorsal cortex of the inferior colliculus; DCN: dorsal cochlear nucleus; DMPO: dorsomedial periolivary nucleus; DNLL: dorsal nucleus of the lateral lemniscus; EC: external cortex of the inferior colliculus; IAS: internal acoustic stria; IC: inferior colliculus; INLL: intermediate nucleus of the lateral lemniscus; LSO: lateral superior olivary nucleus; mc: magnocellular division of the medial geniculate body; MGB: medial geniculate body; MNTB: medial nucleus of the trapezoid body; MSO: medial superior olivary nucleus; PGCL: lateral paragigantocellular nucleus; PnC: caudal pontine reticular nucleus; PnO: oral pontine reticular nucleus; PO: periolivary nuclei; pm: posteromedial part of the ventral nucleus of the lateral lemniscus; PVCNa: anterior part of the posteroventral cochlear nucleus; PVCNp: posterior part of the posteroventral cochlear nucleus; sag: sagulum; SC: superior colliculus; SPN: superior paraolivary nucleus; TB: trapezoid body; VCN: ventral cochlear nculeus; VLMN: ventral medullary nucleus; VLTg: ventral tegmental area; vm: ventromedial part of the ventral nucleus of the lateral lemniscus; VNLL: ventral nucleus of the lateral lemniscus.
The Cochlear Nucleus
Targets within the Cochlear Nucleus
- Intrinsic connections (axons from interneurons)
- Commissural fibers (from the other cochlear nucleus)
Targets to the Cochlear Nucleus
Auditory
- Cortex
- Inferior
f
colliculi
- Medial olivary complex (MOC)
Non-auditory
- Trigeminal nucleus
- Reticular formation
- others..
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The Cochlear Nucleus
Gross Anatomy
Pathways (afferents and efferents)
Cell types
Synaptic Circuitries (intrinsic connections)
Specialized Synapses
Plasticity: deafness and hearing loss
Cajal
Neurons as independent entities
Neuron doctrine
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The Structure of a Neuron
Dendrites - branching fibers that get
narrower as they extend from the
cell body toward the periphery;
information- receiver
Dendritic spines - short outgrowths
that increase the surface area
available for synapses
Cell body - contains the nucleus and
other structures found in most cells
Axon - thin fiber of constant diameter,
in most cases longer then the
dendrites; informationinformation sender
Myelin sheath - insulating material
covering the axons; speed up
communication in the neuron
Presynaptic terminal - the point on the
axon that releases chemicals
Martinotti
Cajal-Retzius
Sertoli
Deiters
Golgi
Purkinje
Lugaro
Meynert
Stellate
Multipolar
Bi l
Bipoloar
Unipolar
Pseudo-unipolar
Octopus
Mitral
Horizontal
Pyramidal
Globular
Fusiform
Granule
Spherical
Projection
Motor
Sensory
Basket
Interneuron
Local
Horizontal
Tuberculoventral
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Neuronal types
Dendritic arborization
Body shape
Function
Dendrites exhibit enormously
diverse forms
The shape of the dendritic arbor
can be related to the of connectivity
among neurons
Complexity of dendrites reflects
the number of connections that
a neuron receives
Cajal
Terms Associated with Neurons
Intrinsic/interneuron -the cell’s dendrites and axon’s are
entirely contained within a single structure
Projection neuron -the cell’s dendrites and axon’s are
contained in different structures
Efferent axon -carries information away from the
structure
Afferent axon -brings information into a structure
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The Cochlear Nucleus
Cytoartichecture
(cell types)
Cajal
Principal neurons (Projection neurons)
Other (interneurons)
The Cochlear Nucleus
Each cochlear nucleus cell type has a unique pattern
of response to sound, consistent wit the idea that each
type is involved in a different aspect of the analysis of the
information of the auditory nerve.
Cajal
The diversity of the pattern can be accounted for by three
features that vary among the principal cells:
1) The pattern of the innervation of the cell by the AN fibers
2) The electrical properties of the cells that shape synaptic inputs
3) The interneuronal circuitry associated with the cell
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The Cochlear Nucleus
Cytoartichecture
Principal neurons (Projection neurons)..
Cajal
.. are arranged in such a way that each type receives input
from AN fibers over the whole tonotopic range. Each principal
cell type carries a separate but complete representation of the
sound coming to the ear on that side of the head.
Project to different targets in the brainstem, they form separate,
parallel pathways
Other (interneurons)
The Cochlear Nucleus
Cytoartichecture
Old classification
Santiago Ramon y Cajal
Rafael Lorente de No
Cajal
Modern Classification
Kristen Osen (1969)
Kent Morest / Nell Cant and colleagues (1974-1984)
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The Cochlear Nucleus
Ventral Cochlear Nucleus (VCN)
Anterior (AVCN)
Posterior (PVCN)
Sound localization in the lateral plane!!
Timing!!!!
The Ventral Cochlear Nucleus (VCN): AVCN
Timing!!!!
Bushy cells
Spherical bushy cells (SBC) (+)
Globular bushy cells (GBC) (+)
Multipolar cells
D-stellate (+)
( )
T-stellate (-)
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The Ventral Cochlear Nucleus (VCN): AVCN
Timing!!!!
Bushy cells
- Spherical bushy cells (SBC) (+):
located in the most rostral region
short dendrites that terminate in a
“bush”
Multipolar cells
located more caudally
y
multiple, long dendrites
T-stellate (-) (planar)
dendrites aligned with AN fibers
D-stellate (+) (radiate)
dendrites not aligned with AN fibers
- Globular bushy cells (GBC) (+)
located more caudally
more ovoid and larger cell bodies
Projections differ
1-2 short dendrites
AN on cell body and dendrites
/different coverage
Projections differ / axons have collateralss
Posteroventral Cochlear Nucleus (PVCN)
“teardrop-shaped area”
Octopus cells
Dendrites are:
- oriented, inspiring their name
- perpendicular to the AN fibers/
- receive a wide range of best frequencies (BFs)
Cell bodies low BF / dendrites towards high BF
Oertel D et al. PNAS 2000
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Rostral
Caudal/Posterior
Hackney et al., 1990
The Cochlear Nucleus
Anterior (AVCN) / Posterior (PVCN)
Dorsal Cochlear Nucleus (DCN)
In nonprimate mammals, the DCN is thought to
play a role in the orientation of the head toward
sounds of interest by integrating acoustic &
somatosensory information
Cajal
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The Dorsal Cochlear Nucleus: Cytoartichecture
Layered structure
Molecular Layer
(ML)
Fusiform Layer
(FCL)
Deep layer
(DL)
Cajal
The Dorsal Cochlear Nucleus: Cytoartichecture
Schematic rendering of part of the circuit of the dorsal cochlear nucleus, looking en face at an isofrequency sheet (top), and looking down from the top of the nucleus at 3 such sheets (bottom).
Hackney et al., 1990
Paul Manis (Chapel Hill North Caroline)
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DCN
Principal Neurons
(projection neurons)
DCN main
interneurons
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The Dorsal Cochlear Nucleus: Cytoartichecture
Layered structure
Molecular Layer (ML)
Cartwheel cells (-)
Stellate cells (-)
Dendrites off ….
Axons of…..
Fusiform Layer (FCL)
Cartwheel cells (-)
Fusiform or pyramidal
cells (+)
Granule cells (+)
Dendrites of….
A
Axons
off …
Deep layer (DL)
Vertical cells (-)
Giant (multipololar)
cells (+)
Dendrites of ….
Axons of ….
The Dorsal Cochlear Nucleus: Cytoartichecture
To the immediate left is a f
schematic rendering of part of the circuit of the dorsal cochlear nucleus, looking en face at an isofrequency sheet (top), and looking down from the top of the nucleus at 3 such sheets (bottom). Pyramidal cells, cartwheel cells, stellate cells, vertical cells, and granule cells.
Paul Manis (Chapel Hill North Caroline)
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Brainstem targets of seven cell types in the ventral cochlear nucleus (A–G) and two cell types in the dorsal cochlear nucleus (H, I). For each cell type the heavy black line indicates the projections that have been identified directly or for which there is solid indirect evidence (see text). The route out of the cochlear nucleus taken by the axons (trapezoid body, )
intermediate or dorsal acoustic stria) is indicated at the origin of the line. The boxes indicate the multiple brainstem targets of the cochlear nucleus; those that are not known to receive inputs from the cell in question are shown in gray outline, and those that do receive inputs are shown in black outline and labeled. The boxes are in the same positions on all parts of the figure. Abbreviations are same as in slide #9; also: POL, lateral periolivary group; POV, ventral periolivary group. (A) Large spherical bushy cell. Dashed line in box labeled MSO indicates that the projection is to only one‐half of the nucleus. (B) Small spherical bushy cell. The LSO is the only known target of these cells. The dashed line ending in a question mark indicates that very little is known about their projections. (C) Globular bushy cell. The projection to LSO has been described in rat but appears to be minor or absent in cats (see text). (D) Octopus cell. (E) Cochlear root neuron. (F) Type I multipolar cell. The LSO and lateral PO groups receive inputs from multipolar cells in the VCN, but it has not been established that these arise from the type I multipolar cells. (G) Type II multipolar cell. (H) Fusiform cell of the DCN. (I) Giant cell of the DCN.
Cant and Benson 2003 Cochlear Nucleus
Parallel Pathways
to IC
Py/Gi
PON & nLL
O
DAS
& IAS
LSO
M
LSO
MSO
MSO
SBC
IHC
GBC
SBC
LnTB
TB
Contra
CN
MnTB
ANF
(modified from Oertel and Young)
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The Cochlear Nucleus
Synaptic circuits
VCN
DCN
Cajal
Human
The auditory pathway
The Cochlear Nucleus as Experimental Model
(rodents; primates)
FUSIFORM CELLS
dorsal cochlear nucleus (DCN)
CARTWHEEL
CELLS
PF
GRANULE
CELLS
VERTICAL
CELLS
EXTRINSIC
INHIBITORY
INPUT
SOMATOSENSORY
INPUT
AUDITORY
NERVE
BUSHY CELLS
ventral cochlear nucleus (VCN)
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Chemical Synapses
Gray Type I: excitatory
Gray Type II: inhibitory
Types of contacts:
Axo-dendritic
Axo-somatic
Dendro-dendritic
Axo-axonic
Glutamate
Acetylcholine
GABA
Glycine
dendrite
Spiny
Non-spiny
Electron microscopy: Ultrastructure
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Glutamate
Acetylcholine
Ultrastructure of Synapses
GABA
Glycine
Multiple Cell Types
Pyramidal Cells
Purkinje Cells
Fusiform Cells
Granule Cells
Afferents
Efferents
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VCN:
The Core
The granular cell domain (GCD; cap)
DCN (layered):
1 Molecular layer
2 Fusiform cell layer
3D
Deep llayer
FUSIFORM CELLS
in the dorsal cochelar nucleus (DCN)
PF
CARTWHEEL
CELLS
GRANULE
CELLS
VERTICAL
CELLS
EXTRINSIC
INHIBITORY INPUT
SOMATOSENSORY
INPUT
AUDITORY
NERVE
BUSHY CELLS
in the anteroventral cochlear nucleus (AVCN)
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The Cochlear Nucleus
Synaptic circuits
VCN
DCN
Synaptic specializations
Deafness and Hearing Loss models
Cajal
Presynaptic membrane
Postynaptic membrane
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Targets of the Auditory nerve in ventral and dorsal divisions of
the cochlear nucleus
FUSIFORM CELLS
in the dorsal CN
Contralateral
Inferior Colliculus
(IC)
Type I
BCs and FCs receive glutamatergic innervation
from the AN, but they respond differently to
sound, they also have different pathways in the
brain. Different morphological characteristics
and the arrangement of neurotransmitter
receptors at those synapses can vary to
facilitate the functional role of each synapse.
dendrite/
cell body
Contralateral
Medial Nucleus of
the Trapezoid Body
(MNTB)
Glycine R:
⟨1, ⟨3?, ®
GABA?
AUDITORY
NERVE
AMPA: GluR2-4
NMDA
mGluRs
BUSHY CELLS
in anteroventral CN
Electron microscopy: Ultrastructure /
Molecular components
AN
AN
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SDS-freeze fracture labeling
(SDS-FRL)
C-terminus
Abs
N-terminus Abs
Gomez-Nieto and Rubio 2009 JCN
Modified from Fujimoto 1995 J Cell Sci
IMP (intramembrane particle) cluster
of Bushy cells
IMPS in basal
dendrites of
Fusiform cells
E-face
AN
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IMP clusters of AN-BC synapses
are compact
IMP clusters of AN-FC synapses
are less compact
DCN: Molecular Layer
Membranes of Cartwheel cell - spines
PF
Golgi-TEM
CwC
AMPARs:
GluR1
GluR2
GluR3
little GluR4
NMDARs:
NR1
Metabotropic
Delta 1/2
These synapses
are plastic:
LTP
(long term potentation)
LTD
(long term depresion)
Wouterlood and Mugnaini JCN ‘84
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PF
CwC
DCN: Molecular Layer
IMP clusters of synapses involved in synaptic plasticity are large
and very irregular in shape
panAMPA (5nm) + NR1 (10nm)
GluR3 (5nm)
Average area IMPs = 0.074+0.015um2
Inhibitory Synapses
GABA and/or Glycine Receptors
Excitatory Synapses
Glutamate Receptors
Ionotropic
AMPA
NMDA
Kainate
Delta
Metabotropic
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Low levels of GluR2 AMPA receptor subunit in the AVCN
GluR2
GluR2/3
The GluR2 subunit is
important for Ca++
permeability.
Low levels of GluR2
makes the AN-BC
Synapse permeable to
Ca++.
GluR2
GluR2/3
Wang et al.,1998
Relevance of Glutamate receptors in the
Excitatory Synaptic Circuit of Fusiform Cells in
the Dorsal Cochlear Nucleus
slow?
PF
Parallel Fibers
AN
fast?
GluR1
GluR2
GluR3
GluR4
NR1
NR2A/B
mGluR1a
Delta 1/2
Auditory Nerve
Rubio and Wenthold 1997 Neuron
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Postembedding immunocitochemistry for AMPA
receptors subunits at excitatory synapses on
fusiform cells revealed
a differential subunit distribution
Parallel Fibers
Auditory Nerve
Rubio and Wenthold 1997 Neuron
Glutamate receptors are
selectively targeted to
postsynaptic sites in neurons
slow?
fast?
Receptors
NUMBER OF GOLD PARTICLES
PER ⎧m OF PSD +SEM
Auditory Nerve Synapses
(basal dendrites)
Parallel Fiber Synapses
(apical dendrites)
17.7 + 4.0
9 1 + 1.1
9.1
11
19.1 + 2.2
6.4 + 1.4
8.0 + 1.3
8.3 + 1.2
16.5 + 3.2
72 + 1
7.2
1.2
2
0
9.8 + 1.3
0
33.9 + 3.1
GluR2/3
GluR2
GluR4
NR2A/B
mGluR1⟨
Delta1/2
Rubio and Wenthold 1997 Neuron
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The Cochlear Nucleus
Synaptic circuits
VCN
DCN
Synaptic specializations
Deafness and Hearing Loss models
Cajal
Deafness and Hearing Loss Plasticity
Molecular-Anatomical approach
Ryugo lab
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Deafness affects the Auditory Nerve Synapse on Bushy Cells Cat CN (Ryugo and Parks, 2003)
Deafness affects the Auditory Nerve Synapse on Bushy Cells Reconstruction of serial electron micrographs
Cat CN (Ryugo and Parks, 2003)
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Time frame after peripheral damage
Unilateral cochlear ablation
D
Degeneration
ti off auditory
dit
nerve fibers
fib
Day 1
Day 0
4 hours
Sprouting
2 days
7 days
ABR
Rubio 2006 Hearing Research
Morphological changes at the postsynaptic sites precede presynaptic
changes at the AN ending in response to peripheral damage
Control
X
Thickn
ness in nm
60
*
4 hours
Control
Ipsilateral side
Rubio 2006 Hearing Research
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Summary/Conclusions:
The synapse is plastic
The auditory nerve maintains synapse morphology
Do changes in synapse morphology reflect function?
Neurotransmitter Receptors
Inhibitory Synapses
GABA and/or Glycine Receptors
Excitatory Synapses
Glutamate Receptors
p
Ionotropic
AMPA
NMDA
Kainate
Delta
Metabotropic
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=?
DNA
RNA
PROTEIN
Changes in AMPA receptors accumulation
Davis 2006 Ann Rev Neurosci
Chronic suppression of neuronal
activity can also lead to
compensatory changes in the
surface expression of excitatory
and inhibitory neurotransmitter
receptors: quantal signaling
Turrigiano and Nelson 2004 Nature Rev Neurosci
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FUSIFORM CELLS
in the dorsal cochelar nucleus (DCN)
PF
CARTWHEEL
CELLS
GRANULE
CELLS
VERTICAL
CELLS
EXTRINSIC
INHIBITORY INPUT
SOMATOSENSORY
INPUT
AUDITORY
NERVE
BUSHY CELLS
in the anteroventral cochlear nucleus (AVCN)
Does conductive hearing loss
lead to changes in the expression
of neurotransmitter receptors
in the adult CNS?
A unilateral
An
il t
l ear-plugging
l
i model
d l
to asses the role of activity
in synaptic organization
Questions to investigate:
1) Whether hearing loss alters the composition of synaptic AMPAR in
cochlear nucleus neurons receiving the AN. Do they respond in the same
manner?
3) Whether cochlear neurons respond to hearing loss by downregulating
synaptic glycine receptors.
2) Whether these changes occurred in a relatively short time (1 day) after
unilateral earplug. Are the changes reversible?
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Ear plug provides ~20 dBA attenuation
ABR response was determined before ear-plugging and quantified by measuring the
latency of P2 as a function of stimulus intensity
Whiting, Moiseff, Rubio 2009 Neuroscience
AN
Plugged Side
AN
SBC
Auditory Nerve/Bushy cell synapse in
VCN responds to earplugging
GluR2/3
SBC
GluR2
AN
AN
SBC
SBC
AN
SBC
AN
GluR4
SBC
Normal Hearing
Density of gold particles/ length of PS
SD
Normal Hearing
45
40
35
30
25
20
15
10
5
0
***
45
40
35
30
25
20
15
10
5
0
45
40
35
30
25
20
15
10
5
0
Plugged side (1 day)
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Plugged Side
AN
AN
GluR2/3
FC
FC
AN
GluR2
AN
FC
Auditory Nerve/Fusiform
cell synapse in DCN
responds to earplugging
FC
AN
GluR4
AN
FC
Density
y of gold particles/ length of PSD
D
Normal Hearing
FC
Normal Hearing
45
40
35
30
25
20
15
10
5
0
***
45
40
35
30
25
20
15
10
5
0
45
40
35
30
25
20
15
10
5
0
***
Plugged side (1 day)
1-day earplugging scales synaptic AMPA receptors at the
auditory nerve on bushy and fusiform cells synapses
Densitty of gold particles/ length of PSD
Normal Hearing
Plugged side (1 day)
Unplugged side (1 day)
45
40
35
30
25
20
15
10
5
0
***
*
FUSIFORM CELLS
In DCN
***
Hearing loss
(20dBA attenuation)
45
40
35
30
25
20
15
10
5
0
BUSHY CELLS
in AVCN
***
**
AUDITORY
NERVE
GluR2/3
GluR2
GluR4
2 animals per group
50 synapses per each condition and antibody
ANOVA
*** P<0.005
* P<0.05
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Parallel fibers do not
show scaling of
AMPA receptors
in response
to earplugging
p gg g
1-day earplugging scales down the synaptic expression of
GlyR⟨1 on bushy and fusiform cells
Plugged Side
Density of gold
particles/ length of P
PSD
AN/Fusiform cells in DCN
45
40
35
30
25
20
15
10
5
0
*
*
Normal Hearing
Plugged Side (1 day)
Unplugged Side (1 day)
AN/Bushy cells in AVCN
Density of gold
particles/ length of PSD
Normal Hearing
45
40
35
30
25
20
15
10
5
0
***
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Synaptic changes in AMPA (GluR3) and GlyR⟨1 receptors
are reversible after ear plug removal
AUDITORY
NERVE
Excitatory/glutamatergic synapses
are found in the E-face membranes
G ll
Gulley,
Wenthold
W th ld and
d Neises
N i
1977
C-terminus
Abs
N-terminus Abs
Modified from Fujimoto 1995 J Cell Sci
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SDS-freeze fracture labeling
(SDS-FRL)
IMP (intramembrane particle) cluster
E-face
Average area IMPs = 0.033+0.004um2
Bushy cells (BC)
David
Ryugo
The Glur3 AMPAR subunit is a major component of the
Auditory Nerve-Bushy Cell synapse
panAMPA
GluR2
GluR3
GluR4
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SDS-FRL detects an upregulation of the GluR3 AMPAR subunit at the
Auditory nerve-Bushy cell synapse in response to hearing loss
Normal Hearing
Earplugged
as well as morphological changes in the IMP cluster
pan-AMPA
GluR3
Student t-test p<0.005
Conclusions:
Hearing reduction leads to changes in synaptic expression
GluR3 and GlyR⟨1 in neurons directly influenced by the AN.
These changes
g are fast,, depend
p
on the cell type
yp and synapse
y p
and are reversible.
The same neurons in the DCN contralateral to the hearing
reduction and with normal AN synaptic input also redistribute
synaptic GluR3 but differ in the expression of GlyR⟨1.
Conductive hearing loss leads to morphological changes of the
AN BC synapse,
AN-BC
synapse and seems to alter intramembrane particles
particles.
The data suggest that the imbalance caused by attenuation of
sound may be compensated by an increase in the excitatory
and a decrease in the inhibitory receptors expression.
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Levels of Brain Organization
Behavioral System
Interregional Circuits
Local (Regional) Circuits
Neurons
Dendritic Trees
Synaptic Microcircuits
Synapses
Molecules Ions
Genes
DCN
ML
PF
PF
CwC
GC
FCL
DL
spine
SS
FC
AN
In nonprimate mammals, the DCN is thought to play a role in the orientation of
the head toward sounds of interest by integrating acoustic & somatosensory
information
(synaptic circuitry; lamination; specific distribution of key proteins; synaptic plasticity)
A putative source for tinnitus
HOWEVER
HOWEVER…..!!!!
!!!!
Humans & higher primates might not use this system because of
reported phylogenetic changes in DCN cytoartichecture & associated
granule cell regions
Rubio et al. 2008 Neuroscience
41
6/1/2010
Phylogenetic changes in DCN cytoartichecture & associated granule cell regions
CAT
ml / fgl / cr
MARMOSET
egl / ml / fl / cr
GIBBON
pbf / mz / cr
floc
ml
egl
pbf
ml
fgl
fl
cr
AVCN
m
mz
AVCN
cr
cr
PVCN
PVCN
PVCN
AVCN
lat
Granular layer
External granular layer
Pbf: pontobulbar fibers
post
(modified from Moore 1980)
egl
pbf
ml
mz
ml
fl
fl
fl
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